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Racovitan V, Goodman E, Cheung WY, Nichols AC, Caulley L, Wurzba S. Human papillomavirus (HPV) related oropharyngeal cancers in Canada: A multicenter retrospective cohort study. Hum Vaccin Immunother 2025; 21:2486768. [PMID: 40264440 PMCID: PMC12026042 DOI: 10.1080/21645515.2025.2486768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/13/2025] [Accepted: 03/27/2025] [Indexed: 04/24/2025] Open
Abstract
Oral human papillomavirus (HPV) infection is a risk for oropharyngeal cancer (OPC), now the leading HPV-related cancer in males in Canada. P16 positivity is a marker of HPV positivity. Since 2015, all major Canadian cancer centers perform routine p16 tumor marker testing of OPCs to define their HPV status but recent data on the HPV-attributable fraction for OPC in Canada do not exist. A retrospective chart review was conducted of all squamous cell OPC cases in patients 18 years and older diagnosed from 2016 to 2020 in 4 major Canadian hospital-based regional oncology centers to determine the HPV attributable fraction for OPC in Canada using p16 as a surrogate marker for HPV. 1154 OPC cases were identified. Most patients (85.4%) were male; about one-third 26 (31.4%) had never smoked. Most OPC (80.6%) were P16 positive. p16 positivity was 27 associated with younger age (mean age p16+ 61.6 vs. p16- 66.5 years, p < 0.0001), male sex 28 (p16+ males 84.0% vs p16+ females 60.9%, p < 0.0001), lower tumor stage (Stage 1 p16+ 29 88.1% vs Stage 4 p16+ 69.4%, p < 0.001), and non-smoking (never smoked 92.3% vs past 30 smoker 82.8% vs current smoker 65.0%, p < 0.001). Logistic regression confirmed these 31 associations. This study, the largest cohort of Canadian patients with OPC yet reported, demonstrates the high attributable fraction for HPV-related OPC. HPV-related OPC was more likely in men, younger individuals, and never smokers. These findings highlight the burden of HPV-related OPC in Canada and support gender-neutral HPV vaccination as an important public health strategy to prevent head and neck cancer.
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Affiliation(s)
- Voica Racovitan
- Global Marketing HPV Strategy, Merck & Co. Inc ., North Wales, PA, USA
| | - Elizabeth Goodman
- Vaccine Outcomes Research, Value and Implementation, Merck and Co., Inc ., North Wales, PA, USA
| | - Winson Y. Cheung
- Departments of Medicine and Oncology, University of Calgary and the Charbonneau Cancer Institute, Calgary, AB, Canada
| | - Anthony C. Nichols
- Department of Otolaryngology – Head and Neck Surgery, University of Western Ontario, London, ON, Canada
| | - Lisa Caulley
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Sabrina Wurzba
- Department of Otolaryngology – Head and Neck Surgery, McGill University and the Jewish General Hospital, Montreal, QC, Canada
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Xue N, Wen X, Wang Q, Shen Y, Qu Y, Xu Q, Chen S, Chen J. Establishing and validating models integrated with hematological biomarkers and clinical characteristics for the prognosis of non-esophageal squamous cell carcinoma patients. Ann Med 2025; 57:2483985. [PMID: 40152751 PMCID: PMC11956093 DOI: 10.1080/07853890.2025.2483985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 03/11/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND This study aimed to construct a novel model and validate its predictive power in non-esophageal squamous cell carcinoma (NESCC) patients. METHODS This retrospective study included 151 patients between October 2006 and September 2016. The LASSO Cox and Random Survival Forest (RSF) models were developed with the help of hematological biomarkers and clinical characteristics. The concordance index (C-index) was used to assess the prognostic power of the LASSO Cox model, RSF model, and TNM staging. Based on the risk scores of the LASSO Cox and RSF models, we divided patients into low-risk and high-risk subgroups. RESULTS We constructed two models in NESCC patients according to LASSO Cox regression and RSF models. The RSF model reached a C-index of 0.841 (95% CI: 0.792-0.889) in the primary cohort and 0.880 (95% CI: 0.830-0.930) in the validation cohort, which was higher than the C-index of the LASSO Cox model 0.656 (95% CI: 0.580-0.732) and 0.632 (95% CI: 0.542-0.720) in the two cohorts. The integrated C/D area under the ROC curve (AUC) values for the LASSO Cox and RSF models were 0.701 and 0.861, respectively. In both two models, Kaplan-Meier survival analysis and the estimated restricted mean survival time (RMST) values indicated that the low-risk subgroup had a better prognostic outcome than the high-risk subgroup (p < 0.05). CONCLUSIONS The RSF model has better prediction power than the LASSO Cox and the TNM staging models. It has a guiding value for the choice of individualized treatment in patients with NESCC.
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Affiliation(s)
- Ning Xue
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou Key Laboratory of Digestive System Tumor Marker Diagnosis, Zhengzhou, P. R. China
| | - Xiaoyan Wen
- Central Sterilization Supply Department, The Guanghua Stomatological College of Sun Yat-sen University, Hospital of Stomatology, SunYat-sen University, Guangzhou, P. R. China
| | - Qian Wang
- Department of radiation oncology, China–Japan Union Hospital of Jilin University, Changchun, P.R. China
| | - Yong Shen
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou Key Laboratory of Digestive System Tumor Marker Diagnosis, Zhengzhou, P. R. China
| | - Yuanye Qu
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou Key Laboratory of Digestive System Tumor Marker Diagnosis, Zhengzhou, P. R. China
| | - Qingxia Xu
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou Key Laboratory of Digestive System Tumor Marker Diagnosis, Zhengzhou, P. R. China
| | - Shulin Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
- Research Center for Translational Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P. R. China
| | - Jing Chen
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou Key Laboratory of Digestive System Tumor Marker Diagnosis, Zhengzhou, P. R. China
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van der Hoek JL, Snoeijink TJ, Mirgolbabaee H, Kunst R, Versluis M, Arens J, Manohar S, Groot Jebbink E. Ultrasound contrast microbubbles to predict the microsphere distribution during transarterial radioembolization with holmium microspheres, an in vitro proof of concept study. Drug Deliv 2025; 32:2505007. [PMID: 40384014 PMCID: PMC12090288 DOI: 10.1080/10717544.2025.2505007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 04/23/2025] [Accepted: 05/07/2025] [Indexed: 05/20/2025] Open
Abstract
Transarterial radioembolization (TARE) is an established treatment method for non-resectable liver tumors. One of the challenges of the approach is the accurate prediction of the microsphere biodistribution in the liver. We propose to use ultrasound contrast microbubbles as holmium microsphere precursors, which allows real-time prediction of the microsphere trajectories and biodistribution using dynamic contrast-enhanced ultrasound (DCE-US). The immediate goal in this in vitro study was to investigate the predictive capabilities of microbubbles as microsphere precursors. The study was conducted in an experimental in vitro model which represents the bifurcating right branch of the hepatic artery. A controlled injection of experimental BR-14 ultrasound contrast microbubbles and non-radioactive holmium-165 microspheres was performed in separate consecutive experiments in an arterial flow phantom. The microbubbles and microspheres were collected separately at the outlets of the phantom and counted using a Coulter counter to determine their distribution over the different outlets. The flow profile, the injection velocity, and the catheter position were monitored during the measurements to ensure stability. The results showed a good correlation between the microbubble and the microsphere distributions (p = 0.0038, r = 0.88) measured at the outlets. Differences in the distributions could be attributed to the characteristics of microbubbles and microspheres alone (e.g. particle size and concentration), since critical parameters were kept stable between the two experiments. The current in vitro study provides confidence that the microsphere biodistribution can be predicted using contrast microbubbles. The comparison provided by this study forms a foundation for the development of a DCE-US guided TARE treatment.
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Affiliation(s)
- Jan L. van der Hoek
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
| | - Tess J. Snoeijink
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
- Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Hadi Mirgolbabaee
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
- Physics of Fluids Group, TechMed Center, University of Twente, Enschede, The Netherlands
| | - Romaine Kunst
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
| | - Michel Versluis
- Physics of Fluids Group, TechMed Center, University of Twente, Enschede, The Netherlands
| | - Jutta Arens
- Engineering Organ Support Technologies Group, Department of Biomechanical Engineering, University of Twente, Enschede, The Netherlands
| | - Srirang Manohar
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
| | - Erik Groot Jebbink
- Multi-Modality Medical Imaging Group, TechMed Center, University of Twente, Enschede, The Netherlands
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Roesel R, Strati F, Basso C, Epistolio S, Spina P, Djordjevic J, Sorrenti E, Villa M, Cianfarani A, Mongelli F, Galafassi J, Popeskou SG, Facciotti F, Caprera C, Melle F, Majno-Hurst PE, Franzetti-Pellanda A, De Dosso S, Bonfiglio F, Frattini M, Christoforidis D, Iezzi G. Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer. Oncoimmunology 2025; 14:2465015. [PMID: 39992705 PMCID: PMC11853554 DOI: 10.1080/2162402x.2025.2465015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 12/15/2024] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of Ruminococcus genera was consistently associated with CR, whereas abundance of Fusobacterium, Porhpyromonas, and Oscillibacter species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC.
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Affiliation(s)
- Raffaello Roesel
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Francesco Strati
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Camilla Basso
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Samantha Epistolio
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Paolo Spina
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Julija Djordjevic
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Elisa Sorrenti
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Martina Villa
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Agnese Cianfarani
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Francesco Mongelli
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Jacopo Galafassi
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Sotirios G. Popeskou
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Federica Facciotti
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
| | - Cecilia Caprera
- Division of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Federica Melle
- Division of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Pietro Edoardo Majno-Hurst
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | | | - Sara De Dosso
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Department of Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Ferdinando Bonfiglio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy
- CEINGE Advanced Biotechnology Franco Salvatore, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Milo Frattini
- Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland
| | - Dimitrios Christoforidis
- Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
- Department of Visceral Surgery, CHUV, University of Lausanne, Lausanne, Switzerland
| | - Giandomenica Iezzi
- Laboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
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Fan HL, Chen JL, Liu ST, Lee JT, Huang SM, Wu ZF, Lai HC. Remimazolam induced cytotoxicity mediated through multiple stress pathways and acted synergistically with tyrosine kinase inhibitors in hepatocellular carcinoma. Redox Rep 2025; 30:2475696. [PMID: 40053437 PMCID: PMC11892054 DOI: 10.1080/13510002.2025.2475696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2025] Open
Abstract
The primary treatment for hepatocellular carcinoma (HCC) involves surgical removal of the primary tumor, but this creates a favorable environment for the proliferation and spread of residual and circulating cancer cells. The development of remimazolam-based balanced anesthesia is crucial for future antitumor applications. It is important to understand the mechanisms of cytotoxicity for HCC in detail. We performed cell viability analysis, western blotting analysis, reverse transcription-polymerase chain reaction analysis, and flow cytometry analysis in two HCC cell lines, HepG2 and Hep3B cells. Our data demonstrated that remimazolam induced cytotoxicity by suppressing cell proliferation, inhibiting G1 phase progression, and affecting mitochondrial reactive oxygen species (ROS) levels, leading to apoptosis, DNA damage, cytosolic ROS elevation, lipid peroxidation, autophagy, mitochondrial depolarization, and endoplasmic reticulum stress. Inhibitors of apoptosis, autophagic cell death, and ferroptosis and a ROS scavenger failed to rescue cell death caused by remimazolam besylate. Our combination index revealed that remimazolam besylate has the potential to act as a sensitizer for targeted tyrosine kinase inhibitor therapy for HCC. Our findings open up new possibilities for combinatory HCC therapy using remimazolam, leveraging its dual functional roles in surgery and drug therapy for liver cancers.
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Affiliation(s)
- Hsiu-Lung Fan
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China
| | - Jia-Lin Chen
- Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Shu-Ting Liu
- Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China
| | - Jia-Tong Lee
- Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China
| | - Shih-Ming Huang
- Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China
| | - Zhi-Fu Wu
- Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of China
- Department of Anesthesiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of China
- Center for Regional Anesthesia and Pain Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan, Republic of China
| | - Hou-Chuan Lai
- Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China
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Luo Y, Zhong X, Sun X, Fan J. The RNA-binding protein ELAVL1 promotes Beclin1-mediated cellular autophagy and thus endometrial cancer development by affecting LncRNA-neat stability. Cancer Biol Ther 2025; 26:2469927. [PMID: 40018990 PMCID: PMC11875488 DOI: 10.1080/15384047.2025.2469927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 12/18/2024] [Accepted: 02/17/2025] [Indexed: 03/01/2025] Open
Abstract
Our study aims to investigate the roles of embryonic lethal abnormal vision-like 1 (ELAVL1) and long non-coding RNA (LncRNA) NEAT1 in endometrial cancer (EC), focusing on their underlying molecular mechanisms.We obtained EC cell lines (HEC-1A, Ishikawa, RL95-2, HEC-1B, and AN3CA) from ATCC. We used siRNAs (si-ELAVL1#1 and si-ELAVL1#2) and overexpression RNAs (OE ELAVL1 and OE-NEAT1) for knockdown or overexpression of ELAVL1 and LncRNA NEAT1. We also employed 3-MA (5mM) or rapamycin (100µM) to inhibit or promote autophagy. Moreover, we conducted RNA immunoprecipitation (RIP) assays to confirm the interaction between LncRNA NEAT1 and ELAVL1. Cell Counting Kit-8 (CCK-8) and transwell assays were utilized to assess cell proliferation and migration. Additionally, we measured the expression of ELAVL1 and Beclin1 through Western blotting and RT-qPCR.ELAVL1 was found to be highly expressed in EC. Furthermore, ELAVL1 promoted the proliferation, invasion, and migration of EC cells through the regulation of Beclin1-related pathways. RIP assays revealed a direct interaction between LncRNA NEAT1 and ELAVL1, with ELAVL1 stabilizing LncRNA NEAT1 mRNA in EC cells. Additionally, we observed that ELAVL1 influenced EC cell proliferation, invasion, and migration through the regulation of LncRNA NEAT1-mediated regulation of Beclin1 expression. Moreover, in an animal study, we determined that ELAVL1 influenced endometrial cancer tumor growth through its interaction with LncRNA NEAT1, which mediated Beclin1 expression in vivo.In summary, our study showed that ELAVL1 regulated the malignant behavior of endometrial cancer cells through the modulation of LncRNA NEAT1-mediated regulation of Beclin1 expression.
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Affiliation(s)
- Yanlu Luo
- Department of Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
| | - Xueyan Zhong
- Department of Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
| | - Xinzhao Sun
- Department of Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
| | - Jiangtao Fan
- Department of Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
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Ulhe A, Raina P, Chaudhary A, Kaul-Ghanekar R. Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines. Epigenetics 2025; 20:2451551. [PMID: 39895102 PMCID: PMC11792827 DOI: 10.1080/15592294.2025.2451551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 11/25/2024] [Accepted: 01/02/2025] [Indexed: 02/04/2025] Open
Abstract
Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5' CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.
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Affiliation(s)
- Amrita Ulhe
- Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Prerna Raina
- Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
- Analytical Department (ADT), Lupin Limited, Pune, India
| | - Amol Chaudhary
- Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Ruchika Kaul-Ghanekar
- Cancer Research Lab, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
- Symbiosis Centre for Research and Innovation (SCRI); Symbiosis International Deemed University (SIU), Pune, India
- Cancer Research Lab, Symbiosis School of Biological Sciences (SSBS), Symbiosis International Deemed University (SIU), Pune, India
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8
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Huang G, Yu Y, Su H, Gan H, Chu L. Integrating RNA-seq and scRNA-seq to explore the prognostic features and immune landscape of exosome-related genes in breast cancer metastasis. Ann Med 2025; 57:2447917. [PMID: 39847423 PMCID: PMC11758802 DOI: 10.1080/07853890.2024.2447917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 08/27/2024] [Accepted: 12/05/2024] [Indexed: 01/24/2025] Open
Abstract
OBJECTIVE This study aims to explore the role of exosome-related genes in breast cancer (BRCA) metastasis by integrating RNA-seq and single-cell RNA-seq (scRNA-seq) data from BRCA samples and to develop a reliable prognostic model. METHODS Initially, a comprehensive analysis was conducted on exosome-related genes from the BRCA cohort in The Cancer Genome Atlas (TCGA) database. Three prognostic genes (JUP, CAPZA1 and ARVCF) were identified through univariate Cox regression and Lasso-Cox regression analyses, and a metastasis-related risk score model was established based on these genes. Immune cell infiltration, immune escape and drug sensitivity disparities between high- and low-risk groups were assessed using CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) methods. High- and low-risk cell populations were discerned based on the expression of prognostic genes in BRCA scRNA-seq data. RESULTS M0 and M1 macrophages significantly promote the metastasis of breast cancer (BRCA). The developed prognostic model demonstrates good predictive performance for patient survival at 1, 3 and 5 years, with AUC values of 0.654, 0.602 and 0.635, respectively. Compared to the low-risk group, the high-risk group exhibits increased immune cell infiltration and higher levels of immune evasion. scRNA-seq data reveal that high-risk cells have significantly higher risk scores and exhibit notable differences in signalling pathways and intercellular communication patterns. CONCLUSIONS This study presents a novel risk score model based on exosome-related genes, validated by comprehensive analyses including differential expression, survival analysis and external dataset validation. The model's clinical significance is reinforced through its ability to stratify patients into high- and low-risk groups with distinct survival outcomes and immune landscape characteristics. The integration of RNA-seq and scRNA-seq data highlights the predictive accuracy of the model and underscores its potential for identifying novel therapeutic targets and improving patient prognosis.
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Affiliation(s)
- Guanyou Huang
- Department of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China
| | - Yong Yu
- Department of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China
| | - Heng Su
- Department of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China
| | - Hongchuan Gan
- Department of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China
| | - Liangzhao Chu
- Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China
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9
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Zheng HL, Zhang LK, Zheng HH, Lv CB, Xu BB, Lin GT, Chen QY, Lin JX, Zheng CH, Huang CM, Xie JW. Timing of postoperative chemotherapy and prognosis in neoadjuvant-treated gastric cancer patients: a multicenter real-world cohort study. Ann Med 2025; 57:2500690. [PMID: 40329795 PMCID: PMC12064125 DOI: 10.1080/07853890.2025.2500690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/27/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND The optimal time to chemotherapy (TTC) in locally advanced gastric cancer (LAGC) patients treated with neoadjuvant chemotherapy (NLAGC) remains unclear. METHODS Consecutive 524 patients with NLAGC between Jan. 2010 and Dec. 2022 were identified. Patients were categorized into three groups: TTC < 6w, 6w ≤ TTC ≤ 8w, and TTC > 8w. Survival analysis was conducted using the Cox proportional hazards model to assess the impact of TTC on gastric cancer-specific mortality (GCSM) and all-cause mortality (ACM). Cumulative competing risk curves were employed to evaluate the incidence of competing events. RESULTS Overall, 451 patients were included.Cumulative competing risk curves showed that the 3-year ACM and GCSM were significantly lower in the 6w ≤ TTC ≤ 8w group (ACM: 19.7% vs. 37.2% vs. 39.7%, GCSM: 19.7% vs. 35.2% vs. 38.8%) compared to the TTC < 6w and TTC > 8w groups. Compared to patients with 6w ≤ TTC ≤ 8w, those with TTC < 6w or >8w had an increased risk of GCSM (HR: 2.792 and HR: 2.343, respectively) and ACM (HR: 3.102 and HR: 2.719, respectively) after adjusting for confounders. Furthermore, 6w ≤ TTC ≤ 8w had later peak recurrence compared to TTC < 6w and TTC > 8w (Peak months: 9.7 vs. 4.3 vs. 3.1). CONCLUSION A postoperative chemotherapy timing of 6-8 weeks was associated with better survival and delayed recurrence in NLAGC patients. These findings suggest that the 6-8 week time-window should be a key timeframe for personalized postoperative adjuvant chemotherapy decisions.
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Affiliation(s)
- Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Ling-Kang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Hong-Hong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chen-Bin Lv
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Bin-Bin Xu
- Department of Digestive Endoscopy, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Guang-Tan Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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10
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Huang M, Ji Q, Huang H, Wang X, Wang L. Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification. Gut Microbes 2025; 17:2486519. [PMID: 40166981 PMCID: PMC11970798 DOI: 10.1080/19490976.2025.2486519] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 03/05/2025] [Accepted: 03/25/2025] [Indexed: 04/02/2025] Open
Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.
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Affiliation(s)
- Mingyao Huang
- School of Basic Medicine, Putian University, Putian, Fujian, China
- Department of Breast Surgery, Clinical Oncology School of Fujian Medical University, Fuzhou, Fujian, China
| | - Quansong Ji
- Department of Urology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Huiyan Huang
- Ward 3, De’an Hospital, Xianyou County, Putian, Fujian, China
| | - Xiaoqian Wang
- Department of Rehabilitation Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Lin Wang
- Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
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11
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Jimenez G, Foiani L, Figueiredo JT, Sá Alves M, Sá Rodrigues N, Bandeira CM, Alves MGO, Dias Almeida J, da Silva Martinho H. Histine, carbohydrates/polysaccharides, and proteins with β-sheet conformation as promising staging markers for oral squamous cell carcinoma. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 340:126296. [PMID: 40373546 DOI: 10.1016/j.saa.2025.126296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 02/04/2025] [Accepted: 04/23/2025] [Indexed: 05/17/2025]
Abstract
Cancers of the oral cavity and lip ranks 15th cancer mortality being oral squamous cell carcinoma (OSCC) the predominant malignant neoplasm in the head and neck region. Liquid optical biopsy using infrared absorption spectroscopy offers rapid and accurate diagnosis of several diseases, including oral cancer. Here we investigated saliva samples from patients with OSCC and healthy individuals using micro-reflectance Fourier-transform infrared absorption spectroscopy. Partial least squares discriminant (PLSDA) and support vector machine (SVM) analysis were employed to mining the set of data. SVM analysis validated the PLSDA findings and presented excellent results with sensitivity of 98.6%, specificity of 97.3%, and area under ROC curve of 0.965. Interestingly we found that bands assigned to histidine, carbohydrates/polysaccharides, and content of proteins with β-sheet conformation contributed to discrimination among groups. Moreover we found that specific changes in these bands could be related to OSCC staging being promising disease gravity markers.
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Affiliation(s)
- Gabrielle Jimenez
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), Av. dos Estados 5001, Santo André, 09210-580, SP, Brazil
| | - Letícia Foiani
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), Av. dos Estados 5001, Santo André, 09210-580, SP, Brazil
| | - Julia Toledo Figueiredo
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), Av. dos Estados 5001, Santo André, 09210-580, SP, Brazil
| | - Mariana Sá Alves
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Nayara Sá Rodrigues
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Celso Muller Bandeira
- Núcleo de Pesquisas Tecnológicas, Universidade Mogi das Cruzes, Mogi das Cruzes-SP, 08780-911, Brazil
| | - Mônica Ghislaine Oliveira Alves
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Janete Dias Almeida
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, São Paulo, Brazil
| | - Herculano da Silva Martinho
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC (UFABC), Av. dos Estados 5001, Santo André, 09210-580, SP, Brazil.
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12
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Yan X, Dong H, Gao L, Liu M, Wang C. Mechanism of selenium-doped black phosphorus nanosheets wrapped with biomimetic tumor cell membrane for prostate cancer immunotherapy. BIOMATERIALS ADVANCES 2025; 176:214339. [PMID: 40393102 DOI: 10.1016/j.bioadv.2025.214339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 04/28/2025] [Accepted: 05/05/2025] [Indexed: 05/22/2025]
Abstract
Prostate cancer (PCa) is commonly considered a "cold tumor" due to its immunosuppressive microenvironment. Cold tumors are typically identified by the absence of T-cell infiltration within the tumor, while other immune populations and myeloid cells can be observed in these tumors. To achieve light-heat combined immunotherapy checkpoint inhibitor treatment for castration-resistant prostate cancer, we aimed to transforming "cold tumors" into "hot tumors". We designed and synthesized a two-dimensional material, selenium-doped black phosphorus (BP), to enhance the photothermal conversion efficiency, and formed Se@BPNSs by liquid-phase exfoliation. To address the issue of enhanced permeability and retention effect, and to achieve efficient targeting, we coated the Se@BPNSs with RM-1 cell membrane derived from mouse prostate cancer cells. By injecting a certain dose of Se@BPNSs into the tumor and irradiating with a 808 nm laser, the Se@BPNSs converted light energy into heat to kill tumor cells at high temperatures while releasing antigens captured by dendritic cells. In addition, we combined the immunotherapy checkpoint inhibitor anti-PD1 to enhance the immune response and promote immune cell infiltration. The successful preparation of Se@BPNSs was verified through material characterization, cell-level and animal-level experiments, and the antitumor effect was meanwhile verified, which further provided guidance for prostate cancer treatment by photothermal synergistic immunotherapy.
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Affiliation(s)
- Xingjian Yan
- Department of Urology, The First Hospital of Jilin University, Changchun City, Jilin Province 130021, China.
| | - Han Dong
- Department of Geriatric, The First Hospital of Jilin University, Changchun City, Jilin Province 130021, China
| | - Liyin Gao
- Department of Urology, The First Hospital of Jilin University, Changchun City, Jilin Province 130021, China
| | - Mengqi Liu
- Key Laboratory of Bionic Engineering, Ministry of Education, College of Biological and Agricultural Engineering, Jilin University, Changchun City, Jilin Province 130022, China
| | - Chunxi Wang
- Department of Urology, The First Hospital of Jilin University, Changchun City, Jilin Province 130021, China.
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13
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Liu H, Xu L, Wang T, Liu Y, Pan J, Xiong W, Zheng F, Wang Y, Sun S. Cathepsin B-induced cascade DNA-AuNP nanomachine for activated tumor theranostics. Talanta 2025; 293:128103. [PMID: 40239587 DOI: 10.1016/j.talanta.2025.128103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/24/2025] [Accepted: 04/05/2025] [Indexed: 04/18/2025]
Abstract
Since targeted and efficient accumulation of nanoparticles into tumors is essential for accurate cancer theranostics, spatiotemporally controlling the aggregation of small nanoparticles (such as gold nanoparticles, AuNPs) in the tumor microenvironment holds significant promise for improving the diagnostic and therapeutic efficiency against tumors. Here, we introduce a cascade DNA-AuNP nanomachine (CNM) that can in situ magnify the protease-catalyzed peptide cleavage via DNA amplification machinery for cathepsin B (Cat B) activity imaging and Cat B-responsive photothermal therapy of tumors. The CNM is composed of a nanomediator formed by tethering a mediator DNA/peptide complex on AuNPs (DpAuNP) and a nanoeffector consisted of AuNPs and DNA modules (DNA-AuNP). In the cascade, Cat B-mediated peptide cleavage of mediator DNA/peptide complex on DpAuNPs initiates both the detachment of fluorescent DNA reporter from DNA-AuNPs for Cat B imaging and the aggregation of AuNPs for tumor photothermal therapy via toehold-mediated stand displacement (TMSD) reaction. Our results demonstrate that the CNM not only offers superior sensitivity and specificity for Cat B imaging, but also facilitates the activated aggregation of AuNPs for enhanced photothermal therapy of tumors. This CNM represents a Cat B-specific sense-and-treat paradigm for cancer theranostics.
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Affiliation(s)
- Huihui Liu
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Limei Xu
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Ting Wang
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Yingqi Liu
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Jiajia Pan
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Weiwei Xiong
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Fenfen Zheng
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Yemei Wang
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
| | - Shasha Sun
- School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu, 212003, China.
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14
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Rath MM, Anirvan P, Varghese J, Tripathy TP, Patel RK, Panigrahi MK, Giri S. Comparison of standard vs auxiliary (contrast or elastography) endoscopic ultrasound-guided fine needle aspiration/biopsy in solid pancreatic lesions: A meta-analysis. World J Methodol 2025; 15:97415. [DOI: 10.5662/wjm.v15.i3.97415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 11/03/2024] [Accepted: 12/02/2024] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is the most common modality for tissue acquisition from pancreatic masses. Despite high specificity, sensitivity remains less than 90%. Auxiliary techniques like elastography and contrast-enhanced EUS may guide tissue acquisition from viable tumor tissue and improve the diagnostic outcomes theoretically. However, data regarding the same have shown conflicting results.
AIM To compare the diagnostic outcomes of auxiliary-EUS-FNA/B to standard EUS-FNA/B for pancreatic lesions.
METHODS The electronic databases of MEDLINE, EMBASE, and Scopus were searched from inception to February 2024 for all relevant studies comparing diagnostic outcomes of auxiliary-EUS-FNA/B to standard EUS-FNA/B for pancreatic lesions. A bivariate hierarchical model was used to perform the meta-analysis.
RESULTS A total of 10 studies were identified. The pooled sensitivity, specificity, and area under the receiver-operated curve (AUROC) for standard EUS-FNA/B were 0.82 (95%CI: 0.79-0.85), 1.00 (95%CI: 0.96-1.00), and 0.97 (95%CI: 0.95-0.98), respectively. The pooled sensitivity, specificity, and AUROC for EUS-FNA/B with auxiliary techniques were 0.86 (95%CI: 0.83-0.89), 1.00 (95%CI: 0.94-1.00), and 0.96 (95%CI: 0.94-0.98), respectively. Comparing the two diagnostic modalities, sensitivity [Risk ratio (RR): 1.04, 95%CI: 0.99-1.09], specificity (RR: 1.00, 95%CI: 0.99-1.01), and diagnostic accuracy (RR: 1.03, 95%CI: 0.98-1.09) were comparable.
CONCLUSION Analysis of the currently available literature did not show any additional advantage of EUS-FNA/B with auxiliary techniques for pancreatic solid lesions over standard EUS-FNA/B. Further randomized studies are required to demonstrate the benefit of auxiliary techniques before they can be recommended for routine practice.
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Affiliation(s)
- Mitali Madhumita Rath
- Department of Pathology, IMS and SUM Hospital Campus-2, Bhubaneshwar 754001, Odisha, India
| | - Prajna Anirvan
- Department of Gastroenterology, Kalinga Gastroenterology Foundation, Cuttack 753001, Odisha, India
| | - Jijo Varghese
- Department of Gastroenterology, NS Memorial Institute of Medical Sciences, Kollam 691020, Kerala, India
| | - Tara Prasad Tripathy
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneshwar 751019, Odisha, India
| | - Ranjan K Patel
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneshwar 751019, Odisha, India
| | - Manas Kumar Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneshwar 751019, Odisha, India
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar 751024, Odisha, India
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15
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Lyu M, Chan CH, Chen Z, Liu Y, Yu Y. Advantages, applications, and future directions of in vivo aptamer SELEX: A review. MOLECULAR THERAPY. NUCLEIC ACIDS 2025; 36:102575. [PMID: 40529298 PMCID: PMC12173102 DOI: 10.1016/j.omtn.2025.102575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/20/2025]
Abstract
In vivo systematic evolution of ligands by exponential enrichment (SELEX) emerged as a transformative technique for directly identifying aptamers within living organisms. Unlike traditional in vitro methods that often fail to capture the complexity of biological interactions in physiological environments, in vivo SELEX leverages whole living organisms as selection targets. This strategy significantly enhances the specificity, functionality, and physiological relevance of the selected aptamers, making them more viable for therapeutic, diagnostic, and imaging applications. The aim of this review is to elucidate the unique advantages of in vivo SELEX compared to conventional in vitro techniques. It focuses on how in vivo SELEX improves aptamer specificity, physiological relevance, and pharmacokinetic properties, thereby enhancing their potential for use in diagnostics and therapeutics. This review highlights the principles, advancements, and challenges of in vivo SELEX, while discussing its potential to bridge the gap between aptamer discovery and clinical translation. By enabling the selection of aptamers under real physiological conditions, in vivo SELEX addresses critical limitations of in vitro methods, such as off-target effects and poor clinical translatability. The review also explores the applications of in vivo SELEX in various fields, including neurology, oncology, and cardiovascular diseases, and provides insights into future directions for optimizing this technology.
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Affiliation(s)
- Minchuan Lyu
- Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Hong Kong SAR 000000, China
| | - Chi Ho Chan
- Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Hong Kong SAR 000000, China
| | - Ziqi Chen
- Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Hong Kong SAR 000000, China
| | - Yumeng Liu
- Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Hong Kong SAR 000000, China
| | - Yuanyuan Yu
- Institute of Integrated Bioinformedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Institute of Systems Medicine and Health Sciences (SMHS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 000000, China
- Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery, Hong Kong SAR 000000, China
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16
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Michel A, Rauschenbach L, Karadachi H, Gümüs M, Ahmadipour Y, Darkwah Oppong M, Pöttgen C, Hense J, Özkan N, Wrede KH, Dammann P, Sure U, Jabbarli R. Surgical treatment of multiple breast cancer brain metastases: clinical characteristics and factors impacting postoperative survival. J Neurooncol 2025; 174:157-165. [PMID: 40299246 PMCID: PMC12198272 DOI: 10.1007/s11060-025-05048-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Accepted: 04/11/2025] [Indexed: 04/30/2025]
Abstract
PURPOSE Breast cancer (BC) is one of the most common primary tumor entities that develop brain metastases (BM) during disease progression. Multiple BM are associated with poorer prognosis, but various surgical, radiotherapeutic and systemic treatment approaches improve survival. We aimed to identify prognostic factors and evaluate the overall survival following BM surgery in patients with multiple BCBM. METHODS All metachronous metastasized female patients with resected BCBM at our institution between 2008 and 2019 were included. Data on clinical, radiologic, and histopathologic parameters were recorded and analyzed using univariate and multivariate regression models. RESULTS Among the 93 patients included in the final analysis, 30 individuals presented with multiple BM. Compared to patients with single BM, those with multiple BM were more likely to have infratentorial BM (adjusted odds ratio [aOR] 3.35, 95% confidence interval [CI] 1.03-10.83, p = 0.044), HER2(human epidermal growth factor receptor 2)-positive BC (aOR 3.93, 95% CI 1.23-12.53, p = 0.021) and hepatic metastases (aOR 5.86, 95% CI 1.34-25.61, p = 0.019). There was no significant difference in postoperative survival between individuals with multiple (median: 12.5 months) and single BM (17.0 months, p = 0.186). In the multivariate Cox regression analysis, adjuvant radiotherapy (adjusted hazard ratio [aHR] 5.93, 95% CI 1.06-33.26, p = 0.043) and trastuzumab treatment (aHR 4.95, 95% CI 1.72-14.25, p = 0.003) were associated with longer postoperative survival multiple BCBM patients. CONCLUSION BC patients with multiple BM show remarkable postoperative survival, particularly if combined with adjuvant radiotherapy. Our data justify the surgery of multiple BCBM in patients with appropriate clinical condition and feasible location of BM.
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Affiliation(s)
- Anna Michel
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany.
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany.
| | - Laurèl Rauschenbach
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
- German Cancer Research Center (DKFZ) Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner Site, University Hospital Essen, Essen, Germany
| | - Hanah Karadachi
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Meltem Gümüs
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Yahya Ahmadipour
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Marvin Darkwah Oppong
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Christoph Pöttgen
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
- Department of Radiotherapy, University Hospital Essen, Essen, Germany
| | - Jörg Hense
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
- Department of Medical Oncology, University Hospital Essen, Essen, Germany
| | - Neriman Özkan
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Karsten H Wrede
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Philipp Dammann
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Ulrich Sure
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
| | - Ramazan Jabbarli
- Department of Neurosurgery and Spine Surgery, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
- Center for Translational Neuro‑ & Behavioral Sciences (C‑TNBS), University Duisburg Essen, Essen, Germany
- German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147, Essen, Germany
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Lei M, Huang H, Li J, Zhang J, Yu G, Jin X, Liu J, Kang F, Liu Z. Design, synthesis and biological evaluation of coumarin-containing 2,4-diphenylpyrimidine derivatives as novel focal adhesion kinase inhibitors for treatment of non-small cell lung cancer. Bioorg Med Chem Lett 2025; 123:130240. [PMID: 40228675 DOI: 10.1016/j.bmcl.2025.130240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/16/2025] [Accepted: 04/10/2025] [Indexed: 04/16/2025]
Abstract
A series of hybrids (8a-h and 11a-h) containing 2,4-diphenylpyrimidine scaffold and coumarin moiety were designed and synthesized as novel focal adhesion kinase (FAK) inhibitors for the intervention of non-small-cell lung cancer (NSCLC). Most compounds effectively suppressed the proliferative of NSCLC cells, and compound 8a was identified as the most active compound with IC50 value of 0.28 μM in H1299 cells, superior to TAE226 (IC50 = 2.28 μM). In addition, 8a was also found to inhibit the invasion and migration of NSCLC cells. Furthermore, 8a exhibited potent kinase inhibitory activity of FAK (IC50 = 4.968 nM) with a considerable selectivity profile against various kinase families, subsequently resulting in cell cycle arrest, apoptosis- inducing as well as the decrease of MMP-2 and MMP-9 expression in H1299 cells dose-dependently. Moreover, 8a was relatively safe to mice and inhibited the growth of implanted NSCLC tumors more potently than TAE226 in mice. Therefore, 8a may be a promising candidate for the treatment of NSCLC.
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Affiliation(s)
- Mengrong Lei
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, PR China
| | - Hanxue Huang
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, PR China
| | - Jiayi Li
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
| | - Jinlin Zhang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
| | - Geng Yu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China
| | - Xin Jin
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, PR China
| | - Junyan Liu
- Department of orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, PR China
| | - Fenghua Kang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
| | - Zhaoqian Liu
- Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, PR China; Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
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18
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Yang M, Zhang Z, Qin H, Lin X, Liu X, Zhang H. The emerging significance of the METTL family as m6A-modified RNA methyltransferases in head and neck cancer. Cell Signal 2025; 132:111798. [PMID: 40239728 DOI: 10.1016/j.cellsig.2025.111798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/18/2025]
Abstract
RNA epigenetic modifications are crucial in tumor development, with N6-methyladenosine (m6A) being the most prevalent epigenetic modification found in all eukaryotic messenger RNAs. Accumulating evidence indicates that m6A modifications significantly influence the progression of various malignancies, including head and neck cancer (HNC). The Methyltransferase-like (METTL) family proteins, a group of methyltransferases identified in recent years, function as the "writers" of m6A modifications. These proteins affect RNA stability, translation efficiency, splicing, and localization, thereby regulating diverse cellular functions and promoting tumorigenesis in multiple cancers through their methylation domains. This review aims to summarize existing literature on the METTL family of m6A-modified RNA to elucidate their roles in HNC, providing a theoretical foundation for their potential use as therapeutic targets.
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Affiliation(s)
- Ming Yang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China; Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, China; The 2nd Medical College of Binzhou Medical University, Yantai, Shandong, China.
| | - Zile Zhang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China; Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, China; The 2nd Medical College of Binzhou Medical University, Yantai, Shandong, China
| | - Hanbin Qin
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China; Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, China
| | - Xinhua Lin
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China; Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, China
| | - Xuexia Liu
- Shandong Stem Cell Engineering Technology Research Center, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China.
| | - Hua Zhang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China; Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, China; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, China.
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19
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Zhou C, Wang J, Zhou L, Li H, Liu X, Wang S, Zhang X, Ye X, Ren H, Zeng K, Li X, Wang D, Ji J. The novel Piperine derivative YL-1-9 exhibits anti-breast Cancer effects by inducing apoptosis via the p53/p21 pathway. Bioorg Med Chem Lett 2025; 123:130231. [PMID: 40204112 DOI: 10.1016/j.bmcl.2025.130231] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/25/2025] [Accepted: 04/05/2025] [Indexed: 04/11/2025]
Abstract
The tumor suppressor protein p53 plays a crucial role in the pathogenesis of breast cancer; however, its function is often compromised due to MDM2 overexpression or mutations in the p53 gene, which occurs in approximately 30-35 % of breast cancer cases. Piperine, a natural bioactive compound, has shown potential in inhibiting breast cancer cell growth by upregulating p53 expression. However, its clinical application is hindered by poor bioavailability, potential toxicity, and the risk of undesirable drug interactions. In the present study, a novel derivative of Piperine, YL-1-9, was synthesized and evaluated for its anticancer activity against breast cancer. YL-1-9, a bicyclic amide derivative of Piperine, was evaluated for antitumor effects both in vitro and in vivo using MTT assays and the chick embryo chorioallantoic membrane (CAM) model. Further investigations into its effects on breast cancer cell clonogenicity, adhesion, invasion, and migration were conducted through colony formation assays, EdU assays, cell adhesion and invasion studies, and wound healing experiments. Western blot analysis was performed to elucidate the effects of YL-1-9 on the cell cycle and apoptosis, which were further validated using YO-PRO-1 and propidium iodide dual staining. YL-1-9 significantly inhibited breast cancer cell proliferation, adhesion, invasion, and migration, while inducing cell cycle arrest and promoting apoptosis. Mechanistically, YL-1-9 downregulated critical proteins in the CDK4/6-cyclin D-Rb-E2F pathway and the Caspase 3/Bax/Bcl-2 apoptosis signaling pathway. These findings position YL-1-9 as a promising candidate for breast cancer therapy; however, further clinical studies are necessary to fully assess its therapeutic potential.
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Affiliation(s)
- Chongyun Zhou
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Jiayun Wang
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Lili Zhou
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Hanxue Li
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Xing Liu
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Sen Wang
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Xingyu Zhang
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Xiaoqing Ye
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Hongyu Ren
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Kaile Zeng
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Xiuming Li
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Dan Wang
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China
| | - Jing Ji
- Jiangsu Key Laboratory for Screening of Marine Pharmaceutical Active Molecules, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222000, PR China; College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou, Jiangsu 225300, PR China.
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20
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Krawiec A, Pietrasik J, Pietrasik Z, Mikuła-Pietrasik J, Książek K. Unveiling the role of extracellular matrix elements and regulators in shaping ovarian cancer growth and metastasis. Cell Signal 2025; 132:111843. [PMID: 40318796 DOI: 10.1016/j.cellsig.2025.111843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/18/2025] [Accepted: 04/29/2025] [Indexed: 05/07/2025]
Abstract
Epithelial ovarian cancer (EOC) progression is determined by numerous intracellular interactions and the interplay between malignant cells, normal cells, and the tumor acellular microenvironment, formed largely by the extracellular matrix (ECM). The structure and biochemical functioning of various ECM components, along with the activity of agents that regulate ECM remodeling, impact the disease's expansion (adhesion, proliferation, invasion), spread, and response to therapy. It is important to note that the involvement of ECM components and their regulators in the progression of EOC is bidirectional and distinctly depends on a particular tissue context. In certain situations, certain components of the ECM enhance the activity of cancer cells, but in other scenarios, they suppress it. In this review, we summarize the newest knowledge regarding diverse aspects of ECM engagement in EOC pathophysiology and chemotherapy. Moreover, we delineate conditions that exacerbate the pro-cancerous properties of ECM, including diabetes-associated glycation, aging, and cellular senescence. We also explore methods to therapeutically alter the properties of the ECM, which could be beneficial in ovarian cancer prevention and treatment.
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Affiliation(s)
- Adrianna Krawiec
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str, 60-781 Poznań, Poland.
| | - Joanna Pietrasik
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str, 60-781 Poznań, Poland
| | - Zofia Pietrasik
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str, 60-781 Poznań, Poland
| | - Justyna Mikuła-Pietrasik
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str, 60-781 Poznań, Poland.
| | - Krzysztof Książek
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str, 60-781 Poznań, Poland.
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21
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Wang Y, Liu W, Zhao X, Li Y, Song C, Huo B, Song Y, Tan B. LINC02679 regulates TRIML2 to promote gastric cancer proliferation and invasion via targeting miR-5004-3p. Noncoding RNA Res 2025; 13:1-14. [PMID: 40276014 PMCID: PMC12017915 DOI: 10.1016/j.ncrna.2025.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 03/15/2025] [Accepted: 04/01/2025] [Indexed: 04/26/2025] Open
Abstract
As a key protein, Tripartite motif family-like 2 (TRIML2) is crucial to the p53-mediated apoptosis and is correlated with tumorigenesis. Emerging evidence showed that long non-coding RNAs (lncRNAs) play roles in the malignant progression of gastric cancer (GC). However, the function and underlying mechanism of LINC02679 in GC are still unclear. In this study, we detected the differentially expressed lncRNA, LINC02679, which was associated with the progression of GC. Herein, we showed that LINC02679 was overexpressed in GC tissues and correlated with poor prognosis, which aggravated GC proliferation, migration, and invasion. Mechanistically, LINC02679 sponged miR-5004-3p to promote the expression of TRIML2, regulating GC tumorigenesis and progression. Moreover, TRIML2 affected the proliferation, migration, and invasion of GC cells through TGF-β1/Smads signaling pathway. Overall, our findings proved a new mechanism and provided a promising strategy for precise therapy of GC by targeting LINC02679.
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Affiliation(s)
- Yingying Wang
- Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Wenbo Liu
- Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Xiaohan Zhao
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Yong Li
- Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Chao Song
- Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Bingjie Huo
- Oncology Department of Integrated Chinese and Western Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
- Key Laboratory for TCM Diagnosis and Treatment of Digestive Tract Tumors in Hebei Province, Shijiazhuang, 050011, PR China
| | - Yanru Song
- Research Center of the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
| | - Bibo Tan
- Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, PR China
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22
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PINDER LF, BERTRAND P, FERTITTA V, CAHAIS V, MWANAHAMUNTU M, NYAMBE N, CHISELE S, SHIBEMBA AL, McKAY-CHOPIN S, CUENIN C, LUCAS E, KORENJAK M, MUWONGE R, GHANTOUS A, HERCEG Z, PARHAM GP, ZAVADIL J, BASU P, GHEIT T. Vaginal microbiome composition in women with HIV undergoing treatment of cervical transformation zone in a screen and treat program in Zambia. AIDS 2025; 39:1303-1306. [PMID: 40568741 PMCID: PMC12204225 DOI: 10.1097/qad.0000000000004187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 03/12/2025] [Indexed: 06/28/2025]
Abstract
This study assessed the vaginal microbiome in women with HIV undergoing cervical transformation zone treatment in Zambia. 16S rRNA sequencing showed lower microbial diversity in successful outcomes (N = 18) than those with treatment failure (N = 17) treatment outcome, with Lactobacillus abundance correlated with success. Moreover, HPV-negative women (N = 12) had higher Lactobacillus levels and less pathogens than HPV-positive women (N = 12). These findings suggest a Lactobacillus-dominated microbiome may be associated with positive treatment outcomes.
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Affiliation(s)
- Leeya F. PINDER
- Department of Obstetrics and Gynecology, Women and Newborn Hospital, Lusaka, Zambia
- Division of Gynecologic Oncology, University of Washington, Seattle, Washington, USA
| | - Pierre BERTRAND
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Veronica FERTITTA
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Vincent CAHAIS
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Mulindi MWANAHAMUNTU
- University Teaching Hospital, Lusaka, Zambia
- University of Zambia School of Medicine, Lusaka, Zambia
| | - Namakau NYAMBE
- Department of Obstetrics and Gynecology, Women and Newborn Hospital, Lusaka, Zambia
| | - Samson CHISELE
- Department of Obstetrics and Gynecology, Women and Newborn Hospital, Lusaka, Zambia
| | - Aaron Lunda SHIBEMBA
- Department of Obstetrics and Gynecology, Women and Newborn Hospital, Lusaka, Zambia
| | - Sandrine McKAY-CHOPIN
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Cyrille CUENIN
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Eric LUCAS
- Early Detection, Prevention & Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Michael KORENJAK
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Richard MUWONGE
- Early Detection, Prevention & Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Akram GHANTOUS
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Zdenko HERCEG
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Groesbeck P. PARHAM
- University Teaching Hospital, Lusaka, Zambia
- University of Zambia School of Medicine, Lusaka, Zambia
| | - Jiri ZAVADIL
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Partha BASU
- Early Detection, Prevention & Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Tarik GHEIT
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
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23
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Huang HQ, Gong FM, Sun CT, Xuan Y, Li L. Brain and scalp metastasis of cervical cancer in a patient with human immunodeficiency virus infection: A case report. World J Clin Cases 2025; 13:103946. [DOI: 10.12998/wjcc.v13.i19.103946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/28/2025] [Accepted: 02/19/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Cervical cancer is the most commonly diagnosed cancer worldwide and the most common cancer in females living with human immunodeficiency virus (HIV). Cervical cancer is classified as an acquired immune deficiency syndrome-defining disease. Brain metastases (BMs) from cervical cancer are extremely rare, with an incidence rate of approximately 0.63%, and there is limited information on optimal treatment protocols and patient outcomes. Since brain lesions are sequestered behind the blood-brain barrier, multimodal treatment approaches are crucial to help improve the prognosis of cervical cancer in patients with BMs who are also living with HIV.
CASE SUMMARY A 42-year-old Chinese female with HIV infection was diagnosed with stage IIIC1r cervical cancer in March 2022 based on the International Federation of Gynecology and Obstetrics system. Fourteen months after undergoing the initial treatment with concurrent chemotherapy and radiotherapy in January 2024, the patient presented to a local hospital with a severe explosive headache. The patient underwent craniotomy and postoperative pathological examination confirmed metastasis of cervical squamous cell carcinoma to the brain on February 1, 2024. Following surgery, the patient received external beam radiotherapy for the metastatic lesions. The patient has been under observation for 7 months with no evidence of tumor recurrence.
CONCLUSION Females living with HIV are more than three times more likely to be diagnosed with cervical cancer. Due to the scarcity of cervical cancer BMs, therapeutic protocol experience is limited. In addition to the existence of the blood-brain barrier, the treatment of cervical cancer BMs appears to be exceptionally complex, and a multi-modal treatment approach consisting of chemotherapy, surgery, and radiation may help prolong patients’ life. For females living with HIV, antiretroviral therapy should be prioritized, as recommended by the Center for Disease Control in China. An intact immune system and a high CD4+ count are positive indicators of treatment response and tumor reduction. The overall survival of patients with cervical cancer after brain metastasis is approximately 3-5 months. However, owing to multimodal therapy and the use of antiretroviral therapy, the patient reported in this case showed no signs of recurrence after prolonged follow-up.
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Affiliation(s)
- Hui-Qiong Huang
- Department of Gynecology and Obstetrics, and Department Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Feng-Ming Gong
- Department of Gynecology and Obstetrics, and Department Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Chun-Tang Sun
- Department of Gynecology and Obstetrics, and Department Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu Xuan
- Department of Gynecology and Obstetrics, and Department Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lin Li
- Department of Gynecology and Obstetrics, and Department Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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24
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He N, Wei X, Sun R, Zhang G, Zhao J, Jiang X, Long B, Yu Z, Shi W, Jiao Z. Targeting Eg5 using Arry520 combats gastric cancer by inducing monopolar spindles. Gene 2025; 955:149458. [PMID: 40187619 DOI: 10.1016/j.gene.2025.149458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 03/12/2025] [Accepted: 03/28/2025] [Indexed: 04/07/2025]
Abstract
Eg5, also known as KIF11, is a motor protein essential for establishing a bipolar spindle and ensuring proper chromosome congression during mitosis. It is amplified in various human cancers and serves as a critical oncogene driving tumour progression. However, the role and clinical significance of Eg5 in gastric cancer has remained elusive. In this study, we showed that Eg5 is upregulation in gastric cancer tissues and is negatively associated with patient prognosis. The ablation of Eg5 inhibits the proliferation and migration of gastric cancer cells and suppresses tumour growth in xenograft mice. Mechanistically, Eg5 ablation induces the formation of monopolar spindle, leading to cell apoptosis and consequent inhibition of tumour growth. Furthermore, Arry520 is demonstrated as a potent Eg5 inhibitor which blocks tumour growth by increasing the formation of cell monopolar spindle and inducing apoptosis. Arry520 exhibits efficiently therapeutic effects on gastric cancer in tumour organoid models, cell-derived xenografts and patient-derived xenografts (PDX) in mice. Collectively, our findings provide evidence for the oncogenic properties of the mitotic protein Eg5 and identify Arry520 as a promising strategy to combat gastric cancer.
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Affiliation(s)
- Na He
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China; The Second Clinical Medical College, Lanzhou University, Gansu, China
| | - Xinyuan Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Ruofei Sun
- Department of Oncology, Dingxi People's Hospital, Gansu, China
| | - Gengyuan Zhang
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China
| | - Jie Zhao
- Department of Pathology, Gansu Provincial Maternity and Chlid-care Hospital, Lanzhou, Gansu, China
| | - Xiangyan Jiang
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China
| | - Bo Long
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China
| | - Zeyuan Yu
- The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China
| | - Wengui Shi
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.
| | - Zuoyi Jiao
- The Second Clinical Medical College, Lanzhou University, Gansu, China; The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.
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Li DL, Ma LL, Guan ZA, Zhao YX, Jiang C. Establishment and validation of a clinical prediction model for colorectal adenoma risk factors. Oncol Lett 2025; 30:322. [PMID: 40370646 PMCID: PMC12076052 DOI: 10.3892/ol.2025.15068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 04/01/2025] [Indexed: 05/16/2025] Open
Abstract
Colorectal adenomas are benign tumors of the colorectal mucosal epithelium that have malignant potential and are regarded as precancerous lesions of colorectal cancer, for which the specific risk factors are unclear. The present study aimed to identify independent risk factors for colorectal adenoma to develop a prediction model and test its predictive value. A retrospective analysis was performed using data from patients who underwent electronic colonoscopy at the Department of Proctology (Affiliated Hospital of Shandong University of Traditional Chinese Medicine; Jinan, China) from January 2013 to December 2023 and had polyps removed during colonoscopy. Patients with colorectal adenoma were included in the case group, whilst those with no visible abnormalities on endoscopy or with non-adenomatous polyps were included as a control group. The patients were randomly divided into a training and validation group in a 7:3 ratio. Variables were screened using single-component analysis and the filtered variables were employed in multivariate logistic regression to create a clinical prediction model. Finally, the model was internally and externally validated. A total of 730 patients were included in the present study, with 286 assigned to the case group and 444 to the control group. After the initial screening of 39 variables, 12 continued to the next round, resulting in four potential predictors including age, daily number of bowel movements, thrombin time and the number of polyps. A prediction model was created based on these variables. Regarding internal validation, the C-index was 0.7054 [95% confidence interval (CI), 0.6596-0.7512] and the prediction probability in the calibration curve was close to the diagonal line of the calibration graph, indicating that the prediction probability of the model was reasonable. Regarding external validation, the C-index in the validation cohort was 0.6306 (95% CI, 0.5560-0.7053) and the calibration curve also demonstrated good identification capabilities. The Hosmer-Lemeshow test revealed that the model had a reasonable calibration degree, with χ2=9.7893, degree of freedom=8 and P=0.28. The receiver operating characteristic curve and decision curve analysis for the training and validation cohorts demonstrated good efficacy and an ideal application value. In conclusion, the model constructed in the present study demonstrated moderate predictive accuracy for colorectal adenoma risk, laying the groundwork for early detection of colorectal adenoma and secondary prevention of colorectal cancer.
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Affiliation(s)
- Dong-Lin Li
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Ling-Ling Ma
- Department of Gastroenterology, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong 257091, P.R. China
| | - Zhong-An Guan
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
| | - Yu-Xin Zhao
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Chuan Jiang
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
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Nakai S, Makino T, Momose K, Yamashita K, Tanaka K, Miyata H, Yamamoto S, Motoori M, Kimura Y, Kawabata R, Hirao M, Matsuyama J, Akamaru Y, Morihara H, Ueyama A, Kurokawa Y, Morii E, Wada H, Eguchi H, Doki Y. Exploring predictive biomarkers of efficacy and survival with nivolumab treatment for unresectable/recurrent esophageal squamous cell carcinoma. Esophagus 2025; 22:360-372. [PMID: 40274705 PMCID: PMC12167336 DOI: 10.1007/s10388-025-01120-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 03/11/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Programmed cell death protein-1 (PD-1) blockade has improved survival for patients with esophageal squamous cell carcinoma (ESCC), but response rates are low. Biomarkers to predict who will benefit from PD-1 blockade are urgently needed. METHODS This multicenter study involved 250 patients with recurrent/unresectable advanced ESCC receiving nivolumab as second- or later-line therapy. We assessed tumor-infiltrating T lymphocytes (TILs) and tertiary lymphoid structure (TLS) density using immunohistochemistry and hematoxylin/eosin staining in surgical specimens and pre-nivolumab endoscopic biopsies. RESULTS In surgical specimens, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ lymphocyte count (160 vs. 95.2 cells/field, P = 0.0494), CD8/Foxp3 ratio (6.52 vs. 2.72, P = 0.0053), and TLS density (0.21/mm2 vs. 0.10/mm2, P = 0.0005). In terms of overall survival, multivariate analysis identified CD8/Foxp3 ratio (hazard ratio [HR] = 1.83, P = 0.0050) and TLS density (HR = 1.67, P = 0.0171 as independent prognostic parameters in surgical specimens. Similarly, in endoscopic biopsies, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ counts (254 cells/mm2 vs. 124 cells/mm2, P = 0.0344), CCR8+ lymphocyte count (62.6 cells/mm2 vs. 140 cells/mm2, P = 0.0355), CD8/Foxp3 ratio (2.09 vs. 0.89, P = 0.040), and CD8/CCR8 ratio (2.34 vs. 0.89, P = 0.0020). Multivariate analysis also identified CD8/CCR8 ratio in endoscopic biopsies (HR = 1.66, P = 0.0313) as an independent prognostic parameter. CONCLUSIONS CD8+ and CCR8+ cell counts, CD8/Foxp3 and CD8/CCR8 ratios, and TLS density may be predictive biomarkers of therapeutic efficacy and survival with PD-1 blockade for ESCC.
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Affiliation(s)
- Shigeto Nakai
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
| | - Kota Momose
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Yutaka Kimura
- Department of Gastroenterological Surgery, Kindai University Nara Hospital, Nara, Japan
| | - Ryohei Kawabata
- Department of Surgery, Sakai City Medical Center, Osaka, Japan
| | - Motohiro Hirao
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Jin Matsuyama
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Osaka, Japan
| | - Yusuke Akamaru
- Department of Surgery, Osaka Rosai Hospital, Osaka, Japan
| | - Hitomi Morihara
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Azumi Ueyama
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
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Jiang C, Wang C, Ao J, Liu Y, Sun F, Shi W, Guo Z, Wu Y, Gan L, Wu M, Zhi Y, Meng Z, Wu W, Wu J, Ye Y, Zhang X, Ren D, Pan M. STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS-Dependent PTEN/AKT1 Signaling. Cancer Med 2025; 14:e70958. [PMID: 40567110 PMCID: PMC12198656 DOI: 10.1002/cam4.70958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 04/16/2025] [Accepted: 04/29/2025] [Indexed: 06/28/2025] Open
Abstract
BACKGROUND Dysregulation of transcription factors is one of the most common factors for the pathogenesis of hepatocellular carcinoma (HCC). To the best of our knowledge, no study has yet investigated the clinical significance and functional role of STOX1 in HCC. METHODS Real-time PCR, Western blotting and immunohistochemistry were performed to examine the expression of STOX1-A in HCC specimens. Animal experiment in vivo and functional cell assays in vitro were used to investigate the tumorigenic and proliferative ability of HCC cells. Luciferase and ROS assays were depolyed to investigate the molecular mechanisms underlying the biologic role of STOX1-A in HCC. RESULTS In this study, we report that STOX1 isoform A (STOX1-A) is significantly upregulated in HCC tissues, and elevated STOX1-A levels are associated with poorer overall survival and progression-free survival in HCC patients. Functional assays demonstrated that STOX1-A upregulation promotes, whereas its silencing suppresses, HCC cell proliferation and growth both in vitro and in vivo. Mechanistic investigations revealed a dual mechanism by which STOX1-A drives HCC progression. First, STOX1-A transcriptionally upregulates cyclin B1, promoting cell proliferation. Second, it activates the AKT1 signaling pathway through reactive oxygen species (ROS)-mediated deactivation of PTEN. Furthermore, a positive correlation between STOX1-A expression and the levels of cyclin B1 and phosphorylated AKT1 (p-AKT1 Ser473) was observed in clinical HCC samples. CONCLUSION Our findings identify a novel dual mechanism by which STOX1-A promotes HCC proliferation and growth, offering potential avenues for the development of anti-tumor therapeutic strategies targeting STOX1-A in HCC.
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Affiliation(s)
- Chunlin Jiang
- Department of Hepatobiliary Surgery II, Zhujiang HospitalSouthern Medical UniversityGuangzhouP. R. China
- General SurgeryThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP. R. China
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education InstitutesGuangzhouP. R. China
| | - Chong Wang
- General SurgeryThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP. R. China
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education InstitutesGuangzhouP. R. China
| | - Jian Ao
- General SurgeryThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP. R. China
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education InstitutesGuangzhouP. R. China
| | - Yangping Liu
- Logistics DepartmentThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouP. R. China
| | - Fengjie Sun
- Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education InstitutesGuangzhouP. R. China
- Division of Neonatology, Department of PediatricsThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP. R. China
| | - Wangpan Shi
- Department of PathologyUniversity of California San Diego Health SystemSan DiegoCaliforniaUSA
| | - Zeyi Guo
- Department of Hepatobiliary Surgery II, Zhujiang HospitalSouthern Medical UniversityGuangzhouP. R. China
| | - Yanping Wu
- Department of Hepatobiliary Surgery II, Zhujiang HospitalSouthern Medical UniversityGuangzhouP. R. China
| | - Luxiang Gan
- Department of Hepatobiliary Surgery II, Zhujiang HospitalSouthern Medical UniversityGuangzhouP. R. China
| | - Meimei Wu
- Jiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental CenterJiangmen Central HospitalJiangmenChina
| | - Yaofeng Zhi
- Jiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental CenterJiangmen Central HospitalJiangmenChina
| | - Zijie Meng
- Jiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental CenterJiangmen Central HospitalJiangmenChina
| | - Wanting Wu
- Jiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental CenterJiangmen Central HospitalJiangmenChina
| | - Juanhua Wu
- Department of Hepatobiliary, Pancreatic and Splenic Surgery, Jiangmen Central HospitalAffiliated Jiangmen Hospital of Sun Yat‐Sen UniversityJiangmenChina
| | - Yong Ye
- Department of Hepatobiliary, Pancreatic and Splenic Surgery, Jiangmen Central HospitalAffiliated Jiangmen Hospital of Sun Yat‐Sen UniversityJiangmenChina
| | - Xin Zhang
- Jiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental CenterJiangmen Central HospitalJiangmenChina
| | - Dong Ren
- Department of PathologyUniversity of California Irvine Medical CenterOrangeCaliforniaUSA
| | - Mingxin Pan
- Department of Hepatobiliary Surgery II, Zhujiang HospitalSouthern Medical UniversityGuangzhouP. R. China
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Ding H, Tang X, Tang W. Effect of adjuvant chemotherapy with toad venom injection in the treatment of intermediate and advanced colon cancer and its effect on cellular immunity, PTEN, and PI3k. Anticancer Drugs 2025; 36:495-500. [PMID: 39964699 DOI: 10.1097/cad.0000000000001706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
The objective of this study is to explore the effect of adjuvant chemotherapy with toad venom injection in patients with intermediate and advanced colon cancer, in order to provide new reference drugs for clinical treatment. Prospectively, 148 patients with mid-stage to late-stage colon cancer in our hospital from January 2021 to May 2023 were selected for the study and randomly divided into two groups of 74 cases each. The control group was treated with FOLFOX4 chemotherapy, and the observation group was treated with four consecutive chemotherapy cycles based on the control group combined with toad venom injection. The treatment effects, adverse reactions, quality of life improvement rate, prognosis and cellular immune indexes [natural killer (NK) cells, CD4 + /CD8 + , CD4 + , CD3 + ], phosphatase tensin gene ( PTEN ), phosphatidylinositol-3-kinase (PI3k), and serine threonine protein kinase (pAKT) protein expression before and after treatment were counted in the two groups. The total effective rate of treatment in the observation group was 58.11% (43/74) after four cycles of chemotherapy, which was higher than that in the control group of 41.89% (31/74) ( P < 0.05). After two cycles of chemotherapy and four cycles of chemotherapy, PTEN , CD4 + /CD8 + , CD4 + , CD3 + , and NK cells in peripheral blood were higher in the observation group than in the control group, and PI3k and pAKT were lower than in the control group ( P < 0.05). There was no statistically significant difference in the rate of adverse reactions in the observation group compared with the control group ( P > 0.05); the improvement rate of quality of life in the observation group was better than that in the control group after four chemotherapy cycles of treatment ( P < 0.05); the survival rate was 75.00% (54/72) in the observation group compared with 54.29% (38/70) in the control group at 1-year follow-up. Toad venom injection adjuvant chemotherapy is effective in treating patients with intermediate and advanced colon cancer, which can upregulate PTEN level, inhibit PI3k and AKT expression, and improve immune function and quality of life of patients, thus improving prognosis.
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Affiliation(s)
- Haijun Ding
- General Surgery, Tianshan Branch of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
| | - Xuedian Tang
- General Surgery, Tianshan Branch of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
| | - Wenjun Tang
- General Surgery, Shanghai Eighth People's Hospital, Shanghai, China
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Ye K, Xu L, Pan B, Li J, Li M, Yuan H, Gong NJ. Deep learning-based image domain reconstruction enhances image quality and pulmonary nodule detection in ultralow-dose CT with adaptive statistical iterative reconstruction-V. Eur Radiol 2025; 35:3739-3749. [PMID: 39792163 DOI: 10.1007/s00330-024-11317-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 11/06/2024] [Accepted: 11/28/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVES To evaluate the image quality and lung nodule detectability of ultralow-dose CT (ULDCT) with adaptive statistical iterative reconstruction-V (ASiR-V) post-processed using a deep learning image reconstruction (DLIR)-based image domain compared to low-dose CT (LDCT) and ULDCT without DLIR. MATERIALS AND METHODS A total of 210 patients undergoing lung cancer screening underwent LDCT (mean ± SD, 0.81 ± 0.28 mSv) and ULDCT (0.17 ± 0.03 mSv) scans. ULDCT images were reconstructed with ASiR-V (ULDCT-ASiR-V) and post-processed using DLIR (ULDCT-DLIR). The quality of the three CT images was analyzed. Three radiologists detected and measured pulmonary nodules on all CT images, with LDCT results serving as references. Nodule conspicuity was assessed using a five-point Likert scale, followed by further statistical analyses. RESULTS A total of 463 nodules were detected using LDCT. The image noise of ULDCT-DLIR decreased by 60% compared to that of ULDCT-ASiR-V and was lower than that of LDCT (p < 0.001). The subjective image quality scores for ULDCT-DLIR (4.4 [4.1, 4.6]) were also higher than those for ULDCT-ASiR-V (3.6 [3.1, 3.9]) (p < 0.001). The overall nodule detection rates for ULDCT-ASiR-V and ULDCT-DLIR were 82.1% (380/463) and 87.0% (403/463), respectively (p < 0.001). The percentage difference between diameters > 1 mm was 2.9% (ULDCT-ASiR-V vs. LDCT) and 0.5% (ULDCT-DLIR vs. LDCT) (p = 0.009). Scores of nodule imaging sharpness on ULDCT-DLIR (4.0 ± 0.68) were significantly higher than those on ULDCT-ASiR-V (3.2 ± 0.50) (p < 0.001). CONCLUSION DLIR-based image domain improves image quality, nodule detection rate, nodule imaging sharpness, and nodule measurement accuracy of ASiR-V on ULDCT. KEY POINTS Question Deep learning post-processing is simple and cheap compared with raw data processing, but its performance is not clear on ultralow-dose CT. Findings Deep learning post-processing enhanced image quality and improved the nodule detection rate and accuracy of nodule measurement of ultralow-dose CT. Clinical relevance Deep learning post-processing improves the practicability of ultralow-dose CT and makes it possible for patients with less radiation exposure during lung cancer screening.
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Affiliation(s)
- Kai Ye
- Department of Radiology, Peking University Third Hospital, Beijing, China
| | - Libo Xu
- Laboratory for Intelligent Medical Imaging, Tsinghua Cross-strait Research Institute, Xiamen, China
| | | | - Jie Li
- Department of Radiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Meijiao Li
- Department of Radiology, Peking University Third Hospital, Beijing, China
| | - Huishu Yuan
- Department of Radiology, Peking University Third Hospital, Beijing, China.
| | - Nan-Jie Gong
- Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, China.
- Institute of Magnetic Resonance and Molecular Imaging in Medicine, East China Normal University, Shanghai, China.
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Jain N, Shahrukh S, Famta P, Shah S, Vambhurkar G, Srinivasarao DA, Sharma A, Pandey G, Wagh S, Shinde S, Khan A, Kumar P, Srivastava S. Combating breast cancer-associated metastasis using paclitaxel and tranilast-loaded human serum albumin nanoparticles. Drug Dev Ind Pharm 2025; 51:786-798. [PMID: 40402157 DOI: 10.1080/03639045.2025.2509861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 04/19/2025] [Accepted: 05/19/2025] [Indexed: 05/23/2025]
Abstract
OBJECTIVE The objective of the current study is to combat breast cancer-associated metastasis using paclitaxel (PTX) and tranilast (TRA)-loaded human serum albumin (HSA) nanoparticles. SIGNIFICANCE This combinatorial therapy uses microtubule stabilizing agent PTX, along with TGFβ inhibitor TRA. TRA may offer an improved therapeutic effect in breast cancer by inhibiting cell proliferation and metastasis. METHODS Inspired by the remarkable anticancer properties of both drugs, they were encapsulated into HSA nanoparticles to enhance tumor site-specific drug accumulation and ensure sustained release over a prolonged period. The HSA nanoparticles were fabricated using the desolvation method and optimized using a Box-Behnken design (BBD) with a three-level, two-factor approach. Further, these nanoparticles were characterized using TEM, FTIR, XRD, and particle size. In vitro experiments were conducted using the MDA-MB-231 cell line, employing cell viability, cellular uptake, nuclear staining, scratch assay, and cell cycle analysis. KEY FINDINGS In vitro release kinetics reveal sustained PTX and TRA release from HSA nanoparticles. Wound healing assay depicted improved anti-migratory activity of PTX-TRA-NPs (30 nM to 75 µM). Furthermore, the novel combination treatment caused G2/M phase cell cycle arrest, as indicated by cell cycle analysis. CONCLUSION HSA nanoparticles enhance the delivery and accumulation of hydrophobic drugs (PTX and TRA) in breast cancer cells, offering improved therapeutic outcomes. This combinatorial strategy permits further preclinical investigation for synergistic breast cancer management.
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Affiliation(s)
- Naitik Jain
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Syed Shahrukh
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Paras Famta
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Saurabh Shah
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Ganesh Vambhurkar
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Dadi A Srinivasarao
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Anamika Sharma
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Giriraj Pandey
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Suraj Wagh
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Swapnil Shinde
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Anjesh Khan
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Prashanth Kumar
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Saurabh Srivastava
- Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
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Middeldorp M, Brouwer JG, Duijster JW, Knol MJ, van Kemenade FJ, Siebers AG, Berkhof J, de Melker HE. The effect of bivalent HPV vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands: a population-based linkage study. THE LANCET REGIONAL HEALTH. EUROPE 2025; 54:101327. [PMID: 40503392 PMCID: PMC12153372 DOI: 10.1016/j.lanepe.2025.101327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/30/2025] [Accepted: 05/05/2025] [Indexed: 06/18/2025]
Abstract
Background The protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We aimed to estimate the effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands, where routine screening starts at age 30 years. Methods We linked the vaccination status of women born in 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded until April 1, 2024, in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses ≥150 days apart), partially vaccinated, and unvaccinated women. Cumulative risk ratios (CRRs) were adjusted for differences in screening participation between vaccine groups. Findings A total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5098 partially vaccinated, and 50,831 unvaccinated. Five cancers (0·011%) were observed in fully vaccinated, two (0·039%) in partially vaccinated, and 42 (0·083%) in unvaccinated women. The CRR for fully vaccinated women compared with unvaccinated women was 0·085 (95% confidence interval 0·025, 0·24) for cancer and 0·19 (0·16, 0·23) for CIN3+. The CRR for partially vaccinated women was 0·52 (0·12, 1·71) for cancer and 0·42 (0·30, 0·57) for CIN3+. Interpretation The risk of cervical cancer and CIN3+ was strongly reduced in vaccinated women indicating that vaccine protection extends at least until age 30. Funding The Dutch Ministry of Health, Welfare, and Sport.
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Affiliation(s)
- Marit Middeldorp
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Department of Epidemiology and Data Science, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands
| | - Jesca G.M. Brouwer
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Janneke W. Duijster
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Mirjam J. Knol
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | | | - Albert G. Siebers
- Palga (the Dutch Nationwide Pathology Databank), Houten, the Netherlands
| | - Johannes Berkhof
- Department of Epidemiology and Data Science, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands
| | - Hester E. de Melker
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
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Orido M, Lotodo TC, Kigen N, Stohler R, Vik TA, Vance GH. Introducing Diagnostic Testing for Chronic Myeloid Leukemia in a Public Hospital Setting in Western Kenya. Arch Pathol Lab Med 2025; 149:613-617. [PMID: 39880022 DOI: 10.5858/arpa.2024-0264-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/31/2025]
Abstract
CONTEXT.— Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by proliferation of the granulocytic cell line. The incidence of CML in Kenya is estimated at near 2000 cases annually. The disorder is associated with a poor prognosis without treatment. Tyrosine kinase inhibitors are approved for treatment in adults and children with confirmed disease. Diagnostic testing for CML in the public setting in Kenya is limited and not covered by the Kenyan National Health Insurance Fund. OBJECTIVE.— To establish a clinical fluorescence in situ hybridization assay for the diagnosis of CML in the Academic Model Providing Access to Healthcare (AMPATH) Reference Laboratory in Eldoret, Kenya. DESIGN.— Peripheral blood and bone marrow smears were split between the AMPATH Reference Laboratory and the Indiana University Cytogenetics Laboratory for concordance studies. RESULTS.— Seventeen specimens from patients with a provisional diagnosis of CML were studied by fluorescence in situ hybridization in both the AMPATH and Indiana University Cytogenetics laboratories. The analysis for 1 specimen could not be completed by both laboratories, and the results for 1 other specimen were discordant. The interpretations of 15 of 16 specimens (93.7%) were concordant. Normal specimens were also studied to establish the normal range for the assay. CONCLUSIONS.— We report the establishment of diagnostic testing for CML in the AMPATH Reference Laboratory and the Moi Teaching and Referral Hospital in Eldoret, Kenya.
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Affiliation(s)
- Millicent Orido
- From the Academic Model Providing Access to Healthcare (AMPATH) Reference Laboratory, Eldoret, Kenya Indiana University School of Medicine, Indianapolis(Orido, Kigen)
| | - Teresa Cherop Lotodo
- From the Department of Pathology, School of Medicine, Moi University, Eldoret, Kenya Indiana University School of Medicine, Indianapolis(Lotodo)
| | - Nicholas Kigen
- From the Academic Model Providing Access to Healthcare (AMPATH) Reference Laboratory, Eldoret, Kenya Indiana University School of Medicine, Indianapolis(Orido, Kigen)
| | - Ryan Stohler
- From the Department of Medical and Molecular Genetics Indiana University School of Medicine, Indianapolis(Stohler, Vance)
| | - Terry A Vik
- From the Department of Medical and Pediatrics Indiana University School of Medicine, Indianapolis (Vik)
| | - Gail H Vance
- From the Department of Medical and Molecular Genetics Indiana University School of Medicine, Indianapolis(Stohler, Vance)
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Zare MS, Abedpoor N, Hajibabaie F, Walker AK. Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents. Neurobiol Dis 2025; 211:106944. [PMID: 40339619 DOI: 10.1016/j.nbd.2025.106944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 05/04/2025] [Accepted: 05/04/2025] [Indexed: 05/10/2025] Open
Abstract
Chemotherapy-related cognitive impairment (CRCI), is a well-recognized phenomenon in cancer patients who have undergone chemotherapy but the exact molecular mechanisms underpinning CRCI remain elusive. Symptoms reported by people with CRCI resemble those experienced by people with age-related neurodegenerative disorders (ARNDDs), yet no clear connection between CRCI and ARNDDs has been reported to date. The existence of shared mechanisms between these conditions offers opportunities for repurposing drugs already approved for the treatment of ARNDDs to improve symptoms of CRCI. Given that there is no available microarray or RNA-Seq data from the brains of people who have experienced CRCI, we investigated to what extent brain gene expression perturbations from validated rodent models of CRCI induced by chemotherapy compared with validated rodent models of Alzheimer's disease and Parkinson's disease. We utilized multiple bioinformatic analyses, including functional enrichment, protein-protein interaction network analyses, gene ontology analyses and identification of hub genes to reveal connections between comparable gene expression perturbations observed in these conditions. Collectively 165 genes overlapped between CRCI and Parkinson's disease and/or Alzheimer's disease, and 15 overlapped between all three conditions. The joint genes between Alzheimer's disease, Parkinson's disease and CRCI demonstrate an average of 83.65% nucleotide sequence similarity to human orthologues. Gene ontology and pathway enrichment analyses suggest mechanisms involved in neural activity and inflammatory response as the key components of the studied neuropathological conditions. Accordingly, genes in which expression was comparably affected in all three condition models could be attributed to neuroinflammation, cell cycle arrest, and changes in physiological neural activity.
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Affiliation(s)
- Mohammad-Sajad Zare
- Department of Chemistry, University of Georgia, Athens, GA, 30602, USA; Iranian Cancer Control Center (MACSA), Isfahan, Iran.
| | - Navid Abedpoor
- Department of Sports Physiology, Isf.C., Islamic Azad University, Isfahan, Iran
| | - Fatemeh Hajibabaie
- Department of Biology, ShK.C., Islamic Azad University, Shahrekord, Iran
| | - Adam K Walker
- Discipline of Psychiatry and Mental Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.; Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick 2031, NSW, Australia..
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Thomsen FF, Petersson RD, Schou-Jensen KS, Rashu BS, Niebuhr MH, Azawi NH. Transperitoneal robot-assisted partial nephrectomy: a comparison of operative and oncological outcomes between posterior and anterolateral tumours. Int Urol Nephrol 2025; 57:2013-2021. [PMID: 39808377 PMCID: PMC12167232 DOI: 10.1007/s11255-025-04372-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 01/07/2025] [Indexed: 01/16/2025]
Abstract
OBJECTIVE To compare operative and oncological outcomes, as well as the risk of postoperative complications in patients who underwent transperitoneal robot-assisted partial nephrectomy (RAPN) for renal tumours located either posteriorly or anterolaterally. METHODS Retrospective, consecutive study including 451 patients who underwent transperitoneal RAPN for non-metastatic, localised renal tumours from May 2016 to April 2023. Operative data included duration of the procedure, warm ischaemia time, and blood loss; oncological data included surgical margins and recurrence; and 90-day postoperative complications were classified according to the Clavien-Dindo classification. RESULTS In total, 140 (31%) patients had tumours with a posterior location. The median follow-up was 3.3 (IQR 1.8-5.0) years. There were no differences in operative outcomes or length of hospital stay between the two groups. Positive surgical margins were recorded in 9% of the patients with posterior tumours compared to 7% of patients with anterolateral tumours, p = 0.60. The estimated probability of recurrence-free survival at 5 years was 95.2% (95% CI 87.4-98.2) for patients with posterior tumours and 96.7% (95% CI 92.3-98.6) for patients with anterolateral tumours, p = 0.4. Patients with posterior tumours had a similar risk of any complication (OR 1.24 [95% CI 0.80-1.91]) and CD ≥ III (OR 0.73 [95% CI 0.28-1.67]) compared to patients with anterolateral tumours. CONCLUSION This study found that patients with posterior tumours had longer operating times and hospital stays following transperitoneal RAPN compared to those with anterolateral tumours but without increased complications or poorer oncological outcomes.
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Affiliation(s)
- Frederik F Thomsen
- Department of Urology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.
| | | | - Katrine S Schou-Jensen
- Department of Urology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Badal S Rashu
- Department of Urology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Malene H Niebuhr
- Department of Urology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Nessn H Azawi
- Department of Urology, Zealand University Hospital, Roskilde, Denmark
- Institute of Clinical Medicine, Copenhagen University, Copenhagen, Denmark
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Sabagh M, Cordts T, Sabetkish N, Polychronidis G, Erhart P, Boecker A, Vogelpohl J, Al-Saeedi M. Reconstruction of a Large Perineal Defect After Radical Oncological Pelvic Exenteration in a Patient With Anal Cancer: An Interdisciplinary Approach and Literature Review. Microsurgery 2025; 45:e70073. [PMID: 40459570 DOI: 10.1002/micr.70073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/04/2025] [Accepted: 05/19/2025] [Indexed: 06/22/2025]
Abstract
INTRODUCTION Recurrent anal cancer (AC) often requires surgical intervention, especially when large perineal defects must be reconstructed. These cases are complicated by poor tissue vascularity and comorbid conditions such as peripheral arterial disease (PAD). METHODS We report the case of a 64-year-old male with PAD and recurrent AC, presenting with a large perineal defect following radical pelvic exenteration. Preoperative iliac artery stenting was performed to ensure adequate perfusion. Surgical reconstruction was conducted in two stages: first, a vertical rectus abdominis myocutaneous (VRAM) flap (7 × 15 cm) for pelvic floor coverage, followed by a free latissimus dorsi (LD) flap (17 × 30 cm) anastomosed to the superior gluteal vessels. RESULTS Postoperative recovery was uneventful. Three vacuum-assisted closures were performed, and the patient was discharged 6 weeks postoperatively. At 6-month follow-up, the flap remained stable with no complications. CONCLUSION This case underscores the importance of preoperative vascular optimization and a staged surgical strategy when addressing large, complex perineal defects. Multidisciplinary collaboration is critical for achieving optimal outcomes.
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Affiliation(s)
- Mohammadsadegh Sabagh
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Ludwigshafen, Germany
- Department of Hand and Plastic Surgery, University of Heidelberg, Heidelberg, Germany
| | - Tomke Cordts
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Ludwigshafen, Germany
- Department of Hand and Plastic Surgery, University of Heidelberg, Heidelberg, Germany
| | - Nastaran Sabetkish
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Georgios Polychronidis
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Philipp Erhart
- Department of Vascular and Endovascular Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Arne Boecker
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Ludwigshafen, Germany
- Department of Hand and Plastic Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julian Vogelpohl
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Ludwigshafen, Germany
- Department of Hand and Plastic Surgery, University of Heidelberg, Heidelberg, Germany
| | - Mohammed Al-Saeedi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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Li X, Wang G, Li D, Li Y. Multitask learning model for predicting non-coding RNA-disease associations: Incorporating local and global context. Methods 2025; 239:10-21. [PMID: 40113152 DOI: 10.1016/j.ymeth.2025.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/19/2025] [Accepted: 03/13/2025] [Indexed: 03/22/2025] Open
Abstract
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are crucial non-coding RNAs involved in various diseases. Understanding these interactions is vital for advancing diagnostic, preventive, and therapeutic strategies. Existing computational methods often address lncRNA-miRNA-disease associations as isolated tasks, resulting in sparse connections and limited generalizability. Additionally, these ncRNA-disease relationships involve higher-order topological information that is frequently overlooked. To address these challenges, we propose the MTL-NRDA model, which employs a multi-task learning framework to simultaneously predict lncRNA-disease associations, miRNA-disease associations, and lncRNA-miRNA interactions. The model integrates multi-source information through a heterogeneous network encompassing lncRNAs, miRNAs, and disease association networks as well as various similarity networks. Node embeddings are optimized by combining local and global contexts, and local features are aggregated using higher-order graph convolutional networks (HOGCN) to capture ncRNA-disease associations, while global features are extracted via a transformer encoder, effectively handling long-range dependencies. MTL-NRDA uses independent bilinear output layers for each task and dynamically adjusts the loss weights to calculate task-specific association probabilities. Experiments on two independent datasets show that MTL-NRDA outperforms existing models. Ablation studies confirmed the effectiveness of the model components and multi-task strategy, whereas hyperparameter tuning further improved the performance. Case studies on breast and liver cancers demonstrated the practical applicability of the model.
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Affiliation(s)
- Xiaohan Li
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, 150040, China
| | - Guohua Wang
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, 150040, China
| | - Dan Li
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, 150040, China.
| | - Yang Li
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, 150040, China.
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Wang X, Chen M, Wu Y, Chen F, Shen T, Wang Z. RORα inhibits proliferation and chemoresistance through AKR1A1-induced glucose and lipid reprogramming in gastric cancer. Cell Signal 2025; 131:111741. [PMID: 40096932 DOI: 10.1016/j.cellsig.2025.111741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 02/22/2025] [Accepted: 03/10/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Abnormal glycolysis and lipid metabolism play important roles in the occurrence and development of gastric cancer (GC). Moreover, dysregulation of circadian genes is associated with metabolic reprogramming in the tumor microenvironment. This study aimed to determine the role of retinoic acid-related orphan receptor alpha (RORα) in glucose and lipid reprogramming in GC. METHODS The effects on cell proliferation and chemoresistance in vitro and in vivo were studied using gain- and loss-of-function experiments. Glycolytic activity and lipid synthesis were assessed using a Seahorse assay and reagent kits. Moreover, the regulatory mechanisms were explored using half-life, coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), luciferase reporter and immunofluorescence colocalization assays in GC cells. In addition, the relationships of RORα with E47 and AKR1A1 were analyzed using public databases and retrospective clinicopathological analyses. RESULTS RORα deletion promoted cell proliferation and fluorouracil (5-FU) chemoresistance by increasing glycolytic activity and lipid synthesis. In contrast, SR1078, an RORα activator, reversed these changes and had a synergistic inhibitory effect on cell proliferation in combination with 2-deoxygulose glucose (2-DG) or atorvastatin. Mechanistically, aldo-keto reductase family 1 member A1 (AKR1A1), is the key driver of RORα-mediated glucose and lipid reprogramming. Specifically, E47 is an AKR1A1 transcription factor, and its stability is affected by β-catenin. RORα deletion indirectly promoted E47 protein stability through the up-regulation of β-catenin, leading to increased AKR1A1 transcriptional activity. Moreover, RORα, E47 and AKR1A1 expression was dysregulated, and associated with clinicopathological parameters and prognosis in patients with GC. These expression patterns including RORα-low, E47-high and AKR1A1-high expression patterns alone or in combination were correlated with reduced responsiveness, poor prognosis, increased standard uptake value (SUV) levels and lipid droplet formation. CONCLUSIONS These findings reveal a novel mechanism by which RORα regulates glucose and lipid reprogramming and may be a promising target for GC treatment.
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Affiliation(s)
- Xiaoshan Wang
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Mengding Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yuwei Wu
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Feixu Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Tong Shen
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
| | - Zhengguang Wang
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
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Sanvisens A, Vidal-Vila A, Puigdemont M, Viñas G, Roqué-Lloveras A, Del Barco S, Pérez-Bueno F, Trallero J, Marcos-Gragera R, Renart G. Population-based analysis of breast cancer incidence and mortality: overall and age-specific temporal trends over 40-year period in Girona, Spain. Breast Cancer Res Treat 2025; 212:97-105. [PMID: 40281345 PMCID: PMC12086112 DOI: 10.1007/s10549-025-07704-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/13/2025] [Indexed: 04/29/2025]
Abstract
PURPOSE Breast cancer (BC) incidence and mortality in women have changed over time. This study aims to analyze population-level incidence and mortality trends over 40 years of observation. METHODS Population-based study of BC conducted by Girona Cancer Registry covering the period 1980-2019. Age-standardized incidence and mortality rates were calculated. Poisson change-point regression models were used to analyze trends, calculating the annual percentage change (APC). RESULTS A total of 12,283 diagnoses of invasive BC between 1980 and 2019. The overall age-standardized incidence rate was 109.9 (95% confidence intervals (CI) 104.4; 115.4) cases per 100,000 women-years. Trend analyses showed a statistically significant incidence increase of 4.2% per year from 1980 to 1994 (95%CI 3.3; 5.1), and a stabilization between 1994 and 2019, with an APC of 0.28% (95%CI - 0.04; 0.56). These trends were similar for the age groups 0-49 years and 50-69 years. In women over 69 years of age, an increase in incidence of 4.4% (95%CI 2.8; 6.0) per year was observed between 1980 and 1995 followed by a non-statistically significant decrease of - 0.35% (95%CI - 0.86; 0.15) between 1995 and 2019. The overall age-standardized mortality rate was 30.3 (95%CI 29.3; 31.3) cases per 100,000 women-years. Mortality rate trends showed a statistically significant decrease of - 1.87% (95%CI - 2.38; - 1.37) per year since 1992. CONCLUSION There has been a stabilization in the incidence of BC and a gradual decline in BC mortality in women. The introduction of mammography in the mid-1990s, alongside early detection and treatment due to screening programs may play a significant role in the reduction of BC burden in women of all ages.
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Affiliation(s)
- Arantza Sanvisens
- Unitat d'Epidemiologia i Registre del Càncer de Girona, Institut Català d'Oncologia, Pla Director d'Oncologia, c/ del Sol 15, 1era planta, 17004, Girona, Spain
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
- Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain
| | - Anna Vidal-Vila
- Unitat d'Epidemiologia i Registre del Càncer de Girona, Institut Català d'Oncologia, Pla Director d'Oncologia, c/ del Sol 15, 1era planta, 17004, Girona, Spain
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
- Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain
| | - Montse Puigdemont
- Unitat d'Epidemiologia i Registre del Càncer de Girona, Institut Català d'Oncologia, Pla Director d'Oncologia, c/ del Sol 15, 1era planta, 17004, Girona, Spain
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
- Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain
| | - Gemma Viñas
- Departament d'Oncologia Mèdica, Institut Català d'Oncologia, Hospital Universitari Dr. Josep Trueta, Girona, Spain
- Precision Oncology Group (OncoGIR-Pro), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
| | - Ariadna Roqué-Lloveras
- Departament d'Oncologia Mèdica, Institut Català d'Oncologia, Hospital Universitari Dr. Josep Trueta, Girona, Spain
- Precision Oncology Group (OncoGIR-Pro), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
| | - Sonia Del Barco
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
- Departament d'Oncologia Mèdica, Institut Català d'Oncologia, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | - Ferran Pérez-Bueno
- Departament d'Anatomia Patològica, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | - Jan Trallero
- Unitat d'Epidemiologia i Registre del Càncer de Girona, Institut Català d'Oncologia, Pla Director d'Oncologia, c/ del Sol 15, 1era planta, 17004, Girona, Spain
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain
- Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain
| | - Rafael Marcos-Gragera
- Unitat d'Epidemiologia i Registre del Càncer de Girona, Institut Català d'Oncologia, Pla Director d'Oncologia, c/ del Sol 15, 1era planta, 17004, Girona, Spain.
- Descriptive Epidemiology, Genetic and Cancer Prevention Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI-CERCA), Girona, Spain.
- Institut de Recerca Contra la Leucèmia Josep Carreras, Girona, Spain.
- Grup de Recerca en Estadística, Econometria i Salut (GRECS), Universitat de Girona, Girona, Spain.
- Departament de Ciències Mèdiques, Universitat de Girona, Girona, Spain.
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
| | - Gemma Renart
- Grup de Recerca en Estadística, Econometria i Salut (GRECS), Universitat de Girona, Girona, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
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Ghosh D, Guin A, Kumar A, Das A, Paul S. Comprehensive insights of etiological drivers of hepatocellular carcinoma: Fostering targeted nano delivery to anti-cancer regimes. Biochim Biophys Acta Rev Cancer 2025; 1880:189318. [PMID: 40222420 DOI: 10.1016/j.bbcan.2025.189318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 04/05/2025] [Accepted: 04/06/2025] [Indexed: 04/15/2025]
Abstract
Hepatocellular carcinoma (HCC) stands as one of the most prevalent and deadliest malignancies on a global scale. Its complex pathogenesis arises from multifactorial etiologies, including viral infections, metabolic syndromes, and environmental carcinogens, all of which drive genetic and molecular aberrations in hepatocytes. This intricate condition is associated with multiple causative factors, resulting in the abnormal activation of various cellular and molecular pathways. Given that HCC frequently manifests within the context of a compromised or cirrhotic liver, coupled with the tendency of late-stage diagnoses, the overall prognosis tends to be unfavorable. Systemic therapy, especially conventional cytotoxic drugs, generally proves ineffective. Despite advancements in therapeutic interventions, conventional treatments such as chemotherapy often exhibit limited efficacy and substantial systemic toxicity. In this context, nanomedicine, particularly lipid-based nanoparticles (LNPs), has emerged as a promising strategy for enhancing drug delivery specificity and reducing adverse effects. This review provides a comprehensive overview of the molecular and metabolic underpinnings of HCC. Furthermore, we explored the role of lipid-based nano-formulations including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers in targeted drug delivery for HCC. We have highlighted recent advances in LNP-based delivery approaches, FDA-approved drugs, and surface modification strategies to improve liver-specific delivery and therapeutic efficacy. It will provide a comprehensive summary of various treatment strategies, recent clinical advances, receptor-targeting strategies and the role of lipid composition in cellular uptake. The review concludes with a critical assessment of existing challenges and future prospects in nanomedicines-driven HCC therapy.
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Affiliation(s)
- Dipanjan Ghosh
- Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata 700019, West Bengal, India
| | - Aharna Guin
- Department of Chemistry, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517619, Andhra Pradesh, India
| | - Aryan Kumar
- Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517619, Andhra Pradesh, India
| | - Amlan Das
- Department of Microbiology & Department of Biochemistry, Royal School of Biosciences, The Assam Royal Global University, Guwahati 781035, Assam, India.
| | - Santanu Paul
- Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517619, Andhra Pradesh, India.
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Song S, Fan Y, Zou G, Huo L, Kumar J, Li Y, Wang R, Dai E, Jin J, Scott AW, Shao S, Pizzi MP, Vykoukal JV, Katayama H, Hanash S, Calin GA, Zhang X, Lee MG, Wang Z, Lo YH, Gan Q, Waters RE, Yin F, Wang L, Cheng X, Ajani JA, Dhar SS. KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB. Cancer Lett 2025; 621:217695. [PMID: 40189014 PMCID: PMC12165730 DOI: 10.1016/j.canlet.2025.217695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 03/31/2025] [Accepted: 04/03/2025] [Indexed: 04/15/2025]
Abstract
Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter and reducing H3K27ac levels. Mass spectrometry identified an interaction between KAP1 and HNRNPAB, further modulating YAP1 signaling. Expression of the KRAB domain of ZFP568 without its DNA-binding zinc fingers inhibited both KAP1 and YAP1 expression, significantly reducing colony formation and tumor growth in vivo. Additionally, emerging antisense oligonucleotides (ASOs) targeting KAP1 or YAP1 effectively suppressed mouse tumor progression. These findings establish KAP1 as a critical driver of tumor progression in GAC through YAP1 regulation and HNRNPAB interaction, highlighting its potential therapeutic target. This study advances our understanding and offers a preclinical framework to improve outcomes for GAC.
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Affiliation(s)
- Shumei Song
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yibo Fan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gengyi Zou
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Longfei Huo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Janani Kumar
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yuan Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China
| | - Ruiping Wang
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Enyu Dai
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ailing W Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shan Shao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jody V Vykoukal
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hiroyuki Katayama
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samir Hanash
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George A Calin
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xing Zhang
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Min Gyu Lee
- Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China
| | - Yuan-Hung Lo
- Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Qiong Gan
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rebecca E Waters
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Feng Yin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Linghua Wang
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaodong Cheng
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Shilpa S Dhar
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Wang H, Matsumoto Y, Maiyulan A, Toyozumi T, Otsuka R, Sekino N, Okada K, Shiraishi T, Kamata T, Matsubara H. Circulating exosome-derived miR-191-5p is a novel therapeutic biomarker for radiotherapy in esophageal squamous cell carcinoma patients. Esophagus 2025; 22:454-466. [PMID: 40064799 PMCID: PMC12167317 DOI: 10.1007/s10388-025-01116-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 03/03/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND Circulating exosomal microRNAs are an easily obtained and minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. It would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance. METHODS A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma exosomes before chemoradiotherapy. miR-191-5p was selected based on a comparison of miRNA signatures and the findings of previous reports. We explored the utility of circulating exosomal miR-191-5p as a prognostic biomarker of chemoradiotherapy along with its target gene, molecular pathway and functions specifically related to radiotherapy in ESCC. RESULTS Overexpression of miR-191-5p promoted ESCC cell proliferation, invasion and migration. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may downregulate death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent treatment, including radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression. CONCLUSION Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.
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Affiliation(s)
- Huan Wang
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
- Department of Thoracic Surgery, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Yasunori Matsumoto
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan.
| | - Abula Maiyulan
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Takeshi Toyozumi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Ryota Otsuka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Nobufumi Sekino
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Koichiro Okada
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Tadashi Shiraishi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Toshiki Kamata
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, Japan
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Wang AJ, Tushar FI, Harowicz MR, Tong BC, Lafata KJ, Tailor TD, Lo JY. The Duke Lung Cancer Screening (DLCS) Dataset: A Reference Dataset of Annotated Low-Dose Screening Thoracic CT. Radiol Artif Intell 2025; 7:e240248. [PMID: 40237601 DOI: 10.1148/ryai.240248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
The Duke Lung Cancer Screening (DLCS) dataset is a large collection of lung cancer screening low-dose CT scans for lung nodule classification with annotations performed in a semiautomated manner, requiring substantially reduced radiologist effort.
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Affiliation(s)
- Avivah J Wang
- Duke University School of Medicine, 40 Duke Medicine Cir, Durham, NC 27710
| | - Fakrul Islam Tushar
- Department of Radiology, Center for Virtual Imaging Trials, Carl E. Ravin Advanced Imaging Laboratories, Duke University School of Medicine, Durham, NC
| | - Michael R Harowicz
- Department of Radiology, Division of Cardiothoracic Imaging, Duke University School of Medicine, Durham, NC
| | - Betty C Tong
- Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of Medicine, Durham, NC
| | - Kyle J Lafata
- Department of Radiology, Center for Virtual Imaging Trials, Carl E. Ravin Advanced Imaging Laboratories, Duke University School of Medicine, Durham, NC
| | - Tina D Tailor
- Department of Radiology, Division of Cardiothoracic Imaging, Duke University School of Medicine, Durham, NC
| | - Joseph Y Lo
- Department of Radiology, Center for Virtual Imaging Trials, Carl E. Ravin Advanced Imaging Laboratories, Duke University School of Medicine, Durham, NC
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Weng M, Zhu X. Thrombospondin-2 induces M2 macrophage polarization through fatty acid metabolism to drive lung adenocarcinoma proliferation. Anticancer Drugs 2025; 36:459-467. [PMID: 40053399 DOI: 10.1097/cad.0000000000001713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2025]
Abstract
Tumor-associated macrophages play a critical role in regulating the progression of lung adenocarcinoma (LUAD). Platelet-derived protein thrombospondin-2 (THBS2) has been identified as a tumor marker and is known to be overexpressed in LUAD. However, the specific role of THBS2 in M2 macrophage polarization within LUAD remains unclear. We conducted bioinformatics analyses to assess the clinical significance of THBS2 expression in LUAD, which was subsequently validated using quantitative PCR. We examined the relationship between THBS2 expression and M2 macrophage infiltration. A coculture system of LUAD cells and M0 macrophages was established to investigate the influence of THBS2 on macrophage infiltration and polarization through immunofluorescence and ELISA. We explored the impact of THBS2 on fatty acid metabolism (FAM) using oil red O staining and relevant kits and elucidated the role of THBS2 in regulating M2 macrophage polarization and LUAD proliferation through cell counting kit-8 (CCK-8) and colony formation assays. Western blot was employed to assess expression changes of Bax and Bcl-2. THBS2 was highly expressed in LUAD and was associated with poor prognosis in patients. In-vitro experiments demonstrated that silencing THBS2 significantly inhibited macrophage infiltration and polarization. THBS2 primarily activated FAM pathways, inducing M2 macrophage polarization and promoting LUAD cell proliferation. THBS2 enhanced LUAD proliferation by regulating FAM to induce M2 macrophage polarization. These findings provide a theoretical basis for targeting THBS2 as a novel therapeutic strategy in LUAD.
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Affiliation(s)
| | - Xiaoping Zhu
- Radiation Oncology, Medical Oncology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
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Yu X, Wu H, Wu Z, Lan Y, Chen W, Wu B, Deng Y, Liu J. Nuclear pore complex protein RANBP2 and related SUMOylation in solid malignancies. Genes Dis 2025; 12:101407. [PMID: 40271196 PMCID: PMC12017851 DOI: 10.1016/j.gendis.2024.101407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 04/28/2024] [Accepted: 06/21/2024] [Indexed: 04/25/2025] Open
Abstract
The growing interest in post-translational protein modification, particularly in SUMOylation, is driven by its crucial role in cell cycle regulation. SUMOylation affects various cell cycle regulators, including oncogenes, suggesting its relevance in cancer. SUMO E3 ligases are pivotal in this process, exhibiting diverse functionalities through structural domains and subcellular localizations. A less-explored SUMO E3 ligase, RANBP2, a component of the vertebrate nuclear pore complex, emerges as a central player in cellular cycle processes, as well as in tumorigenesis. The current studies illuminate the importance of RANBP2 and underscore the need for more extensive studies to validate its clinical applicability in neoplastic interventions. Our review elucidates the significance of RANBP2 across various types of malignancies. Additionally, it delves into exploring RANBP2 as a prospective therapeutic target for cancer treatment, offering insights into the avenues that scholars should pursue in their subsequent research endeavors. Thus, further investigation into RANBP2's role in solid tumorigenesis is eagerly awaited.
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Affiliation(s)
- Xinning Yu
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Huatao Wu
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Zheng Wu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yangzheng Lan
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Wenjia Chen
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Bingxuan Wu
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yu Deng
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Jing Liu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Physiology, Shantou University Medical College, Shantou, Guangdong 515041, China
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Chou WH, Chalker C, Sokolova AO, Isharwal S. Prostate cancer and genetic contributions. Andrology 2025; 13:1149-1157. [PMID: 39611376 PMCID: PMC12119970 DOI: 10.1111/andr.13812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 10/17/2024] [Accepted: 11/15/2024] [Indexed: 11/30/2024]
Abstract
Prostate cancer remains a lethal disease for many men. Knowledge of genetic contributions to this condition has increasingly been used in its management. In this narrative review, we summarize various genetic alterations and syndromes associated with prostate cancer, including hereditary breast and ovarian cancer syndrome, Lynch syndrome, and hereditary prostate cancer, among others. Indications for germline testing are reviewed, as well as incorporation of genetic data at different phases of management for prostate cancer, such as screening and monitoring, and treatment of localized and metastatic disease.
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Affiliation(s)
- Wesley H. Chou
- Department of Urology, Oregon Health & Science University, Portland, OR, USA
| | - Cameron Chalker
- Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Alexandra O. Sokolova
- Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Sudhir Isharwal
- Department of Urology, Oregon Health & Science University, Portland, OR, USA
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Hsu Y, Chou CY, Huang YC, Liu YC, Lin YL, Zhong ZP, Liao JK, Lee JC, Chen HY, Lee JJ, Chen SJ. Oral mucosal lesions triage via YOLOv7 models. J Formos Med Assoc 2025; 124:621-627. [PMID: 39003230 DOI: 10.1016/j.jfma.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 06/25/2024] [Accepted: 07/09/2024] [Indexed: 07/15/2024] Open
Abstract
BACKGROUND/PURPOSE The global incidence of lip and oral cavity cancer continues to rise, necessitating improved early detection methods. This study leverages the capabilities of computer vision and deep learning to enhance the early detection and classification of oral mucosal lesions. METHODS A dataset initially consisting of 6903 white-light macroscopic images collected from 2006 to 2013 was expanded to over 50,000 images to train the YOLOv7 deep learning model. Lesions were categorized into three referral grades: benign (green), potentially malignant (yellow), and malignant (red), facilitating efficient triage. RESULTS The YOLOv7 models, particularly the YOLOv7-E6, demonstrated high precision and recall across all lesion categories. The YOLOv7-D6 model excelled at identifying malignant lesions with notable precision, recall, and F1 scores. Enhancements, including the integration of coordinate attention in the YOLOv7-D6-CA model, significantly improved the accuracy of lesion classification. CONCLUSION The study underscores the robust comparison of various YOLOv7 model configurations in the classification to triage oral lesions. The overall results highlight the potential of deep learning models to contribute to the early detection of oral cancers, offering valuable tools for both clinical settings and remote screening applications.
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Affiliation(s)
- Yu Hsu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Ying Chou
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Yu-Cheng Huang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Chieh Liu
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Yong-Long Lin
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Zi-Ping Zhong
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Jun-Kai Liao
- Department of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan
| | - Jun-Ching Lee
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsin-Yu Chen
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
| | - Jang-Jaer Lee
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Department of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Shyh-Jye Chen
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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Zeng H, Ma Z, Tao Y, Cheng C, Lin J, Fang J, Wei Y, Liu H, Zou F, Cui E, Zhang Y. Predicting early recurrence in hepatocellular carcinoma after hepatectomy using GD-EOB-DTPA enhanced MRI-based model. Eur J Radiol 2025; 188:112130. [PMID: 40305886 DOI: 10.1016/j.ejrad.2025.112130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/19/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
PURPOSE To develop and validate a comprehensive model for predicting postoperative early recurrence of hepatocellular carcinoma (HCC) based on gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI. METHODS 239 patients with HCC who underwent curative surgical resection were recruited from two centers between April 2017 and December 2022. Radiomics features were extracted from the region of interest (ROI) on preoperative Gd-EOB-DTPA-enhanced MR images, and consistency analysis was performed to select stable radiomics features. Significant variables in the univariate and multivariate logistic regression analysis were included in clinical-radiologic model. Nomograms were constructed by combining the best performing radiologic and clinical-radiologic characteristics. Recurrence-free survival (RFS) comparisons were conducted using the log-rank test based on high versus low model-derived scores. RESULTS The radiomics model based on multiple phases MR outperformed all other radiomics models and had the best discrimination for early recurrence, with AUC of 0.799 and 0.743 in the training and validation sets, respectively. In the entire cohort, high-risk patients exhibited significantly lower RFS compared to low-risk patients. CONCLUSION The nomogram integrating Gd-EOB-DTPA enhanced MRI radiomics features and clinical-radiologic characteristics demonstrate superior predictive performance with postoperative early recurrence in patients with HCC. The model can identify patients at high risk and provide support for individualized treatment planning.
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Affiliation(s)
- Hanqiu Zeng
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Zichang Ma
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Yuxi Tao
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Ci Cheng
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Junyu Lin
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Jiayu Fang
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Yuhan Wei
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Huajin Liu
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Feixiang Zou
- Department of Radiology, People's Hospital of Wuchuan Gelao and Miao Autonomous County, Zunyi 5643000 Guizhou, China
| | - Enming Cui
- Department of Radiology, Jiangmen Central Hospital, Jiangmen, China.
| | - Yaqin Zhang
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China.
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Zhong J, Li Y, Liu Y, Qiao J, Wu Y, Kong X, Qi M, Lin Y, Yao Y, Jin Y, Bi C, Zhai A. Hepatitis B virus X protein (HBx)-mediated immune modulation and prognostic model development in hepatocellular carcinoma. PLoS One 2025; 20:e0325363. [PMID: 40577282 DOI: 10.1371/journal.pone.0325363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 05/12/2025] [Indexed: 06/29/2025] Open
Abstract
Hepatitis B virus (HBV) X protein (HBx) is critical in hepatocellular carcinoma (HCC) development, but its influence on tumor immunity and the tumor microenvironment (TME) remains unclear. This study aimed to construct a prognostic model based on HBx-related genes and explore their relationship with immune infiltration and immunotherapy response. Through transcriptome sequencing of our HBx-expressing HepG2 cells and analysis of HCC patient data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx), we identified seven HBx-related genes, nuclear VCP-like (NVL), WD repeat domain 75 (WDR75), NOP58 nucleolar protein (NOP58), Brix domain-containing protein 1 (BRIX1), deoxynucleotidyltransferase terminal interacting protein 2 (DNTTIP2), MKI67 FHA domain interacting nucleolar phosphoprotein (NIFK), and ribosome production factor 2 (RPF2), associated with poor prognosis. LASSO Cox regression narrowed these to four key genes (BRIX1, RPF2, DNTTIP2, and WDR75), which were used to develop a prognostic riskscore signature. High-risk patients exhibited lower survival rates, decreased infiltration of anti-tumor immune cells, poorer responses to immunotherapy, and increased immune evasion. Among the four genes, DNTTIP2 showed higher expression in single-cell data, was linked to migration inhibitory factor (MIF) signaling, and may play a pivotal role in shaping an immunosuppressive TME. Elevated DNTTIP2 expression was confirmed in HBx-expressing HepG2 cells and HBV-infected HCC samples. This study highlights a novel HBx-related four-gene prognostic model that predicts clinical outcomes, immune infiltration, and immunotherapy response, offering insights into HCC progression and potential therapeutic targets.
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Affiliation(s)
- Jianhua Zhong
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yuetong Li
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yang Liu
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jie Qiao
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yiling Wu
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xinyi Kong
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Miao Qi
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yiqi Lin
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yaqi Yao
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Ying Jin
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Changlong Bi
- Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Aixia Zhai
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Yu J, Li M, Qin XZ, Gong L, Qin L, Lv ZB, Guo W, Huang B, Tian YH. Application of modified Roux-en-Y digestive tract reconstruction in total gastrectomy for patients with gastric cancer. World J Gastrointest Surg 2025; 17:106009. [DOI: 10.4240/wjgs.v17.i6.106009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/01/2025] [Accepted: 04/25/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND At present, the concept of surgical treatment of gastric cancer (GC) has changed from “radical treatment” to “care for patients” to a certain extent. The reconstruction method is the most likely to affect the postoperative life of the patient. Currently, the traditional Roux-en-Y esophagojejunostomy anastomosis is a commonly used method for gastrointestinal reconstruction after total gastrectomy for GC. However, more recent studies have shown that the traditional Roux-en-Y anastomosis is complicated in operation procedure, with more reconstruction steps and longer reconstruction time, and the incidence of postoperative complications such as adhesive intestinal obstruction, internal abdominal hernia and volvulus is high. Moreover, the incidence of Roux stasis syndrome is 10%-30% after traditional Roux-en-Y reconstruction. Thus, we modified the traditional Roux-en-Y alimentary tract reconstruction, and designed a new digestive tract reconstruction method for laparoscopy-assisted Roux-en-Y anastomosis for total gastrectomy of GC.
AIM To evaluate the clinical advantages, feasibility, and safety of a modified Roux-en-Y digestive tract reconstruction in laparoscopy-assisted total gastrectomy for the treatment of GC compared with the traditional Roux-en-Y method.
METHODS Ninety-seven patients who underwent laparoscopy-assisted D2 radical gastrectomy (total gastrectomy) for GC were divided into two groups: fifty-four in the conventional Roux-en-Y reconstruction group (Orr group) and forty-three in the modified Roux-en-Y reconstruction group (the modified group). Perioperative and short-term outcomes were analyzed, including complications, postoperative weight loss, hemoglobin levels, and nutritional status.
RESULTS The Orr group and the modified group showed no statistically significant differences in baseline characteristics. Compared with the Orr group, the modified group had shorter digestive tract reconstruction and operation times, less intraoperative bleeding, and shorter postoperative hospital stays compared to the Orr group. Although both groups had similar amounts of intraoperative blood loss, postoperative recovery times, and hospital expenses, the Orr group experienced longer operation times and digestive tract reconstruction times. Furthermore, the modified Roux-en-Y group demonstrated significantly fewer short-term and long-term complications, with a reduced incidence of reflux esophagitis and improved nutritional status.
CONCLUSION The modified Roux-en-Y digestive tract reconstruction method after laparoscopy-assisted total gastrectomy for GC offers safety, simplicity, and a reduction in bile reflux. This method shortens operation times and minimizes postoperative complications, aligns with modern rapid rehabilitation surgery trends and potentially improves patient prognosis and overall survival. This method warrants further clinical application and promotion.
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Affiliation(s)
- Jing Yu
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Min Li
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Xiang-Zhi Qin
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Lei Gong
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Long Qin
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Zhen-Bing Lv
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Wei Guo
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Bin Huang
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
| | - Yun-Hong Tian
- Department of Gastrointestinal Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Gastrointestinal Surgery, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
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Chen X, Nie H, Chen Q, Zhang X, He Z, Chao X, Ou W, Fu X, Chen H. A Innovative Strategy for Identifying Subtypes Through the Analysis of Multi-Omics Data with Adversarial Autoencoders. J Comput Biol 2025. [PMID: 40566761 DOI: 10.1089/cmb.2024.0927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2025] Open
Abstract
Cancer is a disease that is both complex and diverse, and effective diagnosis and treatment require an accurate depiction of tumor subtypes. Traditional methods of cancer identification, which rely on clinical and histopathological criteria, have limitations in identifying key molecular subtypes. With the advancement of high-throughput genomics technologies, the field of cancer research has undergone a transformation, enabling detailed analysis of tumor molecular characteristics on a large scale. The integration of multiple types of genomic data is expected to provide a more comprehensive understanding of the molecular mechanisms of cancer and to promote the discovery of new diagnostic and therapeutic targets. However, achieving this requires the development of new computational techniques. In order to facilitate more efficient feature extraction and dimensionality reduction of multi-omics data, we present MultiDAAE (Multi-omics Double Adversarial Autoencoder), a novel technique that combines autoencoders with two discriminators to form two generative adversarial networks. On several cancer datasets, our method shows outstanding clustering performance when compared to state-of-the-art techniques. To sum up, MultiDAAE can help identify possible molecular pathways and provide information for the development of tailored cancer treatments.
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Affiliation(s)
- Xia Chen
- Aeronautical Electronic Equipment Maintenance College, Changsha Aeronautical Vocational and Technical College, Changsha, China
| | - Hao Nie
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | | | - Xiang Zhang
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Zixing He
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Xiuxiu Chao
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Weihao Ou
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Xiangzheng Fu
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Haowen Chen
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
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