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Zhao HX, Wei Y, Zhao ZL, Peng LL, Li Y, Wu J, Cao SL, Yu N, Yu MA. Clinical study on the relationship between the incidence of complications and tumour size after thermal ablation of benign thyroid nodules. Int J Hyperthermia 2025; 42:2464205. [PMID: 39947643 DOI: 10.1080/02656736.2025.2464205] [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: 10/08/2024] [Revised: 12/25/2024] [Accepted: 02/03/2025] [Indexed: 05/21/2025] Open
Abstract
OBJECTIVE The present study aimed to analyze the relationship between the incidence of complications and tumor size following thermal ablation of benign thyroid nodules (BTNs). METHODS In this retrospective study, 1198 patients who underwent thermal ablation for unifocal BTN were enrolled. Receiver Operating Characteristic analysis was performed to select the cutoff values of the maximum diameter (MD) for dividing patients into different groups or subgroups. Multivariable logistic regression was performed to identify the risk factors. Propensity score matching (PSM) was employed to control for confounding variables. RESULTS The overall complication rate was 3.8% (45/1198). Major complications included hoarseness (2.4%), nodule rupture (0.3%) and delayed hemorrhage (0.1%), whereas minor complications were limited to intraoperative hemorrhage (0.9%). The difference in the overall complication rate between the smaller group (< 3.15 cm) and the larger group (> 3.15 cm) was significant (1.0% vs. 6.5%, p < 0.001). In the subgroup analysis, a significant difference was observed between the 3.15-4.15 cm and > 4.15 cm subgroups (4.2% vs. 8.7%, p = 0.023); however, no significant difference was identified between the < 2.35 and 2.35-3.15 cm subgroups (0.6% vs. 1.6%, p = 0.390). Multivariable logistic regression indicated that MD and the nodule component were associated with complications. After PSM, no significant difference in complication rates was observed between MWA and RFA in either the smaller group (p = 1.000) or the larger group (p = 0.186). CONCLUSIONS The incidence of complications in thermal ablation is greater for larger thyroid nodules, particularly for predominantly solid nodules with MDs greater than 3.15 cm.
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Affiliation(s)
- Han-Xiao Zhao
- China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Ying Wei
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Zhen-Long Zhao
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Li-Li Peng
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Yan Li
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Jie Wu
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Shi-Liang Cao
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Na Yu
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Ming-An Yu
- Department of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China
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Chiaverini L, Ferraro G, Di Leo R, Barresi E, La Mendola D, Bartoli F, Famlonga L, Satriano C, Faviana P, Zucchi A, Pacini M, Gailer J, Giacomelli C, Marzo T. From conventional therapy to novel nano-based approaches. A focus on prostate cancer. Nanomedicine (Lond) 2025:1-18. [PMID: 40329819 DOI: 10.1080/17435889.2025.2501513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/17/2025] [Indexed: 05/08/2025] Open
Abstract
The currently available clinical anticancer approaches pertaining to the treatment of prostate cancer are summarized here. After providing an overview of the main features of this highly impactful global disease, the currently available clinical treatments are briefly reviewed. Then, alternative and innovative nano-based therapeutic options that have been proposed or are currently being explored to significantly improve prostate cancer management (i.e. anti-prostate cancer polymeric nanoparticles loaded with drugs to promote their release and biological activity, including non-targeted and functionalized PLGA-PEG NPs and AuNPs), are introduced. Furthermore, the problem of gathering insights into the mechanistic aspects related to the fate of the nanoformulation in complex matrices, such as blood plasma, is addressed.
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Affiliation(s)
| | - Giarita Ferraro
- Department of Chemical Sciences, University of Naples 'Federico II', Napoli, Italy
| | - Riccardo Di Leo
- Department of Pharmacy, University of Pisa, Pisa, Italy
- Institute of Clinical Physiology, Nationale Research Council (CNR), Pisa, Italy
| | | | | | - Francesco Bartoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Luca Famlonga
- Department of Pharmacy, University of Pisa, Pisa, Italy
| | - Cristina Satriano
- NanoHybrid BioInterfaces Laboratory (NHBIL), Department of Chemical Sciences, University of Catania, Catania, Italy
| | - Pinuccia Faviana
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy
| | - Alessandro Zucchi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Matteo Pacini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Jürgen Gailer
- Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada
| | | | - Tiziano Marzo
- Department of Pharmacy, University of Pisa, Pisa, Italy
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3
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Vishvaja S, Priyadharshini D, Sabarees G, Tamilarasi GP, Gouthaman S, Solomon VR. Optimizing processes and unveiling the therapeutic potential of electrospun gelatin nanofibers for biomedical applications. J Mater Chem B 2025; 13:5202-5225. [PMID: 40171573 DOI: 10.1039/d4tb02769h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2025]
Abstract
Gelatin, derived primarily from animal sources such as bovine, porcine, and fish skin and bones, exhibits remarkable properties that make it an ideal candidate for various contemporary applications. Its unique attributes include excellent biocompatibility, non-toxicity, biodegradability, low immunogenicity, ease of chemical modification, and structural similarity to the extracellular matrix (ECM). These features have led to the development of gelatin-based biomaterials with tunable properties and specialized functionalities. Electrospinning remains the most widely adopted and effective technique for fabricating gelatin nanofibers. These nanofibers are gaining significant attention in the biomedical sector due to their adjustable fiber morphology, enhanced surface properties, controllable porosity, mechanical adaptability, high surface area, multi-scale pore size distribution, and intrinsic bioactive characteristics. Functionalized gelatin-based electrospun nanofibers are a rapidly advancing area in the life sciences, enabling the creation of innovative drug delivery platforms and next-generation scaffolds for tissue regeneration. Their applications span across various domains, including bone and cartilage repair, retinal and vascular engineering, myocardial regeneration, cancer therapy, chronic wound management, and biosensor development. In this article, we provide a comprehensive assessment of the progression of gelatin-based nanofibers, highlight the critical parameters governing the electrospinning of gelatin, and explore recent innovations in diverse biomedical fields, emphasizing significant advancements and research findings.
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Affiliation(s)
- Sivapregassame Vishvaja
- Department of Pharmaceutical Chemistry, Shri Venkateshwara College of Pharmacy, Ariyur, Puducherry 605102, India.
| | | | - Govindaraj Sabarees
- Department of Pharmaceutical Chemistry, Shri Venkateshwara College of Pharmacy, Ariyur, Puducherry 605102, India.
| | - Ganesan Padmini Tamilarasi
- Department of Pharmaceutical Chemistry, Shri Venkateshwara College of Pharmacy, Ariyur, Puducherry 605102, India.
| | - Siddan Gouthaman
- Organic Material Laboratory, Department of Chemistry, Indian Institute of Technology, Roorkee 247667, India
| | - Viswas Raja Solomon
- Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Greater Hyderabad, Sangareddy 502294, India.
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4
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Yang G, Luo S, Greer P. Boosting Skin Cancer Classification: A Multi-Scale Attention and Ensemble Approach with Vision Transformers. SENSORS (BASEL, SWITZERLAND) 2025; 25:2479. [PMID: 40285168 PMCID: PMC12030980 DOI: 10.3390/s25082479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/10/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025]
Abstract
Skin cancer is a significant global health concern, with melanoma being the most dangerous form, responsible for the majority of skin cancer-related deaths. Early detection of skin cancer is critical, as it can drastically improve survival rates. While deep learning models have achieved impressive results in skin cancer classification, there remain challenges in accurately distinguishing between benign and malignant lesions. In this study, we introduce a novel multi-scale attention-based performance booster inspired by the Vision Transformer (ViT) architecture, which enhances the accuracy of both ViT and convolutional neural network (CNN) models. By leveraging attention maps to identify discriminative regions within skin lesion images, our method improves the models' focus on diagnostically relevant areas. Additionally, we employ ensemble learning techniques to combine the outputs of several deep learning models using majority voting. Our skin cancer classifier, consisting of ViT and EfficientNet models, achieved a classification accuracy of 95.05% on the ISIC2018 dataset, outperforming individual models. The results demonstrate the effectiveness of integrating attention-based multi-scale learning and ensemble methods in skin cancer classification.
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Affiliation(s)
- Guang Yang
- School of Information and Physical Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia
| | - Suhuai Luo
- School of Information and Physical Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan NSW 2308, Australia
| | - Peter Greer
- School of Information and Physical Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan NSW 2308, Australia
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Hu WT, Li M, Ma PJ, Yang D, Liu XD, Wang Y. A silence catalyst: CCL5-mediated intercellular communication in cancer. Arch Toxicol 2025:10.1007/s00204-025-04036-w. [PMID: 40167774 DOI: 10.1007/s00204-025-04036-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 03/19/2025] [Indexed: 04/02/2025]
Abstract
Chemokine CCL5 (RANTES), as a key mediator of intercellular communication in cancers, and its role in cancer development, metastasis and immune escape has received increasing attention. CCL5 and its receptors are important components of the tumor microenvironment and play a tumor promoting role in different ways by triggering signaling pathways through binding to the primary receptor CCR5. CCL5 was viewed as indispensable "gate keepers" of immunity and inflammation, it remains unclear of CCL5-mediated intercellular communication. Therefore, in this review, we summarize the latest information on the origin, structure, and characterization of CCL5 and role of CCL5 in the tumor microenvironment. It includes CCL5-mediated intercellular communication through exosomes, microvesicles and others in breast, lung, and ovarian cancers. CCL5 has a multifaceted role in cancer and has potential applications as a biomarker for cancer diagnosis and prognosis, which provides theoretical bases and therapeutic targets for the development of new cancer therapeutic strategies.
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Affiliation(s)
- Wei-Ting Hu
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China
| | - Ming Li
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Pei-Jun Ma
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China
| | - Ding Yang
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China
| | - Xiao-Dong Liu
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
| | - Yun Wang
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
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Barjasteh AH, Jaseb Mazhar AleKassar R, Al-Asady AM, Latifi H, Avan A, Khazaei M, Ryzhikov M, Hassanian SM. Therapeutic Potentials of MiRNA for Colorectal Cancer Liver Metastasis Treatment: A Narrative Review. IRANIAN JOURNAL OF MEDICAL SCIENCES 2025; 50:202-219. [PMID: 40255223 PMCID: PMC12008659 DOI: 10.30476/ijms.2024.102910.3622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 11/01/2024] [Accepted: 11/26/2024] [Indexed: 04/22/2025]
Abstract
Colorectal cancer (CRC) ranks among the most prevalent cancers worldwide and is the fourth leading cause of cancer-related deaths. Metastasis poses a significant obstacle in CRC treatment, as distant metastasis, particularly to the liver, remains the primary cause of mortality. Colorectal liver metastasis (CRLM) occurs frequently due to the liver's direct vascular connection to the colorectal region via the portal vein. Standard treatment approaches for CRLM are limited; only a few patients qualify for surgical intervention, resulting in a persistently low survival rate. Additionally, resistance to chemotherapy is common, emphasizing the need for more effective targeted therapies. Emerging evidence highlights the pivotal role of microRNAs (miRNAs) in modulating critical pathways associated with CRLM, including tumor invasion, epithelial-mesenchymal transition, and angiogenesis. MiRNAs exhibit dual functions as tumor suppressors and oncogenes by targeting multiple genes, thus playing a complex role in both the initiation and progression of metastasis. The regulatory mechanisms of miRNAs could help to identify novel biomarkers for early diagnosis and prognosis of CRLM, as well as promising therapeutic targets to overcome chemoresistance. Despite numerous studies on miRNA involvement in CRC metastasis, dedicated reviews focusing on miRNAs and CRLM remain scarce. This review aims to approach targeted therapies by examining the current understanding of miRNA involvement in CRLM and exploring their potential as diagnostic, prognostic, and therapeutic agents. Through an integrative approach, we aim to provide insights that could transform CRLM management and improve patient outcomes.
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Affiliation(s)
- Amir Hossein Barjasteh
- Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Rawa Jaseb Mazhar AleKassar
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abdulridha Mohammed Al-Asady
- Department of Medical Sciences, Faculty of Nursing, Warith Al-Anbiyaa University, Iraq
- Department of Medical Sciences, Faculty of Dentistry, University of Kerbala, Iraq
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hanieh Latifi
- Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Faculty of Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Seyed Mahdi Hassanian
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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7
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Hu Z, Tang M, Huang Y, Cai B, Sun X, Chen G, Huang A, Li X, Shah AR, Jiang L, Li Q, Xu X, Lu W, Mao Z, Wan X. SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner. Nat Commun 2025; 16:2989. [PMID: 40148340 PMCID: PMC11950185 DOI: 10.1038/s41467-025-58317-0] [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: 09/26/2023] [Accepted: 03/18/2025] [Indexed: 03/29/2025] Open
Abstract
The prognosis of metastatic endometrial carcinoma (EC), one of the most common gynecological malignancies worldwide, remains poor, and the underlying driver of metastases is poorly understood. Dysregulation in estrogen-related signaling and inactivation of tumor suppressor PTEN are two essential risk factors of EC. However, whether and how they are interconnected during EC development remains unclear. Here, we demonstrate that the deacetylase SIRT7 is upregulated in EC patients and mouse models, facilitating EC progression in vitro and in vivo. Mechanistically, in an estrogen-dependent fashion, SIRT7 mediates PTEN deacetylation at K260, promoting PTEN ubiquitination by the E3 ligase NEDD4L, accelerating PTEN degradation and, consequently, expediting EC metastasis. Additionally, SIRT7 expression strongly correlates with poor survival in EC patients with wild-type PTEN, though no significant correlation is observed in PTEN mutation patients. These results lay the foundation for the study of targeting estrogen-SIRT7-PTEN axis, to restore PTEN abundance, offering potential avenues for EC therapy.
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Affiliation(s)
- Zhiyi Hu
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ming Tang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Yujia Huang
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Bailian Cai
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiaoxiang Sun
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Guofang Chen
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ao Huang
- Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmacy, Changsha Medical University, Changsha, China
| | - Xiaoqi Li
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Ab Rauf Shah
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Lijun Jiang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Qian Li
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xianghong Xu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wen Lu
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Zhiyong Mao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
| | - Xiaoping Wan
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
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Diallo MT, Chen B, Yao Q, Yan Z, Sun Q, Wang D. KIF3C inhibits the progression and proliferation of colorectal cancer. BMC Gastroenterol 2025; 25:165. [PMID: 40075273 PMCID: PMC11899393 DOI: 10.1186/s12876-024-03489-0] [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: 06/02/2024] [Accepted: 10/30/2024] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Evidence indicated that KIF3C, a member of the kinesin superfamily of motor proteins, exhibits significant upregulation across various cancer types. Consequently, its impact on cancer advancement, including cell proliferation, migration, and invasion, is evident. Nonetheless, the comprehension of KIF3C's expression and role in colorectal cancer (CRC) remains limited. METHODS Immunohistochemistry was used to evaluate the presence of KIF3C in CRC. The expression levels of KIF3C were assessed in CRC cells through western blot analysis (WB) and real-time polymerase chain reaction (RT-qPCR). KIF3C was knockdown and overexpressed using lentiviral vectors in the human CRC cell lines SW-480, HCT-116, and SW-620. In vitro experiments such as transwell assays, scratch wound healing, colony formation assays, counting cell CCK-8, and signaling pathway experiments were conducted to validate the KIF3C function in CRC cells. RESULTS We demonstrated that KIF3C is highly expressed in cells and tissues of CRC, and this expression is closely associated with tumor prognosis. It was shown that KIF3C knockdown significantly inhibited tumor cell proliferation and migration in CRC cells. Additionally, the KIF3C signaling pathway experiment in this study promoted the CRC progression by upregulating the PI3K/AKT, Bax, and Bcl-2 pathways. CONCLUSIONS KIF3C knockdown promoted CRC proliferation, as it could be a potential therapeutic target for treating CRC.
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Affiliation(s)
- Maladho Tanta Diallo
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China
- Medical College of Yangzhou University, Yangzhou, 225001, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China
| | - Bangquan Chen
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China
| | - Qing Yao
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China
| | - Zhang Yan
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China
| | - Qiannan Sun
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China
| | - Daorong Wang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China.
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, China.
- Medical College of Yangzhou University, Yangzhou, 225001, China.
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, China.
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9
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Jairoun AA, Al-Hemyari SS, Shahwan M, Zyoud SH, Saleh Jaber AA. Community pharmacist-led point-of-care colorectal cancer screening program: Early detection of colorectal cancer in high-risk patients. Res Social Adm Pharm 2025; 21:185-192. [PMID: 39694778 DOI: 10.1016/j.sapharm.2024.12.006] [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: 11/27/2023] [Revised: 08/08/2024] [Accepted: 12/12/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND The prevalence of colorectal cancer (CRC) is on the rise among the younger population, with an anticipated increase in new cases for individuals aged 20-49 years by 2030. The accessibility of community pharmacists and their strong community connections present unique opportunities to enhance patient engagement in a population-based CRC screening program. OBJECTIVES This study seeks to assess the effectiveness of a community pharmacist-led point-of-care CRC screening program utilizing fecal immunochemical test (FIT) kits to identify CRC prevalence in high-risk individuals. METHODS AND MATERIALS Over the course of a 10-month prospective intervention conducted in UAE community pharmacies, we evaluated the impact of a pharmacist-led point-of-care colorectal cancer screening program. Six pharmacies were selected based on their services and capabilities. Eligible participants were those identified during medication reviews as exhibiting colorectal cancer risk factors. Pharmacists provided communication materials, distributed FIT kits, and implemented reminders. Participants collected samples for hemoglobin analysis, which served as an indicator of colorectal bleeding. Collected data encompassed demographics, lifestyle, and health-related characteristics. Pharmacists performed medication reviews and offered recommendations. RESULTS A total of four hundred and one recruited int the study. The mean age of study cohort at baseline was 66.6 ± 11.3 years. In our study with 401 participants, 36.4 % had undiagnosed colorectal cancer (CRC). Univariate logistic regression identified older age, a history of Type 2 diabetes mellitus (DM), and inflammatory bowel disease (IBD) as significant factors associated with increased CRC prevalence, while aspirin users exhibited a lower likelihood of CRC. In the multivariate regression model, the history of Type 2 DM and IBD remained significant predictors for heightened CRC risk. CONCLUSION This study strengthens the plausibility of cause-and-effect relationships between colorectal cancer and demographic variables using epidemiological evidence. The significant relationships found between prevalence of CRC and age, type 2 diabetes, IBD and aspirin use support the effectiveness of using FIT kits in community pharmacist-led point-of-care CRC screening program to identify high-risk individuals. The finding highlights the significance of improving efforts on colorectal cancer prevention and control.
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Affiliation(s)
- Ammar Abdulrahman Jairoun
- Health and Safety Department, Dubai Municipality, Dubai, United Arab Emirates; Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Pulau Pinang, 11500, Malaysia.
| | - Sabaa Saleh Al-Hemyari
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Pulau Pinang, 11500, Malaysia; Pharmacy Department, Emirates Health Services, Dubai, United Arab Emirates.
| | - Moyad Shahwan
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, Ajman, 346, United Arab Emirates; Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, 346, United Arab Emirates.
| | - Samer H Zyoud
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, Ajman, 346, United Arab Emirates; Department of Mathematics and Sciences, Ajman University, P.O. Box 346, Ajman, United Arab Emirates.
| | - Ammar Ali Saleh Jaber
- Department of Clinical Pharmacy & Pharmacotherapeutics, Dubai Pharmacy College for Girls, AlMuhaisanah 1, Al mizhar, Dubai, United Arab Emirates.
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10
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Yan Y, Zhang Y, Chen Y, Zhong G, Huang W, Zhang Y. Prognostic Value of Inflammatory and Nutritional Indicators in Non-Metastatic Soft Tissue Sarcomas. J Inflamm Res 2025; 18:1941-1950. [PMID: 39959645 PMCID: PMC11827485 DOI: 10.2147/jir.s501079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/20/2025] [Indexed: 02/18/2025] Open
Abstract
Background Soft tissue sarcoma (STS) has lacked reliable prognostic indicators. This study evaluates blood-based inflammatory and nutritional indexes to identify good predictors for STS outcomes. These indicators included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), lymphocyte-to-monocyte ratio (PNI), albumin-to-globulin ratio (AGR), and platelet-to-albumin ratio (PAR). Methods A total of 93 were included, and blood indexes were measured preoperatively. Univariate and multivariate regression analyses identified significant predictors, and model performance was assessed using the Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), Concordance Index (C-index), and Likelihood Ratio Chi-Square (LR_χ2). Results Univariate analysis indicated that NLR, PLR, LMR, SIRI, AGR, and PAR show potentially significant differences (P<0.01), except for PNI. Further analysis showed that SIRI and AGR have a high C-index, LR_χ2, and -2 log-likelihood, lower AIC and BIC, indicating a better model fit for overall survival (OS) and disease-free survival (DFS). The combination index of the SIRI+AGR+Enneking stage achieved the best accuracy (C-index: 0.751 for DFS; C-index: 0.755 for OS). Multivariate regression showed higher Enneking staging (HR=2.720, P=0.038), lower AGR (HR=2.091, P=0.014), and higher SIRI (HR=2.078, P=0.034) as independent prognostic factors for DFS. Meanwhile, low AGR (HR=3.729, P=0.034), and high SIRI (HR=3.729, P=0.016) remained independent prognostic factors for OS. Conclusion Preoperative SIRI is a better predictive index compared to NLR, PLR, and LMR. Preoperative SIRI and AGR are independent risk factors for both DFS and OS. The combination index of the SIRI+AGR+Enneking stage provides a more robust prediction of clinical prognosis in STS patients.
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Affiliation(s)
- Yuan Yan
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yunhui Zhang
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yonghan Chen
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Guoqing Zhong
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Wenhan Huang
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Yu Zhang
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
- Department of Orthopaedics Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
- School of Materials Science and Engineering (National Engineering Research Center for Tissue Restoration and Reconstruction), South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Hematol Oncol Clin North Am 2025; 39:1-24. [PMID: 39510667 DOI: 10.1016/j.hoc.2024.08.011] [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: 11/15/2024]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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12
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Li CL, Han Z, Luo DY, Ren H, Ye L, Yao GD, Liu QB. Synthesis of scaberol C amino acid ester derivatives with anti-cancer activity. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2025; 27:189-206. [PMID: 39067002 DOI: 10.1080/10286020.2024.2380737] [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: 01/10/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 07/30/2024]
Abstract
A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC50), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.
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Affiliation(s)
- Cheng-Long Li
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Zheng Han
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Dong-Ya Luo
- School of Pharmaceutical engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Hui Ren
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Li Ye
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Guo-Dong Yao
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Qing-Bo Liu
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
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13
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Suh PS, Baek JH, Lee JH, Chung SR, Choi YJ, Chung KW, Kim TY, Lee JH. Effectiveness of microvascular flow imaging for radiofrequency ablation in recurrent thyroid cancer: comparison with power Doppler imaging. Eur Radiol 2025; 35:597-607. [PMID: 39042304 DOI: 10.1007/s00330-024-10977-0] [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: 02/23/2024] [Revised: 06/13/2024] [Accepted: 07/05/2024] [Indexed: 07/24/2024]
Abstract
OBJECTIVES To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.
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Affiliation(s)
- Pae Sun Suh
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jung Hwan Baek
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Jae Ho Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sae Rom Chung
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Jun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ki-Wook Chung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Tae Yong Kim
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jeong Hyun Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Lv M, Feng Y, Zeng S, Zhang Y, Shen W, Guan W, E X, Zeng H, Zhao R, Yu J. Hotspots and frontiers of autophagy and chemotherapy in lung cancer: a bibliometric and visualization analysis from 2003 to 2023. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1583-1595. [PMID: 39120721 DOI: 10.1007/s00210-024-03354-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/01/2024] [Indexed: 08/10/2024]
Abstract
Autophagy was considered to induce resistance in chemotherapy, which was significantly associated with proliferation of cancer; however, few bibliometric studies on the relation between autophagy and chemotherapy in lung cancer are available. The aim of the present study was to provide a comprehensive overview of the knowledge structure and research hotspots of autophagy and chemotherapy in lung cancer by bibliometric analysis. Publications related to autophagy and chemotherapy in lung cancer from 2003 to 2023 were searched on the Web of Science Core Collection (WoSCC) database. The bibliometric analysis was conducted by using VOSviewers, CiteSpace, and the R package "bibliometrix." A total of 675 articles from 70 countries, led by China and the United States, were included in the analysis. The number of publications related to autophagy and chemotherapy in lung cancer is increasing year by year. Nanjing Medical University, Zhejiang University, China Medical University, and Sichuan University are among the main research institutions contributing to this field. The journal Cancers is the most popular publication in this area, with Autophagy being the most co-cited journal. These publications involve 4481 authors, with Chiu Chien-chih and Gewirtz David having published the most papers, and Noboru Mizushima being the most frequently co-cited author. Studying the relation between autophagy and chemotherapy in the occurrence and development of lung cancer, and exploring therapeutic strategies involving autophagy and chemotherapy in lung cancer, are the primary topics in this research field. "Tumor stem cells," "microRNA," and "EGFR" emerge as the primary keywords in the emerging research hotspots. Indeed, this bibliometric study provides valuable insights into the research trends and developments concerning autophagy and chemotherapy in lung cancer. By identifying recent research frontiers and highlighting hot directions, this study serves as a valuable reference for scholars interested in understanding the relationship between autophagy and chemotherapy in lung cancer. The comprehensive summary of findings offers a foundation for further exploration and advancement in this critical area of cancer research.
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Affiliation(s)
- Minghe Lv
- Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Yue Feng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Su Zeng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Yang Zhang
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Wenhao Shen
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Wenhui Guan
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Xiangyu E
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Hongwei Zeng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
| | - Ruping Zhao
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
| | - Jingping Yu
- Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China.
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
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15
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Jeremy E, Artiga E, Elgamal S, Cheney C, Eicher D, Zalponik K, Orwick S, Mao C, Wasmuth R, Harrington B, Mustonen A, Beshay P, Halley P, Castro C, Williams K, Hing Z, Chen T, Lucas C, Vantangoli NJ, Lapalombella R, Grieselhuber N, Mo X, Hertlein E, Muthusamy N, Mundy-Bosse BL, Byrd JC, Larkin KT. CD37 in acute myeloid leukemia: a novel surface target for drug delivery. Blood Adv 2025; 9:1-14. [PMID: 39348689 PMCID: PMC11732606 DOI: 10.1182/bloodadvances.2024013590] [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: 05/07/2024] [Revised: 08/20/2024] [Accepted: 09/10/2024] [Indexed: 10/02/2024] Open
Abstract
ABSTRACT Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes, which limits broad applicability of targeted therapy. We discovered that the hematopoiesis-restricted tetraspanin CD37 is expressed on the majority of primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype. We demonstrate that the internalization properties of CD37 are distinct in AML blasts when compared with normal blood cells, and that CD37 rapidly accumulates inside AML blasts via dynamin-dependent endocytosis. Our work revealed that the clinically relevant anti-CD37 antibody-drug conjugate (ADC) Debio 1562 (αCD37-DM1) is highly cytotoxic to AML blasts, but not normal hematopoietic stem cells. We found that αCD37-DM1 improved clinical outcomes and overall survival in multiple in vivo models of AML. Together, these data demonstrate that targeting CD37 with an ADC such as αCD37-DM1 is a feasible and promising therapeutic option for the treatment of AML.
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Affiliation(s)
- Erin Jeremy
- Medical Scientist Training Program, Biomedical Sciences Graduate Program, Ohio State College of Medicine, Columbus, OH
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Esthela Artiga
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Sara Elgamal
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
| | - Carolyn Cheney
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
| | - Dalen Eicher
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Kevan Zalponik
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Shelley Orwick
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH
| | - Charlene Mao
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Ronni Wasmuth
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Bonnie Harrington
- Department of Pathology and Diagnostics Investigation, Michigan State University, East Lansing, MI
| | - Allison Mustonen
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
- Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH
| | - Peter Beshay
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH
| | - Patrick Halley
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH
| | - Carlos Castro
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH
| | - Katie Williams
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Zachary Hing
- Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA
| | - Timothy Chen
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Christopher Lucas
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH
| | - Nicholas J. Vantangoli
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH
| | - Rosa Lapalombella
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Nicole Grieselhuber
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Xiaokui Mo
- Center for Biostatistics, The Ohio State University, Columbus, OH
| | - Erin Hertlein
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
| | - Natarajan Muthusamy
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Bethany L. Mundy-Bosse
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
| | - John C. Byrd
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
| | - Karilyn T. Larkin
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH
- Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
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16
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Yoshioka H, Ishida T, Atagi S, Tamiya A, Nishimura T, Iwamoto Y, Kanehara M, Kim YH, Korogi Y, Tomii K, Katakami N, Komuta K, Nishikawa M, Gemma A, Yamaki K, Kawahara M, Miyakoshi C, Mio T. Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01. Clin Lung Cancer 2025; 26:1-8. [PMID: 39482146 DOI: 10.1016/j.cllc.2024.09.004] [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: 12/19/2023] [Revised: 09/15/2024] [Accepted: 09/18/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m2 on day 1 and irinotecan 50mg/m2 on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m2 on day 1 and irinotecan 60mg/m2 on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year. RESULTS A total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death. CONCLUSION Although the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC.
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Affiliation(s)
- Hiroshige Yoshioka
- Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan; Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
| | - Tadashi Ishida
- Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan
| | - Shinji Atagi
- Department of Thoracic Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Japan
| | - Akihiro Tamiya
- Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Japan
| | - Takashi Nishimura
- Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, Japan
| | - Yasuo Iwamoto
- Department of Medical Oncology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Masashi Kanehara
- Department of Respiratory Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Young Hak Kim
- Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan
| | - Yohei Korogi
- Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan; Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan
| | - Keisuke Tomii
- Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Nobuyuki Katakami
- Department of Respiratory Medicine and Medical Oncology, Takarazuka City Hospital, Takarazuka, Japan
| | - Kiyoshi Komuta
- Department of Internal Medicine, Osaka Anti-Tuberculosis Association Osaka Fukujuji Hospital, Osaka, Japan
| | - Masanori Nishikawa
- Department of Respiratory Medicine, Fujisawa City Hospital, Fujisawa, Japan
| | - Akihiko Gemma
- Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital, Tokyo, Japan
| | - Kenichi Yamaki
- Department of Respiratory Medicine, Ichinomiya Nishi Hospital, Ichinomiya, Japan
| | - Masaaki Kawahara
- Department of Respiratory Medicine, Otemae Hospital, Osaka, Japan
| | - Chisato Miyakoshi
- Clinical Research Center and Department of Pediatrics and Neonatology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Tadashi Mio
- Department of Pulmonary Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
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17
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Novinger LJ, Weinzierl NM, Bonetto A. Diversity in chemotherapy-induced cachexia. Am J Physiol Cell Physiol 2025; 328:C139-C147. [PMID: 39636147 DOI: 10.1152/ajpcell.00773.2024] [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: 10/14/2024] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024]
Abstract
Preclinical and clinical studies suggest that chronic administration of cytotoxic drugs (e.g., chemotherapy) may contribute to the occurrence of skeletal muscle wasting and weakness/fatigue (i.e., cachexia). Doxorubicin, folfiri, and cisplatin are known to promote cachexia by triggering common alterations such as skeletal muscle atrophy, protein breakdown, and mitochondrial dysfunction, whereas each also possesses distinguishing features in terms of the activated molecular pathways. Similarly, commonalities exist between different cancer types including the development of muscle wasting early in treatment that can persist for years. The impact of treatment for gastrointestinal, head and neck, and nonsmall cell lung cancers (NSCLCs) on the development of cachexia and survival outcomes is well documented. However, a disconnect occurs between preclinical studies on cachexia, which are often performed on younger mice, and clinical studies on cachexia, which are focused on patients over 60 yr old. Yet, several preclinical studies have examined the impact of age on chemotherapy-induced cachexia. Finally, sex differences have been identified in both preclinical and clinical studies focused on the onset of cachexia consequential to chemotherapy administration and raise the question of whether treatments for this condition should be based on sex specificities. In conclusion, although cancer cachexia has been widely studied for its impact on patients affected by various malignancies, the effects of chemotherapy on the development of cachexia are less explored. Here, we examine diversity in chemotherapy-induced cachexia with respect to specific types of chemotherapy regimens and cancer, and differences based on age and sex.
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Affiliation(s)
- Leah J Novinger
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Natalia M Weinzierl
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Andrea Bonetto
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
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18
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Soldati G, Saccardo C, Raniero D, De Leo D, Turrina S. Unveiling STRs instability in a colorectal cancer FFPE sample: a case report. Int J Legal Med 2025; 139:61-65. [PMID: 39377931 PMCID: PMC11732918 DOI: 10.1007/s00414-024-03341-w] [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: 07/04/2024] [Accepted: 09/20/2024] [Indexed: 10/09/2024]
Abstract
In forensic genetics, sometimes formalin-fixed paraffin-embedded (FFPE) biopsy material taken during life is the only biological sample available for individual identification or paternity testing. In most cases, this biological tissue is characterized by the presence of tumor cells characterized by instability and loss of heterozygosity of microsatellites (MSI/LOH) compared to the DNA present in cells of normal tissue.In this case report, two FFPE samples from the same male subject were available for genetic investigation: one sample with colorectal cancer tissue and the other with normal tissue (no cancerous histopathological features). The comparison of the genetic profiles obtained from DNA extracted from the two tissues showed in the tumor tissue the presence of three genomic instability phenomena affecting FGA, CSF1P0, D21S2055 loci, located on three distinct autosomal chromosomes, and one duplication phenomenon affecting the DYS438. Therefore, due to the MSI/LOH phenomena, the genetic profile acquired from the tumor tissue was distorted and thus generated a fictitious genetic profile, not corresponding to the subject's real one (normal tissue free of tumor cells).
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Affiliation(s)
- Giulia Soldati
- Department of Diagnostics and Public Health, Section of Forensic Medicine, Forensic Genetics Lab, University of Verona, Verona, Italy.
| | - Chiara Saccardo
- Department of Diagnostics and Public Health, Section of Forensic Medicine, Forensic Genetics Lab, University of Verona, Verona, Italy
| | - Dario Raniero
- Department of Diagnostics and Public Health, Section of Forensic Medicine, Forensic Genetics Lab, University of Verona, Verona, Italy
| | - Domenico De Leo
- Department of Diagnostics and Public Health, Section of Forensic Medicine, Forensic Genetics Lab, University of Verona, Verona, Italy
| | - Stefania Turrina
- Department of Diagnostics and Public Health, Section of Forensic Medicine, Forensic Genetics Lab, University of Verona, Verona, Italy
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19
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Abah MO, Ogenyi DO, Zhilenkova AV, Essogmo FE, Ngaha Tchawe YS, Uchendu IK, Pascal AM, Nikitina NM, Rusanov AS, Sanikovich VD, Pirogova YN, Boroda A, Moiseeva AV, Sekacheva MI. Innovative Therapies Targeting Drug-Resistant Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC). Int J Mol Sci 2024; 26:265. [PMID: 39796121 PMCID: PMC11720203 DOI: 10.3390/ijms26010265] [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: 11/14/2024] [Revised: 12/09/2024] [Accepted: 12/14/2024] [Indexed: 01/13/2025] Open
Abstract
A thorough study of Clear Cell Renal Cell Carcinoma (ccRCC) shows that combining tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICI) shows promising results in addressing the tumor-promoting influences of abnormal immunological and molecular biomarkers in metastatic Clear Cell Renal Cell Carcinoma (ccRCC). These abnormal biomarkers enhance drug resistance, support tumor growth, and trigger cancer-related genes. Ongoing clinical trials are testing new treatment options that appear more effective than earlier ones. However, more research is needed to confirm their long-term safety use and potential side effects. This study highlights vital molecular and immunological biomarkers associated with drug resistance in Clear Cell Renal Cell Carcinoma (ccRCC). Furthermore, this study identifies a number of promising drug candidates and biomarkers that serve as significant contributors to the enhancement of the overall survival of ccRCC patients. Consequently, this article offers pertinent insights on both recently completed and ongoing clinical trials, recommending further toxicity study for the prolonged use of this treatment strategy for patients with metastatic ccRCC, while equipping researchers with invaluable information for the progression of current treatment strategies.
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Affiliation(s)
- Moses Owoicho Abah
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
- Department of Cancer Bioinformatics and Molecular Biology, Royal Society of Clinical and Academic Researchers (ROSCAR) International, Abuja 900104, Nigeria
| | - Deborah Oganya Ogenyi
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Angelina V. Zhilenkova
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Freddy Elad Essogmo
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Yvan Sinclair Ngaha Tchawe
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Ikenna Kingsley Uchendu
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
- Medical Laboratory Science Department, Faculty of Health Science and Technology, College of Medicine, University of Nigeria, Enugu Campus, Enugu 410001, Nigeria
| | - Akaye Madu Pascal
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Natalia M. Nikitina
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Alexander S. Rusanov
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Varvara D. Sanikovich
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Yuliya N. Pirogova
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Alexander Boroda
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Aleksandra V. Moiseeva
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
| | - Marina I. Sekacheva
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow 119991, Russia; (D.O.O.); (A.V.Z.); (F.E.E.); (Y.S.N.T.); (A.M.P.); (N.M.N.); (A.S.R.); (V.D.S.); (Y.N.P.); (A.B.); (A.V.M.); (M.I.S.)
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20
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Flinkier A, Chu F, Berman J, Slifirski H, Barnett S, Caragata R, Weinberg L. Financial burden of complications following lung resection: a scoping review protocol. BMJ Open 2024; 14:e083015. [PMID: 39806581 PMCID: PMC11667246 DOI: 10.1136/bmjopen-2023-083015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 11/25/2024] [Indexed: 01/16/2025] Open
Abstract
INTRODUCTION Global healthcare expenditures are rising, driven largely by increased spending in both high- and low-income countries with hospitalisation as a primary contributor. Respiratory diseases, particularly lung cancer, pose significant public health and economic challenges with thoracic surgery as the standard curative treatment. Complications post resection, such as arrhythmias, infections and respiratory failure, result in substantial healthcare costs and resource demands. Although studies have explored the economic impact of surgeries, there is a limited comprehensive analysis of the financial burden of postoperative complications after lung resection surgery. To address this gap, this scoping review aims to map existing literature on lung resection complications and associated costs, providing insights for future research and healthcare policy. METHODS AND ANALYSIS This scoping review will be conducting according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews standards. Eligible peer-reviewed articles and grey literature will be identified across Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database and Cochrane Central Register of Controlled Trials. Cost data will be converted into US dollars as per the Federal Reserve Bank of St Louis and adjusted for inflation as per the US Bureau of Labor Statistics Consumer Price Index inflation calculator. ETHICS AND DISSEMINATION Ethics approval was not required. The results will be communicated through established professional networks, conference presentations and publication in peer-reviewed journals.
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Affiliation(s)
- Ariane Flinkier
- Department of
Anaesthesia, Austin Health, Heidelberg, Victoria, Australia
| | - Fabien Chu
- Department of
Anaesthesia, Austin Health, Heidelberg, Victoria, Australia
| | - Jordan Berman
- Department of
Surgery, Monash Health, Clayton, Victoria, Australia
| | | | - Stephen Barnett
- Department of Thoracic
Surgery, Austin Health, Heidelberg, Victoria, Australia
- Department of
Surgery, The University of Melbourne,
Melbourne, Victoria, Australia
| | - Rebecca Caragata
- Department of
Anaesthesia, Austin Health, Heidelberg, Victoria, Australia
| | - Laurence Weinberg
- Department of
Anaesthesia, Austin Health, Heidelberg, Victoria, Australia
- Department of Critical
Care, The University of Melbourne - Parkville
Campus, Melbourne, Victoria, Australia
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21
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Suha H, Tasnim SA, Rahman S, Alodhayb A, Albrithen H, Poirier RA, Uddin KM. Evaluating the Anticancer Properties of Novel Piscidinol A Derivatives: Insights from DFT, Molecular Docking, and Molecular Dynamics Studies. ACS OMEGA 2024; 9:49639-49661. [PMID: 39713673 PMCID: PMC11656217 DOI: 10.1021/acsomega.4c07808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 11/03/2024] [Accepted: 11/19/2024] [Indexed: 12/24/2024]
Abstract
Cancer is characterized by uncontrolled cell growth and spreading throughout the body. This study employed computational approaches to investigate 18 naturally derived anticancer piscidinol A derivatives (1-18) as potential therapeutics. By examining their interactions with 15 essential target proteins (HIF-1α, RanGAP, FOXM1, PARP2, HER2, ERα, NGF, FAS, GRP78, PRDX2, SCF complex, EGFR, Bcl-xL, ERG, and HSP70) and comparing them with established drugs such as camptothecin, docetaxel, etoposide, irinotecan, paclitaxel, and teniposide, compound 10 emerged as noteworthy. In molecular dynamics simulations, the protein with the strongest binding to the crucial 1A52 protein exceeded druglikeness criteria and displayed extraordinary stability within the enzyme's pocket over varied temperatures (300-320 K). Additionally, density functional theory was used to calculate dipole moments and molecular orbital characteristics, as well as analyze the thermodynamic stability of the putative anticancer derivatives. This finding reveals a well-defined, potentially therapeutic relationship supported by theoretical analysis, which is in good agreement with subsequent assessments of their potential in vitro cytotoxic effects of piscidinol A derivatives (6-18) against various cancer cell lines. Future in vivo and clinical studies are required to validate these findings further. Compound 10 thus emerges as an intriguing contender in the fight against cancer.
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Affiliation(s)
- Humaera
Noor Suha
- Department
of Biochemistry and Microbiology, North
South University, Bashundhara, Dhaka 1229, Bangladesh
| | - Syed Ahmed Tasnim
- Department
of Biochemistry and Microbiology, North
South University, Bashundhara, Dhaka 1229, Bangladesh
| | - Shofiur Rahman
- Biological
and Environmental Sensing Research Unit, King Abdullah Institute for
Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia
| | - Abdullah Alodhayb
- Biological
and Environmental Sensing Research Unit, King Abdullah Institute for
Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia
- Department
of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Hamad Albrithen
- Biological
and Environmental Sensing Research Unit, King Abdullah Institute for
Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia
- Department
of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Raymond A. Poirier
- Department
of Chemistry, Memorial University, St. John’s, Newfoundland
and Labrador A1C 5S7, Canada
| | - Kabir M. Uddin
- Department
of Biochemistry and Microbiology, North
South University, Bashundhara, Dhaka 1229, Bangladesh
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22
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Bulisani BM, Leite MADO, Waisberg J. Liver-first approach to the treatment of patients with synchronous colorectal liver metastases: a systematic review and meta-analysis. EINSTEIN-SAO PAULO 2024; 22:eRW0596. [PMID: 39661858 PMCID: PMC11634356 DOI: 10.31744/einstein_journal/2024rw0596] [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: 05/23/2023] [Accepted: 04/08/2024] [Indexed: 12/13/2024] Open
Abstract
OBJECTIVE The optimal approach to the treatment of colorectal carcinoma and synchronous liver metastases remains controversial. The objective of this review was to analyze the outcomes of adopting the liver-first approach for the treatment of patients with colorectal cancer with synchronous hepatic metastases who initially underwent systemic chemotherapy and/or resection of the metastatic lesions and primary colorectal carcinoma. METHODS This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The MEDLINE, EMBASE, LILACS, and Cochrane Central Register of Controlled Trials databases were searched for the identification and retrieval of eligible studies. Studies that included details of using the liver-first approach for the treatment of synchronous liver metastases of colorectal cancer and its outcomes, including the patients' survival data, were included. Proportional meta-analysis was performed using the random-effects restricted maximum likelihood method to summarize the three- and five-year overall survival and recurrence rates of the patients. RESULTS Eight hundred and fifty-five articles describing the results of studies on the liver-first approach were identified. Three independent reviewers screened the titles and abstracts of the articles and excluded 750 articles. Thereafter, 29 retrospective and comparative studies that met the inclusion criteria were included. No randomized controlled trials were identified in the database search. CONCLUSION Neoadjuvant treatment with systemic chemotherapy for hepatic metastasis can prepare a patient for resection of liver metastases, offering the opportunity for potentially curative treatment of synchronous hepatic metastases initially considered unresectable. The decision regarding the resection of primary colorectal carcinoma and liver metastases should be based on individualized patient response. Prospero database registration ID: CRD42022337047 (www.crd.york.ac.uk/prospero).
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Affiliation(s)
- Bruno Mirandola Bulisani
- Centro Universitário FMABCSanto AndréSPBrazil Centro Universitário FMABC, Santo André, SP, Brazil.
| | | | - Jaques Waisberg
- Centro Universitário FMABCSanto AndréSPBrazil Centro Universitário FMABC, Santo André, SP, Brazil.
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23
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Lacaita PG, Bale R, Lucciarini P, Nguyen VA, Freund M, Gizewski ER, Putzer D. Minimal invasive treatment of liver and kidney metastasis in mucosal melanoma of the right inferior turbinate. Radiol Case Rep 2024; 19:6445-6451. [PMID: 39380816 PMCID: PMC11460375 DOI: 10.1016/j.radcr.2024.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 08/30/2024] [Accepted: 09/03/2024] [Indexed: 10/10/2024] Open
Abstract
This case report describes an 80-year-old female patient who initially presented with nasal epistaxis. The patient had a history of atrial fibrillation and arterial hypertension. Computed tomography of the facial sinuses revealed a large mass in the inferior right turbinate with slight expansion into the maxillary sinus. Endoscopic excision of the right nasal cavity was performed, and the histologic workup revealed mucosal melanoma of the nasal cavity (cT3, cN0, cM0). A medial maxillectomy of the right side, including 2 biopsies within 1 month, showed no signs of recurrence. After 1 year, the patient was diagnosed with liver and renal metastases in a follow-up CT, which were treated with stereotactic radiofrequency ablation. After spending 2 weeks in the intensive care unit due to postoperative complications, the patient recovered and was discharged from the hospital in good condition. A promising alternative minimally invasive therapeutic strategy, highlighted by our case, should be considered as a primary goal of tumor reduction.
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Affiliation(s)
- Pietro G. Lacaita
- Department of Radiology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Reto Bale
- Department of Radiology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Paolo Lucciarini
- Department of Visceral, Transplant and Thoracic Surgery (VTT), Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Van Anh Nguyen
- Department of Dermatology, Venereology and Allergology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Martin Freund
- Department of Radiology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Elke R. Gizewski
- Department of Radiology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
| | - Daniel Putzer
- Department of Radiology, Landeskrankenhaus Innsbruck- Medical University Innsbruck, Innsbruck, Austria
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24
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Draškovič T, Omahen L, Jerše M, Zidar N, Hauptman N. DNA Methylation Panels for the Differentiation of Lung and Gastric Adenocarcinomas from Other Common Primary Adenocarcinomas. Cancers (Basel) 2024; 16:4000. [PMID: 39682186 DOI: 10.3390/cancers16234000] [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] [Received: 10/18/2024] [Revised: 11/21/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objectives: Gastric and lung adenocarcinomas are among the most common adenocarcinomas worldwide. Our research aimed to validate methylation biomarkers that differentiate gastric and lung adenocarcinomas from hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma and paired healthy tissues. Methods: The study analyzed 178 formalin-fixed, paraffin-embedded tissue samples, including 14 gastric adenocarcinomas, 15 lung adenocarcinomas, 15 hepatocellular carcinomas, 15 cholangiocarcinomas, 15 colorectal carcinomas, 15 pancreatic adenocarcinomas and their paired healthy tissues. Methylation status was determined experimentally by methylation-sensitive high resolution melting. The diagnostic panels were validated on bioinformatics datasets from The Cancer Genome Atlas and Gene Expression Omnibus, comprising 1981 and 773 samples, respectively. Sensitivity, specificity, diagnostic accuracy and predictive values for each cancer type were calculated for the experimental, Gene Expression Omnibus and The Cancer Genome Atlas datasets. Results: The gastric cancer-specific panel showed a sensitivity of 78.6-83.9%, a specificity of 86.6-94.6% and a diagnostic accuracy of 89.9-96.1% to differentiate between all tumors, and a sensitivity of 78.6-83.9%, a specificity of 89.2-96.4% and a diagnostic accuracy of 88-96.1% to differentiate between all tumors and healthy tissues. The lung adenocarcinoma-specific panel showed a sensitivity of 61.1-93.3%, a specificity of 70.3-90.8% and a diagnostic accuracy of 74.2-90.6% to differentiate between all tumors, and a sensitivity of 61.1-93.3%, a specificity of 77.9-93.4% and a diagnostic accuracy of 79.2% to 93.1% to differentiate between all tumors and healthy tissues. Conclusions: This study demonstrates the potential of using diagnostic methylation panels to differentiate gastric and lung adenocarcinomas from other common adenocarcinomas and paired healthy tissues.
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Affiliation(s)
- Tina Draškovič
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
| | - Lara Omahen
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
| | - Maja Jerše
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
| | - Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
| | - Nina Hauptman
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
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25
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Kohrt SE, Novak EJ, Tapadar S, Wu B, Strope J, Asante Y, Kim H, Chang MS, Gurdak D, Khalil A, Rood M, Raftery E, Stavreva D, Nguyen HM, Brown LG, Ramser M, Peer C, Meyers WM, Aboreden N, Chakravortee M, Sallari R, Nelson PS, Kelly KK, Graham TGW, Darzacq X, Figg WD, Oyelere AK, Corey E, Adelaiye-Ogala R, Gryder BE. Small-molecule disruption of androgen receptor-dependent chromatin clusters. Proc Natl Acad Sci U S A 2024; 121:e2406239121. [PMID: 39560645 PMCID: PMC11621760 DOI: 10.1073/pnas.2406239121] [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: 03/26/2024] [Accepted: 10/22/2024] [Indexed: 11/20/2024] Open
Abstract
Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models. These molecules bind to the ligand-binding domain of the AR, promote AR localization to the nucleus, yet potently and selectively down-regulate AR-target genes. The molecules BG-15a and the pharmacokinetically optimized BG-15n elicit a decrease in cell and tumor growth in vitro and in vivo in models of mCRPC. BG-15a/n treatment causes the collapse of chromatin loops between enhancers and promoters at key genes in the AR-driven epigenome. AR binding in the promoter, as well as 3D chromatin clustering, is needed for genes to respond. BG-15a/n represent promising agents for treating patients with relapsed AR-driven mCRPC tumors.
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Affiliation(s)
- Sarah E. Kohrt
- Cancer Genomics and Epigenomics Program, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH44106
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | - Emily J. Novak
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | - Subhashish Tapadar
- Parker H. Petit Institute for Bioengineering and Biosciences, Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA30332
| | - Bocheng Wu
- Parker H. Petit Institute for Bioengineering and Biosciences, Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA30332
| | - Jonathan Strope
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Yaw Asante
- Cancer Genomics and Epigenomics Program, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH44106
- Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | - Hyunmin Kim
- Cancer Genomics and Epigenomics Program, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH44106
| | - Matthew S. Chang
- Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | - Douglas Gurdak
- Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | - Athar Khalil
- Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH44106
| | | | - Eric Raftery
- Parker H. Petit Institute for Bioengineering and Biosciences, Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA30332
| | - Diana Stavreva
- Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Holly M. Nguyen
- Department of Urology, University of Washington, Seattle, WA98195
| | - Lisha G. Brown
- Department of Urology, University of Washington, Seattle, WA98195
| | - Maddy Ramser
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Cody Peer
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Warren M. Meyers
- Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BCV6T 1Z3, Canada
| | - Nicholas Aboreden
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA19104
| | | | | | - Peter S. Nelson
- Department of Medicine, University of Washington, Seattle, WA98195
- Division of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA98109
- Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA98109
| | - Kathleen K. Kelly
- Laboratory for Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Thomas G. W. Graham
- Department of Molecular and Cell Biology, University of California, Berkeley, CA94720
| | - Xavier Darzacq
- Department of Molecular and Cell Biology, University of California, Berkeley, CA94720
| | - William D. Figg
- Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD20892
| | - Adegboyega K. Oyelere
- Parker H. Petit Institute for Bioengineering and Biosciences, Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA30332
| | - Eva Corey
- Department of Urology, University of Washington, Seattle, WA98195
| | - Remi Adelaiye-Ogala
- Division of Hematology and Oncology, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY14203
| | - Berkley E. Gryder
- Cancer Genomics and Epigenomics Program, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH44106
- Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH44106
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Haozous E, Yeary K, Maybee W, Porter C, Zoellner J, John B, Henry WAE, Haring RC. Indigenous knowledge and sugar sweetened beverages: Qualitative adaptations towards chronic disease prevention and intervention. Explore (NY) 2024; 20:103066. [PMID: 39418823 DOI: 10.1016/j.explore.2024.103066] [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: 03/30/2024] [Revised: 09/09/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024]
Abstract
Sugar sweetened beverages (SSB) are a concern for Indigenous populations and are associated with multiple chronic diseases. To address this concern, we culturally tailored and tested the feasibility of an evidence-based SSB-reducing curriculum. The modified curriculum was designed for Indigenous men and is thematically based on traditional values, ancestral teachings, and community strengths while promoting healthy lifestyles. A community-based participatory research (CBPR) approach was used to develop an interview guide using an Indigenous-centered theoretical framework. Two Indigenous content experts conducted both individual and focus group interviews (n = 14) with urban community leaders and athletes. Two Indigenous qualitative scientists analyzed the data with the support of an inter-tribal community advisory board. Results included imagery utilization, the importance of water, marketing, taste, and building routine. These findings guided the development of 6-month Indigenous focused SSB intervention consisting of 12 in-person intervention sessions and 27 short messaging service (SMS) messages.
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Affiliation(s)
| | - Karen Yeary
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, USA
| | - Will Maybee
- Department of Indigenous Cancer Health, Roswell Park Comprehensive Cancer Center, USA
| | - Corinne Porter
- Department of Indigenous Cancer Health, Roswell Park Comprehensive Cancer Center, USA
| | - Jamie Zoellner
- Department of Public Health Sciences, University of Virginia, School of Medicine, USA
| | - Brad John
- Cattaraugus Community Center, Seneca Nation of Indians, USA
| | - Whitney Ann E Henry
- Department of Indigenous Cancer Health, Roswell Park Comprehensive Cancer Center, USA
| | - Rodney C Haring
- Department of Indigenous Cancer Health, Roswell Park Comprehensive Cancer Center, USA.
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Türkeş F, Dere Ö, Dinç F, Yazkan C, Özcan Ö, Nazlı O. The Efficacy of MRI-Based ADC Measurements in Detecting Axillary Lymph Node Metastasis: Evaluation of a Prospective Study. Curr Oncol 2024; 31:6598-6607. [PMID: 39590118 PMCID: PMC11592749 DOI: 10.3390/curroncol31110487] [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: 09/08/2024] [Revised: 09/18/2024] [Accepted: 10/23/2024] [Indexed: 11/28/2024] Open
Abstract
Objective: This study aimed to evaluate the efficacy of MRI-based Apparent Diffusion Coefficient (ADC) measurements in detecting axillary lymph node metastasis in breast cancer patients. By comparing preoperative MRI findings with intraoperative sentinel lymph node biopsy (SLNB) and postoperative pathological results, we sought to explore the potential of ADC values as a non-invasive alternative to axillary interventions. Methods: A total of 104 female patients diagnosed with breast cancer between 2019 and 2021 were included in this prospective study. ADC values of axillary lymph nodes, tumors, and muscle tissues were measured using a 3T MRI system. The correlation between these measurements and pathological outcomes was analyzed. Statistical analyses, including t-tests, ANOVA, and ROC curve analysis, were employed to assess the diagnostic performance of ADC values. Results: The results indicated that, while the mean ADC values of metastatic lymph nodes were lower than those of benign nodes, the sensitivity and specificity of MRI-based ADC measurements were inferior to the expected standards. The tumor ADC value and the tumor-to-lymph node ADC ratio were found to be more reliable indicators of metastasis than the lymph node ADC value alone. The diagnostic power of the tumor ADC value was significant, with a sensitivity of 75% and a specificity of 73%. Conclusions: MRI-based ADC measurements, particularly the tumor ADC value and the tumor-to-lymph node ADC ratio, show promise as potential non-invasive markers for axillary lymph node metastasis in breast cancer patients. However, the current results suggest that ADC measurements cannot yet replace SLNB in clinical practice.
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Affiliation(s)
| | - Özcan Dere
- Department of General Surgery, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48121, Turkey; (C.Y.); (Ö.Ö.); (O.N.)
| | - Funda Dinç
- Department of Radiology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48000, Turkey;
| | - Cenk Yazkan
- Department of General Surgery, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48121, Turkey; (C.Y.); (Ö.Ö.); (O.N.)
| | - Önder Özcan
- Department of General Surgery, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48121, Turkey; (C.Y.); (Ö.Ö.); (O.N.)
| | - Okay Nazlı
- Department of General Surgery, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla 48121, Turkey; (C.Y.); (Ö.Ö.); (O.N.)
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28
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Sharabati HH, Innab LR, Hussein SS, Salman AA, Naser AM, Bakri IA. Synovial sarcoma of the ethmoid sinus with extension to the cavernous sinus: a case report and literature review. J Surg Case Rep 2024; 2024:rjae579. [PMID: 39364429 PMCID: PMC11445676 DOI: 10.1093/jscr/rjae579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/06/2024] [Indexed: 10/05/2024] Open
Abstract
Synovial sarcomas are rare soft tissue tumors primarily affecting the extremities but can occasionally manifest in unusual locations such as the ethmoid sinus, posing diagnostic challenges. We present a case of a 38-year-old male with a 7-month history of recurrent throbbing headaches, left eye pain, and facial nerve palsy, evolving into multiple stroke episodes. Radiological studies showed extension to the cavernous sinus, raising an initial suspicion of vasculitis. Histological findings of an endoscopic biopsy, however, confirmed a monophasic synovial sarcoma. The patient was referred to a specialized center for further management. Unfortunately, he developed another stroke before receiving treatment. Management included chemotherapy and definitive radiation therapy targeting the ethmoid sinus. The patient is currently receiving ongoing palliative care for symptom management. This case underscores the importance of early diagnosis and a multidisciplinary approach in managing rare and aggressive tumors such as synovial sarcoma of the ethmoid sinus.
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Affiliation(s)
| | - Laila R Innab
- Al Quds University Faculty of Medicine, Jerusalem, Palestine
| | - Saja S Hussein
- Al Quds University Faculty of Medicine, Jerusalem, Palestine
| | - Ayman A Salman
- Department of Neurosurgery, Al-Makassed Islamic Charitable Hospital, Jerusalem 00970, Palestine
| | - Anis M Naser
- Department of Neurology, Al-Makassed Islamic Charitable Hospital, Jerusalem 00970, Palestine
| | - Izzeddin A Bakri
- Department of Pathology, Al-Makassed Islamic Charitable Hospital, Jerusalem 00970, Palestine
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29
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Bologna E, Licari LC, Franco A, Ditonno F, Manfredi C, De Nunzio C, Perdona S, Brassetti A, Leonardo C, Coogan CL, Cherullo EE, Autorino R. Characteristics, trends, and management of Penile cancer in the United States: A population-based study. Urol Oncol 2024; 42:334.e11-334.e18. [PMID: 38944595 DOI: 10.1016/j.urolonc.2024.05.013] [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: 02/02/2024] [Revised: 04/26/2024] [Accepted: 05/18/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors. OBJECTIVES Primary aim of our study is to evaluate the incidence and risk factors of PeCa and to outline the adopted diagnostic and therapeutic approaches. Secondary aim is to investigate risk factors associated with aggressive disease and to identify the complications arising from its surgical treatment. MATERIALS AND METHODS We conducted a retrospective analysis using the PearlDiver™ Mariner database, from January 1, 2011, to December 31, 2021, identifying all patients diagnosed with PeCa and PeIN, evaluating comorbidities, risk factors, and social and economic conditions. We evaluated the imaging modalities employed for staging as well as the treatment strategies. Finally, we evaluated the most frequent complications associated with inguinal lymphadenectomy (ILND). RESULTS During the study period, 17,494 patients were diagnosed with PeCa and 5,965 with penile intraepithelial neoplasia (PeIN). US was the most frequently utilized imaging modality, followed by PET and PET/CT. Use of CT and MRI was around 5%. Surgical treatment was the predominant strategy, utilized in 31.3% of PeCa and 22.9% of PeIN. Wide Local Excision/Glansectomy emerged as the most common surgical procedures. MLR analysis identified smoking as a risk factor for metastatic PeCa (OR; 95% CI = 1.49; 1.379-1.609), HPV infections were associated with a 35% decrease in risk (OR; 95% CI = 0.65; 0.562-0.744) (all P < 0.001). Lichen sclerosus and phimosis were associated with a doubled risk of demolitive surgery. Approximately 40% of patients experienced complications associated with ILND. CONCLUSION Despite advances in PeCa management, there's no significant move toward more conservative treatments. Surgical treatments are still marked by high rates of complications, potentially affect the sexual and psychosocial health of patients. These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation and treatment.
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Affiliation(s)
- Eugenio Bologna
- Department of Urology, Rush University, Chicago, IL, USA; Department of Maternal-Child and Urological Sciences, Sapienza University Rome, Policlinico Umberto I Hospital, Rome, Italy
| | - Leslie Claire Licari
- Department of Urology, Rush University, Chicago, IL, USA; Department of Maternal-Child and Urological Sciences, Sapienza University Rome, Policlinico Umberto I Hospital, Rome, Italy
| | - Antonio Franco
- Department of Urology, Rush University, Chicago, IL, USA; Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Francesco Ditonno
- Department of Urology, Rush University, Chicago, IL, USA; Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Verona, Italy
| | - Celeste Manfredi
- Department of Urology, Rush University, Chicago, IL, USA; Department of Woman, Unit of Urology, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Cosimo De Nunzio
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Sisto Perdona
- Uro-Gynecological Department, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Naples, Italy
| | - Aldo Brassetti
- Department of Urology, "Regina Elena" National Cancer Institute, Rome, Italy
| | - Costantino Leonardo
- Department of Urology, "Regina Elena" National Cancer Institute, Rome, Italy
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Xie G, Li N, Li K, Xu Y, Zhang Y, Cao S, Huang B, Liu R, Zhou P, Ding Y, Ding Y, Yang J, Jia Z, Huang Z. Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway. Cell Death Dis 2024; 15:665. [PMID: 39261475 PMCID: PMC11390745 DOI: 10.1038/s41419-024-07007-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 09/13/2024]
Abstract
LHPP, a novel, recognized tumor suppressor, exerts a critical influence on the regulation of tumor cell proliferation and survival by modulating various signaling pathways with its phosphatase activity. Here, we unveil a robust correlation between reduced LHPP expression and adverse prognosis in prostate cancer. We demonstrate that LHPP interacts with AKT, thereby dampening AKT phosphorylation and subsequently inhibiting ACSL4 phosphorylation at the T624 site. This interaction impedes phosphorylation-dependent ubiquitination, thwarting SKP2 from recognizing and binding to ACSL4 at the K621 site. As a result, ACSL4 is spared from lysosomal degradation, leading to its accumulation and the promotion of lipid peroxidation, and ferroptosis. Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.
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Affiliation(s)
- Guoqing Xie
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Ningyang Li
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Keqiang Li
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yating Xu
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yu Zhang
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Shun Cao
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Budeng Huang
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Ruoyang Liu
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Peijie Zhou
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yafei Ding
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yinghui Ding
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinjian Yang
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Zhankui Jia
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Zhenlin Huang
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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31
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Pizarro-Mondesir M, Ramirez-Marcano C, Arriaga-Perry R, Rodriguez-Bury V. Unusual Presentation of Bladder Cancer in a Young Male With Significant Tattoo Exposure: A Case Report. Cureus 2024; 16:e69637. [PMID: 39429434 PMCID: PMC11487486 DOI: 10.7759/cureus.69637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2024] [Indexed: 10/22/2024] Open
Abstract
Recent studies have shown that polycyclic aromatic hydrocarbons (PAHs) can be found in commercial black tattoo inks raising suspicion of tattoo-related PAHs exposure to cancer risk. We present a case of a 27-year-old Hispanic nonsmoker male with bladder cancer (BC) following extensive tattoo sessions totaling over 100 hours. The patient was treated with transurethral resection of the bladder tumor (TURBT) and adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy. Although the oncogenesis of urothelial tumors in young patients is unclear, multiple environmental and genetic factors may contribute to the etiology. This case report underscores the importance of conducting toxicological and epidemiological studies on PAHs and emphasizes the need for increased documentation of tattoos in patients diagnosed with BC.
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32
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Oyemolade TA, Adeolu AA, Oyewo OL, Oko-Azu VC. Neuroblastoma of the thoracic spine in an adult: a case report. J Surg Case Rep 2024; 2024:rjae602. [PMID: 39324103 PMCID: PMC11421993 DOI: 10.1093/jscr/rjae602] [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: 07/02/2024] [Accepted: 09/09/2024] [Indexed: 09/27/2024] Open
Abstract
Neuroblastoma (NB) in the adults is extremely rare. Even less encountered is NB involving the adult spine with only a few reported cases. Because of its rarity, there are as yet no well-established treatment guidelines for NB in the adults. Treatment strategies, therefore, are often extrapolated from paediatric data. We report a case of a 51-year-old man with NB involving the thoracic spine who had surgical excision with a good postoperative outcome in the short term.
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Affiliation(s)
- Toyin A Oyemolade
- Division of Neurosurgery, Department of Surgery, Federal Medical Center Owo, PMB 1053, Owo, Ondo, Nigeria
| | - Augustine A Adeolu
- Division of Neurosurgery, Department of Surgery, College of Medicine, University of Ibadan, Queen Elizabeth Road, PMB 5116, Ibadan, Oyo State, Nigeria
- Department of Neurological Surgery, University College Hospital Ibadan, Queen Elizabeth Road, PMB 5116, Ibadan, Oyo, Nigeria
| | - Oluwafunmito L Oyewo
- Division of Neurosurgery, Department of Surgery, Federal Medical Center Owo, PMB 1053, Owo, Ondo, Nigeria
| | - Vivian C Oko-Azu
- Division of Neurosurgery, Department of Surgery, Federal Medical Center Owo, PMB 1053, Owo, Ondo, Nigeria
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Joshi A, Mandal R. Review Article on Molecular Basis of Zinc and Copper Interactions in Cancer Physiology. Biol Trace Elem Res 2024:10.1007/s12011-024-04356-5. [PMID: 39215955 DOI: 10.1007/s12011-024-04356-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
Various clinical manifestations associated with measurable abnormalities of Zn and Cu in serum and tissue were determined in Cancer-Patients (CP), and therefore, these two metals are drawing more and more attention presently than ever before. Cancer is a disease of uncontrolled-abnormal-cell-division with invasion-potential which was exhibited to occur due to dys-regulation/dys-homeostasis of fundamental-biological-pathways (FBP) including antioxidant-enzyme-defense-system, anti-inflammatory and immune-systems, and DNA-damage-repair-system in the human-body resulting in generation of chronic-oxidative-stress induced DNA-damage and gene-mutations, inflammation and compromised immune-system, tumor-induced increased angiogenesis, and inhibition of apoptosis processes. Zn and Cu were recognized to be the most crucial components of FBP and imbalance in Zn/Cu ratios in CP asserted to generate chronic toxicity in human body through various mechanisms including increased chronic oxidative stress linked compromised DNA integrity and gene mutations due to malfunctioning of DNA damage repair enzymes; increased angiogenesis process due to Zn- and Cu-binding proteins metallothionein and ceruloplasmin-induced enhanced expression of tumor growth factors; and elevation in inflammatory response which was further shown to down/upregulate gene expression of multiple Zn transporter proteins leading to dys-homeostasis of intracellular Zn concentrations, and it was determined to disturb the equilibrium between cell growth and division, proliferation, differentiation, and apoptosis processes which lead to cancer progression. Moreover, Zn was reported to affect matrix metalloproteinase activity and influence immune system cells to respond differently to different cytokines and enhance immune-suppressive effects accelerating the angiogenesis, invasion, and metastasis potential in cancer. Further, the most significant use of serum Cu/Zn ratio was recommended in clinical diagnosis, prognosis, tumor stage, patient survival, and cancer follow-up studies which need further investigations to elucidate and explore their roles in cancer physiology for clinical perspective.
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Affiliation(s)
- Amit Joshi
- PG Department of Biotechnology and Microbial Biotechnology, Sri Guru Gobind Singh College, Chandigarh, UT, India
| | - Reshu Mandal
- PG Department of Zoology, Sri Guru Gobind Singh College, Chandigarh, UT, India.
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Mac Eochagain C, Power R, Sam C, Gonzalez-Senac NM, Walsh D, Roy M, Battisti NML. Inclusion, characteristics, and reporting of older adults in FDA registration studies of immunotherapy, 2018-2022. J Immunother Cancer 2024; 12:e009258. [PMID: 39209450 PMCID: PMC11367347 DOI: 10.1136/jitc-2024-009258] [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] [Accepted: 08/13/2024] [Indexed: 09/04/2024] Open
Abstract
Immune checkpoint inhibitors (ICI) have transformed the management of cancer, particularly for older adults, who constitute a majority of the global cancer patient population. This study aimed to assess the inclusion, characteristics, and reporting of older adults enrolled in Food and Drug Administration (FDA) registration clinical trials of ICI between 2018 and 2022. Clinical trials of ICI leading to an FDA approval in solid tumor oncology between 2018 and 2022 were included. Primary study reports and all available secondary publications were assessed. The availability and completeness of older subgroup data for protocol-defined clinical efficacy endpoints, health-related quality of life (HRQOL) and toxicity outcomes, and baseline characteristics were assessed according to predefined criteria which categorized reporting completeness hierarchically in relation to the availability of published data, including effect size, sample size, and measures of precision. 53 registration trials were included, involving a total of 37,094 participants. Most trials (64.2%) were of ICI combination therapy. 42.3% of patients were aged≥65 years; 11.1% were aged≥75. No trials specified an upper age limit for eligibility. 98.1% of trials excluded patients with European Cooperative Oncology Group performance status>1. 87.2% of primary efficacy endpoints and 17.9% of secondary efficacy endpoints were reported completely for older adults. Five studies (9.4%) reported baseline characteristics, three (6.1%) reported HRQOL assessments, and four (7.5%) reported toxicity outcomes completely among older subgroups. No trials conducted baseline geriatric assessments or reported geriatric-specific symptoms or quality of life scales. This analysis highlights significant deficits in the enrollment and reporting of older subgroups in pivotal trials of ICI therapy. The findings highlight an urgent need for improved reporting and inclusion standards in clinical trials of ICI to better inform treatment decisions for older adults.
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Affiliation(s)
- Colm Mac Eochagain
- Department of Medical Oncology, Trinity St James' Cancer Institute, Dublin, Ireland
| | - Robert Power
- Department of Medical Oncology, Trinity St James' Cancer Institute, Dublin, Ireland
| | - Christine Sam
- H Lee Moffitt Cancer Center and Research Center, Tampa, Florida, USA
| | - Nicolas M Gonzalez-Senac
- Geriatrics Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain
- Biopathology of Aging Group, Instituto de Investigacion Sanitaria Hospital General Universitario Gregorio Marañon, Madrid, Spain
| | - Darren Walsh
- Department of Medical Oncology, Waterford University Hospital, Waterford, Ireland
| | - Mukul Roy
- Department of Radiation Oncology, Jaslok Hospital and Research Centre, Mumbai, India
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35
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Tong Y, Zhu T, Xu F, Yang W, Wang Y, Zhang X, Chen X, Liu L. Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis. Heliyon 2024; 10:e35488. [PMID: 39170242 PMCID: PMC11336703 DOI: 10.1016/j.heliyon.2024.e35488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 07/25/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024] Open
Abstract
Background The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients' responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.
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Affiliation(s)
- Yun Tong
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Tao Zhu
- Department of Pharmacy, Beidahuang Industry Group General Hospital, Harbin, 150088, China
| | - Fei Xu
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Wenjun Yang
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Yakun Wang
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Xianze Zhang
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Xiujie Chen
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
| | - Lei Liu
- Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China
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Benslimane Y, Amalfi K, Lapin S, Perrino S, Brodt P. Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment. CANCER RESEARCH COMMUNICATIONS 2024; 4:1963-1977. [PMID: 39007345 PMCID: PMC11306998 DOI: 10.1158/2767-9764.crc-24-0196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 06/06/2024] [Accepted: 07/11/2024] [Indexed: 07/16/2024]
Abstract
Liver metastases (LM) remain a major cause of cancer-related death and are a major clinical challenge. LM and the female sex are predictors of a poorer response to immunotherapy but the underlying mechanisms remain unclear. We previously reported on a sexual dimorphism in the control of the tumor microenvironment (TME) of colorectal carcinoma liver metastases (CRCLM) and identified estrogen as a regulator of an immunosuppressive TME in the liver. Here we aimed to assess the effect of estrogen deprivation on the cytokine/chemokine profile associated with CRCLM, using a multiplex cytokine array and the RNAscope technology, and its effects on the innate and adaptive immune responses in the liver. We also evaluated the benefit of combining the selective estrogen-receptor degrader Fulvestrant with immune checkpoint blockade for the treatment of CRCLM. We show that estrogen depletion altered the cytokine/chemokine repertoire of the liver, decreased macrophage polarization, as reflected in reduced accumulation of tumor infiltrating M2 macrophages and increased the accumulation of CCL5+/CCR5+ CD8+ T and NKT cells in the liver TME. Similar results were obtained in a murine pancreatic ductal adenocarcinoma model. Importantly, treatment with Fulvestrant also increased the accumulation of CD8+CCL5+, CD8+CCR5+ T and NK cells in the liver TME and enhanced the therapeutic benefit of anti-PD1 immunotherapy, resulting in a significant reduction in the outgrowth of LM. Taken together, our results show that estrogen regulates immune cell recruitment to the liver and suggest that inhibition of estrogen action could potentiate the tumor-inhibitory effect of immunotherapy in hormone-independent and immunotherapy-resistant metastatic cancer. SIGNIFICANCE The immune microenvironment of the liver plays a major role in controlling the expansion of hepatic metastases and is regulated by estrogen. We show that treatment of tumor-bearing mice with an estrogen receptor degrader potentiated an anti-metastatic effect of immunotherapy. Our results provide mechanistic insight into clinical findings and a rationale for evaluating the efficacy of combination anti-estrogen and immunotherapy for prevention and/or treatment of hepatic metastases in female patients.
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Affiliation(s)
- Yasmine Benslimane
- Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
- The Research Institute of the McGill University Health Center, Montreal, Canada.
| | - Kevin Amalfi
- Department of Microbiology and Immunology, McGill University, Montreal, Canada.
| | - Sara Lapin
- Department of Microbiology and Immunology, McGill University, Montreal, Canada.
| | - Stephanie Perrino
- The Research Institute of the McGill University Health Center, Montreal, Canada.
| | - Pnina Brodt
- Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
- The Research Institute of the McGill University Health Center, Montreal, Canada.
- Department of Surgery, McGill University, Montreal, Canada.
- Department of Oncology, McGill University, Montreal, Canada.
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Guo L, Liu X, Zhang J, Liu Z, Zhang B, Sun Y, Cui D, Liu J. Circ_0028826 Promotes Growth and Metastasis of NSCLC via Acting as a Sponge of miR-758-3p to Derepress IDH2 Expression. THE CLINICAL RESPIRATORY JOURNAL 2024; 18:e13802. [PMID: 39113352 PMCID: PMC11306285 DOI: 10.1111/crj.13802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 02/05/2024] [Accepted: 06/12/2024] [Indexed: 08/11/2024]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC. METHODS Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR-758-3p. IDH2, Bcl2, Bax, and E-cadherin protein levels were detected using a western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR-758-3p and circ_0028826 or IDH2 was validated using a dual-luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model. RESULTS Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR-758-3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR-758-3p to inhibit tumor growth in vivo. CONCLUSION Circ_0028826 promoted the development of NSCLC via regulation of the miR-758-3p/IDH2 axis, providing a new strategy for NSCLC treatment.
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Affiliation(s)
- Lihong Guo
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Xueqin Liu
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Jie Zhang
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Zhuixing Liu
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Bohao Zhang
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Yang Sun
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Dandan Cui
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
| | - Jinpeng Liu
- Department of OncologyXi'an International Medical Center HospitalXi'anShaanxiChina
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Fuentes-Calvo KJ, Silva-Ramos CS, Arechavala-López SF, Aguilar-Ruiz F, Arias-Ruiz LF, Trejo-Ávila M. Pigmented basal cell carcinoma of the anus: a rare entity with diagnostic challenges. J Surg Case Rep 2024; 2024:rjae554. [PMID: 39211371 PMCID: PMC11358057 DOI: 10.1093/jscr/rjae554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/07/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024] Open
Abstract
Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen.
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Affiliation(s)
| | | | | | | | | | - Mario Trejo-Ávila
- Department of Colon and Rectal Surgery, Hospital Médica Sur, Mexico City, Mexico
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Hushmandi K, Saadat SH, Mirilavasani S, Daneshi S, Aref AR, Nabavi N, Raesi R, Taheriazam A, Hashemi M. The multifaceted role of SOX2 in breast and lung cancer dynamics. Pathol Res Pract 2024; 260:155386. [PMID: 38861919 DOI: 10.1016/j.prp.2024.155386] [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: 02/25/2024] [Revised: 05/09/2024] [Accepted: 05/31/2024] [Indexed: 06/13/2024]
Abstract
Breast and lung cancers are leading causes of death among patients, with their global mortality and morbidity rates increasing. Conventional treatments often prove inadequate due to resistance development. The alteration of molecular interactions may accelerate cancer progression and treatment resistance. SOX2, known for its abnormal expression in various human cancers, can either accelerate or impede cancer progression. This review focuses on examining the role of SOX2 in breast and lung cancer development. An imbalance in SOX2 expression can promote the growth and dissemination of these cancers. SOX2 can also block programmed cell death, affecting autophagy and other cell death mechanisms. It plays a significant role in cancer metastasis, mainly by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, an imbalanced SOX2 expression can cause resistance to chemotherapy and radiation therapy in these cancers. Genetic and epigenetic factors may affect SOX2 levels. Pharmacologically targeting SOX2 could improve the effectiveness of breast and lung cancer treatments.
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Affiliation(s)
- Kiavash Hushmandi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, the Islamic Republic of Iran.
| | - Seyed Hassan Saadat
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, the Islamic Republic of Iran
| | - Seyedalireza Mirilavasani
- Campus Venlo, Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, The Netherlands
| | - Salman Daneshi
- Department of Public Health,School of Health,Jiroft University of Medical Sciences,Jiroft, the Islamic Republic of Iran
| | - Amir Reza Aref
- Department of Translational Sciences, Xsphera Biosciences Inc. Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, V6H3Z6 Canada
| | - Rasoul Raesi
- Department of Health Services Management, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran.; Department of Nursing, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.
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40
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Mohammed Bakheet M, Mohssin Ali H, Jalil Talab T. Evaluation of some proinflammatory cytokines and biochemical parameters in pre and postmenopausal breast cancer women. Cytokine 2024; 179:156632. [PMID: 38701734 DOI: 10.1016/j.cyto.2024.156632] [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: 02/26/2024] [Revised: 04/08/2024] [Accepted: 04/28/2024] [Indexed: 05/05/2024]
Abstract
The study was planned to evaluate the differences in certain proinflammatory cytokines(IL-6, TNF-α) with CRP and biochemical parameters (E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid), between women with pre- and postmenopausal breast cancer and seemingly healthy women in Iraqi women as controls; at medical city in teaching Oncology hospital,70 breast cancer patients women their ages ranged (47.51 ± 1.18) and 20 healthy women with age (44.45 ± 2.66) begun from September (2020) to February (2021). The aims of this study to investigate the evaluation of chemotherapy effects especially doxorubicin and cyclophosphamide only use in this study in pre and postmenopausal breast cancer women on proinflammatory cytokines(IL-6, TNF-α) with CRP and on biochemical parameters(E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid) in pre and postmenapausal breast cancer women. The patients were divided into five groups and each group contains 14 patients women with breast cancer during pre and postmenopausal periods. The control groups were divided into 10 pre and 10 postmenopausal women(Fig. 1). The results of proinflammatory cytokines of and biochemical parameters in premenopausal groups were as the levels of IL-6 (pg/ml),TNF-α(pg/ml) and CRP (ng/ml) showed significant increase differences (P < 0.01)among breast cancer treated (BCT) groups in comparison with control groups,While the Liver enzymes GGT,LDH and TSB showed highly significant increase (P < 0.01) in BCT groups, Estrogen levels (pg/ml) and D3(ng/ml) increased significantly (P < 0.01)among BCT groups. Blood serum calcium and phosphorus with uric acid levels (mg/dl) showed significant difference (P < 0.01); While the result in postmenopausal of IL-6(pg/ml), TNF-α (pg/ml) and CRP (ng/ml) showed highly significant differences (P < 0.01)among BCT groups.While GGT(IU/L), LDH(IU/L) and TSB (mg/dl) enzymes were increased significantly (p < 0.01), Estrogen (pg/ml) and D3(ng/ml) levels showed significant increase (P < 0.01) among BCT groups.Blood calcium and phosphorus showed significant increase (P < 0.01) while uric acid was non-significant increase (P > 0.05).
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Affiliation(s)
| | - Hiba Mohssin Ali
- Department of Biology, College of Science, Mustansiriyah University, Bagdad, Iraq.
| | - Tabarak Jalil Talab
- Department of Biology, College of Science, Mustansiriyah University, Bagdad, Iraq.
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Wehrend J, Gimarc D, Ashwell ZR, Jensen A, Major N, Ho CK. The effect of gadolinium-based intravenous contrast in the initial characterization of musculoskeletal soft tissue tumors. Curr Probl Diagn Radiol 2024; 53:470-476. [PMID: 38480060 DOI: 10.1067/j.cpradiol.2024.03.002] [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: 05/18/2023] [Revised: 02/01/2024] [Accepted: 03/06/2024] [Indexed: 06/17/2024]
Abstract
OBJECTIVE To determine if gadolinium-based contrast agents increase the sensitivity, specificity or reader confidence of malignant potential in musculoskeletal soft tissue tumors. METHODS Pre- and post-contrast MRI studies from 87 patients were read by three independent radiologists of different experience. Readers noted malignant potential and confidence in their diagnosis based on pre-contrast and post-contrast MRI studies. Statistical models assessed for agreement between MRI reader diagnosis and pathologic results as well as analyzing effects of contrast on reader confidence. Inter- and intra-observer variabilities of malignant potential were also calculated. RESULTS 87 patients (48 benign and 39 malignant; mean [± SD] age 51 ± 17.9 and 57.1 ± 17.1, respectively) were evaluated. For all readers, pre-contrast and post-contrast sensitivities were 68.1 % and 70.6 % while pre-contrast and post-contrast specificities were 84.6 % and 83.8 %, respectively without significant change (p=0.88). There was not a significant association with the use of contrast and prediction of malignant potential with or without the resident reader (p=0.65 and p=0.82). Use of contrast was significantly associated with higher levels of reader confidence (p=0.02) for all readers. Inter- and intra-observer variabilities were in good agreement (W = 0.77 and 0.70). CONCLUSION The addition of a post-contrast sequence increased reader confidence in their diagnosis without a corresponding significant increase in accurate prediction of malignant potential.
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Affiliation(s)
- Jonathan Wehrend
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA
| | - David Gimarc
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA
| | - Zachary R Ashwell
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA
| | - Alexandria Jensen
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA
| | - Nancy Major
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA
| | - Corey K Ho
- University of Colorado-Anschutz Medical Campus, Department of Radiology, 12605 E 16th Avenue, Aurora, CO 80045, USA.
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Deane CD, Fischer M, Shelat AA. Bringing chemistry to medicine to redefine the undruggable. Nat Chem Biol 2024; 20:807-809. [PMID: 38609538 DOI: 10.1038/s41589-024-01598-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2024]
Affiliation(s)
- Caitlin D Deane
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
| | - Marcus Fischer
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
| | - Anang A Shelat
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
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He S, Chen H, Yi Y, Hou D, Fu X, Xie J, Zhang J, Liu C, Ru X, Wang J. A novel bioinformatics strategy to uncover the active ingredients and molecular mechanisms of Bai Shao in the treatment of non-alcoholic fatty liver disease. Front Pharmacol 2024; 15:1406188. [PMID: 39005933 PMCID: PMC11239447 DOI: 10.3389/fphar.2024.1406188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 06/10/2024] [Indexed: 07/16/2024] Open
Abstract
Introduction: As a new discipline, network pharmacology has been widely used to disclose the material basis and mechanism of Traditional Chinese Medicine in recent years. However, numerous researches indicated that the material basis of TCMs identified based on network pharmacology was the mixtures of beneficial and harmful substances rather than the real material basis. In this work, taking the anti-NAFLD (non-alcoholic fatty liver disease) effect of Bai Shao (BS) as a case, we attempted to propose a novel bioinformatics strategy to uncover the material basis and mechanism of TCMs in a precise manner. Methods: In our previous studies, we have done a lot work to explore TCM-induced hepatoprotection. Here, by integrating our previous studies, we developed a novel computational pharmacology method to identify hepatoprotective ingredients from TCMs. Then the developed method was used to discover the material basis and mechanism of Bai Shao against Non-alcoholic fatty liver disease by combining with the techniques of molecular network, microarray data analysis, molecular docking, and molecular dynamics simulation. Finally, literature verification method was utilized to validate the findings. Results: A total of 12 ingredients were found to be associated with the anti-NAFLD effect of BS, including monoterpene glucosides, flavonoids, triterpenes, and phenolic acids. Further analysis found that IL1-β, IL6, and JUN would be the key targets. Interestingly, molecular docking and molecular dynamics simulation analysis showed that there indeed existed strong and stable binding affinity between the active ingredients and the key targets. In addition, a total of 23 NAFLD-related KEGG pathways were enriched. The major biological processes involved by these pathways including inflammation, apoptosis, lipid metabolism, and glucose metabolism. Of note, there was a great deal of evidence available in the literature to support the findings mentioned above, indicating that our method was reliable. Discussion: In summary, the contributions of this work can be summarized as two aspects as follows. Firstly, we systematically elucidated the material basis and mechanism of BS against NAFLD from multiple perspectives. These findings further enhanced the theoretical foundation of BS on NAFLD. Secondly, a novel computational pharmacology research strategy was proposed, which would assist network pharmacology to uncover the scientific connotation TCMs in a more precise manner.
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Affiliation(s)
- Shuaibing He
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Hantao Chen
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Yanfeng Yi
- Department of Life Sciences and Health, School of Science and Engineering, Huzhou College, Huzhou, China
| | - Diandong Hou
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Xuyan Fu
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Jinlu Xie
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Juan Zhang
- XinJiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi, China
| | - Chongbin Liu
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Xiaochen Ru
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Juan Wang
- School of Traditional Chinese Medicine, Zhejiang Pharmaceutical University, Ningbo, China
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Chandrasekhar B, Gor R, Ramalingam S, Thiagarajan A, Sohn H, Madhavan T. Repurposing FDA-approved compounds to target JAK2 for colon cancer treatment. Discov Oncol 2024; 15:226. [PMID: 38869738 DOI: 10.1007/s12672-024-01050-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 05/20/2024] [Indexed: 06/14/2024] Open
Abstract
Colorectal cancer is one of the common cancers worldwide and the second leading cause of cancer-related death. The current treatment has the inherent drawbacks and there is a need of developing a new treatment. Interleukin-6 a pleiotropic cytokine involved in immune regulation and activation of JAK2/STAT3 pathway in colorectal cancer. JAK2/STAT3 signaling pathway functions as a critical regulator of cell growth, differentiation, and immune expression. The abnormality in the JAK2/STAT3 pathway is involved in the tumorigenesis of colon cancer including apoptosis. In this study, we identified novel inhibitors for JAK2 protein by performing virtual screening against FDA-approved compounds. To address the selectivity issue, we implemented cross-docking method followed by DFT calculations to understand the chemical reactivity of the identified compounds. Additionally, molecular dynamics (MD) simulations were performed for the top FDA compounds against JAK2 to understand the molecular interactions and structural stability of the complex over a period of 200 ns. Our results indicated that ergotamine, entrectinib, exatecan, dihydroergotamine, and paritaprevir can be used as alternative drugs for colon cancer. In addition, ergotamine was found to efficiently lower the cell viability with IC50 values of 100 µM on colon cancer cell lines. The long-term inhibitory effect of the ergotamine led to a decrease in colony size, and the toxicity properties were studied using hemolysis assay. Our study shows the potential of targeting JAK2 as a novel approach to colon cancer treatment, and demonstrate that ergotamine as a promising effects as an anti-cancer drug.
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Affiliation(s)
- Bavya Chandrasekhar
- Computational Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Potheri, Chengalpattu District, Kattankulathur, 603203, Tamilnadu, India
| | - Ravi Gor
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Potheri, Chengalpattu District, Kattankulathur, 603203, Tamilnadu, India
| | - Satish Ramalingam
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Potheri, Chengalpattu District, Kattankulathur, 603203, Tamilnadu, India
| | - Anuradha Thiagarajan
- Deparment of Physics with Computer Application, Agurchand Manmull Jain College, Meenambakam, Chennai, Tamilnadu, India
| | - Honglae Sohn
- Department of Chemistry and Department of Carbon Materials, Chosun University, Gwangju, South Korea.
| | - Thirumurthy Madhavan
- Computational Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Potheri, Chengalpattu District, Kattankulathur, 603203, Tamilnadu, India.
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Lupi M, Tsokani S, Howell AM, Ahmed M, Brogden D, Tekkis P, Kontovounisios C, Mills S. Anogenital HPV-Related Cancers in Women: Investigating Trends and Sociodemographic Risk Factors. Cancers (Basel) 2024; 16:2177. [PMID: 38927883 PMCID: PMC11202297 DOI: 10.3390/cancers16122177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
The incidences of anogenital HPV-related cancers in women are on the rise; this is especially true for anal cancer. Medical societies are now beginning to recommend anal cancer screening in certain high-risk populations, including high-risk women with a history of genital dysplasia. The aim of this study is to investigate national anogenital HPV cancer trends as well as the role of demographics, deprivation, and ethnicity on anogenital cancer incidence in England, in an attempt to better understand this cohort of women which is increasingly affected by anogenital HPV-related disease. Demographic data from the Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with anal, cervical, vulval and vaginal cancer in England between 2014 and 2020. Outcomes included age, ethnicity, deprivation status and staging. An age over 55 years, non-white ethnicity and high deprivation are significant risk factors for late cancer staging, as per logistic regression. In 2019, the incidences of anal and vulval cancer in white women aged 55-74 years surpassed that of cervical cancer. More needs to be done to educate women on HPV-related disease and their lifetime risk of these conditions.
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Affiliation(s)
- Micol Lupi
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2AZ, UK; (D.B.); (P.T.); (C.K.); (S.M.)
- Department of Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK;
| | - Sofia Tsokani
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;
- Cochrane Methods Support Unit, Evidence Production and Methods Department, Cochrane, London W1G 0AN, UK
| | - Ann-Marie Howell
- Department of Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK;
| | - Mosab Ahmed
- Department of Anesthesiology, State University of New York Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
| | - Danielle Brogden
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2AZ, UK; (D.B.); (P.T.); (C.K.); (S.M.)
| | - Paris Tekkis
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2AZ, UK; (D.B.); (P.T.); (C.K.); (S.M.)
- Department of Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK;
- Department of Colorectal Surgery and Cancer, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, London SW3 6JJ, UK
| | - Christos Kontovounisios
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2AZ, UK; (D.B.); (P.T.); (C.K.); (S.M.)
- Department of Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK;
- Department of Colorectal Surgery and Cancer, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, London SW3 6JJ, UK
- Evangelismos General Hospital, Ipsilantou 45-47, 106 76 Athens, Greece
| | - Sarah Mills
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2AZ, UK; (D.B.); (P.T.); (C.K.); (S.M.)
- Department of Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK;
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Galiana-Melendez F, Huot JR. The Impact of Non-bone Metastatic Cancer on Musculoskeletal Health. Curr Osteoporos Rep 2024; 22:318-329. [PMID: 38649653 DOI: 10.1007/s11914-024-00872-4] [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] [Accepted: 04/14/2024] [Indexed: 04/25/2024]
Abstract
PURPOSE OF REVIEW The purpose of this review is to discuss the musculoskeletal consequences of cancer, including those that occur in the absence of bone metastases. RECENT FINDINGS Cancer patients frequently develop cachexia, a debilitating condition reflected by weight loss and skeletal muscle wasting. The negative effects that tumors exert on bone health represents a growing interest amongst cachexia researchers. Recent clinical and pre-clinical evidence demonstrates cancer-induced bone loss, even in the absence of skeletal metastases. Together with muscle wasting, losses in bone demonstrates the impact of cancer on the musculoskeletal system. Identifying therapeutic targets that comprehensively protect musculoskeletal health is essential to improve the quality of life in cancer patients and survivors. IL-6, RANKL, PTHrP, sclerostin, and TGF-β superfamily members represent potential targets to counteract cachexia. However, more research is needed to determine the efficacy of these targets in protecting both skeletal muscle and bone.
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Affiliation(s)
| | - Joshua R Huot
- Department of Anatomy, Cell Biology & Physiology, Indianapolis, IN, 46202, USA.
- Indiana Center for Musculoskeletal Health, Indianapolis, IN, USA.
- Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
- Department of Kinesiology, School of Health and Human Sciences, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.
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Calicis R, Dubois A, Ritter C, Tinton N, Calicis B, Hoebeke Y, Lepore D, Da Rocha De Sousa F, Cambier E, Corbisier F. Predictive factors of surgery in metastatic colorectal cancer: a retrospective cohort study. Acta Chir Belg 2024; 124:170-177. [PMID: 37605980 DOI: 10.1080/00015458.2023.2231211] [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: 01/23/2023] [Accepted: 06/26/2023] [Indexed: 08/23/2023]
Abstract
INTRODUCTION Current management of metastatic colorectal cancer is based on neoadjuvant chemotherapy. Few studies have reported on surgery procedures in patients with metastatic colorectal cancer. The objective of this study was to describe our institutional experience with emergency surgery performed in patients with metastatic colorectal cancer during chemotherapy. PATIENTS AND METHODS This was a retrospective cohort study including adult patients of ≤80 years with a metastatic colorectal cancer between 2017 and 2020 and undergoing surgery during chemotherapy. Statistical analyses were based on Kaplan-Meier's curve and Cox proportional hazard model. The surgery statistical risk during chemotherapy was studied through all tumor and patient's characteristics. Multivariable logistic regression models were used to identify predictive factors of emergency surgery in these patients. RESULTS Seventy-two cases were identified and 60% patients undergone an emergency surgery. By Kaplan-Meier's analyses, intestinal surgery was much more frequent and early in patients who have severe stenosis (either blocking or only permeable using a gastroscope) at the time of diagnosis. Patients with severe malignant stenosis presented a 6.28 time higher surgery risk (p < .0001). The median time between admission and surgery was 54 days in patients with severe stenosis who were operated. CONCLUSION The degree of colorectal tumor stenosis measured by endoscopy was a risk factor for emergency surgery in patients with metastatic colorectal cancer during neoadjuvant chemotherapy. In this group of patients presenting low survival outcomes, further studies are needed to define the place of preventive surgery, avoiding emergency surgery and morbidity in such fragile patients.
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Affiliation(s)
- Raffaele Calicis
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | - Antoine Dubois
- Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven & Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Leuven Intestinal Failure and Transplantation (LIFT), University Hospitals Leuven, Leuven, Belgium
- Department of Experimental Surgery and Transplantation (CHEX), University Hospital Saint-Luc, Brussels, Belgium
| | - Christian Ritter
- Statistical Methodology and Computing Service, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Nicolas Tinton
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | - Benjamin Calicis
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | - Yves Hoebeke
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | - David Lepore
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | | | - Emmanuel Cambier
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
| | - Fabrice Corbisier
- Department of Abdominal Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
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Wen W, Ertas YN, Erdem A, Zhang Y. Dysregulation of autophagy in gastric carcinoma: Pathways to tumor progression and resistance to therapy. Cancer Lett 2024; 591:216857. [PMID: 38583648 DOI: 10.1016/j.canlet.2024.216857] [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: 02/06/2024] [Revised: 03/22/2024] [Accepted: 04/02/2024] [Indexed: 04/09/2024]
Abstract
The considerable death rates and lack of symptoms in early stages of gastric cancer (GC) make it a major health problem worldwide. One of the most prominent risk factors is infection with Helicobacter pylori. Many biological processes, including those linked with cell death, are disrupted in GC. The cellular "self-digestion" mechanism necessary for regular balance maintenance, autophagy, is at the center of this disturbance. Misregulation of autophagy, however, plays a role in the development of GC. In this review, we will examine how autophagy interacts with other cell death processes, such as apoptosis and ferroptosis, and how it affects the progression of GC. In addition to wonderful its role in the epithelial-mesenchymal transition, it is engaged in GC metastasis. The role of autophagy in GC in promoting drug resistance stands out. There is growing interest in modulating autophagy for GC treatment, with research focusing on natural compounds, small-molecule inhibitors, and nanoparticles. These approaches could lead to breakthroughs in GC therapy, offering new hope in the fight against this challenging disease.
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Affiliation(s)
- Wen Wen
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey.
| | - Ahmet Erdem
- Institute for Quantitative Health Science and Engineering (IQ), Department of Biomedical Engineering, College of Engineering and Human Medicine, Michigan State University, East Lansing, MI, 48824, USA; Department of Biomedical Engineering, Kocaeli University, Umuttepe Campus, Kocaeli, 41001 Turkey.
| | - Yao Zhang
- Department of Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China.
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You Z, Ling S, Zhao S, Han H, Bian Y, He Y, Chen X. Tissue damage from chronic liver injury inhibits peripheral NK cell abundance and proinflammatory function. J Leukoc Biol 2024; 115:1042-1052. [PMID: 38315633 PMCID: PMC11135618 DOI: 10.1093/jleuko/qiae027] [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: 03/19/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 02/07/2024] Open
Abstract
One of the difficulties in the treatment of hepatocellular carcinoma is that it is impossible to eliminate the inhibitory effect of the tumor microenvironment on immune response. Therefore, it is particularly important to understand the formation process of the tumor microenvironment. Chronic inflammation is the core factor of cancer occurrence and the leading stage of inflammation-cancer transformation, and the natural killer cell subsets play an important role in it. Our study confirmed that in the stage of chronic liver injury, the local immunosuppressive microenvironment of the liver (i.e. the damaged microenvironment) has been formed, but this inhibitory effect is only for peripheral natural killer cells and has no effect on tissue-resident natural killer subsets. The markers of damage microenvironment are the same as those of tumor microenvironment.
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Affiliation(s)
- Zonghao You
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
| | - Shaoxue Ling
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
| | - Shuwu Zhao
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
| | - Haixing Han
- SINOSH (Tianjin) Group Co., Ltd, Tianjin, P. R. China
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
| | - Yongzhi He
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
| | - Xi Chen
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P. R. China
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50
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Ghosal N, Tapadar P, Biswas D, Pal R. ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2). Mol Biol Rep 2024; 51:671. [PMID: 38787503 DOI: 10.1007/s11033-024-09615-1] [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: 10/12/2023] [Accepted: 05/06/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND TRAIL protein on binding to its cognate death receptors (DR) can induce apoptosis specifically in breast tumor cells sparing normal cells. However, TRAIL also binds to decoy receptors (DCR) thereby inhibiting the apoptotic pathways thus causing TRAIL resistance. Also, one of the barriers due to which TRAIL-based therapy could not become FDA-approved might be because of resistance to therapy. Therefore, in the current study we wanted to explore the role of transcription factors in TRAIL resistance with respect to breast cancer. METHODS Microarray data from TRAIL-sensitive (TS) and TRAIL-resistant (TR) MDA-MB-231 cells were reanalyzed followed by validation of the candidate genes using quantitative PCR (qPCR), immunoblotting and immunofluorescence technique. Overexpression of the candidate gene was performed in MDA-MB-231 and MCF7 cells followed by cell viability assay and immunoblotting for cleaved caspase-3. Additionally, immunoblotting for DCR2 was carried out. TCGA breast cancer patient survival was used for Kaplan-Meier (KM) plot. RESULTS Validation of the candidate gene i.e. ELF3 using qPCR and immunoblotting revealed it to be downregulated in TR cells compared to TS cells. ELF3 overexpression in MDA-MB-231 and MCF7 cells caused reversal of TRAIL resistance as observed using cell viability assay and cleaved caspase-3 immunoblotting. ELF3 overexpression also resulted in DCR2 downregulation in the MDA-MB-231 and MCF7 cells. Furthermore, KM analysis found high ELF3 and low DCR2 expression to show better patient survival in the presence of TRAIL. CONCLUSION Our study shows ELF3 to be an important factor that can influence TRAIL-mediated apoptosis in breast cancer. Also, ELF3 and DCR2 expression status should be taken into consideration while designing strategies for successful TRAIL-based therapy.
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Affiliation(s)
- Nirajan Ghosal
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India
| | - Poulami Tapadar
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India
| | - Divisha Biswas
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India
| | - Ranjana Pal
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, 700073, India.
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