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Gavioli C, Vlooswijk C, Janssen SHM, Kaal SEJ, Kerst JM, Tromp JM, Bos MEMM, van der Hulle T, van der Graaf WTA, Lalisang RI, Nuver J, Bijlsma RM, Kouwenhoven MCM, Husson O, Beijer S. Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors: results from the SURVAYA study. J Cancer Surviv 2025; 19:1028-1042. [PMID: 38224397 PMCID: PMC12081526 DOI: 10.1007/s11764-023-01529-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 12/27/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. METHODS A population-based, cross-sectional study was performed among long-term (5-20 years) AYA cancer survivors (18-39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. RESULTS The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5-7.0) (n = 3668). Sixty-one percent adhered to "limit the consumption of sugar sweetened drinks," 28% to "be a healthy weight," 25% to "fruit and vegetable consumption," and 31% to "limit alcohol consumption." Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14-1.85, and ORhigh = 1.87, 95% CI = 1.46-2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30-1.83, and ORhigh = 1.87, 95% CI = 1.46-2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50-0.92, and ORhigh = 0.30, 95% CI = 0.21-0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39-0.86, and ORhigh = 0.45, 95% CI = 0.30-0.69). CONCLUSIONS Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. IMPLICATIONS FOR CANCER SURVIVORS Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.
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Affiliation(s)
- Costanza Gavioli
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, 3511 DT, Utrecht, The Netherlands
| | - Carla Vlooswijk
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, 3511 DT, Utrecht, The Netherlands
| | - Silvie H M Janssen
- Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands
- Department of Medical Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
| | - Suzanne E J Kaal
- Department of Medical Oncology, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
| | - J Martijn Kerst
- Department of Medical Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
| | - Jacqueline M Tromp
- Department of Medical Oncology, Amsterdam University Medical Center, 1105 AZ, Amsterdam, The Netherlands
| | - Monique E M M Bos
- Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD, Rotterdam, The Netherlands
| | - Tom van der Hulle
- Department of Medical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands
| | - Winette T A van der Graaf
- Department of Medical Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands
- Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD, Rotterdam, The Netherlands
| | - Roy I Lalisang
- Department of Internal Medicine, GROW-School of Oncology and Reproduction, Maastricht UMC+ Comprehensive Cancer Center, 6229 HX, Maastricht, The Netherlands
| | - Janine Nuver
- Department of Medical Oncology, University Medical Center Groningen, 9713 GZ, Groningen, The Netherlands
| | - Rhodé M Bijlsma
- Department of Medical Oncology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
| | - Mathilde C M Kouwenhoven
- Department of Neurology, Amsterdam UMC, Amsterdam University Medical Centers, Location VUmc, 1081 HV, Amsterdam, The Netherlands
| | - Olga Husson
- Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
- Department of Medical Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, 1066 CX, Amsterdam, The Netherlands.
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, The Netherlands.
| | - Sandra Beijer
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, 3511 DT, Utrecht, The Netherlands
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Kiss Z, Berki TL, Maráz A, Horváth Z, Nagy P, Fábián I, Kovács V, Rokszin G, Surján G, Barcza Z, Kenessey I, Wéber A, Wittmann I, Molnár GA, Szabó TG, Buga V, Karamousouli E, Darida M, Abonyi-Tóth Z, Bertókné Tamás R, Fürtős VD, Bogos K, Moldvay J, Gálffy G, Tamási L, Müller V, Krasznai ZT, Ostoros G, Pápai-Székely Z, Branyiczkiné Géczy G, Hilbert L, Polgár C, Vokó Z. Overall Survival of Hungarian Cancer Patients Diagnosed Between 2011 and 2019, Based on the Health Insurance Fund Database. Cancers (Basel) 2025; 17:1670. [PMID: 40427166 PMCID: PMC12110003 DOI: 10.3390/cancers17101670] [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: 04/07/2025] [Revised: 05/02/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Assessing cancer survival trends is crucial for monitoring progress in cancer management and prevention. As part of the broader HUN-CANCER EPI study, this analysis examined overall survival (OS) in the Hungarian cancer population between 2011 and 2019. Methods: Using data extracted from the Hungarian National Health Insurance Fund (NHIF) database, short- and long-term OS were estimated for various cancer types according to age, sex, and diagnostic period using Kaplan-Meier analysis. The study also identified cancer types with significant early mortality following diagnosis. Results: From 2011 to 2019, a total of 528,808 patients were diagnosed with cancer. During the 2015-2019 diagnostic period, the lowest 5-year OS rates were observed for esophageal (7.0%), pancreatic (10.7%), liver (12.5%), gallbladder (13.9%), and lung cancer (18.4%). Conversely, tumor types with better OS included testicular cancer (91.6%), thyroid cancer (89.0%), Hodgkin's lymphoma (84.0%), melanoma (78.6%), and breast cancer (74.1%). A notable proportion of deaths occurred within 2 months of diagnosis for liver (33.2%), pancreatic (27.9%), and gallbladder cancer (29.0%). Significant early mortality within 6 months post-diagnosis was also noted for esophageal (51.3%), stomach (42.9%), and lung cancer (41.7%). Conclusions: The HUN-CANCER EPI study conducted between 2011 and 2019 provides valuable insights into cancer survival patterns in Hungary, emphasizing the importance of early detection and targeted interventions to improve patient outcomes.
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Affiliation(s)
- Zoltán Kiss
- MSD Pharma Hungary Ltd., 1095 Budapest, Hungary
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, 7624 Pécs, Hungary
| | - Tamás László Berki
- Center for Health Technology Assessment, Semmelweis University, 1085 Budapest, Hungary
| | - Anikó Maráz
- Department of Oncotherapy, University of Szeged, 6720 Szeged, Hungary
| | - Zsolt Horváth
- Department of Oncology, Bács-Kiskun County Teaching Hospital, 6000 Kecskemét, Hungary
| | - Péter Nagy
- Department of Molecular Immunology and Toxicology, National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary
- Department of Anatomy and Histology, HUN-REN–UVMB Laboratory of Redox Biology Research Group, University of Veterinary Medicine, 1078 Budapest, Hungary
- Chemistry Institute, University of Debrecen, 4032 Debrecen, Hungary
| | - Ibolya Fábián
- RxTarget Ltd., 5000 Szolnok, Hungary
- Department of Biostatistics, University of Veterinary Medicine, 1078 Budapest, Hungary
| | | | | | - György Surján
- Department of Deputy Chief Medical Officer II., National Public Health Center, 1097 Budapest, Hungary
- Institute of Digital Health Sciences, Semmelweis University, 1085 Budapest, Hungary
| | - Zsófia Barcza
- Syntesia Medical Communications Ltd., 1065 Budapest, Hungary
| | - István Kenessey
- Hungarian National Cancer Registry and National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1085 Budapest, Hungary
| | - András Wéber
- Hungarian National Cancer Registry and National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary
| | - István Wittmann
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, 7624 Pécs, Hungary
| | - Gergő Attila Molnár
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, 7624 Pécs, Hungary
| | | | | | | | | | - Zsolt Abonyi-Tóth
- RxTarget Ltd., 5000 Szolnok, Hungary
- Department of Biostatistics, University of Veterinary Medicine, 1078 Budapest, Hungary
| | - Renáta Bertókné Tamás
- Department of Deputy Chief Medical Officer II., National Public Health Center, 1097 Budapest, Hungary
| | - Viktória Diána Fürtős
- Department of Deputy Chief Medical Officer II., National Public Health Center, 1097 Budapest, Hungary
| | - Krisztina Bogos
- Directorate of Institution, National Korányi Institute of Pulmonology, 1121 Budapest, Hungary
| | - Judit Moldvay
- 1st Department of Pulmonology, National Korányi Institute of Pulmonology, 1121 Budapest, Hungary
- Department of Pulmonology, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary
| | - Gabriella Gálffy
- Pulmonology Center of the Reformed Church in Hungary, Department of Pulmonology, 2045 Törökbálint, Hungary
| | - Lilla Tamási
- Department of Pulmonology, Semmelweis University, 1085 Budapest, Hungary
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, 1085 Budapest, Hungary
| | - Zoárd Tibor Krasznai
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Gyula Ostoros
- Directorate of Institution, National Korányi Institute of Pulmonology, 1121 Budapest, Hungary
| | - Zsolt Pápai-Székely
- Fejér County Szent György, University Teaching Hospital, 8000 Székesfehérvár, Hungary
| | | | - Lászlóné Hilbert
- Demographic Statistics Department, Hungarian Central Statistical Office, 1024 Budapest, Hungary
| | - Csaba Polgár
- National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary
- Department of Oncology, Semmelweis University, 1085 Budapest, Hungary
| | - Zoltán Vokó
- Center for Health Technology Assessment, Semmelweis University, 1085 Budapest, Hungary
- Syreon Research Institute, 1145 Budapest, Hungary
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary
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Atas E, Berchtold K, Schlederer M, Prodinger S, Sternberg F, Pucci P, Steel C, Matthews JD, James ER, Philippe C, Trachtová K, Moazzami AA, Artamonova N, Melchior F, Redmer T, Timelthaler G, Pohl EE, Turner SD, Heidegger I, Krueger M, Resch U, Kenner L. The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer. Mol Cancer 2025; 24:134. [PMID: 40320521 PMCID: PMC12051277 DOI: 10.1186/s12943-025-02320-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 04/01/2025] [Indexed: 05/08/2025] Open
Abstract
Prostate cancer (PCa) and Type 2 diabetes (T2D) often co-occur, yet their relationship remains elusive. While some studies suggest that T2D lowers PCa risk, others report conflicting data. This study investigates the effects of peroxisome proliferator-activated receptor (PPAR) agonists Bezafibrate, Tesaglitazar, and Pioglitazone on PCa tumorigenesis. Analysis of patient datasets revealed that high PPARG expression correlates with advanced PCa and poor survival. The PPARγ agonists Pioglitazone and Tesaglitazar notably reduced cell proliferation and PPARγ protein levels in primary and metastatic PCa-derived cells. Proteomic analysis identified intrinsic differences in mTORC1 and mitochondrial fatty acid oxidation (FAO) pathways between primary and metastatic PCa cells, which were further disrupted by Tesaglitazar and Pioglitazone. Moreover, metabolomics, Seahorse Assay-based metabolic profiling, and radiotracer uptake assays revealed that Pioglitazone shifted primary PCa cells' metabolism towards glycolysis and increased FAO in metastatic cells, reducing mitochondrial ATP production. Furthermore, Pioglitazone suppressed cell migration in primary and metastatic PCa cells and induced the epithelial marker E-Cadherin in primary PCa cells. In vivo, Pioglitazone reduced tumor growth in a metastatic PC3 xenograft model, increased phosho AMPKα and decreased phospho mTOR levels. In addition, diabetic PCa patients treated with PPAR agonists post-radical prostatectomy implied no biochemical recurrence over five to ten years compared to non-diabetic PCa patients. Our findings suggest that Pioglitazone reduces PCa cell proliferation and induces metabolic and epithelial changes, highlighting the potential of repurposing metabolic drugs for PCa therapy.
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Affiliation(s)
- Emine Atas
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria.
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
| | | | | | | | - Felix Sternberg
- Department of Biological Sciences and Pathobiology, Unit of Physiology and Biophysics, University of Veterinary Medicine, Vienna, Austria
- Department of Nutritional Science, University of Vienna, Vienna, Austria
| | - Perla Pucci
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Christopher Steel
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Jamie D Matthews
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Emily R James
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Cécile Philippe
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - Karolína Trachtová
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria
- Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic
| | - Ali A Moazzami
- Department of Molecular Sciences, Swedish University of Agricultural Sciences, 75007, Uppsala, Sweden
| | | | - Felix Melchior
- Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Torben Redmer
- Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Gerald Timelthaler
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Elena E Pohl
- Department of Biological Sciences and Pathobiology, Unit of Physiology and Biophysics, University of Veterinary Medicine, Vienna, Austria
| | - Suzanne D Turner
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Isabel Heidegger
- Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Marcus Krueger
- Institute for Genetics, Cologne Excellence Cluster of Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Ulrike Resch
- Center of Physiology and Pharmacology, Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Lukas Kenner
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria.
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
- Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.
- Center for Biomarker Research in Medicine GmbH (CBmed), Graz, Austria.
- Department of Molecular Biology, Umeå University, Umea, Sweden.
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4
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Hajikarimloo B, Mohammadzadeh I, Tos SM, Habibi MA, Hashemi R, Hezaveh EB, Najari D, Hasanzade A, Hooshmand M, Bana S. Machine learning in prediction of epidermal growth factor receptor status in non-small cell lung cancer brain metastases: a systematic review and meta-analysis. BMC Cancer 2025; 25:818. [PMID: 40312289 PMCID: PMC12044993 DOI: 10.1186/s12885-025-14221-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 04/24/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Epidermal growth factor receptor (EGFR) mutations are present in 10-60% of all non-small cell lung cancer (NSCLC) patients and are associated with dismal prognosis. Lung cancer brain metastases (LCBM) are a common complication of lung cancer. Predictions of EGFR can help physicians in decision-making and, through optimizing treatment strategies, can result in more favorable outcomes. This systematic review and meta-analysis evaluated the predictive performance of machine learning (ML)-based models in EGFR status in NSCLC patients with brain metastasis. METHODS On December 20, 2024, the four electronic databases, Pubmed, Embase, Scopus, and Web of Science, were systematically searched. Studies that evaluated EGFR status in patients with brain metastasis from NSCLC were included. RESULTS Twenty studies with 3517 patients with 6205 NSCLC brain metastatic lesions were included. The majority of the best-performance models were ML-based (70%, 7/10), and deep learning (DL)-based models comprised 30% (6/20) of models. The area under the curve (AUC) and accuracy (ACC) of the best-performance models ranged from 0.765 to 1 and 0.69 to 0.93, respectively. The meta-analysis of the best-performance model revealed a pooled AUC of 0.91 (95%CI: 0.88-0.93) and ACC of 0.82 (95%CI: 0.79-0.86) along with a pooled sensitivity of 0.87 (95%CI: 0.83-0.9), specificity of 0.86 (95%CI: 0.79-0.9), and diagnostic odds ratio (DOR) of 35.2 (95%CI: 21.2-58.4). The subgroup analysis did not show significant differences between ML and DL models. CONCLUSION ML-based models demonstrated promising predictive outcomes in predicting EGFR status. Applying ML-based models in daily clinical practice can optimize treatment strategies and enhance clinical and radiological outcomes.
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Affiliation(s)
- Bardia Hajikarimloo
- Department of Neurological Surgery, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ibrahim Mohammadzadeh
- Skull Base Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Salem M Tos
- Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA
| | - Mohammad Amin Habibi
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Rana Hashemi
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ehsan Bahrami Hezaveh
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Dorsa Najari
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arman Hasanzade
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Hooshmand
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Bana
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Yan Y, Fang M, Zhao C, Lin X, Tong C, Xiang C, Ran Y, Wang X, Li S, Chen G, Fu L. Dl-3-n-butylphthalide attenuates DOX-induced cardiotoxicity in mice by inhibiting Nrf2/Keap1 complex formation. Front Pharmacol 2025; 16:1542296. [PMID: 40365306 PMCID: PMC12069325 DOI: 10.3389/fphar.2025.1542296] [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: 12/09/2024] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Introduction Drug-induced cardiotoxicity (DICT), defined as myocardial injury caused by direct or indirect toxicity of therapeutic agents, disrupts cardiovascular homeostasis, underscoring the urgent need for preventive strategies in clinical practice. Doxorubicin (DOX), a clinically established anthracycline chemotherapeutic, induces dose-dependent cardiotoxicity driven by reactive oxygen species overproduction. Notably, Dl-3-n-butylphthalide (NBP), a bioactive phytochemical derived from celery, has shown potential in mitigating DOX-induced cardiomyopathy via its antioxidant activity. Therefore, this study aimed to investigate the protective effects of NBP on DOX-induced cardiomyopathy, with a focus on elucidating the underlying mechanisms. Method We developed both in vivo and in vitro models of DOX-induced cardiotoxicity. For the animal model, male C57BL/6 mice were administered with DOX (4 mg/kg, i.p.) once a week for 3 weeks. For the cell model, H9C2 myoblasts were exposed to 1 μM DOX for at least 6 h to establish acute cardiotoxicity. Results Our results demonstrate that NBP significantly improves cardiac function, as evidenced by approximately 10% increase in cardiac functional parameters (ejection fraction and left ventricular shortening fraction). Besides, NBP exerts favorable effects on cardiac inflammation, apoptosis, fibrosis, and mitochondrial damage both in vivo and in vitro. Further mechanistic investigations revealed that NBP blocks the interaction between Kelch-like ECH-associated protein-1 (Keap1) and Nrf2, thereby preventing the formation of the Nrf2/Keap1 complex. Discussion This study indicate that NBP alleviates DOX-induced cardiotoxicity by inhibiting Nrf2/Keap1 complex formation, highlighting its potential as a therapeutic agent for DICT and suggest that Nrf2/Keap1 may be a potential therapeutic target for the management of this condition.
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Affiliation(s)
- Yixiao Yan
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mingzhen Fang
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Cong Zhao
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xinru Lin
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chen Tong
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Cheng Xiang
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ya Ran
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuelian Wang
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shuixin Li
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Gaozhi Chen
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Lili Fu
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
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6
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Cochetti G, Guadagni L, Paladini A, Russo M, La Mura R, Vitale A, Saqer E, Mangione P, Esposito R, Gioè M, Pastore F, De Angelis L, Ricci F, Mearini M, Vannuccini G, Mearini E. Evaluation of Urinary miRNA in Renal Cell Carcinoma: A Systematic Review. Cancers (Basel) 2025; 17:1336. [PMID: 40282512 PMCID: PMC12026426 DOI: 10.3390/cancers17081336] [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: 02/20/2025] [Revised: 04/06/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
Background and Objective. The significance of microRNAs (miRNAs) in relation to neoplastic diseases; such as renal carcinoma carcinoma (RCC); has been brought to light by recent studies. Analyzing the main urinary miRNAs implicated in RCC and their potential diagnostic use was the goal of this systematic review of the literature. Methods. This systematic review was performed following the PROSPERO protocol CRD42024550716. Our literature search strategies were deciding which database to include (Pubmed; EMBASE and Clinicaltrial.gov) and composing strings with words related to urinary miRNA in patients with RCC. Key findings and limitations. After screening; 10 papers were included from the 593 records that the systematic review found. No miRNA was investigated in more than one paper by different authors. The miR-210 and let-7 family were the most investigated and resulted upregulated in RCC cases compared to controls. Five papers reported different expression of miRNAs in urine samples before and after surgery: miR-15a; miR-34a-5p; miR-200a-3p; miR-205-5p; miR-210; miR-210-3p; miR-365a-3p and let-7d-5p levels decreased after nephrectomy. Meta-analysis was not performed since the included studies were heterogeneous; in terms of studied miRNA; of the normalizer used during stabilization phase; and histologic type of RCC (clear cell RCC; papillary RCC; unspecified RCC). Conclusions. Considering the variability and heterogeneity of the obtained results; as well as the vastness of the topic; expanding research in this field appears highly promising. To support further advancements; it would be useful to establish a database that consolidates international findings.
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Affiliation(s)
| | | | - Alessio Paladini
- Urology Clinic, Department of Medicine and Surgery, Santa Maria della Misericordia Hospital, University of Perugia, 06129 Perugia, Italy; (G.C.); (L.G.); (M.R.); (R.L.M.); (E.S.); (P.M.); (R.E.); (M.G.); (F.P.); (L.D.A.); (F.R.); (M.M.); (G.V.); (E.M.)
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7
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Zhao Y, Han J, Yang R, Wang S, Zhao X, Wang Z, Lu H. Evaluating the predictive significance of D-dimer in conjunction with CA724 for the postoperative outcomes in gastric cancer: A retrospective cohort analysis. PLoS One 2025; 20:e0320193. [PMID: 40198649 PMCID: PMC11978037 DOI: 10.1371/journal.pone.0320193] [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: 11/25/2024] [Accepted: 02/15/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Gastric cancer represents a highly aggressive form of malignant tumor originating from the epithelial cells lining the gastric mucosa. Despite notable improvements in treatment approaches over the last few years, the associated mortality rate continues to be considerably high. Therefore, there is a pressing requirement for dependable biomarkers that can be utilized to predict and monitor prognosis, as well as to formulate targeted treatment strategies for patient groups at high risk. METHODS We conducted an analysis of data collected from patients who were diagnosed with gastric cancer and underwent radical gastrectomy at Shanxi Cancer Hospital from June 2017 to June 2018, with follow-up data gathered over a five-year duration until 2023. Patient follow-up information was sourced from the hospital's monitoring system. The analysis focused on the variances in effectiveness of D-dimer against different tumor markers through Cox stratification analysis. The tumor marker that exhibited the most pronounced impact was selected to formulate a novel combined indicator. Furthermore, we examined how this combined indicator influences five-year overall survival (OS) outcomes following gastric cancer surgery using Cox multivariate regression analysis. RESULTS The Cox multivariate regression analysis revealed that the effect value of the D_Dimer-CA724 Middle group on the overall survival rate post-surgery for gastric cancer was found to be 1.42 (1.13-1.78), p = 0.003 (<0.05), in comparison with the D_Dimer-CA724 Low group. For the D_Dimer-CA724 High group, the effect value on overall survival after gastric cancer surgery was 2.11 (1.65-2.68), p < 0.001. Additionally, the trend test results indicated a value of 1.46 (1.29-1.64) with p < 0.001, demonstrating statistical significance. When compared to the D_Dimer-CA724 Low group, both the D_Dimer-CA724 Middle and High groups showed markedly poorer prognoses, with increased risks of 42% and 111%, respectively, highlighting a highly significant finding in clinical practice. CONCLUSION The integrated measure of D-dimer and CA724, referred to as D-dimer_CA724, serves as an independent predictor for the postoperative outcomes of gastric cancer, demonstrating superior predictive capability compared to the individual markers. In clinical settings, patients with gastric cancer exhibiting elevated levels of D-dimer_CA724 tend to experience worse prognoses following surgery. This measure holds significant potential for widespread application and promotion within clinical practice.
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Affiliation(s)
- Yuanzheng Zhao
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Jiaqi Han
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Rong Yang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, ChinaNo. 3, Zhigong New Street, Taiyuan City, Shanxi Province, China
| | - Shuqin Wang
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Xinran Zhao
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Ziyuan Wang
- Fenyang College Shanxi Medical University, Shanxi, China; No.16 College Road, Lvliang City, Shanxi Province, China
| | - Hongxia Lu
- Department of Gastroenterology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Shanxi, ChinaNo. 3, Zhigong New Street, Taiyuan City, Shanxi Province, China
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8
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Abdelfattah EK, Hosny SM, Kassem AB, Moustafa HAM, Tawfeik AM, Abdelhafez MN, El-Sheshtawy W, Alsfouk BA, Saleh A, Salem HA. Pharmacogenetics as a Future Tool to Risk-Stratify Breast Cancer Patients According to Chemotoxicity Potential from the Doxorubicin Hydrochloride and Cyclophosphamide (AC) Regimen. Pharmaceuticals (Basel) 2025; 18:539. [PMID: 40283974 PMCID: PMC12029990 DOI: 10.3390/ph18040539] [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: 03/13/2025] [Revised: 03/31/2025] [Accepted: 04/01/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Studying single-nucleotide polymorphisms (SNPs) in xenobiotic-transporting and metabolizing enzyme genes before administering the doxorubicin hydrochloride and cyclophosphamide (AC) regimen may help optimize breast cancer (BC) treatment for individual patients. Objective: Genotyping specific SNPs on genes encoding for the transport and metabolism of the AC regimen and study their association with its chemotherapeutic toxicity. Method: This prospective cohort study was conducted in two hospitals in Egypt. Before receiving AC therapy, venous blood was collected from female patients with BC for DNA extraction and the genotyping of four SNPs: rs2228100 in ALDH3A1 gene, rs12248560 in CYP2C19 gene, rs1045642 in ABCB1 gene, and rs6907567 in SLC22A16 gene. Patients were then prospectively monitored for hematological, gastrointestinal, and miscellaneous toxicities throughout the treatment cycles. Results: The ALDH3A1 gene polymorphism demonstrated a significant increase in nausea, stomachache, and peripheral neuropathy among patients carrying the GC+CC genotype, compared to those with the GG genotype (p = 0.023, 0.036, and 0.008, respectively). Conversely, patients with the GG genotype exhibited significantly higher fever grades after cycles 1, 2, and 3 of the AC regimen compared to those with the GC+CC genotype (p = 0.009, 0.017, and 0.018, respectively). Additionally, fatigue severity was significantly increased among patients with the GG genotype compared to those with the GC+CC genotype following AC administration (p = 0.008). Conclusions: The SNP variation of ALDH3A1 (rs2228100) gene significantly influenced AC regimen toxicity in female BC patients. Meanwhile, SNPs in CYP2C19 (rs12248560), ABCB1 (rs1045642), and SLC22A16 (rs6907567) genes showed a significant influence on the recurrence rate of certain toxicities.
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Affiliation(s)
- Esraa K. Abdelfattah
- Department of Clinical Pharmacy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, Egypt; (E.K.A.); (S.M.H.)
| | - Sanaa M. Hosny
- Department of Clinical Pharmacy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, Egypt; (E.K.A.); (S.M.H.)
| | - Amira B. Kassem
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour 22514, Egypt
| | | | - Amany M. Tawfeik
- Medical Microbiology and Immunology Department, Faculty of Medicine, Badr University in Cairo, Cairo 11829, Egypt;
- Medical Microbiology and Immunology Department, Faculty of Medicine, Al Azhar University (Girls) Cairo, Cairo 11754, Egypt
| | - Marwa N. Abdelhafez
- Department of Medical Oncology, National Cancer Institute, Cairo University, Al Giza 12613, Egypt;
| | - Wael El-Sheshtawy
- Department of Medical Oncology, Faculty of Medicine, Al Azhar University, Cairo 11651, Egypt;
| | - Bshra A. Alsfouk
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia; (B.A.A.); (A.S.)
| | - Asmaa Saleh
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia; (B.A.A.); (A.S.)
| | - Hoda A. Salem
- Department of Pharmacy Practice, University of Tabuk, Tabuk 47512, Saudi Arabia;
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Somlyai G, Papp A, Somlyai I, Kovács BZ, Debrődi M. Real-World Data Confirm That the Integration of Deuterium Depletion into Conventional Cancer Therapy Multiplies the Survival Probability of Patients. Biomedicines 2025; 13:876. [PMID: 40299476 PMCID: PMC12025113 DOI: 10.3390/biomedicines13040876] [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: 03/06/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Over thirty years of basic research has demonstrated that the deuterium-to-hydrogen ratio plays a pivotal role in regulating metabolism and cell growth via a sub-molecular regulatory system that orchestrates the intricate complexity of life in eukaryotic organisms. Deuterium depletion, achieved through deuterium-depleted water (DDW), has shown anticancer effects in vitro, in vivo, and in Phase 2 prospective and retrospective clinical studies. Methods: In this population-based observational study, 2649 cancer patients undergoing conventional therapy and consuming DDW were included between October 1992 and October 2024. With various cancer types and stages and conventional therapies received, they are representing a broad spectrum of the Hungarian cancer population. Survival was selected as the primary endpoint, and the median survival time (MST) of these patients and various subgroups was calculated and compared to the overall Hungarian cancer population's MST of 2.4 years. Results: For the entire study population, MST from diagnosis was 12.4 years (95% CI: 9.8-14.9), and from the initiation of DDW treatment, 7.6 years (95% CI: 5.9-9.3). Conclusions: Utilizing DDW enables targeted intervention in the sub-molecular regulatory system, paving the way for innovative therapeutic applications and a more profound understanding of cellular processes. Integrating deuterium depletion into conventional cancer therapies has the potential to significantly enhance survival rates and reduce cancer-related mortality by 75-80%.
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Affiliation(s)
- Gábor Somlyai
- HYD LLC for Cancer Research and Drug Development, Villányi út 97, 1118 Budapest, Hungary (B.Z.K.); (M.D.)
| | - András Papp
- Department of Public Health, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary;
| | - Ildikó Somlyai
- HYD LLC for Cancer Research and Drug Development, Villányi út 97, 1118 Budapest, Hungary (B.Z.K.); (M.D.)
| | - Beáta Zs Kovács
- HYD LLC for Cancer Research and Drug Development, Villányi út 97, 1118 Budapest, Hungary (B.Z.K.); (M.D.)
| | - Mária Debrődi
- HYD LLC for Cancer Research and Drug Development, Villányi út 97, 1118 Budapest, Hungary (B.Z.K.); (M.D.)
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10
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Kumar S, Noushad N, Viswanathan MP, Raj A. Surgical Outcomes and Survival in Pancreatic and Periampullary Cancers: A Single Centre Experience. Indian J Surg Oncol 2025; 16:621-626. [PMID: 40337025 PMCID: PMC12052644 DOI: 10.1007/s13193-024-02116-4] [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: 05/27/2023] [Accepted: 10/14/2024] [Indexed: 05/09/2025] Open
Abstract
Pancreatic cancer is an aggressive malignancy with many cases diagnosed at locally advanced stages making pancreaticoduodenectomy a technically challenging surgery with significant mortality and morbidity. This study analyses the surgical outcomes and survival after surgery for pancreatic cancers from a single centre in south India. This is a retrospective analysis of pancreatic and periampullary cancer patients who were treated in our institute between January 2014 and November 2022 (n = 71). The median age at diagnosis was 55 years. In about 2/3rd of cases, tumour was located in periampullary region and 62 out of 71 patients underwent curative resection. The most common histopathological diagnosis was adenocarcinoma (87%). Nodal metastasis were detected in 13% of specimens. The predominant morbidity was delayed gastric emptying (DGE 12.7%) and clinically relevant postoperative pancreatic fistula (CR-POPF 11%) with a combined overall morbidity of 35.2% and 30-day mortality of 7.3%. Pre-op nutritional status had a strong association with postoperative morbidity. The median time of survival was 20 months, with a median follow-up of 22 months. Age less than 60 years (P value = 0.0264) and receiving all 6 or more cycles of chemo were significantly associated with improved survival (P value = 0.0297). Lower-stage cancers (T1, T2, and N0) were associated with better survival. The patient characteristics, histological factors, and perioperative outcomes were similar to the reports from other Indian studies. The 3-year survival rate was 30%. There was an increasing trend of survival in patients with age less than 60 years and in patients who received 6 or more cycles of chemotherapy.
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Affiliation(s)
- Suresh Kumar
- Department of Surgical Oncology, Tamil Nadu Government Multi Super Specialty Hospital, Chennai, Tamil Nadu India
| | - Navin Noushad
- Department of Surgical Oncology, Tamil Nadu Government Multi Super Specialty Hospital, Chennai, Tamil Nadu India
| | - M. P. Viswanathan
- Department of Surgical Oncology, Tamil Nadu Government Multi Super Specialty Hospital, Chennai, Tamil Nadu India
| | - Arvind Raj
- Department of Surgical Oncology, Tamil Nadu Government Multi Super Specialty Hospital, Chennai, Tamil Nadu India
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11
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Pérez M, Lozano JJ, Ingelmo-Torres M, Domenech M, Fernández Ramón C, Witjes JA, van der Heijden AG, Requena MJ, Coy A, Calderon R, Mellado B, Alcaraz A, Vilaseca A, Ribal MJ. Biomarker-Based Nomogram to Predict Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer. Biomedicines 2025; 13:740. [PMID: 40149716 PMCID: PMC11939915 DOI: 10.3390/biomedicines13030740] [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: 02/17/2025] [Revised: 03/02/2025] [Accepted: 03/11/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: The aim of this study was to identify response prediction and prognostic biomarkers in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). Methods: A retrospective multicentre study including 191 patients with MIBC who received NAC previous to radical cystectomy (RC) between 1996 and 2013. Gene expression patterns were analysed in 34 samples from transurethral resection of the bladder (TURB) using Illumina microarrays. The expression levels of 45 selected differentially expressed genes between responders and non-responders to NAC were validated by quantitative PCR in an independent cohort of 157 patients. Regression analysis was used to identify predictors of downstaging and relapse. A nomogram for predicting downstaging and relapse-including clinicopathological and gene expression variables-was developed. Results: The expression levels of 1352 transcripts differed between responders and non-responders to NAC. A nomogram based on the most predictive clinical variables (age, Tis (in situ), gender, history of NMIBC, and lymphadenopathy) and genes selected following the Akaike information criterion (AIC) (CBTB16, CHMP6, DDX54, CASP8, LOR, and PLEC) was then created. In addition, a three-gene expression prognostic model to predict tumour relapse was generated. This model was able to discriminate between two groups of patients with a significantly different probability of tumour relapse (HR: 2.11; CI: 1.16-3.83, p = 0.01). Conclusions: Our nomogram based on gene expression and clinical data is a useful tool to predict downstaging and tumour relapse after NAC in MIBC patients. Further validation is warranted.
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Affiliation(s)
- Meritxell Pérez
- Department of Urology, Hospital Universitari Terrassa, 08221 Terrassa, Spain;
| | - Juan José Lozano
- Plataforma Bioinformatica, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Mercedes Ingelmo-Torres
- Department of Urology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Montserrat Domenech
- Medical Oncology Department, Fundació Althaia, Xarxa Assintencial Universitària de Manresa, 08242 Manresa, Spain
| | - Caterina Fernández Ramón
- Urology Department, Fundació Althaia, Xarxa Assintencial Universitària de Manresa, 08242 Manresa, Spain
| | - J. Alfred Witjes
- Department of Urology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | | | - Maria José Requena
- Department of Urology, Reina Sofía University Hospital, IMIBIC, Cordoba University, 14014 Córdoba, Spain
| | - Antonio Coy
- Fundación Instituto Valenciano de Oncologia (IVO), 46009 Valencia, Spain
| | - Ricard Calderon
- Department of Urology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Begoña Mellado
- Translational Genomics and Targeted Therapeutics in Solid Tumors, Medical Oncology Department, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic de Barcelona, 08036 Barcelona, Spain
- Uro-Oncology Unit, Medical Oncology Department, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Antonio Alcaraz
- Uro-Oncology Unit, Department of Urology, Hospital Clinic de Barcelona, 08036 Barcelona, Spain
| | - Antoni Vilaseca
- Uro-Oncology Unit, Department of Urology, Hospital Clinic de Barcelona, 08036 Barcelona, Spain
| | - Maria J. Ribal
- Uro-Oncology Unit, Department of Urology, Hospital Clinic de Barcelona, 08036 Barcelona, Spain
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12
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Vásquez LI, Saiz M, Arroyave I. Advances and challenges of reducing adult educational inequalities in stomach cancer: a time series study, Colombia, 1998-2015. CIENCIA & SAUDE COLETIVA 2025; 30:e23962021. [PMID: 40136186 DOI: 10.1590/1413-81232025303.23962021] [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: 12/21/2022] [Accepted: 12/21/2023] [Indexed: 03/27/2025] Open
Abstract
Trends in educational inequalities in adult (25 years old and over) gastric cancer mortality by sex and age group in Colombia from 1998-2015 were analyzed. An ecological time series study was conducted using Colombian vital statistics and official population estimations. Age-standardized mortality rates (ASMR per 100,000 person-years) for gastric cancer were calculated separately by educational level, sex, and grouped age. A Poisson regression model was used to calculate rates ratios (RR) and the Relative Index of Inequalities (RII). The changes over time of the ASMR and RII were analyzed using a joinpoint analysis. During the study period, 80,520 deaths from gastric cancer were recorded among adults, 60% among men. Higher ASMRs were found in the lower educational levels. The inequality measured by the RII was lower among women compared to men. Young and middle-aged men suffered from the highest relative inequalities, while older men bore the toll of higher mortality rates and a greater increase in relative inequalities. It is necessary to address public health programs aimed at strengthening the quality of life of the populations identified as at risk of stomach cancer.
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Affiliation(s)
| | - Martha Saiz
- Universidad Pedagógica y Tecnológica de Colombia. Tunja Boyacá Colombia
| | - Ivan Arroyave
- National School of Public Health, University of Antioquia. Calle 62 #52-59. 050010474 Medellin Colombia.
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Kim J, Park SY, Kim JH, Lee SW, Park JY, Kim JH, Kim YM, Kim DY. Real-world efficacy and toxicity of olaparib maintenance therapy in Korean ovarian cancer patients with an exploratory analysis of BRCA mutations. Gynecol Oncol 2025; 194:25-32. [PMID: 39923681 DOI: 10.1016/j.ygyno.2025.01.013] [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: 11/06/2024] [Revised: 12/17/2024] [Accepted: 01/28/2025] [Indexed: 02/11/2025]
Abstract
OBJECTIVE To evaluate the real-world efficacy and toxicity of olaparib maintenance therapy in Korean patients with BRCA-mutated ovarian cancer (OC), with an exploratory analysis of BRCA mutations. METHODS We conducted a retrospective analysis of Korean BRCA-mutated OC patients treated with olaparib maintenance therapy as first-line (1Lm) or second-/subsequent-line (2Lm +) at Asan Medical Center, South Korea, from August 2015 to April 2023. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), as well as toxicity, were analyzed with patient characteristics and BRCA mutations. RESULTS In 1Lm (n = 70), the 2-year PFS was 75.5 % and the 3-year OS was 98.5 %. In 2Lm + (n = 83), the 2-year PFS was 54.8 % and the 3-year OS was 87.3 %. The pathogenic p.Leu1780Pro BRCA1 mutation was a poor prognostic factor for PFS in 1Lm (hazard ratio [HR], 5.66). In 2Lm +, platinum-free interval ≥ 12 months was associated with better PFS (adjusted HR [aHR], 0.48) and OS (aHR, 0.31), whereas CA-125 ≥ 10 IU/mL at olaparib initiation was a poor prognostic factor (aHR, 2.12). A longer time interval between the last chemotherapy and maintenance therapy in 1Lm correlated with reduced hematologic toxicity ≥ grade 3 (odd ratio, 0.75) during maintenance therapy. Drug discontinuation due to toxicity occurred in 1.4 % of 1Lm and 6.0 % of 2Lm + . CONCLUSIONS Olaparib maintenance therapy was effective and tolerable in Korean BRCA-mutated OC patients, though the poor prognosis of the p.Leu1780Pro BRCA1 mutation in 1Lm warrants further investigation.
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Affiliation(s)
- Junhwan Kim
- Center for Gynecologic Cancer, National Cancer Center, Goyang 10408, Republic of Korea
| | - So-Yeon Park
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Ju-Hyun Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Shin-Wha Lee
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jeong-Yeol Park
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jong-Hyeok Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Yong-Man Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Dae-Yeon Kim
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
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Cochetti G, Guadagni L, Paladini A, Russo M, La Mura R, Vitale A, Saqer E, Mangione P, Esposito R, Gioè M, Pastore F, De Angelis L, Ricci F, Vannuccini G, Mearini E. An Evaluation of Serum miRNA in Renal Cell Carcinoma: A Systematic Review. Cancers (Basel) 2025; 17:816. [PMID: 40075664 PMCID: PMC11898939 DOI: 10.3390/cancers17050816] [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: 01/15/2025] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
Background: In recent years, research has highlighted the importance of microRNAs (miRNAs) in the context of oncological diseases, including renal cell carcinoma (RCC). The aim of this systematic review of the literature was to analyze the main serum miRNAs involved in RCC and their potential diagnostic power. Methods: This systematic review was performed following the PROSPERO protocol CRD42024550709. Literature search strategies were developed composing strings with text words related to serum miRNA in RCC for PubMed, EMBASE and Clinicaltrial.gov. The studies enrolling adult populations with RCC and healthy controls measuring circulating miRNAs were included. Results: We found 500 records, and 26 papers were included after screening. Four studies found that miR-210, the most investigated miRNA, was overexpressed in RCC patients compared to controls, while one reported no statistical difference. The expression of some miRNAs was consistently lower in cases compared to healthy controls, such as miR-1-3p and miR-129-5p, while others (miR-221, miR-222, miR-224-5p and miR-1233) were consistently upregulated. Conclusions: Circulating miRNAs represent a promising avenue for the non-invasive diagnosis of RCC. Future research should focus on standardization, validation in larger cohorts and the development of multi-marker diagnostic panels to address these current limitations and pave the way for miRNA-based diagnostics in RCC.
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Affiliation(s)
| | | | - Alessio Paladini
- Urology Clinic, Department of Medicine and Surgery, Santa Maria della Misericordia Hospital, University of Perugia, 06129 Perugia, Italy; (G.C.); (L.G.); (M.R.); (R.L.M.); (A.V.); (E.S.); (P.M.); (R.E.); (M.G.); (F.P.); (L.D.A.); (F.R.); (G.V.); (E.M.)
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15
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Wang YY, Xie ZN, Cao YQ, Dai ZK, Ye HF. Comparing the outcomes of robotic vs. open partial nephrectomy in obese patients: a meta-analysis and systematic review. J Robot Surg 2025; 19:76. [PMID: 39976852 DOI: 10.1007/s11701-025-02237-0] [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: 01/02/2025] [Accepted: 02/09/2025] [Indexed: 05/10/2025]
Abstract
This meta-analysis examines and compares the perioperative results (such as complications, recovery, and other surgical outcomes) in obese patients who undergo either robotic-assisted partial nephrectomy (RPN) or open partial nephrectomy (OPN). Essentially, the study is looking at how these two types of surgeries perform in obese patients, specifically focusing on outcomes related to the surgery process itself. We conducted a comprehensive search of major databases, including PubMed, Cochrane Library, and Web of Science, focusing on English studies, up to November 2024. Review articles, research protocols without published data, conference abstracts, and irrelevant studies were excluded. We performed data analysis using the Cochran-Mantel-Haenszel method and random-effects models, followed by mean differences, inverse variance, and 95% confidence intervals (CIs). The results were presented as odds ratios (ORs) and 95% CIs, and data with p values less than 0.05 were identified. This meta-analysis included three cohort studies with a total of 604 patients. Compared to OPN, RPN was associated with significantly shorter hospital stays (WMD - 2.27, 95% CI - 3.67 to - 0.87; p = 0.002), lower overall complication rates (OR 0.50, 95% CI 0.34-0.73; p = 0.0004), and reduced estimated blood loss (WMD - 125.12, 95% CI - 198.02 to - 52.22; p = 0.0008). No significant differences were found between the two groups in transfusion rates, major complications, renal ischemia times, or operative times. RPN offers a safe and feasible option for obese patients compared to OPN, with advantages such as shorter hospital stays, reduced blood loss, and fewer overall complications.
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Affiliation(s)
- Yan-Yan Wang
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhen-Ni Xie
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yi-Qin Cao
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhi-Kai Dai
- North Sichuan Medical College, Nanchong, China
| | - Hong-Fang Ye
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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16
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Tampakoudis G, Anastasiou OE. Trends in Human Papillomavirus-Related Health Burden in Greece from 1996 to 2021 with a Focus on Cervical and Lip, Oral Cavity, and Pharyngeal Cancer. Pathogens 2025; 14:197. [PMID: 40005573 PMCID: PMC11858740 DOI: 10.3390/pathogens14020197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/13/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
This study aimed to evaluate the burden of HPV-related hospitalization and mortality in Greece, with a focus on invasive cervical cancer and lip, oral cavity, and pharyngeal (LOCP) cancers. A retrospective query using data from the Greek Statistical Office and Eurostat was executed. The query included hospital admission and standardized mortality rates (SDRs) on cervical dysplasia and cervical, vulvar, and vaginal; anal; penile; and LOCP cancers. The hospitalization rate for invasive cervical cancer decreased over time, exhibiting a sharp decrease after 2010, while the hospitalization rate for LOCP cancer decreased after 2011, preceded by a sustained increase from 1996. The hospitalization rate of HPV-attributable diseases in total showed a declining tendency between 2013 and 2017. SDR due to cervical cancer showed a slightly decreasing trend in Greece and the European Union, while SDR due to LOCP cancer showed a slightly increasing trend in Greece, but a decrease in the European Union. The decline in hospitalization rates for HPV-related disease in Greece, especially for cervical cancer and dysplasia, and also the declining SDR for invasive cervical cancer in Greece and the EU, are indications of the positive public health impact of screening programs and the implementation of HPV vaccination.
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Affiliation(s)
- Georgios Tampakoudis
- Maternal-Fetal Medicine and Obstetrics Saint Luke’s Hospital, 55236 Thessaloniki, Greece;
- Obstetrics and Gynecology Unit, General Hospital of Goumenissa, 61300 Kilkis, Greece
| | - Olympia E. Anastasiou
- Institute for Virology, Essen University Hospital, University of Duisburg-Essen, 45147 Essen, Germany
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Tang X, Dang S, Qiu J, Zhou R, Ling J, Zhang L, Peng X, Li Q, Liu J, Liao W, Mei Q, Xie M, Sun Y, Huang J, Du X, Song W. Calcium-dependent adhesion protein CDH18, a potential biomarker for prognosis in uterine corpus endometrial carcinoma. Front Mol Biosci 2025; 12:1530253. [PMID: 40017628 PMCID: PMC11864935 DOI: 10.3389/fmolb.2025.1530253] [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: 11/18/2024] [Accepted: 01/27/2025] [Indexed: 03/01/2025] Open
Abstract
Background Uterine corpus endometrial carcinoma (UCEC) is one of the most common cancers in women, yet lacks specific and sensitive tumor markers for diagnosis, as traditional markers like CA125 show limited specificity. This study investigates the clinical significance and prognostic value of CDH18, a calcium-dependent adhesion protein linked to tumor progression, in UCEC. Methods Clinical data from UCEC patients were sourced from The Cancer Genome Atlas (TCGA) database. Pan-cancer analysis, differential expression examination, and survival analysis were conducted to investigate the differential expression of the calcium associated protein-CDH18 and its prognostic relevance. CDH18 mutations in UCEC were examined using the cBioPortal database. Additional analyses included functional enrichment, tumor mutational burden, tumor microenvironment (TME) estimates via ESTIMATE, and immune infiltration assessment to clarify CDH18's potential mechanisms in UCEC. Drug sensitivity testing was utilized to identify more suitable therapeutic options for patients. Immunofluorescence staining (IF) and Real-Time Polymerase Chain Reaction techniques (RT-PCR) confirmed CDH18 expression in UCEC tumor. Results CDH18 expression was markedly increased in UCEC and showed a significant association with poorer prognosis, which was confirmed by our IF and RT-PCR results. Thirteen mutation sites were identified, and survival analysis showed that patients with higher CDH18 expression had shorter overall survival. The expression of CDH18 was confirmed to be an independent predictor of overall survival by multivariate COX regression analysis. Additionally, a predictive nomogram model was developed to accurately forecast outcomes for individuals with UCEC. Correlation analysis revealed that CDH18 expression exhibited a negative correlation with CD8 T cell levels and a positive correlation with resting NK cell and macrophage M2 levels. In the group with high CDH18 expression, the IC50 values for (5Z)-7-Oxozeaenol, AG-014699, CEP-701, Mitomycin C, PD-0325901, PD-0332991, PHA-665752, SL 0101-1, and SN-38 were notably elevated. Conclusion CDH18 is a novel promising biomarker in UCEC, uniquely associating tumor progression, immune modulation, and chemotherapy resistance, offering enhanced prognostic accuracy and guiding individualized therapeutic strategies for improved patient outcomes.
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Affiliation(s)
- Xiaoxuan Tang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Shanxing Dang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Jie Qiu
- School of Computer Science and Engineering, Yulin Normal University, Yulin, China
| | - Ruilan Zhou
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Jing Ling
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Limei Zhang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Xiaopeng Peng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Qingyun Li
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Jin Liu
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Wei Liao
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Qingxiu Mei
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Miao Xie
- School of Computer Science and Engineering, Yulin Normal University, Yulin, China
| | - Yehong Sun
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Jianmei Huang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Xuelian Du
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Wencong Song
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
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Başaranoğlu M, Nebioğlu A, Bozlu M, Gökçe A, Akbay E. Prevention of infectious complications after transrectal ultrasound-guided prostate biopsy: comparison of povidone-iodine, chlorhexidine, and formalin disinfection. World J Urol 2025; 43:107. [PMID: 39918597 PMCID: PMC11805847 DOI: 10.1007/s00345-025-05498-4] [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: 10/27/2024] [Accepted: 02/03/2025] [Indexed: 02/09/2025] Open
Abstract
PURPOSE We aimed to compare the efficacy of three different antiseptic methods to determine the most effective prophylactic approach to prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB). The methods evaluated were transrectal povidone-iodine injection (TRPI), biopsy needle disinfection with chlorhexidine, and biopsy needle disinfection with formalin. METHODS Between January 2018 and January 2023, 904 patients who underwent TRUS-PB were retrospectively analyzed. All patients had prophylactic antibiotic use and negative urine/rectal culture results. Patients were divided into three groups according to the antiseptic protocol: Group 1 (n = 245) received only TRPI injection into the rectum before biopsy, Group 2 (n = 295) received only chlorhexidine needle disinfection before biopsy, and Group 3 (n = 364) received only formalin needle disinfection before biopsy. The biopsy needles used in our clinic are not single-use and are used on other patients after sterilization. The primary endpoint was the incidence of infectious complications within 30 days post-procedure. Continuous variables were analyzed using the Mann-Whitney U test, while categorical variables were analyzed using the Chi-square test, and post-hoc analysis was applied for pairwise comparisons between groups. Univariate and multivariate logistic regression analysis was performed to evaluate factors associated with postoperative infection. RESULTS The overall infection rate was 20.4%. Infection rates were 4.5% in the TRPI group, 16.6% in the chlorhexidine group, and 34.1% in the formalin group (p < 0.001). The TRPI group showed significantly lower rates of all infectious complications compared to other groups. Disinfection of biopsy needles with chlorhexidine was found to be significantly more effective in preventing infectious complications compared to disinfection with formalin (p < 0.001). CONCLUSION TRPI injection before TRUS-PB appears to be more effective in preventing post-biopsy infectious complications compared to needle disinfection with chlorhexidine or formalin. This method may be considered as a preferred antiseptic approach for TRUS-PB procedures.
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Affiliation(s)
- Mert Başaranoğlu
- Department of Urology, Mersin University Faculty of Medicine, Ciftlikkoy Campus, Yenişehir, Mersin, Turkey.
| | - Ali Nebioğlu
- Department of Urology, Mersin City Training and Research Hospital, Mersin, Turkey
| | - Murat Bozlu
- Department of Urology, Mersin University Faculty of Medicine, Ciftlikkoy Campus, Yenişehir, Mersin, Turkey
| | - Ali Gökçe
- Department of Obstetrics and Gynecology, Ankara University Medical School, Ankara, Turkey
| | - Erdem Akbay
- Department of Urology, Mersin University Faculty of Medicine, Ciftlikkoy Campus, Yenişehir, Mersin, Turkey
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Chalopin T, Macro M, Decaux O, Royer B, Gounot R, Bobin A, Karlin L, Mohty M, Frenzel L, Perrot A, Manier S, Vincent L, Dib M, Slama B, Richez V, Allangba O, Zunic P, Newinger-Porte M, Mariette C, Joly B, Gay J, Botoc I, Malfuson JV, Garlantezec R, Hulin C. Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025; 25:e103-e109.e1. [PMID: 39462749 DOI: 10.1016/j.clml.2024.09.006] [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: 07/13/2024] [Revised: 09/02/2024] [Accepted: 09/18/2024] [Indexed: 10/29/2024]
Abstract
INTRODUCTION Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study. PATIENTS Between 2017 and 2021 we included 4383 patients of which 894 (20.3%) were aged ≥ 80 years. Four cohorts of patients aged ≥ 80 years were analysed: line 1 (L1), line 2 (L2), line 3 (L3) or line 4+ (L4+). RESULTS The proportion of patients ≥ 80 years old was 20.8% in L1, 21.3% in L2, 20.9% in L3 and 17.8% in L4+. L1 patients received more treatment including a proteasome inhibitor (PI) (42.9%), L2 patients received mainly an immunomodulator (IMID) (65.9%) or an anti-CD38 (31.5%). For L3, IMID was used in 71.4% than an anti-CD38 (33.5%). L4+ patients received a PI (40.6%), IMID (33.2%) or an anti-CD38 (29.1%). Regarding efficacy, the median progression-free survival was 18.4 months in L1, 15.1 months in L2, 10.4 months in L3 and 6.5 months in L4+. The median overall survival was 49 months in L1, 31.3 months in L2, 21.4 months in L3 and 13.6 months in L4+. CONCLUSION EMMY cohort confirmed that patients ≥ 80 years of age represent an important proportion of MM patients, in the de novo or relapse setting. This study is an important step in improving our comprehension and management of treatment in elderly patients.
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Affiliation(s)
- T Chalopin
- Service d'Hématologie et Thérapie Cellulaire, CHU Tours, Hôpital Bretonneau, Tours, France.
| | - M Macro
- Service d'hématologie, Hôpital Caen, Caen, France
| | - O Decaux
- Service d'hématologie, Hôpital Rennes, Rennes, France
| | - B Royer
- Service d'hématologie, Hôpital Saint-Louis, Paris, France
| | - R Gounot
- CHU Henri Mondor, Unité fonctionnelle Hémopathies Lymphoides, Créteil, France
| | - A Bobin
- Service d'hématologie, Hôpital Poitiers, Poitiers, France
| | - L Karlin
- Service d'hématologie, Hôpital Lyon, Lyon, France
| | - M Mohty
- Saint-Antoine Hospital (AP-HP), Sorbonne University, Paris, France
| | - L Frenzel
- Service d'hématologie, Hôpital Necker, Paris, France
| | - A Perrot
- Service d'hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O), Toulouse, France
| | - S Manier
- Service d'hématologie, Hôpital Lille, Lille, France
| | - L Vincent
- Service d'hématologie, Hôpital Montpellier, Montpelier, France
| | - M Dib
- Service d'hématologie, Hôpital Angers, Angers, France
| | - B Slama
- Service d'hématologie, Hôpital Avignon, Avignon, France
| | - V Richez
- Service d'hématologie, Hôpital Nice, Nice, France
| | - O Allangba
- Service d'hématologie, Hôpital Saint-Brieuc, Saint-Brieuc, France
| | - P Zunic
- Service d'hématologie, Hôpital Saint-Pierre, Saint-Pierre, France
| | | | - C Mariette
- Service d'hématologie, Hôpital Grenoble, Grenoble, France
| | - B Joly
- Service d'hématologie, Hôpital Corbeil-Essonnes, Corbeil-Essones, France
| | - J Gay
- Service d'hématologie, Hôpital Bayonne, Bayonne, France
| | - I Botoc
- Service d'hématologie, Hôpital Saint-Malo, Saint-Malo, France
| | - J V Malfuson
- Service d'hématologie, Hôpital Clamart, Clamart, France
| | - R Garlantezec
- Service d'hématologie, Hôpital Rennes, Rennes, France
| | - C Hulin
- Service d'hématologie, Hôpital Haut-Lévêque, Bordeaux, Pessac
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Hanf D, Fasching P, Gass P, Matthias W Beckmann, Hack CC, Heindl F, Lothar Häberle, John N, Erber R, Press MF, Rübner M, Pöschke P. Impact of CCND1 amplification on the prognosis of hormone receptor-positive, HER2-negative breast cancer patients-correlation of clinical and pathological markers. Breast Cancer Res Treat 2025; 210:125-134. [PMID: 39586971 PMCID: PMC11787164 DOI: 10.1007/s10549-024-07545-x] [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: 08/13/2024] [Accepted: 10/30/2024] [Indexed: 11/27/2024]
Abstract
PURPOSE The cyclin D1 gene (CCND1) encodes a key cell-cycle regulatory protein. Resistance to endocrine therapy is reportedly observed more often in patients with CCND1-amplified tumors. CCND1 amplification is known to be a driving event in breast cancer, but contradictory findings are reported for its association with prognosis. This study therefore investigated the prognostic value of CCND1 amplification in hormone receptor (HR)-positive breast cancer patients. METHODS A cohort of 894 unselected breast cancer patients from the Bavarian Breast Cancer Cases and Controls (BBCC) study was included. The CCND1 amplification rate was evaluated in tissue microarrays using fluorescence in situ hybridization. A CCND1/CEP11 ratio ≥ 2.0 was considered amplified. Statistical analysis was conducted on cases with ratios based on a range of 20-100 nuclei analyzed per case. A univariable Cox regression model was fitted with disease-free survival (DFS) and overall survival (OS). RESULTS CCND1 gene status was assessable in 511 patients. The CCND1 amplification rate was 12.9% (66 patients). Most patients with CCND1 amplification had luminal B-Like-(51.5%, n = 34) or luminal A-Like tumors (25.8%, n = 17), 13 patients with HER2-positive disease (19.7%) and only two patients had triple-negative tumors (3.0%). Survival analysis, focused on HR-positive, HER2-negative patients, showed no statistically significant differences in the DFS and OS with and without CCND1 amplification (P = 0.20 and 0.14, respectively, in the unadjusted analysis). CONCLUSIONS CCND1 amplification is a recurring event in breast cancer, occurring most frequently in luminal B-like and HER2-amplified subtypes. A trend toward less favorable outcomes was observed among CCND1-amplified HR-positive, HER2-negative tumors.
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Affiliation(s)
- Dorothea Hanf
- Department of Translational Medical Oncology, National Center for Tumor Diseases Dresden (NCT/UCC) and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Translational Medical Oncology, Faculty of Medicine, Carl Gustav Carus University Hospital, TUD Dresden University of Technology, Dresden, Germany
- Partner Site Dresden, German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Peter Fasching
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Paul Gass
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Matthias W Beckmann
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Carolin C Hack
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Felix Heindl
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Lothar Häberle
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Biostatistics Unit, Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Nelson John
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Biostatistics Unit, Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Ramona Erber
- Institute of Pathology, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany
| | - Michael F Press
- Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Matthias Rübner
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany
| | - Patrik Pöschke
- Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN) / Friedrich Alexander University of Erlangen-Nuremberg (FAU), Universitätsstrasse 21-23, 91054, Erlangen, Germany.
- Comprehensive Cancer Center Alliance WERA (CCC), Erlangen, Germany.
- Bavarian Center for Cancer Research (BZKF), Erlangen, Germany.
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Yu Y, Tao Y, Ma J, Li J, Song Z. Targeting the tumor microenvironment with mesenchymal stem cells based delivery approach for efficient delivery of anticancer agents: An updated review. Biochem Pharmacol 2025; 232:116725. [PMID: 39746456 DOI: 10.1016/j.bcp.2024.116725] [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: 09/02/2024] [Revised: 11/14/2024] [Accepted: 12/18/2024] [Indexed: 01/04/2025]
Abstract
Drug delivery to cancer cells continues to present a major therapeutic challenge. Mesenchymal stem cells (MSCs) possess an intrinsic ability to migrate specifically to tumor tissues, making them promising candidates for targeted drug delivery. Evidence from preclinical studies indicates that MSCs loaded with therapeutic anti-cancer agents exhibit considerable anti-tumor activity. Moreover, several clinical trials are currently evaluating their effectiveness in cancer patients. The integration of MSCs with synthetic nanoparticles (NPs) enhances their therapeutic potential, particularly through the use of cell membrane-coated NPs, which represent a significant advancement in the field. This review systematically investigates the tumor microenvironment, the sources of MSCs, the tumor homing mechanisms, and the methods of loading and releasing anticancer drugs from MSCs. Furthermore, cutting-edge strategies to improve the efficacy of MSCs based drug delivery systems (DDS) including the innovative use of MSC membrane coated nanoparticles have been discussed. The study concludes with an overview of the therapeutic use of MSCs as drug carriers, including a detailed analysis of the mechanisms by which MSCs deliver therapeutics to cancer cells, enabling targeted drug delivery. It aims to elucidate the current state of this approach, identify key areas for development, and outline potential future directions for advancing MSCs based cancer therapies.
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Affiliation(s)
- Yang Yu
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Ying Tao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - Jingru Ma
- Department of Clinical Laboratory, the Second Hospital of Jilin University, Changchun 130000, China
| | - Jian Li
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Zhidu Song
- Department of Ophthalmology, the Second Hospital of Jilin University, Changchun 130000, China.
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Rong RZ, Zhang P, Zhao M, He CE. Transperitoneal vs retroperitoneal robotic partial nephrectomy: a meta-analysis and systematic review of propensity-matched studies. J Robot Surg 2025; 19:56. [PMID: 39878809 DOI: 10.1007/s11701-025-02217-4] [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: 01/01/2025] [Accepted: 01/14/2025] [Indexed: 01/31/2025]
Abstract
The main aim of this meta-analysis is to assess and compare the impact of two different surgical approaches, transperitoneal and retroperitoneal, on perioperative outcomes in robotic partial nephrectomy. A systematic search of MEDLINE, PubMed, Google Scholar, and the Cochrane Database was conducted to identify relevant studies published between January 2000 and January 2025. Included were nine non-randomized controlled trials with a total of 2420 patients with matching propensity scores. Among these patients, 1321 had robotic TPPN and 1099 had robotic RPPN, the abbreviation for robotic partial nephrectomy. Shorter operating times, shorter hospital stays, less estimated intraoperative blood loss, and fewer total postoperative problems were related to RPPN compared to TPPN. There were no notable disparities between the two groups when comparing the duration of renal ischemia, the fall in postoperative glomerular filtration rate (GFR), the occurrence of serious postoperative sequelae, or the necessity for blood transfusions. Compared to TPPN, RPPN demonstrates certain advantages in perioperative metrics such as surgical time, hospital stay, and overall complication rates. However, further high-quality studies are needed to confirm these findings.
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Affiliation(s)
- Ruo-Zeng Rong
- Department of Urology, Zibo Central Hospital, Zibo, 255036, Shandong Province, China
| | - Pan Zhang
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Mei Zhao
- Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Cui-E He
- Department of Clinical Laboratory, Zibo Central Hospital, Zibo, 255036, Shandong Province, China.
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Gareeballah A, Gameraddin M, Alshoabi SA, Alsaedi A, Elzaki M, Alsharif W, Daoud IM, Aldahery S, Alelyani M, AbdElrahim E, Alhazmi FH, Hamd ZY, Ahmed Abouraida R, Khandaker MU, Adam M. The diagnostic performance of International Ovarian Tumor Analysis: Simple Rules for diagnosing ovarian tumors-a systematic review and meta-analysis. Front Oncol 2025; 14:1474930. [PMID: 39902128 PMCID: PMC11788135 DOI: 10.3389/fonc.2024.1474930] [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: 08/02/2024] [Accepted: 12/17/2024] [Indexed: 02/05/2025] Open
Abstract
INTRODUCTION Adnexal masses are a common health issue in gynecology; the challenge lies in the differential diagnosis of these masses. The International Ovarian Tumor Analysis Simple Rules (IOTA-SR) offers the first scoring system to aid in diagnosis. It is based on a set of five ultrasound imaging features indicative of a malignant ovarian tumor and five features indicative of a benign tumor. This review aims to assess the diagnostic performance of IOTA-SR for classifying ovarian tumors as benign or malignant. METHODS A systematic review was conducted on MEDLINE, Embase, Google Scholar, Scopus, and Web of Science. The terminologies "IOTA-SR", "adnexal, mass", and "ovarian tumors scoring" were employed. Twenty-seven research articles conducted from 2008 to 2022 were included in the meta-analysis; the publication outcome indicates that performance quality tests were extracted directly or indirectly, including true positive (TP), false positive (FP), true negative (TN), and false negative (FN). The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the study quality and estimate the risk of bias. After estimating the pooled effect of the sensitivity, specificity, and diagnostic odds ratio (DOR), the summary receiver operating characteristic (SROC) curve was estimated using the bivariate random effects model. Utilizing Cochran's Q statistics and Higgins's inconsistency test through the I2 index for pooled analysis, the heterogeneity of studies was quantitatively evaluated. The funnel plot and Egger's test were utilized to visually and quantitatively evaluate potential publication bias. RESULTS Among 27 studies, including 7,841 adnexal masses, the results of this meta-analysis showed excellent diagnostic performance with a pooled sensitivity of 92% [95% confidence interval (CI), 0.89-0.94] and a pooled specificity of 92% (95% CI, 0.89-0.94). The IOTA-SR was applicable in 85.7% of adnexal masses. CONCLUSION The IOTA-SR is highly effective in the presurgical differentiation of malignant versus benign adnexal masses when applied by an expert ultrasonography operator.
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Affiliation(s)
- Awadia Gareeballah
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Moawia Gameraddin
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
- Faculty of Radiological Sciences and Medical Imaging, Alzaiem Alazhari University, Khartoum, Sudan
| | - Sultan Abdulwadoud Alshoabi
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Amirah Alsaedi
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Maisa Elzaki
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Walaa Alsharif
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Ibrahim Mohamed Daoud
- Department of Obstetrics and Gynecology, Faculty of Medicine, Alneelain University, Khartoum, Sudan
- Department of Obstetrics and Gynecology, Batterjee Medical College (BMC), Abha, Saudi Arabia
| | - Shrooq Aldahery
- Department of Applied Radiologic Technology, College of Applied Medical Sciences, University of Jeddah, Jeddah, Saudi Arabia
| | - Magbool Alelyani
- Department of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Elrashed AbdElrahim
- Radiological Sciences Department, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Fahad H. Alhazmi
- Department of Diagnostic Radiology, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
| | - Zuhal Y. Hamd
- Department of Radiological Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Raga Ahmed Abouraida
- Department of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway, Malaysia
- Faculty of Graduate Studies, Daffodil International University, Savar, Bangladesh
- Department of Physics, College of Science, Korea University, Seoul, Republic of Korea
| | - Mohamed Adam
- Department of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
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Ataollahi F, Amirheidari B, Amirheidari Z, Ataollahi M. Clinical and mechanistic insights into biomedical application of Se-enriched probiotics and biogenic selenium nanoparticles. Biotechnol Lett 2025; 47:18. [PMID: 39826010 DOI: 10.1007/s10529-024-03559-z] [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: 06/14/2024] [Revised: 11/13/2024] [Accepted: 12/16/2024] [Indexed: 01/20/2025]
Abstract
Selenium is an essential element with various industrial and medical applications, hence the current considerable attention towards the genesis and utilization of SeNPs. SeNPs and other nanoparticles could be achieved via physical and chemical methods, but these methods would not only require expensive equipment and specific reagents but are also not always environment friendly. Biogenesis of SeNPs could therefore be considered as a less troublesome alternative, which opens an excellent window to the selenium and nanoparticles' world. bSeNPs have proved to exert higher bioavailability, lower toxicity, and broader utility as compared to their non-bio counterparts. Many researchers have reported promising features of bSeNP such as anti-oxidant and anti-inflammatory, in vitro and in vivo. Considering this, bSeNPs have been tried as effective agents for health disorders, especially as constituents of probiotics. This article briefly reviews selenium, selenium nanoparticles, Se-enriched probiotics, and bSeNPs' usage in an array of health disorders. Obviously, there are very many articles on bSeNPs, but we wanted to summarize studies on prominent bSeNPs features published in the twenty-first century. This review is hoped to give an outlook to researchers for their future investigations, ultimately serving better care of health disorders.
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Affiliation(s)
- Farshid Ataollahi
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Bagher Amirheidari
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Medical University Campus, Haft-Bagh Highway, Kerman, 76169-13555, Iran.
| | - Zohreh Amirheidari
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahshid Ataollahi
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Xu L, Hu B, He J, Fu X, Liu N. Intratumor microbiome-derived butyrate promotes chemo-resistance in colorectal cancer. Front Pharmacol 2025; 15:1510851. [PMID: 39881872 PMCID: PMC11774648 DOI: 10.3389/fphar.2024.1510851] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 11/14/2024] [Indexed: 01/31/2025] Open
Abstract
Introduction Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally. Although tumor immunotherapy is widely recognized for treating unresectable CRC, challenges such as ineffective immunotherapy and drug resistance remain prevalent. While intratumor microbiome-derived butyrate has been implicated in promoting lung cancer metastasis, its role in CRC chemoresistance is not well understood. This study aimed to explore the relationship between intratumor butyrate and chemoresistance in CRC. Methods We performed a comprehensive analysis of the microbiome composition in CRC patients with varying resistance-free survival (RFS) durations, utilizing 16S rRNA sequencing. Furthermore, we assessed the prognostic significance of circulating microbiome DNA (cmDNA) and examined the effects of exogenous butyrate supplementation on the chemosensitivity of CRC cell lines. Results Our 16S sequencing analysis revealed a reduction in microbial diversity within tumor samples of patients with resistance, as indicated by metrics such as observed taxonomic units, Shannon, and Simpson indices. Notably, Roseburia and Fusobacteria emerged as prominent biomarkers for the resistance group, whereas Bifidobacterium, Helicobacter, and Akkermansia were identified as biomarkers for the non-resistant group. Utilizing a Lasso regression model, we identified six genera-Roseburia, Helicobacter, Gardnerella, Flavonifractor, Coprococcus, and Anaerostipes-that significantly correlated with recurrence-free survival. Furthermore, both the intratumor microbiome signature and circulating microbiome DNA were effective in accurately predicting CRC resistance. Experimental assays, including CCK8 and wound-healing, demonstrated that intratumor microbiome-derived butyrate enhances the proliferation and migration of HCT15 cells in a time- and concentration-dependent manner. Cell survival analysis further indicated that butyrate treatment significantly increased the IC50 value, suggesting heightened drug resistance in HCT15 cells. Mechanistically, this resistance was attributed to butyrate's activation of the PI3K-AKT signaling pathway. Conclusion Our results suggest that intratumor microbiome-derived butyrate contributes to chemoresistance in colorectal cancer, highlighting the potential prognostic and therapeutic significance of the intratumor microbiome.
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Affiliation(s)
- Linsheng Xu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Gastroenterology, Anqing 116 Hospital, Anqing, China
| | - Bingde Hu
- Department of Gastroenterology, Anqing 116 Hospital, Anqing, China
| | - Jingli He
- Department of Gastroenterology, Anqing 116 Hospital, Anqing, China
| | - Xin Fu
- Department of Gastroenterology, Anqing 116 Hospital, Anqing, China
| | - Na Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Davila-Batista V, Viallon V, Fontvieille E, Jansana A, Kohls M, Bondonno NP, Tjønneland A, Dahm CC, Antoniussen CS, Katzke V, Bajrachaya R, Schulze MB, Agnoli C, Ricceri F, Panico S, Zamora-Ros R, Rodriguez-Barranco M, Amiano P, Chirlaque MD, Moreno-Iribas C, Papier K, Tsilidis KK, Aune D, Gunter MJ, Weiderpass E, Jenab M, Ferrari P, Freisling H. Associations between cardiometabolic comorbidities and mortality in adults with cancer: multinational cohort study. BMJ MEDICINE 2025; 4:e000909. [PMID: 40151205 PMCID: PMC11948348 DOI: 10.1136/bmjmed-2024-000909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 02/24/2025] [Indexed: 03/29/2025]
Abstract
ABSTRACT Objective To examine separate and joint associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer. Design Multinational cohort study. Setting Seven European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1 January 1992 to 31 December 2013. Participants 26 987 participants (54% women) who developed a first primary cancer. 2113 had a history of type 2 diabetes, 1529 had a history of cardiovascular disease, and 531 had a history of both, at the time of diagnosis of cancer. Main outcome measures Hazard ratios (95% confidence intervals, CIs) for associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer, estimated with multivariable Cox regression models. Associations were also estimated by groups of five year relative survival of cancer (survival ≤40%, 40-80%, and ≥80%) according to Surveillance, Epidemiology, and End Results (SEER) statistics, and for the most common site specific cancers. Results At the time of diagnosis of cancer, 84.5% (n=22 814) of participants had no history of a cardiometabolic disease, 7.8% (n=2113) had a history of type 2 diabetes, 5.7% (n=1529) had a history of cardiovascular disease, and 2.0% (n=531) had a history of both cardiovascular disease and type 2 diabetes. 12 782 deaths (10 492 cancer deaths) occurred over a mean follow-up period of 7.2 years. After multivariable adjustments, pre-existing comorbidities were positively associated with all cause mortality, with hazard ratios 1.25 (95% CI 1.17 to 1.34), 1.30 (1.21 to 1.39), and 1.60 (1.42 to 1.80) for participants with type 2 diabetes, cardiovascular disease, or both, respectively, compared with participants with no cardiometabolic comorbidity. Corresponding hazard ratios for cancer specific mortality were 1.13 (95% CI 1.05 to 1.22), 1.13 (1.04 to 1.23), and 1.33 (1.16 to 1.53), respectively. Associations for all cause mortality were stronger among participants with cancers with a five year relative survival ≥80%. In a subsample, duration of type 2 diabetes (Pinteraction=0.73) or cardiovascular disease (Pinteraction=0.24), categorised as <5 years or ≥5 years, did not modify associations between these comorbidities and all cause mortality. Conclusions In this study, cardiovascular disease or type 2 diabetes, or a combination of both, before a diagnosis of cancer, was associated with increased mortality (all cause mortality, and cancer and cardiovascular disease specific mortality). These findings support a direct role of cardiometabolic comorbidities on the prognosis of cancer.
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Affiliation(s)
- Veronica Davila-Batista
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
- University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
- Instituto de Salud Carlos III, Madrid, Spain
| | - Vivian Viallon
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Emma Fontvieille
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Anna Jansana
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Mirjam Kohls
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
- LMU Munich, Munich, Germany
| | | | - Anne Tjønneland
- Danish Cancer Society, Copenhagen, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | | | | | - Verena Katzke
- German Cancer Research Centre (DKFZ), Heidelberg, Germany
| | | | - Matthias B Schulze
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- University of Potsdam, Potsdam, Germany
| | - Claudia Agnoli
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Salvatore Panico
- Università degli Studi di Napoli Federico II Dipartimento di Medicina Clinica e Chirurgia, Napoli, Italy
| | - Raul Zamora-Ros
- Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Miguel Rodriguez-Barranco
- Instituto de Salud Carlos III, Madrid, Spain
- Escuela Andaluza de Salud Publica, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada, Granada, Spain
| | - Pilar Amiano
- Instituto de Salud Carlos III, Madrid, Spain
- Ministry of Health of the Basque Government, San Sebastian, Spain
| | | | - Conchi Moreno-Iribas
- Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Pamplona, Spain
| | - Keren Papier
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Konstantinos K Tsilidis
- Imperial College London, London, UK
- University of Ioannina Faculty of Medicine, Ioannina, Greece
| | - Dagfinn Aune
- Imperial College London, London, UK
- Oslo New University College, Oslo, Norway
- Cancer Registry of Norway, Oslo, Norway
| | - Marc J Gunter
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Imperial College London, London, UK
| | | | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Pietro Ferrari
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
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Pan X, Guo X, Wang J, Yang C, Chen M, Qiu H, Wu Q. Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers. Int Immunopharmacol 2024; 143:113268. [PMID: 39357206 DOI: 10.1016/j.intimp.2024.113268] [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: 06/19/2024] [Revised: 09/24/2024] [Accepted: 09/24/2024] [Indexed: 10/04/2024]
Abstract
BACKGROUND Immunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. METHODS We retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. RESULTS A total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74-22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). CONCLUSIONS The combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.
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Affiliation(s)
- Xinyu Pan
- School of Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xiaowan Guo
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Juan Wang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Chunxu Yang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Min Chen
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Hui Qiu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
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Wan X, Deng Q, Chen A, Zhang X, Yang W. Bioinformatics analysis and experimental validation of the oncogenic role of COL11A1 in pan-cancer. 3 Biotech 2024; 14:290. [PMID: 39507058 PMCID: PMC11534945 DOI: 10.1007/s13205-024-04133-0] [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: 07/11/2024] [Accepted: 10/19/2024] [Indexed: 11/08/2024] Open
Abstract
The intricate expression patterns and oncogenic attributes of COL11A1 across different cancer types remain largely elusive. This study used several public databases (TCGA, GTEx, and CCLE) to investigate the pan-cancer landscape of COL11A1 expression, its prognostic implications, interplay with the immune microenvironment, and enriched signaling cascades. Concurrently, western blot analyses were performed to verify COL11A1 expression in lung adenocarcinoma (LUAD) cell lines and clinical samples. In addition, COL11A1 knockout cell lines were generated to scrutinize the functional consequences of COL11AI expression on cancer cell behavior by use MTT, colony formation, and scratch wound healing assays. A comprehensive database investigation revealed that COL11A1 was upregulated in a majority of tumor tissues and its expression was highly correlated with a patient's prognosis. Notably, genetic alterations in COL11A1 predominantly occurred as mutations, while its DNA methylation status inversely mirrored gene expression levels across multiple promoter regions. Our findings suggest that COL11A1 helps to modulate the tumor immune landscape and potentially acts through the epithelial-mesenchymal transition (EMT) pathway to exert its oncogenic function. Western blot analyses further substantiated the specific upregulation of COL11A1 in LUAD cell lines and tissues, suggesting a close association with the EMT process. Ablation of COL11A1 in cancer cells significantly reduced their proliferative, clonogenic, and migratory abilities, underscoring the functional significance of COL11A1 in tumor cell behavior. Collectively, this research revealed the prevalent overexpression of COL11A1 in pan-cancer tissues, its profound prognostic and microenvironmental correlations, and the mechanistic underpinnings of its tumor-promoting effects as mediated via EMT signaling. Our findings suggest that COL11A1 could serve as a prognostic and diagnostic biomarker and therapeutic target for cancer.
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Affiliation(s)
- Xiaofeng Wan
- Department of Laboratory, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui China
| | - Qingmei Deng
- Department of Laboratory, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui China
| | - Anling Chen
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031 Anhui China
- Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, China
| | - Xinhui Zhang
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031 Anhui China
| | - Wulin Yang
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031 Anhui China
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Figaroa O, Zondervan P, Kessels R, Berkhof J, Aarts M, Hamberg P, Los M, Piersma D, Rikhof B, Suelmann B, Tascilar M, van der Veldt A, Verhagen P, Westgeest H, Yildirim H, Bex A, Bins A. PrimerX: A Bayesian Multistage Cohort Embedded Randomised Trial to Evaluate the Role of Deferred Local Therapy of the Primary Tumour in Combination with Immune Checkpoint Inhibitor-based First-line Therapy in Metastatic Renal Cell Carcinoma Patients. EUR UROL SUPPL 2024; 70:28-35. [PMID: 39483517 PMCID: PMC11525453 DOI: 10.1016/j.euros.2024.09.002] [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: 09/19/2024] [Indexed: 11/03/2024] Open
Abstract
Background Historically, patients with metastatic renal cell carcinoma (mRCC) have been offered upfront cytoreductive nephrectomy (CN) followed by systemic therapy. Currently, CN is no longer the standard of care (SOC) based on the randomised phase 3 CARMENA study performed in the vascular endothelial growth factor receptor tyrosine kinase inhibitor era. With the advent of immune checkpoint inhibitor (ICI) combination therapy in first line, the role of CN needs to be reassessed. There is indirect evidence from small retrospective series that deferred CN after ICI combination therapy may lead to better outcomes. To reassess the role of CN, we designed PrimerX, a randomised controlled trial following the Trial within Cohorts (TwiCs) study design. The primary objective of this study is to re-evaluate the benefit of deferred local treatment in the current era of immunotherapy. Study design This PrimerX study has been designed as a TwiCs study within the Dutch Prospective Renal Cell Carcinoma (PRO-RCC) cohort. The PRO-RCC cohort includes patients with mRCC and nonmetastatic RCC, and has been set up for prospective collection of long-term clinical data and as an infrastructure for initiating TwiCs studies. The PrimerX TwiCs trial follows a Bayesian adaptive multistage design to allow for early discontinuation due to futility or efficacy. PrimerX has appropriate ethics approval and is registered at clinical.trials.gov (NCT05941169). End points The primary clinical endpoint is overall survival, defined as the time from randomisation to death from any cause. The secondary endpoint is the objective response rate within the primary tumour prior to local therapy, as assessed by a computed tomography scan. Patients and methods A maximum of 700 patients with synchronous mRCC and absence of progression at metastatic sites following at least 6 mo of standard first-line ICI combination therapy will be assigned randomly to receive local treatment of the primary tumour (experimental arm) or SOC (control arm). The experimental intervention consists of (partial) CN, any form of ablative local therapy, or magnetic resonance imaging guided ablative stereotactic radiotherapy, performed within 6 mo and 1.5 yr after the start of systemic treatment.
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Affiliation(s)
- Orlane Figaroa
- Department of Medical Oncology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
- Department of Urology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Patricia Zondervan
- Department of Urology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | - Rob Kessels
- Julius Center for Health Sciences and Primary Care, Department of Data Science and Biostatistics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Johannes Berkhof
- Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit, Amsterdam, The Netherlands
| | - Maureen Aarts
- Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Paul Hamberg
- Department of Internal Medicine, Franciscus Gasthuis, Vlietland, Rotterdam/Schiedam, The Netherlands
| | - Maartje Los
- Department of Medical Oncology, St. Antonius Ziekenhuis, Nieuwegein/Utrecht, The Netherlands
| | - Djura Piersma
- Department of Medical Oncology, Medical Spectrum Twente, Enschede, The Netherlands
| | - Bart Rikhof
- Department of Medical Oncology, Leeuwarden Medical Center, Leeuwarden, The Netherlands
| | - Britt Suelmann
- Department of Medical Oncology, Utrecht University Medical Centre, Utrecht, The Netherlands
| | - Metin Tascilar
- Department of Medical Oncology, Isala Medical Centre, Zwolle, The Netherlands
| | - Astrid van der Veldt
- Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Paul Verhagen
- Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Hans Westgeest
- Department of Medical Oncology, Amphia Medical Centre, Breda, The Netherlands
| | - Hilin Yildirim
- Department of Medical Oncology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Axel Bex
- Department of Urology, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Specialist Centre for Kidney Cancer, The Royal Free London NHS Foundation Trust, London, UK
| | - Adriaan Bins
- Department of Medical Oncology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam University Medical Centres, Amsterdam, The Netherlands
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Kim J, Ham WS, Koo KC, Lee J, Ahn HK, Jeong JY, Baek SY, Lee SJ, Lee KS. Evaluation of the Diagnostic Efficacy of the AI-Based Software INF-M01 in Detecting Suspicious Areas of Bladder Cancer Using Cystoscopy Images. J Clin Med 2024; 13:7110. [PMID: 39685568 DOI: 10.3390/jcm13237110] [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: 10/16/2024] [Revised: 11/18/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objectives: We aimed to evaluate the accuracy of the artificial intelligence (AI)-based software INF-M01 in diagnosing suspected bladder tumors using cystoscopy images. Additionally, we aimed to assess the ability of INF-M01 to distinguish and mark suspected bladder cancer using whole cystoscopy images. Methods: A randomized retrospective clinical trial was conducted using a total of 5670 cystoscopic images provided by three institutions, comprising 1890 images each (486 bladder cancer images and 1404 normal images). The images were randomly distributed into five sets (A-E), each containing 1890 photographs. INF-M01 analyzed the images in set A to evaluate sensitivity, specificity, and accuracy. Sets B to E were analyzed by INF-M01 and four urologists, who marked the suspected bladder tumors. The Dice coefficient was used to compare the ability to differentiate bladder tumors. Results: For set A, the sensitivity, specificity, accuracy, and 95% confidence intervals were 0.973 (0.955-0.984), 0.921 (0.906-0.934), and 0.934 (0.922-0.945), respectively. The mean value of the Dice coefficient of AI was 0.889 (0.873-0.927), while that of clinicians was 0.941 (0.903-0.963), indicating that AI showed a reliable ability to distinguish bladder tumors from normal bladder tissue. AI demonstrated a sensitivity similar to that of urologists (0.971 (0.971-0.983) vs. 0.921 (0.777-0.995)), but a lower specificity (0.920 (0.882-0.962) vs. 0.991 (0.984-0.996)) compared to the urologists. Conclusions: INF-M01 demonstrated satisfactory accuracy in the diagnosis of bladder tumors. Additionally, it displayed an ability to distinguish and mark tumor regions from normal bladder tissue, similar to that of urologists. These results suggest that AI has promising diagnostic capabilities and clinical utility for urologists.
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Affiliation(s)
- Jongchan Kim
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Department of Urology, Yongin Severance Hospital, Yonsei University Health System, Yongin 16995, Republic of Korea
| | - Won Sik Ham
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Kyo Chul Koo
- Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
| | - Jongsoo Lee
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hyun Kyu Ahn
- Department of Urology, Ewha Womans University Seoul Hospital, Seoul 07804, Republic of Korea
| | - Jae Yong Jeong
- Department of Urology, National Health Insurance Service Ilsan Hospital, Goyang 10444, Republic of Korea
| | | | - Su Jin Lee
- Infinyx Corporation, Daegu 42988, Republic of Korea
| | - Kwang Suk Lee
- Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
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Grigorascu S, Langbein T, Rauscher I, D'Alessandria C, Maurer T, Hekimsoy T, Weber WA, Eiber M. Influence of fasting prior to 18F-rhPSMA-7.3 (Flotufolastat F-18) PET/CT on biodistribution and tumor uptake. EJNMMI Res 2024; 14:104. [PMID: 39531171 PMCID: PMC11557739 DOI: 10.1186/s13550-024-01165-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 08/29/2024] [Indexed: 11/16/2024] Open
Affiliation(s)
- Sonia Grigorascu
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
| | - Thomas Langbein
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Isabel Rauscher
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Calogero D'Alessandria
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Tobias Maurer
- Department of Urology and Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Türkay Hekimsoy
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Wolfgang A Weber
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - Matthias Eiber
- School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
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Brassetti A, Cacciatore L, Proietti F, Pallares-Méndez R, Bove AM, Anceschi U, Mastroianni R, Misuraca L, Tuderti G, Chiacchio G, Ferriero M, Flammia RS, Leonardo C, Simone G. The Role of Robotic Cystectomy in the Salvage and Palliative Setting: A Retrospective, Single-Center, Cohort Study. Cancers (Basel) 2024; 16:3784. [PMID: 39594739 PMCID: PMC11592956 DOI: 10.3390/cancers16223784] [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: 09/30/2024] [Revised: 11/06/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Introduction: This article compares surgical and survival outcomes of robot-assisted and open radical cystectomy with cutaneous ureterostomy for the treatment of frail bladder cancer patients with limited life expectancy. Methods: The institutional database was searched for cystectomy cases with cutaneous ureterostomy, from 1 June 2016 to 31 August 2022. The study population was split into two groups, according to the surgical approach. The baseline characteristics and surgical outcomes were compared. Logistic regression analyses identified predictors of major bleeding events (hemoglobin loss ≥ 3.5 g/dL or blood transfusion) and re-operation within 30 days from surgery. The Kaplan-Meier method estimated the impact of the robotic approach on overall survival and Cox regression analysis assessed its predictors. Results: A total of 145 patients were included: 30% (n = 43) underwent robotic cystectomy. Patients' characteristics and tumor stages distribution were comparable in the two groups but those receiving a minimally invasive treatment showed significantly reduced times to flatus, bowel and hospital discharge (all p < 0.001). Although operation times were longer in this cohort, major bleeding events (60% vs. 89%) and postoperative severe complications (0 vs. 8%) (both p < 0.001) were less frequent compared to the open approach. A logistic regression showed that robotic surgery independently predicted major bleeding events (OR: 0.26; 95%CI 0.09-0.72; p = 0.02) but not the need for re-intervention. A Kaplan-Meier analysis showed that robotic cystectomy was associated with a significant advantage in terms of overall survival (LogRank = 0.03), and this result was confirmed by Cox regression analysis (HR: 0.39; 95%CI 0.14-0.94; p = 0.04). Conclusions: Robotic cystectomy with cutaneous ureterostomy may represent a viable option to treat frail bladder cancer patients, as the minimally invasive approach reduces the risk of bleeding and serious complications and provides a prompt restoration of bowel function and a shorter hospital stay compared to open surgery.
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Affiliation(s)
| | - Loris Cacciatore
- Department of Urology, IRCCS “Regina Elena” National Cancer Institute, 00144 Rome, Italy; (A.B.); (F.P.); (R.P.-M.); (A.M.B.); (U.A.); (R.M.); (L.M.); (G.T.); (G.C.); (M.F.); (R.S.F.); (C.L.); (G.S.)
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Gugu Nkosi PW, Chandran R, Abrahamse H. Hypocrellin: A Natural Photosensitizer and Nano-Formulation for Enhanced Molecular Targeting of PDT of Melanoma. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1997. [PMID: 39568119 PMCID: PMC11579242 DOI: 10.1002/wnan.1997] [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: 04/11/2024] [Revised: 06/29/2024] [Accepted: 09/10/2024] [Indexed: 11/22/2024]
Abstract
Nano-formulation has generated attention in the battle against cancer, because of its great flexibility, reduced adverse side effects, and accuracy in delivering drugs to target tissues dependent on the size and surface characteristics of the disease. The field of photodynamic treatment has advanced significantly in the past years. Photodynamic techniques that use nano-formulations have surfaced to further the field of nanotechnology in medicine, especially in cancer treatment. The pharmaceutical industry is seeing a growing trend toward enhanced drug formulation using nano-formulations such as liposomes, polymeric nanoparticles, dendrimers, nano-emulsions, and micelles. Natural extracts have also shown adverse effects when employed as photosensitizers in cancer therapy because they are cytotoxic when activated by light. Still, natural photosensitizers are a big part of cancer treatment. However, some shortcomings can be minimized by combining nano-formulations with these natural photosensitizers. The synergistic improvement in medication delivery that maintains or increases the mechanism of cell death in malignant cells has also been demonstrated by the combination of photodynamic therapy with nano-formulations and natural photosensitizers. Lastly, this review assesses the feasibility and potential of a photodynamic therapy system based on nano-formulations and natural photosensitizers in clinical treatment applications and briefly discusses the removal of toxic compounds associated with nano-formulations within cells.
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Affiliation(s)
| | - Rahul Chandran
- Laser Research Centre, Faculty of Health SciencesUniversity of JohannesburgDoornfonteinSouth Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health SciencesUniversity of JohannesburgDoornfonteinSouth Africa
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Firouzjaei AA, Mohammadi-Yeganeh S. The intricate interplay between ferroptosis and efferocytosis in cancer: unraveling novel insights and therapeutic opportunities. Front Oncol 2024; 14:1424218. [PMID: 39544291 PMCID: PMC11560889 DOI: 10.3389/fonc.2024.1424218] [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: 05/01/2024] [Accepted: 10/04/2024] [Indexed: 11/17/2024] Open
Abstract
The complex interplay between ferroptosis and efferocytosis in cancer has attracted significant interest recently. Efferocytosis, the process of eliminating apoptotic cells, is essential for preserving tissue homeostasis and reducing inflammation. However, dysregulation of efferocytosis can have profound effects on cancer. Apoptotic cells accumulate because of impaired efferocytosis, which triggers chronic inflammation and the release of pro-inflammatory chemicals. Surprisingly, accumulating evidence suggests that dysregulation of ferroptosis- a form of controlled cell death characterized by lipid peroxidation and the buildup iron-dependent reactive oxygen species (ROS)-can influence efferocytic activities within the tumor microenvironment. Dysfunctional iron metabolism and increased lipid peroxidation, are associated with ferroptosis, resulting in inadequate apoptotic cell clearance. Conversely, apoptotic cells can activate ferroptotic pathways, increasing oxidative stress and inducing cell death in cancer cells. This reciprocal interaction emphasizes the complex relationship between efferocytosis and ferroptosis in cancer biology. Understanding and managing the delicate balance between cell clearance and cell death pathways holds significant therapeutic potential in cancer treatment. Targeting the efferocytosis and ferroptosis pathways may offer new opportunities for improving tumor clearance, reducing inflammation, and sensitizing cancer cells to therapeutic interventions. Further research into the interaction between efferocytosis and ferroptosis in cancer will provide valuable insights for the development of novel therapies aimed at restoring tissue homeostasis and improving patient outcomes.
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De Marco P, Ricciardi V, Montesano M, Cassano E, Origgi D. Transfer learning classification of suspicious lesions on breast ultrasound: is there room to avoid biopsies of benign lesions? Eur Radiol Exp 2024; 8:121. [PMID: 39466515 PMCID: PMC11519280 DOI: 10.1186/s41747-024-00480-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/19/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Breast cancer (BC) is the most common malignancy in women and the second cause of cancer death. In recent years, there has been a strong development in artificial intelligence (AI) applications in medical imaging for several tasks. Our aim was to evaluate the potential of transfer learning with convolutional neural networks (CNNs) in discriminating suspicious breast lesions on ultrasound images. METHODS Transfer learning performances of five different CNNs (Inception V3, Xception, Densenet121, VGG 16, and ResNet50) were evaluated on a public and on an institutional dataset (526 and 392 images, respectively), customizing the top layers for the specific task. Institutional images were contoured by an expert radiologist and processed to feed the CNNs for training and testing. Postimaging biopsies were used as a reference standard for classification. The area under the receiver operating curve (AUROC) was used to assess diagnostic performance. RESULTS Networks performed very well on the public dataset (AUROC 0.938-0.996). The direct generalization to the institutional dataset resulted in lower performances (max AUROC 0.676); however, when tested on BI-RADS 3 and BI-RADS 5 only, results were improved (max AUROC 0.792). Good results were achieved on the institutional dataset (AUROC 0.759-0.818) and, when selecting a threshold of 2% for classification, a sensitivity of 0.983 was obtained for three of five CNNs, with the potential to spare biopsy in 15.3%-18.6% of patients. CONCLUSION In conclusion, transfer learning with CNNs may achieve high sensitivity and might be used as a support tool in managing suspicious breast lesions on ultrasound images. RELEVANCE STATEMENT Transfer learning is a powerful technique to exploit the performances of well-trained CNNs for image classification. In a clinical scenario, it might be useful for the management of suspicious breast lesions on breast ultrasound, potentially sparing biopsy in a non-negligible number of patients. KEY POINTS Properly trained CNNs with transfer learning are highly effective in differentiating benign and malignant lesions on breast ultrasound. Setting clinical thresholds increased sensitivity. CNNs might be useful as support tools in managing suspicious lesions on breast ultrasound.
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Affiliation(s)
- Paolo De Marco
- Medical Physics Unit, IEO European Institute of Oncology IRCCS, Milan, Italy.
| | - Valerio Ricciardi
- Medical Physics Unit, IEO European Institute of Oncology IRCCS, Milan, Italy
- Medical Physics School, University of Milan, Milan, Italy
| | - Marta Montesano
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Enrico Cassano
- Breast Imaging Division, Radiology Department, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Daniela Origgi
- Medical Physics Unit, IEO European Institute of Oncology IRCCS, Milan, Italy
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Wang S, Bai Y, Ma J, Qiao L, Zhang M. Long non-coding RNAs: regulators of autophagy and potential biomarkers in therapy resistance and urological cancers. Front Pharmacol 2024; 15:1442227. [PMID: 39512820 PMCID: PMC11540796 DOI: 10.3389/fphar.2024.1442227] [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: 06/01/2024] [Accepted: 10/14/2024] [Indexed: 11/15/2024] Open
Abstract
The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm. LncRNAs do not translate to proteins and they have been implicated in the regulation of tumorigenesis. On the other hand, One way cells die is by a process called autophagy, which breaks down proteins and other components in the cytoplasm., while the aberrant activation of autophagy allegedly involved in the pathogenesis of diseases. The autophagy exerts anti-cancer activity in pre-cancerous lesions, while it has oncogenic function in advanced stages of cancers. The current overview focuses on the connection between lncRNAs and autophagy in urological cancers is discussed. Notably, one possible role for lncRNAs is as diagnostic and prognostic variablesin urological cancers. The proliferation, metastasis, apoptosis and therapy response in prostate, bladder and renal cancers are regulated by lncRNAs. The changes in autophagy levels can also influence the apoptosis, proliferation and therapy response in urological tumors. Since lncRNAs have modulatory functions, they can affect autophagy mechanism to determine progression of urological cancers.
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Affiliation(s)
- Shizong Wang
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Yang Bai
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Jie Ma
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Liang Qiao
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
| | - Mingqing Zhang
- Department of Urology, Weifang People’s Hospital, Weifang, Shandong, China
- Shangdong Provincial Key Laboratory for Prevention and Treatment of Urological Diseases in Medicine and Health, Weifang, Shandong, China
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Khaleel AQ, Alshahrani MY, Rizaev JA, Malathi H, Devi S, Pramanik A, Mustafa YF, Hjazi A, Muazzamxon I, Husseen B. siRNA-based strategies to combat drug resistance in gastric cancer. Med Oncol 2024; 41:293. [PMID: 39428440 DOI: 10.1007/s12032-024-02528-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: 08/17/2024] [Accepted: 09/27/2024] [Indexed: 10/22/2024]
Abstract
Chemotherapy is a key treatment option for gastric cancer, but over 50% of patients develop either inherent or acquired resistance to these drugs, resulting in a 5-year survival rate of only about 20%. The primary treatment for advanced gastric cancer typically involves chemotherapy based on platinum or fluorouracil. Several factors can contribute to platinum resistance, including decreased drug uptake, increased drug efflux or metabolism, enhanced DNA repair, activation of pro-survival pathways, and inhibition of pro-apoptotic pathways. In recent years, there has been significant progress in biology aimed at finding innovative and more effective methods to overcome chemotherapy resistance. Small interfering RNAs (siRNAs) have emerged as a significant advancement in gene expression regulation, showing promise in enhancing the sensitivity of gastric cancer cells to chemotherapy drugs. However, siRNA therapies still face major challenges, particularly in terms of stability and efficient delivery in vivo. This article discusses the advances in siRNA therapy and its potential role in overcoming resistance to chemotherapeutic drugs such as cisplatin, 5-FU, doxorubicin, and paclitaxel in the treatment of gastric cancer.
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Affiliation(s)
- Abdulrahman Qais Khaleel
- Department of Medical Instruments Engineering, College of Engineering, University of Al Maarif, Ramadi, Al Anbar, 31001, Iraq.
| | - Mohammad Y Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Jasur Alimdjanovich Rizaev
- Department of Public Health and Healthcare Management, Rector, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, Uzbekistan.
| | - H Malathi
- Department of Biotechnology and Genetics, School of Sciences Jain (Deemed to be University), Bangalore, Karnataka, India
| | - Seema Devi
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjheri, Mohali, 140307, Punjab, India
| | - Atreyi Pramanik
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | - Ismoilova Muazzamxon
- Department of Propaedeutics of Internal Diseases, Fergana Medical Institute of Public Health, Fergana, Uzbekistan
- Western Caspian University, Scientific Researcher, Baku, Azerbaijan
| | - Beneen Husseen
- Medical Laboratory Technique College, the Islamic University, Najaf, Iraq
- Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical Laboratory Technique College, the Islamic University of Babylon, Babylon, Iraq
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Hosseini FS, Nikparast A, Etesami E, Javaheri-Tafti F, Asghari G. The association between empirical dietary inflammatory pattern and risk of cancer and cancer-specific mortality: a systematic review and meta-analysis of prospective cohort studies. Front Nutr 2024; 11:1462931. [PMID: 39494310 PMCID: PMC11527705 DOI: 10.3389/fnut.2024.1462931] [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: 07/10/2024] [Accepted: 10/01/2024] [Indexed: 11/05/2024] Open
Abstract
Background/aim Current evidence indicates a correlation between the inflammatory potential of diet and the risk of cancer and cancer-specific mortality. This study aimed to assess the association between empirical dietary inflammatory pattern (EDIP), which has recently been designed based on the inflammatory potential of the diet, and the risk of cancer and cancer-specific mortality. Methods A systematic literature search was conducted across the PubMed/Medline, Scopus, and Web of Science databases from January 2016 to March 2024. A random effects model was used to calculate the pooled effect size (ES) and 95% confidence intervals (95% CI). Heterogeneity between studies was assessed using the Cochran Q test and the I 2 statistic. Results From the initial 229 records, 24 prospective cohort studies with 2,683,350 participants and 37,091 cancer incidence cases, as well as 20,819 cancer-specific mortality, were included in our study. Pooled results indicated a significant association between higher adherence to the EDIP and an increased risk of total cancer (ES: 1.10; 95% CI: 1.05-1.15; I 2 = 41.1), colorectal cancer (ES: 1.19; 95% CI: 1.11-1.27; I 2 = 41.1), and liver cancer (ES: 1.48; 95% CI: 1.14-1.94; I 2 = 36.9). However, no significant association between increased adherence to the EDIP and an increased risk of ovarian or endometrial cancer was found. Furthermore, greater adherence to the EDIP was significantly associated with an increased risk of cancer-specific mortality (ES: 1.18; 95% CI: 1.05-1.33; I 2 = 45.4). Conclusion Our results showed that a diet with higher inflammatory properties is associated with an increased risk of cancer and cancer-specific mortality. Systematic review registration PROSPERO registration no. CRD42024496912.
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Affiliation(s)
- Fatemeh S. Hosseini
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Ali Nikparast
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elahe Etesami
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Javaheri-Tafti
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golaleh Asghari
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Longo F, Panza E, Rocca L, Biffoni B, Lucinato C, Cintoni M, Mele MC, Papa V, Fiorillo C, Quero G, De Sio D, Menghi R, Alfieri S, Langellotti L. Enhanced Recovery After Surgery (ERAS) in Pancreatic Surgery: The Surgeon's Point of View. J Clin Med 2024; 13:6205. [PMID: 39458155 PMCID: PMC11508928 DOI: 10.3390/jcm13206205] [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: 09/08/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Pancreatic surgery is complex and associated with higher rates of morbidity and mortality compared to other abdominal surgeries. Over the past decade, the introduction of new technologies, such as minimally invasive approaches, improvements in multimodal treatments, advancements in anesthesia and perioperative care, and better management of complications, have collectively improved patient outcomes after pancreatic surgery. In particular, the adoption of Enhanced Recovery After Surgery (ERAS) recommendations has reduced hospital stays and improved recovery times, as well as post-operative outcomes. The aim of this narrative review is to highlight the surgeon's perspective on the ERAS program for pancreatic surgery, with a focus on its potential advantages for perioperative functional recovery outcomes.
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Affiliation(s)
- Fabio Longo
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Edoardo Panza
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Lorenzo Rocca
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Beatrice Biffoni
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Chiara Lucinato
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Marco Cintoni
- UOC Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (M.C.); (M.C.M.)
- Centro di Ricerca e Formazione in Nutrizione Umana, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Cristina Mele
- UOC Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (M.C.); (M.C.M.)
- Centro di Ricerca e Formazione in Nutrizione Umana, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Valerio Papa
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 4, 00168 Roma, Italy
| | - Claudio Fiorillo
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 4, 00168 Roma, Italy
| | - Davide De Sio
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
| | - Roberta Menghi
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 4, 00168 Roma, Italy
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 4, 00168 Roma, Italy
| | - Lodovica Langellotti
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (E.P.); (L.R.); (B.B.); (C.L.); (V.P.); (C.F.); (G.Q.); (D.D.S.); (R.M.); (S.A.); (L.L.)
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van den Brink L, Debelle T, Gietelink L, Graafland N, Ruiter A, Bex A, Beerlage HP, van Moorselaar RJA, Lagerveld B, Zondervan P. A National Study of the Rate of Benign Pathology After Partial Nephrectomy for T1 Renal Cell Carcinoma: Should We Be Satisfied? Cancers (Basel) 2024; 16:3518. [PMID: 39456612 PMCID: PMC11506599 DOI: 10.3390/cancers16203518] [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: 09/02/2024] [Revised: 09/16/2024] [Accepted: 09/18/2024] [Indexed: 10/28/2024] Open
Abstract
Objectives: To determine the rate of benign pathology in cT1 tumors following partial nephrectomy in the Netherlands, thereby evaluating the rate of overtreatment. Methods: Data were collected from a nationwide database containing histopathology of resected renal tissue from 2014 to 2022. Patients who underwent partial nephrectomy for suspected RCC staged T1a-b were extracted for analysis. Data are shown in percentages, and multivariable logistic regression was performed to determine predictive factors for benign pathology. Results: 3409 cases were analyzed, of which 403 (12%) were benign and 3006 (88%) malignant. Subtype analysis showed 2126 (62%) cases of clear-cell RCC, followed by 604 (18%) of papillary RCC and 344 (10%) oncocytomas. Mean age was 63 years among patients with malignant pathology versus 65 years for patients with benign lesions (p < 0.001). Mean tumor size was 3.2 cm for malignant pathology and 2.9 cm for benign (p < 0.001). The rates of benign and malignant pathology did not change between 2014 and 2022 (p = 0.377). Multivariable regression showed age ≥ 65 years (65-79 years [OR 1.881, p = 0.002], ≥ 80 years [OR 3.642, p < 0.001]) and tumor size (OR 0.793, p < 0.001) as predictors for benign pathology. The main limitation of this study is that we do not know the biopsy rate of our cohort. Conclusion: This study reports a low rate of 12% benign pathology after partial nephrectomy in the Netherlands. It remains debatable whether these rates are acceptable, or if renal tumor biopsies should be utilized more frequently to reduce overtreatment.
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Affiliation(s)
- Luna van den Brink
- Department of Urology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
- Department of Urology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, 1081 HV Amsterdam, The Netherlands
| | - Tess Debelle
- Department of Urology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Lieke Gietelink
- Department of Urology, Spaarne Gasthuis, 2035 RC Haarlem, The Netherlands
| | - Niels Graafland
- Department of Urology, Netherlands Cancer Institute (NKI), 1066 CX Amsterdam, The Netherlands
| | - Annebeth Ruiter
- Department of Urology, OLVG, 1091 AC Amsterdam, The Netherlands
| | - Axel Bex
- Department of Urology, Netherlands Cancer Institute (NKI), 1066 CX Amsterdam, The Netherlands
- Department of Urology, Royal Free Hospital, London NW3 2QG, UK
| | - Harrie P. Beerlage
- Department of Urology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | | | | | - Patricia Zondervan
- Department of Urology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
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Xavier SP, da Silva KM, Galvão ND, das Neves MAB, de Queiroz Neves Almeida A, Mario Cândido da Silva A. Time to death from cervical cancer and its predictors in hospitalized patients: a survival approach study in Mato Grosso, Brazil. World J Surg Oncol 2024; 22:269. [PMID: 39385163 PMCID: PMC11463162 DOI: 10.1186/s12957-024-03518-y] [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: 07/11/2024] [Accepted: 09/01/2024] [Indexed: 10/11/2024] Open
Abstract
BACKGROUND Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023. METHODS Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed. RESULTS The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12-36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40-59 years (AHR = 1.39, p = 0.027) and 60-74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001). CONCLUSION This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services.
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Affiliation(s)
- Sancho Pedro Xavier
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil.
| | - Kátia Moreira da Silva
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil
| | - Noemi Dreyer Galvão
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil
- State Secretary of Health of Mato Grosso, Cuiabá, Mato Grosso, Brazil
| | - Marco Aurélio Bertúlio das Neves
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil
- State Secretary of Health of Mato Grosso, Cuiabá, Mato Grosso, Brazil
| | - Adila de Queiroz Neves Almeida
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil
| | - Ageo Mario Cândido da Silva
- Institute of Collective Health, Federal University of Mato Grosso, Av. Fernando Correa da Costa, nº 2367 - Bairro Boa Esperança, Cuiabá, Mato Grosso, 78060-900, Brazil
- State Secretary of Health of Mato Grosso, Cuiabá, Mato Grosso, Brazil
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Bojarska J, Breza M, Borowiecki P, Madura ID, Kaczmarek K, Ziora ZM, Wolf WM. An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions. ROYAL SOCIETY OPEN SCIENCE 2024; 11:40962. [PMID: 39386982 PMCID: PMC11462612 DOI: 10.1098/rsos.240962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 10/12/2024]
Abstract
Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular 'chameleonicity' related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the (R)-(2-tert-butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene (1), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C-H…O and C-O…π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of 'atoms-in-molecules' (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand-protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood-brain barrier permeation was also revealed.
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Affiliation(s)
- Joanna Bojarska
- Chemistry Department, Institute of Ecological and Inorganic Chemistry, Technical University of Lodz, 116 Zeromskiego St., Lodz90-924, Poland
| | - Martin Breza
- Department of Physical Chemistry, Slovak Technical University, Radlinskeho 9, BratislavaSK-81237, Slovakia
| | - Paweł Borowiecki
- Laboratory of Biocatalysis and Biotransformation, Department of Drugs Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, 75 Koszykowa St., Warsaw00-662, Poland
| | - Izabela D. Madura
- Faculty of Chemistry, Warsaw University of Technology, 3 Noakowskiego St., Warsaw00-664, Poland
| | - Krzysztof Kaczmarek
- Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Zeromskiego St., Lodz90-924, Poland
| | - Zyta M. Ziora
- Institute for Molecular Bioscience, The University of Queensland, St LuciaQLD 4072, Australia
| | - Wojciech M. Wolf
- Chemistry Department, Institute of Ecological and Inorganic Chemistry, Technical University of Lodz, 116 Zeromskiego St., Lodz90-924, Poland
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Kiss Z, Szabó TG, Polgár C, Horváth Z, Nagy P, Fábián I, Kovács V, Surján G, Barcza Z, Kenessey I, Wéber A, Wittmann I, Molnár GA, Gyöngyösi E, Benedek A, Karamousouli E, Abonyi-Tóth Z, Bertókné Tamás R, Fürtős DV, Bogos K, Moldvay J, Gálffy G, Tamási L, Müller V, Krasznai ZT, Ostoros G, Pápai-Székely Z, Maráz A, Branyiczkiné Géczy G, Hilbert L, Tamás Berki L, Rokszin G, Vokó Z. Revising cancer incidence in a Central European country: a Hungarian nationwide study between 2011-2019 based on a health insurance fund database. Front Oncol 2024; 14:1393132. [PMID: 39411131 PMCID: PMC11474687 DOI: 10.3389/fonc.2024.1393132] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 08/27/2024] [Indexed: 10/19/2024] Open
Abstract
Background The nationwide HUN-CANCER EPI study examined cancer incidence and mortality rates in Hungary from 2011 to 2019. Methods Using data from the National Health Insurance Fund (NHIF) and Hungarian Central Statistical Office (HCSO), our retrospective study analyzed newly diagnosed malignancies between Jan 1, 2011, and Dec 31, 2019. Age-standardized incidence and mortality rates were calculated for all and for different tumor types using both the 1976 and 2013 European Standard Populations (ESP). Findings The number of newly diagnosed cancer cases decreased from 60,554 to 56,675 between 2011-2019. Age-standardized incidence rates were much lower in 2018, than previously estimated (475.5 vs. 580.5/100,000 person-years [PYs] in males and 383.6 vs. 438.5/100,000 PYs in females; ESP 1976). All-site cancer incidence showed a mean annual decrease of 1.9% (95% CI: 2.4%-1.4%) in men and 1.0% (95% CI:1.42%-0.66%) in women, parallel to mortality trends (-1.6% in males and -0.6% in females; ESP 2013). In 2018, the highest age-standardized incidence rates were found for lung (88.3), colorectal (82.2), and prostate cancer (62.3) in men, and breast (104.6), lung (47.7), and colorectal cancer (45.8) in women. The most significant decreases in incidence rates were observed for stomach (4.7%), laryngeal (4.4%), and gallbladder cancers (3.5%), with parallel decreases in mortality rates (3.9%, 2.7% and 3.2%, respectively). Interpretation We found a lower incidence of newly diagnosed cancer cases for Hungary compared to previous estimates, and decreasing trends in cancer incidence and mortality, in line with global findings and the declining prevalence of smoking.
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Affiliation(s)
- Zoltán Kiss
- MSD Pharma Hungary Ltd, Budapest, Hungary
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, Pécs, Hungary
| | | | - Csaba Polgár
- National Institute of Oncology and National Tumor Biology Laboratory, Budapest, Hungary
- Department of Oncology, Semmelweis University, Budapest, Hungary
| | - Zsolt Horváth
- Department of Oncology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary
| | - Péter Nagy
- Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
- Department of Anatomy and Histology, HUN-REN–UVMB Laboratory of Redox Biology Research Group, University of Veterinary Medicine, Budapest, Hungary
- Chemistry Coordinating Institute, University of Debrecen, Debrecen, Hungary
| | - Ibolya Fábián
- RxTarget Ltd., Szolnok, Hungary
- University of Veterinary Medicine, Budapest, Hungary
| | | | - György Surján
- Department of Deputy Chief Medical Officer II., National Public Health Center, Budapest, Hungary
- Institute of Digital Health Sciences, Semmelweis University, Budapest, Hungary
| | - Zsófia Barcza
- Syntesia Medical Communications Ltd, Budapest, Hungary
| | - István Kenessey
- Hungarian National Cancer Registry and National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - András Wéber
- Hungarian National Cancer Registry and National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary
| | - István Wittmann
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, Pécs, Hungary
| | - Gergő Attila Molnár
- Second Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, Pécs, Hungary
| | | | | | | | - Zsolt Abonyi-Tóth
- RxTarget Ltd., Szolnok, Hungary
- University of Veterinary Medicine, Budapest, Hungary
| | - Renáta Bertókné Tamás
- Department of Deputy Chief Medical Officer II., National Public Health Center, Budapest, Hungary
| | - Diána Viktória Fürtős
- Department of Deputy Chief Medical Officer II., National Public Health Center, Budapest, Hungary
| | - Krisztina Bogos
- National Korányi Institute of Pulmonology, Budapest, Hungary
| | - Judit Moldvay
- 1st Department of Pulmonology, National Korányi Institute of Pulmonology, Budapest, Hungary
- Department of Pulmonology, Albert Szent-Györgyi Medical Centre, University of Szeged, Szeged, Hungary
| | - Gabriella Gálffy
- Department of Pulmonology, Pulmonology Hospital Törökbálint, Törökbálint, Hungary
| | - Lilla Tamási
- Department of Pulmonology, Semmelweis University, Budapest, Hungary
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, Budapest, Hungary
| | - Zoárd Tibor Krasznai
- Faculty of Medicine, Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, Hungary
| | - Gyula Ostoros
- National Korányi Institute of Pulmonology, Budapest, Hungary
| | - Zsolt Pápai-Székely
- Fejér County Szent György, University Teaching Hospital, Székesfehérvár, Hungary
| | - Anikó Maráz
- Department of Oncotherapy, University of Szeged, Szeged, Hungary
| | | | - Lászlóné Hilbert
- Department of Population Statistics, Hungarian Central Statistical Office, Budapest, Hungary
| | - Láśzló Tamás Berki
- Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary
| | | | - Zoltán Vokó
- Center for Health Technology Assessment, Semmelweis University, Budapest, Hungary
- Syreon Research Institute, Budapest, Hungary
- Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary
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Calvo I, González-Rodríguez M, Neria F, Gallegos I, García-Sánchez L, Sánchez-Gómez R, Pérez S, Arenas MF, Estévez LG. An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population. Clin Transl Oncol 2024; 26:2541-2548. [PMID: 38734800 PMCID: PMC11410912 DOI: 10.1007/s12094-024-03469-6] [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: 03/11/2024] [Accepted: 03/18/2024] [Indexed: 05/13/2024]
Abstract
PURPOSE Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. METHODS This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. RESULTS The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52 years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. CONCLUSIONS This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.
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Affiliation(s)
- Isabel Calvo
- Breast Cancer Unit- Oncology, MD Anderson Cancer Center, Madrid, Spain.
- Fundación MD Anderson Internacional España, Madrid, Spain.
| | - Marta González-Rodríguez
- Breast Cancer Unit- Oncology, MD Anderson Cancer Center, Madrid, Spain
- Fundación MD Anderson Internacional España, Madrid, Spain
| | - Fernando Neria
- Facultad de Medicina, Universidad Francisco de Vitoria, Madrid, Spain
| | - Isabel Gallegos
- Breast Cancer Unit- Oncology, Hospital de Segovia, Segovia, Spain
| | | | | | - Silvia Pérez
- Breast Cancer Unit- Radiology, MD Anderson Cancer Center, Madrid, Spain
| | | | - Laura G Estévez
- Breast Cancer Unit- Oncology, MD Anderson Cancer Center, Madrid, Spain
- Fundación MD Anderson Internacional España, Madrid, Spain
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Guerrero-Ramos F, González-Padilla DA, Pérez-Cadavid S, García-Rojo E, Tejido-Sánchez Á, Hernández-Arroyo M, Gómez-Cañizo C, Rodríguez-Antolín A. Muscle-Invasive Bladder Cancer in Non-Curative Patients: A Study on Survival and Palliative Care Needs. Cancers (Basel) 2024; 16:3330. [PMID: 39409950 PMCID: PMC11475499 DOI: 10.3390/cancers16193330] [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: 08/30/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
OBJECTIVE To assess the survival outcomes of patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not candidates for curative treatment and to identify the factors influencing these outcomes. METHODS We conducted an analysis of patients diagnosed with MIBC who were either unable or unwilling to undergo curative therapy. We evaluated overall survival (OS) and cancer-specific survival (CSS) and examined their associations with various clinical variables. Additionally, we assessed emergency department visits and palliative procedures. RESULTS The study included 142 patients with a median age of 79.4 years and a Charlson Comorbidity Index of 9.8. At diagnosis, 59.2% of the patients had localized disease, 23.2% had metastatic disease, and 49.3% presented with hydronephrosis. Curative treatment was excluded due to comorbidities in 40.1% of cases and advanced disease stage in 36.6%. The 1-year and 2-year OS rates were 42.8% and 23.6%, respectively, with a median survival of 10.6 months. The 1-year and 2-year CSS rates were 49.6% and 30.2%, respectively, with a median survival of 11.9 months. Worse survival outcomes were associated with advanced disease stage and the presence of hydronephrosis. Patients excluded from curative treatment solely due to age had a relatively better prognosis. On average, patients visited the emergency department three times: 19% underwent palliative transurethral resection of the bladder tumor, 14.8% received radiotherapy to control hematuria, and nephrostomy tubes were placed in 26.1% of cases. CONCLUSIONS Patients with MIBC who are unable or unwilling to undergo curative treatment have a median overall survival of less than one year, with worse outcomes observed in those with advanced disease stage and hydronephrosis.
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Affiliation(s)
- Félix Guerrero-Ramos
- Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
| | | | | | | | - Ángel Tejido-Sánchez
- Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
| | - Mario Hernández-Arroyo
- Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
| | - Carmen Gómez-Cañizo
- Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
| | - Alfredo Rodríguez-Antolín
- Department of Urology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain
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Shams A. Leveraging State-of-the-Art AI Algorithms in Personalized Oncology: From Transcriptomics to Treatment. Diagnostics (Basel) 2024; 14:2174. [PMID: 39410578 PMCID: PMC11476216 DOI: 10.3390/diagnostics14192174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Continuous breakthroughs in computational algorithms have positioned AI-based models as some of the most sophisticated technologies in the healthcare system. AI shows dynamic contributions in advancing various medical fields involving data interpretation and monitoring, imaging screening and diagnosis, and treatment response and survival prediction. Despite advances in clinical oncology, more effort must be employed to tailor therapeutic plans based on each patient's unique transcriptomic profile within the precision/personalized oncology frame. Furthermore, the standard analysis method is not compatible with the comprehensive deciphering of significant data streams, thus precluding the prediction of accurate treatment options. METHODOLOGY We proposed a novel approach that includes obtaining different tumour tissues and preparing RNA samples for comprehensive transcriptomic interpretation using specifically trained, programmed, and optimized AI-based models for extracting large data volumes, refining, and analyzing them. Next, the transcriptomic results will be scanned against an expansive drug library to predict the response of each target to the tested drugs. The obtained target-drug combination/s will be then validated using in vitro and in vivo experimental models. Finally, the best treatment combination option/s will be introduced to the patient. We also provided a comprehensive review discussing AI models' recent innovations and implementations to aid in molecular diagnosis and treatment planning. RESULTS The expected transcriptomic analysis generated by the AI-based algorithms will provide an inclusive genomic profile for each patient, containing statistical and bioinformatics analyses, identification of the dysregulated pathways, detection of the targeted genes, and recognition of molecular biomarkers. Subjecting these results to the prediction and pairing AI-based processes will result in statistical graphs presenting each target's likely response rate to various treatment options. Different in vitro and in vivo investigations will further validate the selection of the target drug/s pairs. CONCLUSIONS Leveraging AI models will provide more rigorous manipulation of large-scale datasets on specific cancer care paths. Such a strategy would shape treatment according to each patient's demand, thus fortifying the avenue of personalized/precision medicine. Undoubtedly, this will assist in improving the oncology domain and alleviate the burden of clinicians in the coming decade.
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Affiliation(s)
- Anwar Shams
- Department of Pharmacology, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; or ; Tel.: +00966-548638099
- Research Center for Health Sciences, Deanship of Graduate Studies and Scientific Research, Taif University, Taif 26432, Saudi Arabia
- High Altitude Research Center, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
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Wang D, Li Y, Chang W, Feng M, Yang Y, Zhu X, Liu Z, Fu Y. CircSEC24B activates autophagy and induces chemoresistance of colorectal cancer via OTUB1-mediated deubiquitination of SRPX2. Cell Death Dis 2024; 15:693. [PMID: 39333496 PMCID: PMC11436887 DOI: 10.1038/s41419-024-07057-y] [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: 01/17/2024] [Revised: 09/01/2024] [Accepted: 09/04/2024] [Indexed: 09/29/2024]
Abstract
Circular RNAs (circRNAs) are a type of regulatory RNA that feature covalently closed single-stranded loops. Evidence suggested that circRNAs play important roles in the progression and development of various cancers. However, the impact of circRNA on autophagy-mediated progression of colorectal cancer (CRC) remains unclear. The objective of this project was to investigate the influence of circSEC24B on autophagy and its underlying mechanisms in CRC. To validate the presence and circular structure of circSEC24B in CRC cells and tissues, PCR and Sanger sequencing techniques were employed. Drug resistance and invasive phenotype of CRC cells were evaluated using CCK8, transwell, and Edu assays. Gain- and loss-of-function experiments were conducted to assess the effects of circSEC24B and its protein partner on the growth, invasion, and metastasis of CRC cells in vitro and in vivo. Interactions between circSEC24B, OTUB1, and SRPX2 were analyzed through immunofluorescence, RNA-pulldown, and RIP assays. Mass spectrometry analysis was used to identify potential binding proteins of circRNA in CRC cells. Vectors were constructed to investigate the specific structural domain of the deubiquitinating enzyme OTUB1 that binds to circSEC24B. Results showed that circSEC24B expression was increased in CRC tissues and cell lines, and it enhanced CRC cell proliferation and autophagy levels. Mechanistically, circSEC24B promoted CRC cell proliferation by regulating the protein stability of SRPX2. Specifically, circSEC24B acted as a scaffold, facilitating the binding of OTUB1 to SRPX2 and thereby enhancing its protein stability. Additionally, evidence suggested that OTUB1 regulated SRPX2 expression through an acetylation-dependent mechanism. In conclusion, this study demonstrated that circSEC24B activated autophagy and induced chemoresistance in CRC by promoting the deubiquitination of SRPX2, mediated by the deubiquitinating enzyme OTUB1.
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Affiliation(s)
- Di Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yongge Li
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weilong Chang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Meina Feng
- Department of Neurology, Wuhan Brain Hospital, General Hospital of the YANGTZE River Shipping, Wuhan, China
| | - Yiming Yang
- Department of General Surgery, Ruijin-Hainan Hospital, Shanghai Jiao Tong University School of Medicine, Hainan, China
| | - Xiuxiang Zhu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhibo Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Yang Fu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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48
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Sarejloo S, Babadi S, Khanzadeh S, Salimi A, Clark A, Khazaeli D, Khanzadeh M, Ghaedi A, Lucke-Wold B. Diagnostic and prognostic role of NLR in testicular cancer. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2024; 5:1177-1198. [PMID: 39465013 PMCID: PMC11502077 DOI: 10.37349/etat.2024.00270] [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: 11/28/2023] [Accepted: 05/15/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND To summarize the results of available studies for investigating the role of neutrophil to lymphocyte ratio (NLR) in testicular cancer (tCa). METHODS The search was conducted on PubMed, Scopus, and Web of Science up to November 21, 2021. Finally, a total of 31 studies were included in this review. RESULTS NLR was higher in tCa patients compared to healthy controls and benign testis pathologies, and decreased significantly after orchiectomy. An elevated NLR predicts poor prognosis, advanced stage, presence of nodal or distant metastases, contralateral tumor development, lower time-to-cancer specific death, worse OS, and poorer response to chemotherapy. However, NLR could not differentiate between seminomas and non-seminomatous tCa. DISCUSSION NLR has a significant diagnostic and prognostic value in tCa.
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Affiliation(s)
- Shirin Sarejloo
- Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz 767545, Iran
| | - Saghar Babadi
- Student Research Committee, Ahvaz Jundishapur University of Medical Science, Ahvaz 868765, Iran
| | - Shokoufeh Khanzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz 585658, Iran
| | - Amirhossein Salimi
- Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd 876576, Iran
| | - Alec Clark
- University of Central Florida College of Medicine, Orlando, FL 32608, USA
| | - Dinyar Khazaeli
- Urology Department, Imam Khomeini Hospital, Ahvaz 687667, Iran
| | - Monireh Khanzadeh
- Geriatric & Gerontology Department, Medical School, Tehran University of Medical and Health Sciences, Tehran 865476, Iran
| | - Arshin Ghaedi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz 767545, Iran
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA
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Lei X, Yamamoto D, Kitamura H, Kita K, Inaki N, Murakami K, Nakayama M, Oshima H, Oshima M. Neutral selection and clonal expansion during the development of colon cancer metastasis. J Biochem 2024; 176:187-195. [PMID: 38889670 DOI: 10.1093/jb/mvae044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 05/24/2024] [Accepted: 06/12/2024] [Indexed: 06/20/2024] Open
Abstract
Intratumour heterogeneity has been shown to play a role in the malignant progression of cancer. The clonal evolution in primary cancer has been well studied, however, that in metastatic tumorigenesis is not fully understood. In this study, we established human colon cancer-derived organoids and investigated clonal dynamics during liver metastasis development by tracking barcode-labelled subclones. Long-term subclone co-cultures showed clonal drift, with a single subclone becoming dominant in the cell population. Interestingly, the selected subclones were not always the same, suggesting that clonal selection was not based on cell intrinsic properties. Furthermore, liver tumours developed by co-transplantation of organoid subclones into the immunodeficient mouse spleen showed a progressive drastic reduction in clonal diversity, and only one or two subclones predominated in the majority of large metastatic tumours. Importantly, selections were not limited to particular subclones but appeared to be random. A trend towards a reduction in clonal diversity was also found in liver metastases of multiple colour-labelled organoids of mouse intestinal tumours. Based on these results, we propose a novel mechanism of metastasis development, i.e. a subclone population of the disseminated tumour cells in the liver is selected by neutral selection during colonization and constitutes large metastatic tumours.
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Affiliation(s)
- Xuelian Lei
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Daisuke Yamamoto
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, 13-1 Takara-machi, Japan
| | - Hirotaka Kitamura
- Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, 2-1 Kuratsuki-Higashi, Kanazawa 920-8530, Japan
| | - Kenji Kita
- Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, 13-1 Takara-machi, Japan
| | - Kazuhiro Murakami
- Division of Epithelial Stem Cell Biology, Cancer Research Institute, Kakuma-machi, Kanazawa University, Kanazawa 920-1192, Japan
| | - Mizuho Nakayama
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
- WPI Nano-Life Science Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Hiroko Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
- WPI Nano-Life Science Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
| | - Masanobu Oshima
- Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
- WPI Nano-Life Science Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
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50
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Zhang Z, Gao Z, Fang H, Zhao Y, Xing R. Therapeutic importance and diagnostic function of circRNAs in urological cancers: from metastasis to drug resistance. Cancer Metastasis Rev 2024; 43:867-888. [PMID: 38252399 DOI: 10.1007/s10555-023-10152-9] [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: 06/10/2023] [Accepted: 10/31/2023] [Indexed: 01/23/2024]
Abstract
Circular RNAs (circRNAs) are a member of non-coding RNAs with no ability in encoding proteins and their aberrant dysregulation is observed in cancers. Their closed-loop structure has increased their stability, and they are reliable biomarkers for cancer diagnosis. Urological cancers have been responsible for high mortality and morbidity worldwide, and developing new strategies in their treatment, especially based on gene therapy, is of importance since these malignant diseases do not respond to conventional therapies. In the current review, three important aims are followed. At the first step, the role of circRNAs in increasing or decreasing the progression of urological cancers is discussed, and the double-edged sword function of them is also highlighted. At the second step, the interaction of circRNAs with molecular targets responsible for urological cancer progression is discussed, and their impact on molecular processes such as apoptosis, autophagy, EMT, and MMPs is highlighted. Finally, the use of circRNAs as biomarkers in the diagnosis and prognosis of urological cancer patients is discussed to translate current findings in the clinic for better treatment of patients. Furthermore, since circRNAs can be transferred to tumor via exosomes and the interactions in tumor microenvironment provided by exosomes such as between macrophages and cancer cells is of importance in cancer progression, a separate section has been devoted to the role of exosomal circRNAs in urological tumors.
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Affiliation(s)
- Zhibin Zhang
- College of Traditional Chinese Medicine, Chengde Medical College, Chengde, 067000, Hebei, China.
| | - Zhixu Gao
- Chengde Medical College, Chengde, 067000, Hebei, China
| | - Huimin Fang
- Chengde Medical College, Chengde, 067000, Hebei, China
| | - Yutang Zhao
- Chengde Medical College, Chengde, 067000, Hebei, China
| | - Rong Xing
- Chengde Medical College, Chengde, 067000, Hebei, China
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