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Chouaid C, Grossi F, Ta Thanh Minh C, Raymond R, Bosch-Barrera J. Pooled analysis of oral vinorelbine as single agents in patients with advanced NSCLC. Lung Cancer Manag 2025; 14:2477418. [PMID: 40116568 DOI: 10.1080/17581966.2025.2477418] [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: 06/21/2024] [Accepted: 03/06/2025] [Indexed: 03/23/2025] Open
Abstract
OBJECTIVES This was a pooled analysis of data from weekly vinorelbine (VNR) treatment arms of four individual open-label, phase II studies to assess and refine the efficacy and tolerance of weekly oral VNR in a larger cohort of patients with advanced NSCLC. MATERIALS AND METHODS All patients included in this pooled analysis received oral VNR at the dose of 60 mg/m2 weekly at cycle 1 (3-week cycle), followed by an increase to 80 mg/m2 weekly for subsequent cycles until disease progression or toxicity. Efficacy was based on objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR). RESULTS A total of 247 patients were included. The ORR and DCR were 8.9% and 57.5% respectively, median PFS and OS were 3.3 and 8.5 months, respectively. Less than half (40.7%) of patients reported ≥1 serious AE (regardless of causality), with 12.3% reporting ≥1 treatment-related serious AE (grade ≥3: 11.1%). The most reported grade ≥3 AEs were neutropenia (17.6%), fatigue (5.8%), and decreased appetite (4.9%). CONCLUSION This pooled analysis showed that weekly oral VRN is a valid option, with an acceptable safety profile, in this population of patients with advanced NSCLC, confirming results from previous individual studies.
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Affiliation(s)
| | - Francesco Grossi
- Department of Medicine and Technological Innovation, Università degli Studi dell'Insubria, Varese - Medical Oncology Division, ASST Sette Laghi, Varese, Italy
| | | | - Romain Raymond
- Medical & Patient/Consumer Division, Pierre Fabre, Boulogne-Billancourt, France
| | - Joaquim Bosch-Barrera
- Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital; Precision Oncology Group (OncoGIR-Pro), Institut d'Investigació Biomèdica de Girona (IDIBGI); Department of Medical Sciences, Medical School, University of Girona, Girona, Spain
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2
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Lin T, Li Z, Yuan J, Ren T, Pang W, Xu S. Design, synthesis and evaluation of diphenyl ether-based kaiso inhibitors with enhanced potency. Bioorg Med Chem Lett 2025; 121:130158. [PMID: 40049243 DOI: 10.1016/j.bmcl.2025.130158] [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: 12/12/2024] [Revised: 02/10/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025]
Abstract
Kaiso, a potential target for the treatment of lung cancer. Our research focuses on Kaiso inhibitros. Through virtual screening and molecular dynamic simulations, we discovered a promising Kaiso inhibitor called compound 5 (ZINC20577650). By modifying the structure of compound 5, a series of novel Kaiso inhibitors that contain a diphenyl ether ring were synthesized. Among them, compound 20 exhibited the strongest inhibitory activity against A549 cells (IC50 = 0.34 μM). Notably, its inhibitory activity surpassed that of the positive control MIRA-1 (IC50 = 654.065 μM). Molecular docking and dynamic studies revealed that the binding of the compound's amino and ester moieties to the active site of kaiso protein, as well as the extension of the benzene ring towards the Asn561 position in the cavity, contributed significantly to its potency. These findings provide valuable insights for the development of new Kaiso inhibitors.
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Affiliation(s)
- Taofeng Lin
- College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
| | - Zhongqi Li
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University. Nanchang, China
| | - Juanchan Yuan
- College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
| | - Tinfeng Ren
- College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
| | - Wan Pang
- College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
| | - Songhui Xu
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University. Nanchang, China; Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China.
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Hu D, Zhang Z, Wang Y, Li S, Zhang J, Wu Z, Sun M, Jiang J, Liu D, Ji X, Wang S, Wang Y, Luo X, Huang W, Xia L. Transcription factor ELF4 in physiology and diseases: Molecular roles and clinical implications. Genes Dis 2025; 12:101394. [PMID: 40083328 PMCID: PMC11904542 DOI: 10.1016/j.gendis.2024.101394] [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: 02/13/2024] [Revised: 06/21/2024] [Accepted: 07/28/2024] [Indexed: 03/16/2025] Open
Abstract
Transcription factor E74 like ETS transcription factor 4 (ELF4), a member of the ETS family, is highly expressed in normal human hematopoietic tissue, ovary, placenta, colon, and certain pathological cell lines. During normal physiological processes, ELF4 regulates differentiation in osteogenic, adipocyte, and neuronal types. It also exerts a critical impact on the development of the immune system. However, its function is dysregulated through posttranslational modifications, gene fusions, and complex signaling crosstalk under pathological conditions. Furthermore, serving as a double-edged sword in cancer, ELF4 exhibits both tumor-suppressing and tumor-promoting effects. Specifically, ELF4 plays a critical role in cancer metastasis, proliferation, and modulation of the tumor microenvironment. This review provides an in-depth overview of the molecular structure and post-translational modifications of ELF4. It also summarizes the hallmarks of ELF4 in physiology and diseases, with a particular focus on its significance in oncology. Notably, this review underscores the potential of ELF4 as a prognostic biomarker, highlighting its clinical relevance. Finally, it discusses unresolved questions and future research directions of ELF4. An in-depth understanding of ELF4 biology could facilitate its clinical translation and offer promising targeted therapeutic strategies.
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Affiliation(s)
- Dian Hu
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Zerui Zhang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Yijun Wang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Siwen Li
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Jiaqian Zhang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Zhangfan Wu
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Mengyu Sun
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Junqing Jiang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Danfei Liu
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xiaoyu Ji
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Shuai Wang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang 310006, China
| | - Yufei Wang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Xiangyuan Luo
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Wenjie Huang
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei 430030, China
| | - Limin Xia
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shannxi 710032, China
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Wang H, Wu Y, Yang Y, Pang Y, Hu H, Gou Y. Circ_DLG1 facilitates cell proliferation and metastasis of esophageal squamous cell carcinoma via upregulating MAP3K9. Esophagus 2025; 22:250-263. [PMID: 40042790 DOI: 10.1007/s10388-025-01115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 02/25/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND Circ_DLG1 is found to be aberrantly expressed in esophageal squamous cell carcinoma (ESCC) tissues, but its role in the progression of ESCC remains to be elucidated. METHODS The expression of circ_DLG1, miR-338-3p and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was measured by qRT-PCR. Cell cycle, viability, migration and invasion were investigated using flow cytometry, MTT assay and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2 (ERKs), phosphor ERKs (p-ERKs) were detected by western blot. Dual-luciferase reporter assay and RIP assay were performed to verify the putative relationship between miR-338-3p and circ_DLG1 or MAP3K9. Animal experiments were performed to ascertain the role of circ_DLG1 in vivo. RESULTS Circ_DLG1 expression was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC, and its overexpression rescued the effects of circ_DLG1 knockdown on cell proliferation and metastasis. Besides, circ_DLG1 positively regulated MAP3K9 expression by competitively targeting miR-338-3p. Also, miR-338-3p inhibition or MAP3K9 overexpression recovered the inhibiting effect of circ_DLG1 knockdown on the phosphorylated levels of p38 and ERKs. In addition, circ_DLG1 knockdown blocked the tumor growth in vivo by regulating the miR-338-3p/MAP3K9 axis. CONCLUSION Circ_DLG1 promoted malignant progression of ESCC by mediating the miR-338-3p/MAP3K9/p38/ERK pathway, indicating that targeted inhibition of the circ_DLG1/miR-338-3p/MAP3K9/p38/ERK axis might be an effective strategy for the treatment of ESCC.
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Affiliation(s)
- Huilin Wang
- Department of Thoracic Surgery 2, Gansu Provincial Hospital, No.204 Donggang West Road, Lanzhou, 730000, Gansu, China
| | - Yafan Wu
- School of Basic Medicine, Gansu Health Vocational College, Lanzhou, Gansu, China
| | - Yi Yang
- Department of Thoracic Surgery 2, Gansu Provincial Hospital, No.204 Donggang West Road, Lanzhou, 730000, Gansu, China
| | - Yao Pang
- Department of Thoracic Surgery 2, Gansu Provincial Hospital, No.204 Donggang West Road, Lanzhou, 730000, Gansu, China
| | - Hongxia Hu
- Department of Thoracic Surgery 2, Gansu Provincial Hospital, No.204 Donggang West Road, Lanzhou, 730000, Gansu, China
| | - Yunjiu Gou
- Department of Thoracic Surgery 2, Gansu Provincial Hospital, No.204 Donggang West Road, Lanzhou, 730000, Gansu, China.
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Duranti L, Tavecchio L, Rolli L, Solli P. New Perspectives on Lung Cancer Screening and Artificial Intelligence. Life (Basel) 2025; 15:498. [PMID: 40141842 DOI: 10.3390/life15030498] [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: 02/06/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Lung cancer is the leading cause of cancer-related death worldwide, with 1.8 million deaths annually. Early detection is vital for improving patient outcomes; however, survival rates remain low due to late-stage diagnoses. Accumulating data supports the idea that screening methods are useful for improving early diagnosis in high-risk patients. However, several barriers limit the application of lung cancer screening in real-world settings. The widespread diffusion of artificial intelligence (AI), radiomics, and machine learning has dramatically changed the current diagnostic landscape. This review explores the potential of AI and biomarker-driven methods, particularly liquid biopsy, in enhancing early lung cancer detection. We report the findings of major randomized controlled trials, cohort studies, and research on AI algorithms that use multi-modal imaging (e.g., CT and PET scans) and liquid biopsy to identify early molecular alterations. AI algorithms enhance diagnostic accuracy by automating image analysis and reducing inter-reader variability. Biomarker-driven methods identify molecular alterations in patients before imaging signs of cancer are evident. Both AI and liquid biopsy show the potential to improve sensitivity and specificity, enabling the detection of early-stage cancers that traditional methods, like low-dose CT (LDCT) scans, might miss. Integrating AI and biomarker-driven methods offers significant promise for transforming lung cancer screening. These technologies could enable earlier, more accurate detection, ultimately improving survival outcomes. AI-driven lung cancer screening can achieve over 90% sensitivity, compared to 70-80% with traditional methods, and can reduce false positives by up to 30%. AI also boosts specificity to 85-90%, with faster processing times (a few minutes vs. 30-60 min for radiologists). However, challenges remain in standardizing these approaches and integrating them into clinical practice. Ongoing research is essential to fully realize their clinical benefits and enhance timely interventions.
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Affiliation(s)
- Leonardo Duranti
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20131 Milan, Italy
| | - Luca Tavecchio
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20131 Milan, Italy
| | - Luigi Rolli
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20131 Milan, Italy
| | - Piergiorgio Solli
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20131 Milan, Italy
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Sharma P, Das D, Khanna D, Budukh A, Khokhar A, Pradhan S, Khanna AK, Chaturvedi P, Badwe R. Prevalence and associated factors of mammography uptake among the women aged 45 years and above: policy implications from the longitudinal ageing study in India wave I survey. BMC Public Health 2025; 25:1073. [PMID: 40108533 PMCID: PMC11924914 DOI: 10.1186/s12889-025-22261-x] [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: 04/12/2024] [Accepted: 03/10/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Breast cancer emerged as number one cancer among women worldwide in terms of incidence and mortality. Majority of breast cancers diagnosed in India are among women aged 45 years and above. A low proportion of Indian female population in reproductive age group (30-49 years) underwent breast cancer screening. The national operational framework includes mammography as one of the investigation modalities under the algorithm for early detection and management of breast cancer. This study describes prevalence and associated factors of mammography uptake in women aged 45 years and above. METHODS We utilized data from 35,083 women aged ≥ 45 years in the Longitudinal Aging Study of India, a nationwide representative survey of the Indian population. The outcome variable was self-reported history of undergoing mammography in past two years before the survey as a representation of early detection of breast cancer. Demographic, behavioural, and clinical characteristics were taken as independent variables. Univariable and multivariable models were applied for the following age groups: 45-59 years and ≥ 60 years, and unadjusted and adjusted odds ratios were calculated. RESULTS The prevalence of mammography was 1.3% among Indian women aged 45 years and above, 1.7% among 45-59 years and 0.9% among women ≥ 60 years. The highest prevalence was reported in Kerala and the lowest was in Nagaland. Among women in 45-59 years age group, secondary or higher education, being currently in union, having diabetes, neurological illness, hearing problems, and reproductive health problems, better cognition level, and self-history of cancer were found to be associated with increased mammography uptake. Urban residence, being currently in union, having bone/joint disease, hearing problem, and one or multi-morbidity, better cognition level and self and family history of cancer were associated with higher mammography uptake among elderly women. CONCLUSIONS Low rates of mammography among women across the country, along with inter-state disparities, highlight inadequate coverage of early detection of breast cancer under National program. Increasing burden of breast cancer in all states underscores need to implement early detection program proactively. Disparities in mammography uptake by age, residence and co-morbidities reflect the need for special focus and context-specific research for pragmatic interventions.
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Affiliation(s)
- Priyanka Sharma
- Department of Community Medicine, ESIC Medical College & Hospital, Faridabad, Haryana, 121012, India
| | - Dipak Das
- Centre for Cancer Epidemiology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, 410210, India
| | - Divya Khanna
- Department of Preventive Oncology, Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centres, Varanasi, Uttar Pradesh, 221005, India.
- Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India.
| | - Atul Budukh
- Centre for Cancer Epidemiology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, 410210, India
- Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India
| | - Anita Khokhar
- Department of Community Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029, India
| | - Satyajit Pradhan
- Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India
- Department of Radiation Oncology, Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centres, Varanasi, Uttar Pradesh, 221005, India
| | - Ajay Kumar Khanna
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University Varanasi, Varanasi, Uttar Pradesh, 221005, India
| | - Pankaj Chaturvedi
- Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
- Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, 410210, India
| | - Rajendra Badwe
- Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, Maharashtra, 400094, India
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, 400012, India
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7
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Cai R, Lin H, Mao Q, Zhang C, Tan Y, Cheng Q. Research hotspots and trends in cancer rehabilitation: a bibliometric analysis (2013-2023). Support Care Cancer 2025; 33:296. [PMID: 40100306 PMCID: PMC11919980 DOI: 10.1007/s00520-025-09355-3] [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: 08/26/2024] [Accepted: 03/10/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Advances in medical care have made cancer rehabilitation an essential component of comprehensive cancer treatment. However, bibliometric analyses in this field remain limited. This study maps the global research landscape of cancer rehabilitation over the past decade. METHODS Relevant publications on cancer rehabilitation from 2013 to 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and the R package "Bibliometrics." RESULTS A total of 6743 publications from 98 countries demonstrated sustained growth, peaking in 2022. The USA (1581 publications) and China (974) led in research output, while the Netherlands recorded the highest citation impact (32.75 citations per paper). Key institutions included the University of Texas MD Anderson Cancer Center (148 publications) and Memorial Sloan Kettering Cancer Center (40.58 citations per paper). Supportive Care in Cancer ranked as the most influential journal. Research efforts primarily focused on exercise interventions (n = 404), quality of life (n = 688), and breast cancer rehabilitation (n = 440). Recent trends highlighted telemedicine, digital health, and breast cancer-related lymphedema. CONCLUSION This analysis highlights the dominance of high-income countries in cancer rehabilitation research and identifies exercise, quality of life, and breast cancer as enduring focal points. Emerging priorities include technology-driven interventions and lymphedema management. However, critical gaps remain, such as the underrepresentation of low-resource regions, limited focus on pediatric populations, and insufficient integration of advanced technologies (e.g., AI, wearables). Future efforts should emphasize equitable resource distribution, evidence-based pediatric rehabilitation models, and scalable technology-driven solutions to address global disparities and improve survivorship care.
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Affiliation(s)
- Ruijuan Cai
- Guang'Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongsheng Lin
- Guang'Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Qiyuan Mao
- Guang'Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chuchu Zhang
- Institute of Chinese Medicine Information, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ying Tan
- Guang'Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Sun X, Zhai J. Research Status and Trends of Gut Microbiota and Intestinal Diseases Based on Bibliometrics. Microorganisms 2025; 13:673. [PMID: 40142565 DOI: 10.3390/microorganisms13030673] [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: 02/17/2025] [Revised: 02/27/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.
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Affiliation(s)
- Xiao Sun
- Natural Reserve Planning and Research Institute, East China University of Technology, Nanchang 330013, China
- College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330029, China
| | - Jiancheng Zhai
- Natural Reserve Planning and Research Institute, East China University of Technology, Nanchang 330013, China
- School of Earth Sciences, East China University of Technology, Nanchang 330013, China
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9
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Mao Y, Ye F, Jiang Q, Liu S, Gong Y. A visualization analysis of global research trends in targeted therapies for thyroid carcinoma (2013-2023). Medicine (Baltimore) 2025; 104:e41835. [PMID: 40101080 PMCID: PMC11922479 DOI: 10.1097/md.0000000000041835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2025] Open
Abstract
This study aims to analyze and identify primary research trends in targeted therapy for thyroid carcinoma (TC). It seeks to provide a factual foundation for researchers, as TC often presents with advanced stages and aggressive subtypes, leading to unfavorable clinical outcomes. The evolution of targeted therapies introduces promising treatment possibilities, necessitating a bibliometric analysis to better understand the current state and trends in this field. A comprehensive bibliometric analysis was conducted using data from the Web of Science Core Collection (WOSCC). Advanced search queries established a literature database, and the analysis was performed using tools such as VOSviewer, CiteSpace, Tableau, and Microsoft Excel. The study focused on publications from 2013 to 2023, examining patterns, geographical contributions, institutional output, and influential journals. The analysis identified 763 publications on TC targeted therapy during the study period, with significant contributions from the United States, China, and Italy, and the United States leading in output. Research activity peaked in 2021, showing overall fluctuating growth. Key contributing institutions included the University of Texas MD Anderson Cancer Center and the University of Pisa. Notable journals, such as Cancers and Thyroid, were among the most cited, underscoring their impact in the field. The study highlighted an increase in global research output and robust international collaborations, particularly among the leading contributing countries. This bibliometric analysis provides a comprehensive overview of significant contributions and trends in targeted therapy research for TC. It identifies key development processes and research hotspots, offering valuable insights to guide future research directions. The findings aim to stimulate further studies and foster advancements in this critical area of oncology.
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Affiliation(s)
- Yu Mao
- Department of Thyroid Surgery, the Second Xiangya Hospital, Central South University, Changsha, P.R. China
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Kim K, Syeed S, Au T, Diaz A, Schabath MB, Cass A, Hall R, Pai L, Li C, Balmaceda N, Palumbo A, Carey A, Lalla M, Henry M, Brixner D, Stenehjem D. Real-world comparative outcomes of EGFR-TKIs for first-line treatment of EGFR+ metastatic non-small-cell lung cancer. Cancer Treat Res Commun 2025; 43:100898. [PMID: 40120239 DOI: 10.1016/j.ctarc.2025.100898] [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: 04/22/2024] [Revised: 10/28/2024] [Accepted: 03/12/2025] [Indexed: 03/25/2025]
Abstract
PURPOSE Osimertinib is a third-generation EGFR-TKI and preferred first-line (1L) treatment for EGFR positive (EGFR+) metastatic non-small cell lung cancer (mNSCLC). This study compared real-world clinical outcomes of 1L osimertinib versus 1st or 2nd generation EGFR-TKIs (1/2G-TKIs) in patients with EGFR+ mNSCLC. METHODS Nine academic cancer centers in the US participated in the retrospective cohort study. Patients aged ≥18 years with EGFR+ mNSCLC and treated with 1L EGFR-TKI were included. Clinical outcomes included real-world progression-free survival (rwPFS), duration of treatment (DOT), time to next treatment (TTNT), central nervous system incidence-free survival (CNS-IFS), and overall survival (OS). Multivariable regression models were used to control for differences in patient characteristics (p < 0.1) between the osimertinib and 1/2G-TKI cohorts. RESULTS The study included 181 osimertinib patients and 171 1/2G-TKI patients. Osimertinib had a longer rwPFS compared to 1/2G-TKIs (median PFS, 95 % confidence interval [CI]: 16.2 months (13.2-19.7) vs. 10.8 months (9.5-12.7); hazard Ratio [HR], 95 % CI: 0.60 (0.44-0.82). DOT and TTNT were significantly longer in patients treated with osimertinib versus 1/2G-TKI (HR, 95 % CI: 0.51 (0.38-0.68) for DOT; 0.54 (0.39-0.74) for TTNT). The respective HR point estimate for CNF-IFS and OS of 0.62 and 0.83 preferred osimertinib. However, small patient counts and number of events posed challenges in drawing conclusion regarding the significance of the delayed CNS-IFS or OS. CONCLUSION Patients treated with osimertinib had a prolonged time to progression and longer time maintain the treatment compared to 1/2G-TKI. This real-world evidence is aligned with clinical trial results.
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Affiliation(s)
- Kibum Kim
- University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA; University of Illinois Chicago, Department of Pharmacy Systems, Outcomes and Policy, Chicago, IL, USA.
| | - Sakil Syeed
- University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA
| | - Trang Au
- University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA
| | - Amber Diaz
- Oregon Health & Science University, Portland, OR, USA
| | | | - Amanda Cass
- Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard Hall
- University of Virginia Medical Center, Charlottesville, VA, USA
| | - Lori Pai
- Tufts Medical Center, Boston, MA, USA
| | - Chenghui Li
- University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
| | | | | | - Autumn Carey
- College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | | | - Matthew Henry
- University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
| | - Diana Brixner
- University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA
| | - David Stenehjem
- University of Utah, Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, Salt Lake City, UT, USA; University of Minnesota, Department of Pharmacy Practice and Pharmaceutical Sciences, Duluth, MN, USA
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11
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Li Y, Fan C, Jiang F, Zhang J, Li Y, Jiang Y, Zhang R, Yu Z, Wang S. Identification of LIMK1 as a biomarker in clear cell renal cell carcinoma: from data mining to validation. J Cancer Res Clin Oncol 2025; 151:104. [PMID: 40056237 DOI: 10.1007/s00432-025-06146-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/20/2025] [Indexed: 03/10/2025]
Abstract
PURPOSE Clear cell renal cell carcinoma (ccRCC) is one of the most common types of renal cancer. LIM kinase 1 (LIMK1) reportedly plays an important role in tumorigenesis. However, the involvement of LIMK1 in the progression of ccRCC remains ambiguous. METHODS Based on the TCGA and CPTAC databases, the expression of LIMK1 in ccRCC was evaluated. In the TCGA-ccRCC cohort, the relationships between LIMK1 and immune cell infiltration as well as immune checkpoints were assessed. The high expression of LIMK1 in ccRCC was verified by qRT-PCR in four RCC cell lines. Immunohistochemistry was used to evaluate the expression of LIMK1 in clinical samples. The association between LIMK1 expression and survival prognosis was explored via Kaplan-Meier survival curve in the TCGA-ccRCC and local cohorts. The effects of LIMK1 knockdown on the proliferation, migration, and invasion abilities of RCC cells were evaluated via colony, CCK-8, wound healing, and Transwell assays. RESULTS Elevated expression level of LIMK1 was found in the TCGA-ccRCC cohort and was confirmed in RCC cell lines and clinical samples. Up-regulation of LIMK1 was found to be correlated with poor prognosis in TCGA-ccRCC and external cohorts. In addition, high-LIMK1 was associated with clinicopathological stage, immune cell infiltration and immune checkpoint in ccRCC. Importantly, knockdown of LIMK1 diminished the capability of proliferation, migration, and invasion in RCC cells. CONCLUSION LIMK1 may serve as a promising diagnostic and prognostic biomarker of ccRCC.
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Affiliation(s)
- Yifei Li
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Congcong Fan
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Feng Jiang
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Jingnan Zhang
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Yanzhen Li
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Yanjie Jiang
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Rui Zhang
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Zhixian Yu
- Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Siqi Wang
- Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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12
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Liu J, Han X, Wang Q, Qin S, Xi Y, Liang G. Hotspots and trends in gastric cancer stem cell research: a visualization and bibliometric analysis. Front Oncol 2025; 15:1523465. [PMID: 40110193 PMCID: PMC11919667 DOI: 10.3389/fonc.2025.1523465] [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: 11/15/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Background Gastric cancer (GC) is a type of malignant tumor that seriously endangers human health. As the understanding of the mechanisms underlying gastric cancer deepens, in recent years, investigations on gastric cancer stem cells (GCSCs) have garnered significant interest. They are pivotal in the onset, progression, recurrence, and pharmacoresistance of GC. Comprehensive research on GCSCs is expected to provide new strategies for the diagnosis and treatment of GC. This article endeavors to comprehensively assess the current status and future trends of GCSCs research through bibliometric analysis, thereby providing a valuable reference for further in - depth studies in this field. Methods English - language academic journals related to GCSCs research in the Web of Science database were retrieved. Subsequently, VOSviewer was utilized to conduct network collinear analysis of the exported source institutions, literature authors, references, and keywords. And CiteSpace was used to perform statistical analysis of the annual publication count, keyword clustering, references, and keyword burst. Results A total of 3882 documents that met the criteria were incorporated. The quantity of published papers has shown a consistent upward trend annually since 2003. Among the authors of the literature, multiple stable core author groups represented by Zhu, Wei, Wang, Mei, Xu, Wenrong, etc. have been formed. There are 335 associated institutions in total. The Japan National Cancer Center has the strongest relevance and the largest number of published papers. There are 7 clustering labels formed among the keywords, including main clustering modules such as activation, cancer stem cells, DNA content aneuploidy, and expression. 25 burst keywords were generated, and the burst keywords in the past two years include mesenchymal stem cells, drug resistance, proliferation, etc. The emergence of references indicates that eight references have been cited up to now and are the focus of current research. Conclusion The research overview of GCSCs in the past 30 years was visually presented by visual maps. In the past decade, scholars' research in this field has gradually intensified, and the development trend is good. Through the deeper study of the GCSCs mechanism, intervention GCSCs in the future will be a new promising treatment approach for GC patients. This hot topic still deserves more attention in the future.
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Affiliation(s)
- Jinfeng Liu
- School of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xinhui Han
- School of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Qingyi Wang
- School of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Sihui Qin
- School of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yujie Xi
- School of Clinical Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Guoying Liang
- Department of Gastroenterology 1, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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13
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Y M, L D. Gastric cancer peritoneal metastasis: a bibliometric study from 2000 to 2024 using VOSviewer software. Front Oncol 2025; 15:1489043. [PMID: 40104504 PMCID: PMC11913700 DOI: 10.3389/fonc.2025.1489043] [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: 08/31/2024] [Accepted: 02/13/2025] [Indexed: 03/20/2025] Open
Abstract
Background Gastric cancer remains a prevalent malignancy worldwide, with peritoneal metastasis being the predominant form of recurrence and metastasis, which are clear predictors of prognosis. The aim of this comprehensive bibliometric analysis was to assess the current status of the research landscape and to identify impending trends in gastric cancer peritoneal metastasis (GCPM). Methods Relevant studies of GCPM were retrieved from the Web of Science Core Collection database. Qualified articles were screened based on the inclusion and exclusion criteria for further analysis. The selected publications were then subjected to bibliometric analysis utilizing VOSviewer software. Results In total, 1,100 publications were included for analysis. The results revealed a consistent upward trend in the number of publications annually from 2000 to 2024, with an anticipated continuation of this growth in future research. The National Cancer Center Japan, emerged as the institution with the most publications and Professor Kodera and Annals of Surgical Oncology were identified as the most influential author and journal, respectively, in the domain of GCPM. In terms of international collaborations, the USA, Japan, and France were the most engaged countries. Yonemura was recognized as the most frequently cited author. Gastrectomy, systemic chemotherapy, and intraperitoneal therapy are the current research hotspots within this domain. Conclusion Research related to GCPM had rapidly increased over the past two decades. These findings identify the most influential countries, institutions, authors, journals, and academic collaboration networks, while also clarifying hotspots and future trends in GCPM research.
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Affiliation(s)
- Manting Y
- College of Integrative Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Dongfang L
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
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14
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Tan M, Gao Z, Wang X, Wang X, Lin C, Huang Y, Chen W, Zhang Y, Hou Z. MnO 2@CeO x-GAMP radiosensitizer with oxygen vacancies depended mimicking enzyme-like activities for radiosensitization-mediated STING pathway activation. Biomaterials 2025; 314:122797. [PMID: 39255531 DOI: 10.1016/j.biomaterials.2024.122797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/31/2024] [Accepted: 08/31/2024] [Indexed: 09/12/2024]
Abstract
Activation of the stimulator of interferon genes (STING) pathway by radiotherapy (RT) has a significant effect on eliciting antitumor immune responses. The generation of hydroxyl radical (·OH) storm and the sensitization of STING-relative catalytic reactions could improve radiosensitization-mediated STING activation. Herein, multi-functional radiosensitizer with oxygen vacancies depended mimicking enzyme-like activities was fabricated to produce more dsDNA which benefits intracellular 2', 3'-cyclic GMP-AMP (cGAMP) generation, together with introducing exogenous cGAMP to activate immune response. MnO2@CeOx nanozymes present enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities due to induced oxygen vacancies accelerate the redox cycles from Ce4+ to Ce3+ via intermetallic charge transfer. CeOx shells not only serve as radiosensitizer, but also provide the conjugation site for AMP/GMP to form MnO2@CeOx-GAMP (MCG). Upon X-ray irradiation, MCG with SOD-like activity facilitates the conversion of superoxide anions generated by Ce-sensitization into H2O2 within tumor microenvironment (TME). The downstream POD-like activity catalyzes the elevated H2O2 into a profusion of ·OH for producing more damage DNA fragments. TME-responsive decomposed MCG could supply exogenous cGAMP, meanwhile the releasing Mn2+ improve the sensitivity of cyclic GMP-AMP synthase to dsDNA for producing more cGAMP, resulting in the promotion of STING pathway activation.
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Affiliation(s)
- Meiling Tan
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China; Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510095, PR China
| | - Zhimin Gao
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Xinyi Wang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Xiaozhao Wang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Chen Lin
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Yongxin Huang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China
| | - Wei Chen
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China; The Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan, 511518, PR China
| | - Yaru Zhang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China; The Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan, 511518, PR China
| | - Zhiyao Hou
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China; Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510095, PR China; The Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan, 511518, PR China.
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15
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Chen P, Li K, Chen J, Hei H, Geng J, Huang N, Lei M, Jia H, Ren J, Jin C. Enhanced effect of radiofrequency ablation on HCC by siRNA-PD-L1-endostatin Co-expression plasmid delivered. Transl Oncol 2025; 53:102319. [PMID: 39938403 PMCID: PMC11869540 DOI: 10.1016/j.tranon.2025.102319] [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: 10/14/2024] [Revised: 01/07/2025] [Accepted: 02/02/2025] [Indexed: 02/14/2025] Open
Abstract
Hepatocellular carcinoma (HCC) poses a significant clinical challenge due to high mortality and limited treatment options. Radiofrequency ablation (RFA) is commonly used but can be limited by tumor recurrence. This study explores the potential of combining RFA with an attenuated Salmonella strain carrying siRNA-PD-L1 and endostatin to enhance HCC treatment. In this study, an H22 subcutaneous tumor mouse model was used, with animals divided into five groups for treatment with a blank control, a blank Salmonella plasmid, RFA alone, siRNA-PD-L1-endostatin, or a combination of RFA and siRNA-PD-L1-endostatin. The combination therapy significantly reduced tumor growth, angiogenesis, and PD-L1/VEGF expression in tumor tissues post-RFA. Additionally, it induced tumor cell apoptosis, inhibited proliferation and migration, and increased the infiltration of T lymphocytes, granzyme B+T cells, and CD86+macrophages within tumors. There was also a notable rise in T and NK cell populations in the spleen. In conclusion, combining RFA with siRNA-PD-L1-endostatin delivered by attenuated Salmonella synergistically enhances anti-tumor effects, boosts the anti-tumor immune response, and improves RFA efficacy for HCC.
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Affiliation(s)
- Pengfei Chen
- Department of Radiology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, PR China; Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - Kun Li
- Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - Jinwei Chen
- Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - He Hei
- Department of Radiology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, PR China
| | - Jiaxin Geng
- Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan, PR China
| | - Nannan Huang
- Department of Orthopedics, Zhengyang county traditional Chinese medicine hospital, Zhumadian, Henan, PR China
| | - Mengyu Lei
- Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan, PR China
| | - Huijie Jia
- Xinxiang Engineering Technology Research Center of immune checkpoint drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan, PR China
| | - Jianzhuang Ren
- Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - Chenwang Jin
- Department of Radiology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, PR China; Shaanxi Engineering Research Center of Computational Imaging and Medical Intelligence, 277 West Yanta Road, Xi'an, Shaanxi 710061, PR China.
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16
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Fortin J, Rudd É, Trudel-Fitzgerald C, Cordova MJ, Marin MF, Brunet A. Understanding mental health in breast cancer from screening to Survivorship: an integrative phasic Model and tool. PSYCHOL HEALTH MED 2025; 30:437-459. [PMID: 39580147 DOI: 10.1080/13548506.2024.2430796] [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: 10/03/2024] [Accepted: 11/12/2024] [Indexed: 11/25/2024]
Abstract
Integrative models of mental illness and health in psycho-oncology are aimed at all types of cancer, although the patients' experiences and issues may vary. This review summarizes the different theories and models of mental illness and health pertaining to the breast cancer experience and proposes an integrative phasic model applicable to the breast cancer trajectory. Five databases were searched for studies related to breast cancer mental health and illness theories and models. The PRISMA checklist form was used to extract the essential information from the included studies. Eleven theories and models on the experience of breast cancer were found. The integrative model based on these theories and models illustrates that the breast cancer experience is conceptualized as a trajectory with seven landmark 'events', each associated with a pathogenic 'challenge' leading to six possible 'symptoms', 1) psychological distress with anxious features, 2) psychological distress with depressive features, 3) non-specific distress 4) psychological distress with trauma-related features 5) low health-related quality of life, and 6) fear of recurrence. The Breast Cancer Psychological Integrative Phasic Model is supported by a simple clinical tool (BreastCancerPsych - Integrative Clinical Tool) that serves as a valuable resource throughout the care trajectory. These integrative phasic model and clinical tool are designed to help mental health clinicians formulate treatments that are tailored to the needs of their patients, especially for trajectories that are not marked by resilience.
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Affiliation(s)
- Justine Fortin
- Department of Psychology, Université du Québec à Montréal, Montréal, Canada
- Department of Psychosocial Science, Douglas Institute Research Centre, Verdun, Canada
- Research Center of the Institut Universitaire en Santé Mentale de Montréal, Montréal, Canada
| | - Émilie Rudd
- Research Center of the Institut Universitaire en Santé Mentale de Montréal, Montréal, Canada
| | - Claudia Trudel-Fitzgerald
- Research Center of the Institut Universitaire en Santé Mentale de Montréal, Montréal, Canada
- Department of Psychology, Université du Québec à Trois-Rivières, Trois-Rivières, Canada
- Lee Kum Sheung Center for Health and Happiness, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Marie-France Marin
- Department of Psychology, Université du Québec à Montréal, Montréal, Canada
- Research Center of the Institut Universitaire en Santé Mentale de Montréal, Montréal, Canada
| | - Alain Brunet
- Department of Psychosocial Science, Douglas Institute Research Centre, Verdun, Canada
- Department of Psychiatry, McGill University, Montréal, Canada
- National PTSD Research Centre, University of the Sunshine Coast, Sunshine Coast, Australia
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Tian C, Feng Y, Zhang H, Mao X, Zhu X, Wang X, Hou C, Han X, Yang H, Liu J. Discovery of highly oxygenated cytochalasans with antiproliferative activity from an endophytic fungus Boeremia exigua. Bioorg Chem 2025; 156:108198. [PMID: 39864369 DOI: 10.1016/j.bioorg.2025.108198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/15/2025] [Accepted: 01/18/2025] [Indexed: 01/28/2025]
Abstract
Eleven cytochalasans (1-11), including six undescribed analogues (1-3 and 5-7) and a new natural product (4), were obtained from the endophytic fungus Boeremia exigua. Their structures and absolute configurations were determined by a combination of extensive spectroscopic techniques, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Boerelasin E (1) represented the first cytochalasan possessing a cis-configured Δ21(22) double bond. The growth-inhibitory activities of all the isolates 1-11 against five human tumor cells were examined. Boerelasin E (1) exhibited the most potent inhibitory effect on MCF-7 cells with an IC50 value of 4.89 μM, even about four times lower than positive control cis-platin (IC50 = 20.52 μM). Further mechanistic investigations revealed that 1 could inhibit the complete cell division of MCF-7 cells by arresting them in the G2/M phase and induced apoptosis.
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Affiliation(s)
- Chun Tian
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China
| | - Yuanyuan Feng
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China; Science & Technology Industrial Parks of Anhui University of Chinese Medicine, Hefei 230012 China
| | - Hanqi Zhang
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China; Science & Technology Industrial Parks of Anhui University of Chinese Medicine, Hefei 230012 China
| | - Xinyu Mao
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China
| | - Xinyao Zhu
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China
| | - Xiang Wang
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China
| | - Chang Hou
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China
| | - Xiaoyang Han
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China; Science & Technology Industrial Parks of Anhui University of Chinese Medicine, Hefei 230012 China.
| | - Huixiang Yang
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China; Science & Technology Industrial Parks of Anhui University of Chinese Medicine, Hefei 230012 China.
| | - Jikai Liu
- Anhui Province Key Laboratory of Bioactive Natural Products, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012 China; Science & Technology Industrial Parks of Anhui University of Chinese Medicine, Hefei 230012 China.
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Priya S, Kma L. Identification of novel microRNAs: Biomarkers for pathogenesis of hepatocellular carcinoma in mice model. Biochem Biophys Rep 2025; 41:101896. [PMID: 39881957 PMCID: PMC11774814 DOI: 10.1016/j.bbrep.2024.101896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/26/2024] [Accepted: 12/09/2024] [Indexed: 01/31/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the most fatal cancer that has affected both male and female populations globally. With poor diagnosis and patient survival rates, it has become a global need for scientists to come to the aid. The main objective of the study was to profile the miRNAs in the serum of Control and DEN-treated mice at different time intervals (4 Weeks, 8 Weeks, 12 Weeks, and 16 Weeks) and identify HCC-associated miRNA as putative early biomarkers along with the miRNA regulated candidate gene which may be involved in HCC. Our study group involves 4,8,12, & 16 weeks 16-week-old treated male mice. Each group was sacrificed and analyzed for the stages of HCC. We employed in silico techniques for the small RNA-Seq and bioinformatics pipeline for further analysis. Our analysis revealed over 400 differentially expressed miRNAs in each treated sample and 10 novel miRNAs. The downstream analysis of these differentially expressed miRNAs, and their target genes opened an arena of different biological processes and pathways that these miRNAs affect during the development of HCC. The work has a promising role as the miRNAs predicted through this study can be used as biomarkers for early detection of HCC.
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Affiliation(s)
- Shivani Priya
- Department of Chemistry & Biochemistry, Sharda School of Basic Sciences & Research, Sharda University, Noida, UP, India
| | - Lakhon Kma
- Department of Biochemistry, North Eastern Hill University, Shillong, India
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Liu Y, Liu H, Xiong Y. Metabolic pathway activation and immune microenvironment features in non-small cell lung cancer: insights from single-cell transcriptomics. Front Immunol 2025; 16:1546764. [PMID: 40092988 PMCID: PMC11906459 DOI: 10.3389/fimmu.2025.1546764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 02/04/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction In this study, we aim to provide a deep understanding of the tumor microenvironment (TME) and its metabolic characteristics in non-small cell lung cancer (NSCLC) through single-cell RNA sequencing (scRNAseq) data obtained from public databases. Given that lung cancer is a leading cause of cancer-related deaths globally and NSCLC accounts for the majority of lung cancer cases, understanding the relationship between TME and metabolic pathways in NSCLC is crucial for developing new treatment strategies. Methods Finally, machine learning algorithms were employed to construct a risk signature with strong predictive power across multiple independent cohorts. After quality control, 29,053 cells were retained, and PCA along with UMAP techniques were used to distinguish 13 primary cell subpopulations. Four highly activated metabolic pathways were identified within malignant cell subpopulations, which were further divided into seven distinct subgroups showing significant differences in differentiation potential and metabolic activity. WGCNA was utilized to identify gene modules and hub genes closely associated with these four metabolic pathways. Results Our analysis showed that DEGs between tumor and normal tissues were predominantly enriched in immune response and cell adhesion pathways. The comprehensive examination of our model revealed substantial variations in clinical and pathological characteristics, enriched pathways, cancer hallmarks, and immune infiltration scores between high-risk and low-risk groups. Wet lab experiments validated the role of KRT6B in NSCLC, demonstrating that KRT6B expression is elevated and it stimulates the proliferation of cancer cells. Discussion These observations not only enhance our understanding of metabolic reprogramming and its biological functions in NSCLC but also provide new perspectives for early detection, prognostic evaluation, and targeted therapy. However, future research should further explore the specific mechanisms of these metabolic pathways and their application potentials in clinical practice.
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Affiliation(s)
- Yanru Liu
- Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Pediatric Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hanmin Liu
- Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Ying Xiong
- Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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20
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Sullivan M, Lei X, Karuturi M, Malinowski C, Giordano SH, Chavez-MacGregor M. Use of adjuvant capecitabine in older patients with early-stage triple-negative breast cancer. Breast Cancer Res Treat 2025:10.1007/s10549-025-07637-2. [PMID: 40019667 DOI: 10.1007/s10549-025-07637-2] [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: 10/09/2024] [Accepted: 02/04/2025] [Indexed: 03/01/2025]
Abstract
PURPOSE Patients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant chemotherapy (NACT) benefit from adjuvant capecitabine. Older patients are not always treated according to guidelines, likely due to concerns regarding tolerance. We examined the use of adjuvant capecitabine, its association with outcomes, and subsequent emergency room visits (ER) and hospitalizations (HSP) among older patients with early-stage TNBC. METHODS Retrospective, observational study using data in the SEER-Medicare database. Older patients (≥ 66 years) with early-stage TNBC, diagnosed in 2010-2019, who received NACT, underwent surgery, and were prescribed adjuvant capecitabine were included. We analyzed capecitabine use, its association with overall survival and breast-cancer specific survival, and time to first ER/HSP. Logistic regression, Kaplan-Meier estimates, and Cox regression models with propensity score adjustments were used. RESULTS 239 of 1,799 older patients with TNBC received adjuvant capecitabine. Capecitabine use increased from 1.3% in 2010 to 29.6% in 2019. Older age, ≥ 71 years, (OR = 0.54, 95%CI 0.32-0.92) and ≥ 2 comorbidities (OR = 0.42, 95%CI 0.2-0.9) were associated with decreased odds of receiving ≥ 6 cycles of capecitabine. Increasing number of cycles of capecitabine was associated with decreased risks of death (HR = 0.74, 95%CI 0.66-0.83) and breast cancer-specific death (HR = 0.73, 95%CI 0.61-0.89). 55 patients (23%) treated with capecitabine experienced ER/HSP. CONCLUSION In recent years, adjuvant capecitabine is increasingly used for patients with early-stage TNBC. Patients with older age and more comorbidities received fewer cycles of capecitabine. While one-fourth of patients had ER/HSP, receipt of more cycles was associated with better survival.
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Affiliation(s)
- Marija Sullivan
- Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiudong Lei
- Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Unit 1444, Houston, TX, USA
| | - Meghan Karuturi
- Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Catalina Malinowski
- Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Unit 1444, Houston, TX, USA
| | - Sharon H Giordano
- Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Unit 1444, Houston, TX, USA
- Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mariana Chavez-MacGregor
- Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Unit 1444, Houston, TX, USA.
- Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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21
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Kröger K, Pepper NB, Ventura D, Troschel FM, Backhaus P, Rahbar K, Glasbrenner B, Brüwer M, Pascher A, Schäfers M, Eich HT, Roll W. FAPI-PET/CT guided radiotherapy for patients with esophageal cancer. Radiat Oncol 2025; 20:29. [PMID: 40022163 PMCID: PMC11871644 DOI: 10.1186/s13014-025-02606-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: 01/10/2025] [Accepted: 02/20/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Cancer associated fibroblasts have become a target of interest in different malignancies for positron emission tomography (PET) imaging, using positron emitter labelled fibroblast activation protein inhibitors (FAPI). New data underline the advanced imaging properties of FAPI-PET/CT for the staging of esophageal cancer compared to standard imaging. Potential benefits of FAPI-PET/CT in radiation therapy planning are the subject of this investigation. METHODS Ten patients with newly diagnosed esophageal cancer treated with radiochemotherapy (RCT) were retrospectively analyzed. All patients underwent [68Ga]OncoFAP-PET/CT in treatment position to facilitate radiation treatment planning. Six patients received neoadjuvant RCT as part of a trimodal therapy and four patients underwent definitive RCT. In five cases, restaging after initial treatment was performed with FAPI-PET/CT. RESULTS [68Ga]OncoFAP-PET/CT based imaging showed a high correlation with the endoscopic staging for initial imaging. In three cases, new sites of disease were unmasked, not visible in CT- and endosonographic staging. [68Ga]OncoFAP-PET/CT based RT delineation offered good definition of clinical target volumes, especially in retro-/paracardial areas and the gastroesophageal junction. CONCLUSION [68Ga]OncoFAP-PET/CT may aid and improve radiation treatment planning for patients with esophageal cancer.
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Affiliation(s)
- Kai Kröger
- Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany.
| | | | - David Ventura
- Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
| | - Fabian M Troschel
- Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany
| | - Philipp Backhaus
- Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
- European Institute for Molecular Imaging, University of Münster, Muenster, Germany
| | - Kambiz Rahbar
- Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
| | - Bernhard Glasbrenner
- Department of Medicine B, Gastroenterology, St. Franziskus-Hospital Muenster, Muenster, Germany
| | - Matthias Brüwer
- Department of General and Visceral Surgery, Gastroenterology, St. Franziskus-Hospital Muenster, Muenster, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Muenster, Germany
| | - Michael Schäfers
- Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
- European Institute for Molecular Imaging, University of Münster, Muenster, Germany
| | - Hans Theodor Eich
- Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany
| | - Wolfgang Roll
- Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
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22
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Yamada Y, Wang YC, Liu HP, Gerongano GR, Tseng CY, Liu SC, Liao GR, Chang CC, Liao JW, Wang ML, Chang YY, Lin FY, Hsu WL. Development of attenuated Orf virus as a safe oncolytic viral vector for nasopharyngeal carcinoma treatment. Virol J 2025; 22:50. [PMID: 40001231 PMCID: PMC11863438 DOI: 10.1186/s12985-025-02672-3] [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: 10/02/2024] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Orf virus (ORFV) is gaining attention as a promising viral vector for cancer therapy because of its unique properties. Recent studies have shown that ORFV could be effective against various cancers, particularly nasopharyngeal carcinoma. This research explores the ability of wild-type ORFV and recombinant ORFVs, which lack specific virulence factors, to kill NPC cells and modulate the immune response. METHODS Two NPC cell lines, HK1 (from Hong Kong) and TW02 (from Taiwan), were infected with wild-type ORFV and two recombinant ORFVs lacking either vascular endothelial growth factor (VEGF) or chemokine binding protein (CBP) virulence factors. The oncolytic effects were evaluated by assessing cell death pathways, particularly pyroptosis, which was monitored through the cleavage of gasdermin E (GSDME). The activation of survival pathways, such as focal adhesion kinase (FAK) and AKT, was also analyzed. In addition, the influence of ORFV infection on natural killer (NK) cell recruitment and cytotoxicity was investigated. In vivo experiments were conducted in a xenograft mouse model in which HK1 tumors were used to evaluate the antitumor activity of wild-type ORFV and two deletion-mutant ORFVs. RESULTS Wild-type ORFV effectively killed NPC cells, especially HK1 cells. The recombinant ORFVs, despite being attenuated by the loss of VEGF or CBP, retained the ability to infect and cause NPC cell death, with the CBP-deleted virus showing notable effectiveness in HK1 cells. Early ORFV infection led to pyroptosis via GSDME cleavage, causing cell detachment and a reduction in FAK and AKT activation. ORFV also enhanced NK cell recruitment and boosted NK cell-mediated cytotoxicity in infected NPC cells. In the HK1 xenograft model, CBP-deleted ORFV significantly inhibited tumor growth. CONCLUSION ORFV, particularly the wild-type and CBP-deleted variants, has significant potential as an oncolytic viral vector for NPC therapy. It induces cell death via pyroptosis and enhances immune-mediated tumor cell destruction through NK cells. The attenuated CBP-deleted ORFV offers a safer and effective option for cancer treatment, making it a promising candidate for future therapeutic applications.
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Affiliation(s)
- Yumiko Yamada
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yu-Chih Wang
- Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Hao-Ping Liu
- Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Greg Ryan Gerongano
- Department of Pathology, Corazon Locsin Montelibano Memorial Regional Hospital, Bacolod City, Philippines
| | - Ching-Yu Tseng
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Shu-Chen Liu
- Department Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan
| | - Guan-Ru Liao
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Chao-Chin Chang
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Jiunn-Wang Liao
- Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Mei-Lin Wang
- Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yuan-Yen Chang
- Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Fong-Yuan Lin
- Department of Animal Healthcare, Hungkuang University, Taichung, Taiwan
| | - Wei-Li Hsu
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
- The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
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23
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Izumo W, Kawaida H, Saito R, Nakata Y, Amemiya H, Higuchi Y, Nakayama T, Maruyama S, Takiguchi K, Shoda K, Shiraishi K, Furuya S, Kawaguchi Y, Ichikawa D. Evaluation of the validity of pancreatoduodenectomy for octogenarian patients with biliary tract carcinoma from the perspective of recurrence. Scand J Gastroenterol 2025:1-10. [PMID: 39987921 DOI: 10.1080/00365521.2025.2469123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/26/2025] [Accepted: 02/13/2025] [Indexed: 02/25/2025]
Abstract
OBJECTIVE To clarify the short- and long-term validity of pancreatoduodenectomy in octogenarian patients with biliary tract carcinoma. METHODS We compared 23 and 141 patients aged ≥80 and <80 years, who underwent pancreatoduodenectomy for biliary tract carcinoma (distal cholangiocarcinomas and ampullary carcinomas) and evaluated the relationship between age, clinicopathological factors, and surgical and oncological outcomes, especially in terms of recurrence. RESULTS Median overall survival time of distal cholangiocarcinoma and ampullary carcinoma was 92 and 109 months (p = 0.13). Postoperative complications, mortality, and adjuvant chemotherapy rates did not differ between the groups. Although the 5-year recurrence-free survival rate was similar, the 5-year disease-specific survival and overall survival rate were significantly shorter in octogenarians (≥80 years: 43.5, 47.1, and 35.3%; <80 years: 54.1, 69.2, and 63.0%; p = 0.41, 0.016, and 0.034, respectively). The median time from recurrence to death for octogenarian patients was significantly shorter than that of younger patients (3.3 vs. 16.1 months, p < 0.001). At recurrence, the serum albumin level, prognostic nutritional index, controlling nutritional status score, and treatment rate for recurrence were lower in octogenarians. The multivariate analysis identified age ≥80 years (hazard ratio: 3.8), low prognostic nutritional index (hazard ratio: 2.9), high serum carbohydrate antigen 19-9 (hazard ratio: 2.6), and failure to implement treatment after recurrence (hazard ratio: 3.0) as independent risk factors for a short time from recurrence to death. Furthermore, age ≥80 years (odds ratio 0.09) was an independent risk factor for treatment implementation after recurrence. CONCLUSIONS Octogenarians had a shorter survival time after recurrence, resulting from low nutritional indices and a reduced rate of treatment implementation at the time of recurrence.
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Affiliation(s)
- Wataru Izumo
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Hiromichi Kawaida
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Ryo Saito
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Yuuki Nakata
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Hidetake Amemiya
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Yudai Higuchi
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Takashi Nakayama
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Suguru Maruyama
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Koichi Takiguchi
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Katsutoshi Shoda
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Kensuke Shiraishi
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Shinji Furuya
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Yoshihiko Kawaguchi
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
| | - Daisuke Ichikawa
- Department of Digestive Surgery, University of Yamanashi Hospital, Yamanashi, Japan
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Ko SY, Park S, Choi YH. Protocatechualdehyde Induced Breast Cancer Stem Cell Death via the Akt/Sox2 Signaling Pathway. Int J Mol Sci 2025; 26:1811. [PMID: 40076435 PMCID: PMC11899452 DOI: 10.3390/ijms26051811] [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: 01/16/2025] [Revised: 02/13/2025] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
Breast cancer (BC) is most frequently recognized in women and characterized by histological and molecular heterogeneity. Among the various subtypes, triple-negative BC remains the most challenging disease owing to the lack of effective molecular targets and the high frequency of breast cancer stem cells (BCSCs), which account for both recurrence and resistance to conventional treatments. Despite the availability of hormonal therapies and targeted treatments, patients still face early and late relapses, necessitating new cytotoxic and selective treatment strategies. Our study focuses on investigating the effects of protocatechualdehyde (PCA), a potent bioactive compound derived from Artemisia princeps, on CSCs in BC cells. PCA inhibited BC growth and mammosphere formation as the concentration increased. This agent decreased the fraction of the CD44+/CD24- population, the aldehyde dehydrogenase 1A-expressing population, and the protein level of Sox2 in breast CSCs by downregulating Akt and pAkt. Moreover, PCA treatment reduced the tumor volume and weight in 4T1-challenged BALB/c mice. Collectively, our findings support the anti-tumor effect of Akt/Sox2-targeting PCA, suggesting a novel utilization of PCA in BC therapy.
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Affiliation(s)
- Seung-Yeon Ko
- Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea; (S.-Y.K.); (S.P.)
- Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea
| | - Seonghee Park
- Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea; (S.-Y.K.); (S.P.)
| | - Youn-Hee Choi
- Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea; (S.-Y.K.); (S.P.)
- Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea
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25
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Wang Z, Liu Z, Lv M, Luan Z, Li T, Hu J. Novel histone modifications and liver cancer: emerging frontiers in epigenetic regulation. Clin Epigenetics 2025; 17:30. [PMID: 39980025 PMCID: PMC11841274 DOI: 10.1186/s13148-025-01838-8] [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: 11/06/2024] [Accepted: 02/08/2025] [Indexed: 02/22/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and its onset and progression are closely associated with epigenetic modifications, particularly post-translational modifications of histones (HPTMs). In recent years, advances in mass spectrometry (MS) have revealed a series of novel HPTMs, including succinylation (Ksuc), citrullination (Kcit), butyrylation (Kbhb), lactylation (Kla), crotonylation (Kcr), and 2-hydroxyisobutyrylation (Khib). These modifications not only expand the histone code but also play significant roles in key carcinogenic processes such as tumor proliferation, metastasis, and metabolic reprogramming in HCC. This review provides the first comprehensive analysis of the impact of novel HPTMs on gene expression, cellular metabolism, immune evasion, and the tumor microenvironment. It specifically focuses on their roles in promoting tumor stem cell characteristics, epithelial-mesenchymal transition (EMT), and therapeutic resistance. Additionally, the review highlights the dynamic regulation of these modifications by specific enzymes, including "writers," "readers," and "erasers."
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Affiliation(s)
- Zhonghua Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Ziwen Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Mengxin Lv
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Zhou Luan
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Tao Li
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Jinhua Hu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.
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Kibralew G, Wassie YA, Kelebie M, Rtbey G, Tadesse G, Melkam M, Tsega A, Andualem F, Setegn A, Tinsae T, Fentahun S, Nakie G. Psychological distress among cancer patients in African countries: a systematic review and meta-analysis study. BMC Psychol 2025; 13:128. [PMID: 39962603 PMCID: PMC11834563 DOI: 10.1186/s40359-025-02447-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: 11/19/2024] [Accepted: 02/03/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Cancer is a disease causing abnormal cell proliferation, and can cause stress, anxiety, and emotional reactions in patients. Despite studies in Africa showing psychological distress in cancer patients, a systematic review on this topic has not yet been conducted. METHODS To find papers, searches were conducted using PubMed, Scopus, Cochrane Library, Science Direct, African Journal Online, and Google Scholar. This systematic review and meta-analysis encompassed fifteen primary articles from seven African countries that underwent assessment and inclusion. A Microsoft Excel spreadsheet was used to extract the data, which were then transferred to STATA version 14 for analysis. The statistical heterogeneity was evaluated by using Cochran's Q and I2 statistics. Egger regression tests and funnel plot analysis were employed to look for publication bias. A sensitivity analysis and a subgroup analysis were performed. RESULT This systematic review and meta-analysis comprised a total of 1567 research participants from 15 different investigations. In Africa, 42.83% of cancer patients overall had a pooled prevalence of psychological distress (95% CI: 19.40, 66.27). Being a rural area (AOR = 2.30; 95% CI: 1.49 to 3.55), having no social support (AOR = 4.63; 95% CI: 2.18 to 9.86), being in stage II cancer (AOR = 2.72; 95% CI: 1.38 to 5.38), having a co-occurring chronic illness (AOR = 2.78; 95% CI: 1.34, 5.74), experiencing financial difficulties (AOR = 16.52; 3.56, 76.63), and experiencing difficult emotional life (AOR = 2.53; 1.07, 5.97) were associated with psychological distress. CONCLUSION This study shows that there is a high prevalence of psychological distress among cancer patients in Africa. We have also found a significant relationship between psychological distress and rural living, a lack of social support, an advanced stage of the disease, coexisting medical conditions, financial problems, and emotional difficulties. Early detection to lessen psychological discomfort in this susceptible population is essential to reduce the burden of psychological distress among cancer patients.
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Affiliation(s)
- Getasew Kibralew
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia.
| | - Yilkal Abebaw Wassie
- Department of Medical Nursing, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Mulualem Kelebie
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Gidey Rtbey
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Gebresilassie Tadesse
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Mamaru Melkam
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Aklile Tsega
- Department of Nursing, College of Medicine and Health Science, Hawassa University, Awasa, Ethiopia
| | - Fantahun Andualem
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Abebaw Setegn
- Department of Medical Parasitology, School of Biomedical and Laboratory Science, University of Gondar, Gondar, Ethiopia
| | - Techilo Tinsae
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Setegn Fentahun
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Girum Nakie
- Department of Psychiatry, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
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Tang XS, Xu CL, Li N, Zhang JQ, Tang Y. Landscape of four different stages of human gastric cancer revealed by single-cell sequencing. World J Gastrointest Oncol 2025; 17:97125. [PMID: 39958562 PMCID: PMC11756019 DOI: 10.4251/wjgo.v17.i2.97125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 10/12/2024] [Accepted: 11/08/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) poses a substantial risk to human health due to its high prevalence and mortality rates. Nevertheless, current therapeutic strategies remain insufficient. Single-cell RNA sequencing (scRNA-seq) offers the potential to provide comprehensive insights into GC pathogenesis. AIM To explore the distribution and dynamic changes of cell populations in the GC tumor microenvironment using scRNA-seq techniques. METHODS Cancerous tissues and paracancerous tissues were obtained from patients diagnosed with GC at various stages (I, II, III, and IV). Single-cell suspensions were prepared and analyzed using scRNA-seq to examine transcriptome profiles and cell-cell interactions. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry were applied for measuring the expression of cluster of differentiation (CD) 2, CD3D, CD3E, cytokeratin 19, cytokeratin 8, and epithelial cell adhesion molecules. RESULTS Transcriptome data from 73645 single cells across eight tissues of four patients were categorized into 25 distinct cell clusters, representing 10 different cell types. Variations were observed in these cell type distribution. The adjacent epithelial cells in stages II and III exhibited a degenerative trend. Additionally, the quantity of CD4 T cells and CD8 T cells were evidently elevated in cancerous tissues. Interaction analysis displayed a remarkable increase in interaction between B cells and other mast cells in stages II, III, and IV of GC. These findings were further validated through qRT-PCR and flow cytometry, demonstrating elevated T cells and declined epithelial cells within the cancerous tissues. CONCLUSION This study provides a comprehensive analysis of cell dynamics across GC stages, highlighting key interactions within the tumor microenvironment. These findings offer valuable insights for developing novel therapeutic strategies.
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Affiliation(s)
- Xu-Shan Tang
- Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
| | - Chun-Lei Xu
- Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
| | - Na Li
- Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
| | - Jian-Qing Zhang
- Department of Outpatient, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
| | - Yong Tang
- Department of Gastroenterology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, Xinjiang Uighur Autonomous Region, China
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Nasir S. Topological Descriptors of Colorectal Cancer Drugs and Characterizing Physical Properties Via QSPR Analysis. Int J Anal Chem 2025; 2025:5512172. [PMID: 39990204 PMCID: PMC11846678 DOI: 10.1155/ianc/5512172] [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: 11/26/2024] [Accepted: 01/18/2025] [Indexed: 02/25/2025] Open
Abstract
Topological descriptors and QSPR analysis are statistical techniques that are highly beneficial for analyzing various physical and chemical characteristics of molecular graphs without necessitating expensive and time-consuming laboratory experiments. The topological descriptor alters the compound to a number and helps in finding physicochemical properties. It more correctly reproduces the theoretical properties of drugs. In this article, the author investigated colorectal drugs capecitabine, leucovorin, tipiracil hydrochloride, etc. and implemented QSPR analysis. Physical qualities such as molar volume, complexity, polarity, and refractivity are the subject of the current study. The outcomes of this study allow for more effective physical property prediction through the use of QSPR models. First, we calculate Tds and secondly perform QSPR analysis. Current work on TIs and QSPR modeling shows a good correlation with physical properties. Moreover, estimated drug results depict and predict the physical properties in an efficient way.
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Affiliation(s)
- Sumiya Nasir
- Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd University, Khobar 31952, Saudi Arabia
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Sever ÖN, Başoğlu T, Yıldırım S. Relationship of Tumor Localization and Lipid Parameters with Survival in Patients with Colorectal Cancer. J Clin Med 2025; 14:1302. [PMID: 40004832 PMCID: PMC11856523 DOI: 10.3390/jcm14041302] [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: 01/02/2025] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Colorectal cancer (CRC) remains a global health challenge. Metabolic disorders, including dyslipidemia, have been linked to CRC progression, yet the relationship between lipid profiles, tumor location, and survival outcomes remains controversial. This study investigates the association between blood lipid parameters, tumor localization, and survival in CRC patients. Methods: A retrospective analysis was conducted on 126 CRC patients diagnosed between 2017 and 2024 at Kartal Dr. Lütfi Kırdar City Hospital. Patients with comorbidities affecting lipid metabolism or who were on lipid-lowering drugs were excluded. Clinical, pathological, and lipid data, including total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and carcinoembryonic antigen (CEA), were analyzed. Tumor location was categorized as right-sided or left-sided. Overall survival (OS) was evaluated with a statistical analysis using Kaplan-Meier and Cox regression models. Results: Higher HDL-C levels and a lower TC/HDL-C ratio were significantly associated with improved OS (p: 0.004 and p: 0.016, respectively). This relationship remained significant in early- and advanced-stage disease (p: 0.04 for HDL-C and p: 0.03 for TC/HDL-C). In patients with tumors located in the right colon, LDL-C levels of 150 mg/dL and below were found to be statistically positively correlated with overall survival, while in patients with tumors located in the left colon, HDL-C levels of 45 mg/dL and above and TC/HDL-C levels of 4.16 and above were found to be statistically positively correlated with overall survival. A multivariate analysis confirmed that age, stage, HDL-C, and TC/HDL-C were independent predictors of OS. Conclusions: Our study highlights the potential role of lipid profiles, particularly HDL-C and the TC/HDL-C ratio, as prognostic factors in CRC. Further research, including molecular and genetic analyses, is needed to better understand the mechanisms underlying the relationship between lipid metabolism and CRC progression.
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Affiliation(s)
- Özlem Nuray Sever
- Department of Medical Oncology, Medical Park Bahcelievler Hospital, Istanbul 34180, Türkiye
| | - Tuğba Başoğlu
- Department of Medical Oncology, Health Science University, Kartal Dr. Lütfi Kirdar City Hospital, Istanbul 34865, Türkiye; (T.B.); (S.Y.)
| | - Sedat Yıldırım
- Department of Medical Oncology, Health Science University, Kartal Dr. Lütfi Kirdar City Hospital, Istanbul 34865, Türkiye; (T.B.); (S.Y.)
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30
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Mohamed AO, Otifi H, Hassan H, Yousif AA, Mustafa SA, Elsiddig SA, Babker AM, Ali EI, Elhag OO. Exploring the efficacy of AMACR, ERG, and AR immunostains in prostatic adenocarcinoma and their association with novel grade groups. Eur J Histochem 2025; 69:4172. [PMID: 39931952 PMCID: PMC11864098 DOI: 10.4081/ejh.2025.4172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 02/04/2025] [Indexed: 02/28/2025] Open
Abstract
The study examines the utility of AMACR, ERG, and AR immunostains in diagnosing prostatic adenocarcinoma (PCa) and assessing prognosis in comparison to the Gleason score and new WHO grading groups. Seventeen PCa biopsies and five benign prostatic hyperplasia (BPH) biopsies were analyzed. Immunoreactivity, scored from 1 to 3 based on percentage of positive cells and intensity of expression, was assessed, revealing 76.47% positivity for AMACR, 35.29% for ERG, and 94.12% for AR in PCa cases, with variable scores and intensity among markers and grade groups. AMACR sensitivity and ERG specificity were noted. Higher-grade PCa exhibited increased positivity for both markers, indicating prognostic significance. In BPH cases, AMACR showed positivity in 2 cases, ERG in 1, and AR in all cases, albeit with lower expression. Differential expression was observed among immunomarkers and grade groups of malignancy. AMACR and ERG stains serve as sensitive and specific markers for PCa diagnosis and prognosis. Their increasing positivity with higher-grade groups underscores prognostic value. These findings highlight the importance of immunostains in refining PCa diagnosis and prognostication.
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Affiliation(s)
- Andarawi O. Mohamed
- Pathology Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Hassan Otifi
- Pathology Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Hesham Hassan
- Pathology Department, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Adil A. Yousif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Saadalnour A. Mustafa
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Saudi Arabia
| | - Shawgi A. Elsiddig
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Asaad Ma Babker
- Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | - Elryah I. Ali
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia
| | - Omer Osman Elhag
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Sudan
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Linn Z, Gu Z, Wang L, Cai S. Stem Cell Transplantation for Ovarian Cancer Patient with Associated Myelodysplasia After Maintenance Therapy with Olaparib: A Case Report. Int Med Case Rep J 2025; 18:241-248. [PMID: 39959715 PMCID: PMC11829593 DOI: 10.2147/imcrj.s491062] [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: 09/01/2024] [Accepted: 01/24/2025] [Indexed: 02/18/2025] Open
Abstract
Ovarian cancer remains a significant cause of morbidity and mortality in women worldwide. Olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, has been shown in studies to increase the time that people with cancer do not get worse. However, reports have indicated rare adverse effects, like myelodysplastic syndrome (MDS). In this report, we highlight the case of a 42-year-old female patient who was diagnosed with ovarian endometrioid carcinoma, FIGO Stage IIB. Following surgery and chemotherapy, the patient commenced maintenance therapy with Olaparib. After two years, she experienced abnormal blood test results, which ultimately led to a diagnosis of myelodysplastic syndrome (MDS), confirmed through a bone marrow biopsy. Despite initial obstacles, the patient underwent stem cell transplantation as a treatment for MDS. After undergoing stem cell transplantation, the patient experienced a notable improvement in their condition. Upon reevaluation, the transplantation proved successful as it resolved the abnormalities related to MDS. Furthermore, the ovarian cancer status showed a positive response, with no signs of disease progression during the follow-up period. This particular case emphasizes the importance of being vigilant for uncommon adverse effects, such as MDS, in ovarian cancer patients undergoing Olaparib maintenance therapy. Early diagnosis and treatment, which may include stem cell transplantation, can lead to favorable results, not only in managing MDS but also in possibly slowing down the progression of ovarian cancer that is causing it. Additional research is necessary to understand the risk factors and the most effective management approaches for these complications in this specific group of patients.
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Affiliation(s)
- Zeyar Linn
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Naval Medical University (Changhai Hospital), Naval Medical University, Shanghai, People’s Republic of China
| | - Zhongyi Gu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Naval Medical University (Changhai Hospital), Naval Medical University, Shanghai, People’s Republic of China
| | - Libing Wang
- Department of Hematology, The First Affiliated Hospital of Naval Medical University (Changhai Hospital), Naval Medical University, Shanghai, People’s Republic of China
| | - Shengyun Cai
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Naval Medical University (Changhai Hospital), Naval Medical University, Shanghai, People’s Republic of China
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Zhang R, Guo R, Xin Y, Jiang Q, Qiu J. A bibliometric analysis of immune response in oral cancer. Discov Oncol 2025; 16:146. [PMID: 39928177 PMCID: PMC11811321 DOI: 10.1007/s12672-025-01912-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 02/03/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC), a type of oral cancer, has a high mortality rate and unfavorable outcomes. Its tumor microenvironment (TME) is intricate and adaptable, with research frequently focusing on the immune reaction. Scholars are exploring ways to enhance survival by bolstering the immune response within the TME. However, a comprehensive trend analysis is lacking. Bibliometric analysis can address this by visualizing research patterns. This study aimed to map these trends in OSCC immunology from 2003 to 2023. METHODS An immunology-focused search on OSCC was executed within the Web of Science Core Collection, spanning 2003 to 2023. Despite its narrow focus, the search offers a telling glimpse of current researches in this domain. Bibliometric analysis was performed using VOSviewer, Citespace, Scimago Graphica, and R software. RESULTS From 2003 to 2023, the field has published 805 publications, predominantly from China and the United States. The most valuable contributing author is Friedman Jay, topping co-citation counts. The journal Oral Oncology is the leading journal with the highest publication volume. An analysis of keyword bursts indicated that research into nivolumab and chemotherapy is a prevalent area of interest within the clinical community. These findings suggest that neoadjuvant immunotherapy represents a promising avenue for future therapeutic development. CONCLUSIONS This study presented a summary of the current trends and research frontiers in the field of immunological aspects of OSCC. This summary can serve as a valuable reference and a source of new insights into this area of research.
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Affiliation(s)
- Rongrong Zhang
- Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Key Laboratory of Oral Science, Nanchang First Affiliated Hospital, Nanchang, Jiangxi, China
- Medical College, Nanchang University, Nanchang, China
| | - Runying Guo
- Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Key Laboratory of Oral Science, Nanchang First Affiliated Hospital, Nanchang, Jiangxi, China
- Medical College, Nanchang University, Nanchang, China
| | - Yuqi Xin
- Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Key Laboratory of Oral Science, Nanchang First Affiliated Hospital, Nanchang, Jiangxi, China
- Medical College, Nanchang University, Nanchang, China
| | - Qingkun Jiang
- Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Key Laboratory of Oral Science, Nanchang First Affiliated Hospital, Nanchang, Jiangxi, China
- Medical College, Nanchang University, Nanchang, China
| | - Jiaxuan Qiu
- Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
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Papakonstantinou M, Fantakis A, Torzilli G, Donadon M, Chatzikomnitsa P, Giakoustidis D, Papadopoulos VN, Giakoustidis A. A Systematic Review of Disappearing Colorectal Liver Metastases: Resection or No Resection? J Clin Med 2025; 14:1147. [PMID: 40004679 PMCID: PMC11856073 DOI: 10.3390/jcm14041147] [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: 01/05/2025] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.
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Affiliation(s)
- Menelaos Papakonstantinou
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Antonios Fantakis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy;
| | - Matteo Donadon
- Surgical Oncology Program, University Maggiore Hospital, University of Piemonte Orientale, 28100 Novara, Italy;
| | - Paraskevi Chatzikomnitsa
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Dimitrios Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Vasileios N. Papadopoulos
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Alexandros Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
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Mekonnen EG, Birhanu A, Yimer M, Bizuneh S, Gizachew M, Gelaw B. Colonization of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and its associated factors in cancer patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. PLoS One 2025; 20:e0318242. [PMID: 39919122 DOI: 10.1371/journal.pone.0318242] [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: 06/20/2024] [Accepted: 01/12/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Cancer patients are predisposed to methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci colonization. However, the prevalence of these pathogens among cancer cases in Northwestern Ethiopia remains underreported. OBJECTIVE To determine the prevalence of colonization of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and associated factors among cancer patients at the University of Gondar Comprehensive Specialized Hospital, Northwestern Ethiopia. METHOD A cross-sectional study enrolled 288 confirmed cancer participants through stratified systematic random sampling, gathering socio-demographic and clinical data via pretested structured questionnaires from May 1 to July 30, 2023. Each participant provided two specimens: a nasal swab and a fecal sample. Nasal swabs were collected using sterile swabs, inserted at least 1 cm into each nostril, and rotated against the nasal membrane for 10 to 15 seconds, which were then placed in Amies transport medium. Fecal specimens were collected in leak-proof plastic containers, swabbed, and transferred to Cary Blair transport medium. Nasal swabs and fecal specimens were cultured on Mannitol salt agar at 37°C for Staphylococcus aureus identification, which was confirmed by coagulase testing and Gram staining. Enterococci were cultured on Bile esculin agar at 43°C and identified at the genus level by cultural characteristics, with confirmation through Gram reaction and catalase tests. Antibiotic susceptibility was evaluated using the Kirby-Bauer disk diffusion method, with minimum inhibitory concentrations for vancomycin determined via E-test strips. To detect methicillin-resistant Staphylococcus aureus, a cefoxitin disk was used. Inducible clindamycin resistance in Staphylococcus aureus was determined by the D test. Epi-info version 7 and SPSS version 27 were used for data entry and data analysis, respectively. The Pearson Chi-Square test was initially used to evaluate the association between factors and outcomes as the preliminary analysis, with a significance threshold of p < 0.05. Variables meeting this criterion underwent bivariable and multivariable logistic regression analyses, using p-value cutoffs of < 0.2 for bivariable and < 0.05 for multivariable analyses. RESULT The study involved 288 participants, with 51.0% being men and a mean age of 45.6 years. The prevalence of methicillin-resistant Staphylococcus aureus was 11.1% (95% CI: 7.5-14.7%), while vancomycin-resistant Enterococci had a prevalence of 2.8% (95% CI: 0.9-4.7%). Inducible clindamycin-resistant Staphylococcus aureus comprised 13.5% of the isolates. The multidrug-resistant proportion of Staphylococcus aureus and Enterococci were 56.2% and 55.2%, respectively. Both organisms exhibited the highest resistance to the antibiotic classes of penicillin and tetracycline. Significant associations were identified between methicillin-resistant Staphylococcus aureus colonization and low absolute neutrophil count (AOR = 13.050, 95% CI: 1.362-125.00, P = 0.026), and between vancomycin-resistant Enterococci colonization and having undergone an invasive procedure (AOR = 8.648, 95% CI: 1.870-39.992, P = 0.006). CONCLUSION The study reveals a significant prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci colonization among cancer patients, raising public health concerns. High antibiotic resistance rates complicate treatment and may impact patient outcomes. Notably, the high inducible clindamycin resistance report, highlights the need for D-testing. Screening for methicillin-resistant Staphylococcus aureus is recommended as an important antibiotic stewardship measure, while early detection of vancomycin-resistant Enterococci colonization is crucial to reduce complications.
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Affiliation(s)
- Eden Getaneh Mekonnen
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
| | - Abebe Birhanu
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
| | - Mulugeta Yimer
- Department of Pediatrics and Child Health, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
| | - Segenet Bizuneh
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
| | - Mucheye Gizachew
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
| | - Baye Gelaw
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Northwest Ethiopia
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Khalaf HS, El-Manawaty MA, Kotb ER, Abdelrahman MT, Shamroukh AH. Reactivity of 2-((3-Cyano-4-(4-Fluorophenyl)-6-(Naphthalen-2-yl)Pyridin-2-yl)Oxy)Acetohydrazide Toward Some Reagents for Preparing a Promising Anticancer Agents and Molecular Docking Study. Chem Biodivers 2025:e202403463. [PMID: 39910835 DOI: 10.1002/cbdv.202403463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/04/2025] [Accepted: 02/05/2025] [Indexed: 02/07/2025]
Abstract
This study aims to synthesize a novel series of nicotinonitriles incorporating pyrazole, oxadiazole, isoindoline, thiadiazole, and thiazolidinone moieties (compounds 4-11). The synthesis utilizes 2-((3-cyano-4-(4-fluorophenyl)-6-(naphthalen-2-yl)pyridin-2-yloxy)acetohydrazide (3) as a key starting material to enhance potential anticancer activity. The molecular structures of compounds 4-11 were elucidated using various spectroscopic techniques and elemental analysis. The synthesized compounds were screened for cytotoxic activity against human cancer cell lines, including MCF-7 (human Caucasian breast adenocarcinoma), MDA-MB-231 (breast ductal carcinoma), and PC-3 (prostate cancer), using an MTT assay with doxorubicin as a reference drug. Among the tested compounds, 4, 6b, and 7 exhibited the most promising cytotoxic activity, with IC50 values ranging from 22.5 to 91.3 µM. The safety profile of these compounds was further evaluated using noncancerous human skin fibroblast cells (BJ-1). Notably, 6b and 7 demonstrated high selectivity indices (SI > 3) against cancer cells, indicating preferential cytotoxicity, whereas compound 4 lacked selectivity. Docking studies, consistent with experimental data, further supported the potential anticancer properties of compounds 4, 6b, and 7. Given their significant inhibitory effects on cancer cell lines with minimal to no impact on normal cells, compounds 6b and 7 are strong candidates for further drug development as potential anticancer agents.
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Affiliation(s)
- Hemat S Khalaf
- Photochemistry Department, Chemical Industries Research Institute, National Research Centre, Cairo, Egypt
| | - May A El-Manawaty
- Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt
| | - Eman R Kotb
- Photochemistry Department, Chemical Industries Research Institute, National Research Centre, Cairo, Egypt
| | - Mohamad T Abdelrahman
- Radioisotopes Department, Nuclear Research Centre, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Ahmed H Shamroukh
- Photochemistry Department, Chemical Industries Research Institute, National Research Centre, Cairo, Egypt
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Zouzoulas D, Tsolakidis D, Karalis T, Aristotelidis M, Topalidou M, Grimbizis G. The impact of delay from diagnosis to surgery in endometrial cancer. Arch Gynecol Obstet 2025; 311:395-404. [PMID: 39636392 DOI: 10.1007/s00404-024-07855-x] [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] [Accepted: 11/22/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE When oncological waiting lists are prolonged, gynecological oncology units are forced to delay operations, especially for endometrial cancer (EC) due to its good prognosis among gynecological cancers. The aim of this study is to evaluate the impact of delay in the oncological outcomes of these patients. METHODS This is a retrospective analysis of all women with EC treated in our clinic, 2012-2019. Delay was calculated as the time interval between histological diagnosis of endometrial biopsy and definite surgery. The cutoff point was set at 8 weeks. Patients' characteristics, treatment options and follow-up information were collected. Primary outcomes were the need of adjuvant treatment and survival rates. RESULTS 259 Patients met the inclusion criteria. Based on the 8-week cutoff point, patients were divided into 2 groups: 119 underwent surgery up to 8 weeks (group A) and 140 over 8 weeks (group B). There was no statistical difference in the FIGO stage or the preoperative CA-125 levels between the two groups. However, patients in group A were younger, with lower body mass index (BMI) and less comorbidities. Furthermore, patients in group B had a significantly higher probability of receiving pelvic radiation with or without brachytherapy (p = 0.0053). Concerning survival rates, there was a statistically difference in disease-free (p = 0.0312), but no difference was found in overall survival (p = 0.146). CONCLUSION Delaying EC surgery over 8 weeks may not have an impact on the mortality of the patients, but increases the need of adjuvant pelvic radiation and worsens recurrence rates. As a result, patients experience more side effects which subsequently had negative impact on their quality of life.
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Affiliation(s)
- Dimitrios Zouzoulas
- 1st Department of Obstetrics - Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece.
| | - Dimitrios Tsolakidis
- 1st Department of Obstetrics - Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece
| | - Tilemachos Karalis
- 1st Department of Obstetrics - Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece
| | - Michalis Aristotelidis
- 1st Department of Obstetrics - Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece
| | - Maria Topalidou
- Department of Radiotherapy, "Papageorgiou" Hospital, Thessaloniki, Greece
| | - Grigorios Grimbizis
- 1st Department of Obstetrics - Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece
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Raza MH, Bhutta ME, Siddique MH. Proactive strategies for fracture risk in androgen deprivation therapy: a call for multidisciplinary collaboration. Osteoporos Int 2025; 36:369-370. [PMID: 39680119 DOI: 10.1007/s00198-024-07330-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/29/2024] [Indexed: 12/17/2024]
Affiliation(s)
- Muhammad Hunain Raza
- Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
| | - Muhammad Eeman Bhutta
- Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan.
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Tonui P, Itsura P, Omenge O, Faiza N, Keter A, Mburu A, Oguda J, Hassan AR, Cu-Uvin S. Digital cervicography using mobile phones with real-time consultation (DCRC) to improve performance of Visual Inspection with Acetic Acid (VIA) in cervical cancer screening of HIV-infected women. A cross-sectional study. Gynecol Oncol Rep 2025; 57:101661. [PMID: 39817117 PMCID: PMC11733201 DOI: 10.1016/j.gore.2024.101661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 12/02/2024] [Accepted: 12/11/2024] [Indexed: 01/18/2025] Open
Abstract
Introduction Visual Inspection with Acetic Acid (VIA) has been adopted for cervical cancer screening in Kenya and other Low-Middle Income Countries despite providing suboptimal results among HIV-infected women. It is mostly performed by nurses in health centers. Innovative ways of improving the performance of VIA in HIV-infected women are desired. Objective To establish the feasibility of screening with VIA and Digital Cervicography with Real-time Consultation (VIA-DCRC), and compare its performance to screening with VIA alone among HIV + women. Methods This was a cross-sectional analytical study of two hundred HIV + women. There were two groups of women who underwent either VIA or VIA/DCRC cervical cancer screening arms. In the VIA/DCRC arm, a trained nurse did the VIA, captured an image of the cervix, uploaded it, and electronically shared it in real-time with three blinded study consultants (gynecologic oncologists) who separately assessed the digital image and classified it as VIA/DCRC positive or negative. Any two opinions of the gynecologic oncologists that concurred were considered as the final diagnosis.All participants who screened positive underwent colposcopy and biopsy prior to treatment. Tissues obtained were subjected to histopathological examination. A fraction (15 %) of those who screened negative for VIA and VIA/ DCRC had random cervical biopsies taken at 12 and 6o'clock positions. We estimated the measures of accuracy using the Bayesian method. Results The mean age was 39.7 +/- 10.7 years. Average CD4 + count and plasma viral load (log base 10) were 492.2 (SD: 255.3) cells per mm3, and 2.6 (SD: 0.7) copies per ml respectively. None of the women was a smoker.The median (IQR) time taken for at least one gynecologic oncologist to respond to a digital consultation was 2.0 (IQR 1.0, 4.0) minutes, range: 1.0 - 47.0.Overall, 60.5 % were diagnosed with cervical pre-malignancies (VIA: 23.1 % (95 % Credible Bounds (CB): 10.1, 37.5), VIA/DCRC: 37.5 % (95 % CB: 26.6, 50.1)).VIA sensitivity, specificity, positive predictive value and negative predictive value were 28.1 % (95 % CB: 11.2, 6.8), 97.8 % (95 % CB: 93.0, 99.7), 79.8 % (95 % CB: 47.3, 96.8), and 80.4 % (95 % CB: 71.0, 87.5) while that of VIA/DCRC was 69.3 % (95 % CB: 47.8, 89.7), 87.9 % (95 % CB: 76.3, 94.4), 77.6 % (95 % CB: 61.9, 89.3), and 80.3 % (95 % CB: 70.2, 88.9) respectively. Compared to the VIA/DCRC group, there was evidence of better sensitivity, comparable negative predictive value, but poor specificity, RR: 2.46 (95 % CB: 1.06, 6.26), RR: 1.65 (95 % CB: 1.00, 3.50), and RR: 0.90 (95 % CB: 0.78, 0.98) respectively. Conclusions Cervical cancer screening in HIV + women using VIA/DCRC is feasible and it significantly improves the sensitivity, and comparable negative predictive value of VIA in diagnosing the presence of cervical pre-malignancies by more than double, and 65 % respectively.
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Affiliation(s)
| | | | | | | | - A. Keter
- Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya
| | | | - J. Oguda
- Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya
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Afzal H, Shaukat A, Ul Haq MZ, Khaliq N, Zahid M, Shakeel L, Wasay Zuberi MA, Akilimali A. Serum metabolic profiling analysis of chronic gastritis and gastric cancer by untargeted metabolomics. Ann Med Surg (Lond) 2025; 87:583-597. [PMID: 40110261 PMCID: PMC11918594 DOI: 10.1097/ms9.0000000000002977] [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: 08/27/2024] [Accepted: 01/12/2025] [Indexed: 03/22/2025] Open
Abstract
Chronic gastritis (CG), particularly when associated with Helicobacter pylori (H. pylori) infection, is a significant precursor to gastric cancer (GC), a leading cause of cancer-related deaths worldwide. The persistent inflammation in CG, driven by factors such as H. pylori, induces oxidative stress and DNA damage in gastric epithelial cells, which can lead to malignant transformation. Atrophic gastritis, a form of CG, can be categorized into autoimmune and H. pylori-associated types, both of which increase the risk of GC development, particularly when compounded by external factors like smoking and dietary habits. This manuscript explores the pathophysiological mechanisms underlying CG and its progression to GC, highlighting the critical role of metabolomics in advancing our understanding of these processes. Metabolomics, the comprehensive study of metabolites, offers a novel approach to identifying biomarkers that could facilitate early detection and improve the accuracy of GC diagnosis and prognosis. The analysis of metabolic alterations, particularly in glucose, lipid, and amino acid metabolism, reveals distinct biochemical pathways associated with the progression from benign gastritis to malignancy. Integrating metabolomic profiling with traditional diagnostic methods can revolutionize GC management, enabling more personalized treatment strategies and improving clinical outcomes. However, significant challenges remain, including the need to validate biomarkers across diverse populations and standardize metabolomic techniques. Future research should address these challenges to fully realize the potential of metabolomics in early GC detection and treatment, ultimately aiming to reduce the global burden of this deadly disease.
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Affiliation(s)
- Hadiya Afzal
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Ayesha Shaukat
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Muhammad Zain Ul Haq
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Nawal Khaliq
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Maha Zahid
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Laiba Shakeel
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | | | - Aymar Akilimali
- Department of Research, Medical Research Circle (MedReC), Goma, Democratic Republic of the Congo
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Lv M, Feng Y, Zeng S, Zhang Y, Shen W, Guan W, E X, Zeng H, Zhao R, Yu J. Hotspots and frontiers of autophagy and chemotherapy in lung cancer: a bibliometric and visualization analysis from 2003 to 2023. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1583-1595. [PMID: 39120721 DOI: 10.1007/s00210-024-03354-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/01/2024] [Indexed: 08/10/2024]
Abstract
Autophagy was considered to induce resistance in chemotherapy, which was significantly associated with proliferation of cancer; however, few bibliometric studies on the relation between autophagy and chemotherapy in lung cancer are available. The aim of the present study was to provide a comprehensive overview of the knowledge structure and research hotspots of autophagy and chemotherapy in lung cancer by bibliometric analysis. Publications related to autophagy and chemotherapy in lung cancer from 2003 to 2023 were searched on the Web of Science Core Collection (WoSCC) database. The bibliometric analysis was conducted by using VOSviewers, CiteSpace, and the R package "bibliometrix." A total of 675 articles from 70 countries, led by China and the United States, were included in the analysis. The number of publications related to autophagy and chemotherapy in lung cancer is increasing year by year. Nanjing Medical University, Zhejiang University, China Medical University, and Sichuan University are among the main research institutions contributing to this field. The journal Cancers is the most popular publication in this area, with Autophagy being the most co-cited journal. These publications involve 4481 authors, with Chiu Chien-chih and Gewirtz David having published the most papers, and Noboru Mizushima being the most frequently co-cited author. Studying the relation between autophagy and chemotherapy in the occurrence and development of lung cancer, and exploring therapeutic strategies involving autophagy and chemotherapy in lung cancer, are the primary topics in this research field. "Tumor stem cells," "microRNA," and "EGFR" emerge as the primary keywords in the emerging research hotspots. Indeed, this bibliometric study provides valuable insights into the research trends and developments concerning autophagy and chemotherapy in lung cancer. By identifying recent research frontiers and highlighting hot directions, this study serves as a valuable reference for scholars interested in understanding the relationship between autophagy and chemotherapy in lung cancer. The comprehensive summary of findings offers a foundation for further exploration and advancement in this critical area of cancer research.
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Affiliation(s)
- Minghe Lv
- Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Yue Feng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Su Zeng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Yang Zhang
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Wenhao Shen
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Wenhui Guan
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Xiangyu E
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China
| | - Hongwei Zeng
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
| | - Ruping Zhao
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
| | - Jingping Yu
- Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China.
- Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhang Heng Road, Pudong New Area, Shanghai, 201203, China.
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Marino L, Kim A, Ni B, Celi FS. Thyroid hormone action and liver disease, a complex interplay. Hepatology 2025; 81:651-669. [PMID: 37535802 PMCID: PMC11737129 DOI: 10.1097/hep.0000000000000551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 07/05/2023] [Indexed: 08/05/2023]
Abstract
Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease.
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Affiliation(s)
- Luigi Marino
- Department of Medicine, UConn Health, University of Connecticut, Farmington, Connecticut, USA
| | - Adam Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, UConn Health, University of Connecticut, Farmington, Connecticut, USA
| | - Bin Ni
- Alliance Pharma, Philadelphia, Pennsylvania, USA
| | - Francesco S. Celi
- Department of Medicine, UConn Health, University of Connecticut, Farmington, Connecticut, USA
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Chuang J, Chen Y, Wang J. Narrative review of neoadjuvant therapy in patients with locally advanced colon cancer. Kaohsiung J Med Sci 2025; 41:e12926. [PMID: 39717937 PMCID: PMC11827549 DOI: 10.1002/kjm2.12926] [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: 11/13/2024] [Revised: 11/28/2024] [Accepted: 12/10/2024] [Indexed: 12/25/2024] Open
Abstract
Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide, with more than 1.9 million new cases reported in 2020, and is associated with major survival challenges, particularly in patients with locally advanced colon cancer (LACC). LACC often involves T4 invasion or extensive nodal involvement and requires a multidisciplinary approach for management. Radical surgery followed by adjuvant chemotherapy remains the primary treatment strategy for LACC. However, achieving complete tumor resection (R0) is challenging because locally advanced colon tumors typically infiltrate adjacent organs or nodes. Advancements in LACC treatment have involved neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), and neoadjuvant immunotherapy (NAIT). Studies such as FOxTROT and PRODIGE 22 have demonstrated that NACT, particularly with FOLFOX or CAPOX, can lead to major tumor downstaging, improved survival rates, and increased R0 resection rates. Predictive biomarkers, such as mismatch repair (MMR) status and T stage, are crucial in identifying candidates who may benefit from NACT. NACRT has demonstrated promise in enhancing tumor regression, particularly in patients with rectal cancer, underscoring its potential for use with LACC. NAIT, particularly for deficient MMR tumors, has emerged as a novel approach, with studies such as NICHE-2 and NICHE-3 reporting excellent pathologic responses and pathologic complete responses. Integrating these therapies can enhance the surgical and survival outcomes of patients with LACC, highlighting the importance of personalized treatment strategies based on tumor characteristics and response to neoadjuvant interventions. This review discusses the evolving landscape of LACC management, focusing on optimizing treatment approaches for improved patient outcomes.
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Affiliation(s)
- Jen‐Pin Chuang
- Chiayi HospitalMinistry of Health and WelfareChiayiTaiwan
- Department of Surgery, Faculty of Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of SurgeryNational Cheng Kung University HospitalTainanTaiwan
| | - Yen‐Chen Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
- Graduate Institute of Clinical Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Department of Surgery, Faculty of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
| | - Jaw‐Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
- Graduate Institute of Clinical Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Department of Surgery, Faculty of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Graduate Institute of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Center for Cancer ResearchKaohsiung Medical UniversityKaohsiungTaiwan
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Paschou SA, Andrikopoulou A, Mili N, Svarna A, Kaparelou M, Stefanaki K, Dedes N, Liatsou E, Thomakos N, Haidopoulos D, Psaltopoulou T, Kastritis E, Zagouri F, Dimopoulos MA, Liontos M. Possible Prognostic Role of BMI Before Chemotherapy in the Outcomes of Women with Ovarian Cancer. Nutrients 2025; 17:556. [PMID: 39940415 PMCID: PMC11820758 DOI: 10.3390/nu17030556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need to identify modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, both prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conflicting data on the associations of body mass index (BMI) with progression-free survival (PFS) and overall survival (OS) in ovarian cancer patients necessitate further exploration. This study aims to investigate the prognostic role of BMI before chemotherapy in women with ovarian cancer, specifically focusing on PFS and OS. METHODS A retrospective analysis encompassed 1,136 patients diagnosed with ovarian carcinomas between 1995 and 2018. Patients were categorized based on BMI at presentation, and a comprehensive examination of clinicopathological, treatment, and survival data was conducted. RESULTS In the patient population, normal weight patients (BMI < 25 kg/m2) demonstrated a median PFS of 12.8 months (95% CI 11.7-13.9 months), while overweight/obese patients (BMI ≥ 25 kg/m2) exhibited a significantly longer median PFS of 14.9 months (95% CI 13.6-16.4 months, P = 0.006). No statistically significant difference was noted in median OS between the two BMI groups. Subgroup analysis for different histological subtypes revealed a statistically significant benefit for overweight and obese patients with serous and endometrioid histology (mPFS 12.9 months, 95% CI 11.7-14.0 vs. 15.6 months, 95% CI 13.9-17.3, P = 0.012 and 14.6 months 95% CI 13.7-15.5 vs. 25.6 months, 95% CI 9.5-41.7, P = 0.031, respectively). Additionally, BMI ≥ 25 kg/m2 demonstrated a significant advantage in advanced-stage disease. CONCLUSIONS The study underscores the intricate association between BMI and ovarian cancer prognosis. While a statistically significant difference in progression-free survival was noted between normal weight and overweight/obese patients, with the latter group experiencing a survival benefit, no such difference was observed in overall survival.
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Affiliation(s)
- Stavroula A. Paschou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 Vasilisis Sophias, 11528 Athens, Greece; (S.A.P.); (K.S.)
| | - Angeliki Andrikopoulou
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Nikoletta Mili
- 2nd Department of Obstetrics and Gynaecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Anna Svarna
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Maria Kaparelou
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Katerina Stefanaki
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 80 Vasilisis Sophias, 11528 Athens, Greece; (S.A.P.); (K.S.)
| | - Nikolaos Dedes
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Efstathia Liatsou
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Nikolaos Thomakos
- 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (N.T.); (D.H.)
| | - Dimitrios Haidopoulos
- 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (N.T.); (D.H.)
| | - Theodora Psaltopoulou
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Efstathios Kastritis
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Flora Zagouri
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Meletios-Athanasios Dimopoulos
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
| | - Michalis Liontos
- Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece; (A.A.); (A.S.); (M.K.); (N.D.); (E.L.); (T.P.); (E.K.); (F.Z.); (M.-A.D.)
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Huang C, Zhang C, Li J, Duan Y, Tang Q, Bi F. Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma. Cell Biol Toxicol 2025; 41:35. [PMID: 39871031 PMCID: PMC11772449 DOI: 10.1007/s10565-024-09979-x] [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: 07/24/2024] [Accepted: 12/21/2024] [Indexed: 01/29/2025]
Abstract
Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora. Pirfenidone (PFD) can augment Sora's inhibitory effect on hepatocellular carcinoma by specifically targeting p38γ. Our study further uncovers that pirfenidone can synergistically boost the anti-hepatocellular carcinoma impact of Sora by impeding the autophagy heightened by p38γ. Taken together, our findings suggest that pirfenidone can work in concert with Sora to intensify its anti-tumor effect on hepatocellular carcinoma, thereby offering a novel therapeutic approach for Sora-mediated tumor treatment.
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Affiliation(s)
- Chen Huang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China
- Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China
| | - Chenliang Zhang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China
- Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China
| | - Jiajin Li
- Sichuan University, West China Hospital of Sichuan University, Chengdu, China
| | - Yichun Duan
- Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China
| | - Qiulin Tang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China
| | - Feng Bi
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.
- Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Cancer Center, 610041, Chengdu, Sichuan Province, China.
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Toma C, Popa R, Ciobanu L, Baldea I, Amorim I, Bochynska D, Wolfe A, Negoescu A, Gal C, Taulescu M. Overexpression of IL-6 and STAT3 may provide new insights into ovine pulmonary adenocarcinoma development. BMC Vet Res 2025; 21:29. [PMID: 39833798 PMCID: PMC11744984 DOI: 10.1186/s12917-024-04429-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 12/04/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Ovine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV) and is considered an important potential animal model for human lung cancer. The precise mechanisms of OPA oncogenesis are still uncertain. The transcription factor signal transducer and activator of transcription 3 (STAT3) is activated by interleukin-6 (IL-6) in many cancers, but this aspect is unknown in OPA. We therefore aimed to evaluate the expression of IL-6 and STAT3 in OPA for its potential role in pulmonary carcinogenesis. RESULTS Lung tissues from 9 grossly normal and JRSV-negative sheep and 20 cases of JSRV-positive OPA sheep were included in the study. Tissue samples were stained with antibodies against IL-6, STAT3, and JSRV-MA. IL-6 and STAT3 were further quantified in both groups using Western Blot (WB). Immunohistochemically, IL‑6 was expressed in stromal, inflammatory, and epithelial cells in all cases of OPA, while STAT3 immunoexpression was restricted to epithelial cells. In the OPA group, the percentage of immunolabelled cells for STAT3 accounted for a mean value of 96%. Using the H-SCORE method, 95% of cases were considered positive for STAT3 expression. Control tissues showed multifocal and weak immunoexpression for both markers. Using WB analyses, a highly significant amount of both IL-6 (p = 0.0078) and STAT3 (p < 0.0001) proteins were present in lung neoplasms, by comparison to the control lungs. CONCLUSIONS Our data showed overexpression of IL-6 and STAT3 in lung tissues from OPA compared to lungs from JSRV-negative sheep. These results suggest a potential role of IL6-STAT3 in OPA carcinogenesis.
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Affiliation(s)
- Corina Toma
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania.
| | - Roxana Popa
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Lidia Ciobanu
- Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj-Napoca, Romania
| | - Ioana Baldea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj- Napoca, Romania
| | - Irina Amorim
- Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
- Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal
| | - Diana Bochynska
- Ross University School of Veterinary Medicine, Basseterre, St. Kitts and Nevis
| | - Alan Wolfe
- Pathobiology Section, School of Veterinary Medicine, University College Dublin, Dublin, Ireland
| | - Andrada Negoescu
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Claudiu Gal
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
- Synevovet laboratory, Bucharest, Romania
| | - Marian Taulescu
- Department of Veterinary Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
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Vasu S, Verma D, Souraph S OS, Anki Reddy K, Packirisamy G, S UK. In Situ Ag-Seeded Lamellar Ti 3C 2 Nanosheets: An Electroactive Interface for Noninvasive Diagnosis of Oral Carcinoma via Salivary TNF-α Sensing. ACS APPLIED BIO MATERIALS 2025; 8:420-434. [PMID: 39787292 DOI: 10.1021/acsabm.4c01379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
In the fast-paced quest for early cancer detection, noninvasive screening techniques have emerged as game-changers, offering simple and accessible avenues for precession diagnostics. In line with this, our study highlights the potential of silver nanoparticle-decorated titanium carbide MXene nanosheets (Ti3C2_AgNPs) as an electroactive interface for the noninvasive diagnosis of oral carcinoma based on the prevalence of the salivary biomarker, tumor necrosis factor-α (TNF-α). An in situ reduction was utilized to synthesize the Ti3C2_AgNPs nanohybrid, wherein Ti3C2 acts as the reducing agent, and the resulting nanohybrid was subjected to various characterization techniques to examine the optical, structural, and morphological attributes. The results revealed that spherical AgNPs formed on the surface of Ti3C2 MXene nanosheets by virtue of the low-valent Ti species present in Ti3C2, which facilitated the reduction of AgNO3 to AgNPs. Furthermore, the electrochemical characterization of the nanohybrid-modified screen-printed electrode (Ti3C2_AgNPs/SPE) indicated enhanced heterogeneous electron transfer kinetics. With these encouraging results, the Ti3C2_AgNPs nanohybrid was employed as an immobilization matrix for TNF-α antibodies and applied for electrochemical sensing. Analytical studies of the fabricated immunosensor, conducted by differential pulse voltammetry (DPV), exhibited a broader linear range (1 to 180 pg mL-1), a low limit of detection (0.97 pg mL-1), and high sensitivity (1.214 μA mL pg-1 cm-2) and specificity, even in artificial saliva, indicating its reliability for oral carcinoma diagnosis. Therefore, the Ti3C2_AgNP nanohybrid seems a promising candidate for the effective sensing of TNF-α and could also be explored for other biomarkers.
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Affiliation(s)
- Sunil Vasu
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh 517619, India
| | - Damini Verma
- Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | - Omal Surya Souraph S
- Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | - Katha Anki Reddy
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh 517619, India
| | - Gopinath Packirisamy
- Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | - Uday Kumar S
- Department of Chemical Engineering, Indian Institute of Technology Tirupati, Tirupati, Andhra Pradesh 517619, India
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El-Saghier AM, Hashem H, Maher SA, Enaili SS, Alkhammash A, Bräse S, Aziz HA. Design, Synthesis, Anticancer Screening, and Mechanistic Study of Spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide Derivatives. Int J Mol Sci 2025; 26:863. [PMID: 39859577 PMCID: PMC11766273 DOI: 10.3390/ijms26020863] [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: 11/13/2024] [Revised: 12/31/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. The in vitro anticancer evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound 1) exhibited significant anticancer efficacy as a selective inhibitor of tumor-associated isoforms of carbonic anhydrase. Compound 1 demonstrated considerable efficacy against the renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, with IC50 values of 7.01 ± 0.39, 24.3 ± 1.29, and 9.55 ± 0.51 µM, respectively. In comparison, doxorubicin exhibited IC50 values of 13.54 ± 0.82, 13.50 ± 0.71, and 6.08 ± 0.32 µM for the corresponding cell lines. Importantly, compound 1 exhibited lower toxicity to the normal WI 38 cell line than doxorubicin, with IC50 values of 46.20 ± 2.59 and 18.13 ± 0.93 µM, respectively, indicating greater selectivity of the target compound compared to the standard anticancer agent doxorubicin. Also, mechanistic experiments demonstrated that compound 1 exhibits inhibitory activity against human carbonic anhydrase hCA IX and XII, with IC50 values of 0.477 ± 0.03 and 1.933 ± 0.11 μM, respectively, indicating enhanced selectivity for cancer-associated isoforms over cytosolic isoforms hCA I and II, with IC50 values of 7.353 ± 0.36 and 12.560 ± 0.74 μM, respectively. Cell cycle studies revealed that compound 1 caused G1 phase arrest in RXF393 cells, and apoptosis experiments verified a substantial induction of apoptosis with significant levels of early and late apoptosis, as well as necrosis (11.69%, 19.78%, and 3.66%, respectively), comparable to those induced by the conventional cytotoxic agent doxorubicin, at 9.91%, 23.37%, and 6.16%, respectively. Molecular docking experiments confirmed the strong binding affinity of compound 1 to the active sites of hCA IX and XII, highlighting significant interactions with zinc-binding groups and hydrophobic residues. These findings underscore the target compound's potential as a viable anticancer agent via targeting CA.
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Affiliation(s)
- Ahmed M. El-Saghier
- Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt
| | - Hamada Hashem
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt
| | - Sherif A. Maher
- Department of Biochemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt;
| | - Souhaila S. Enaili
- Department of Chemistry, Faculty of Science, University of Zawia, Az Zawiyah 16418, Libya;
| | - Abdullah Alkhammash
- Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia;
| | - Stefan Bräse
- Institute for Biological and Chemical System, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany
| | - Hossameldin A. Aziz
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt;
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Walle GT, Kitaw TA, Adane S. Incidence and determinants of mortality among patients with colorectal cancer in oncology centers of Amhara region, Ethiopia, 2024: multicenter retrospective follow up study. BMC Cancer 2025; 25:102. [PMID: 39827340 PMCID: PMC11742809 DOI: 10.1186/s12885-025-13462-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: 07/31/2024] [Accepted: 01/06/2025] [Indexed: 01/22/2025] Open
Abstract
INTRODUCTION Colorectal cancer is a significant cause of mortality globally, with several factors impacting patient outcomes, including access to healthcare, early detection, and treatment. Despite this, the specific factors affecting incidence of death among colorectal cancer patients in the Amhara region have not been thoroughly investigated. Thus, this study seeks to assess incidence and determinants of mortality among colorectal cancer patients in Amhara Region oncology centers. RESULTS The mean age of the participants was 48.6 years (SD ± 15). Median survival time was 23.8 months. The overall incidence rate or incidence density of a colorectal cancer mortality rate was 2.9 per 100 person-months (95% CI: 2.5-3.4). Survival rates of colorectal cancer patients 1and 5 year was 69.78% and 16.1%, respectively. The result of the multivariable analysis showed that colorectal cancer patients who had presenting symptoms [AHR = 2.67 (95% CI: 1.95, 3.67)], Base line HGB level < 12.5 mg/dl [AHR = 1.63 (95% CI: 1.12, 2.37)], WHO or ECOG poor performance status [AHR = 2.99 (95% CI: 2.17, 4.12), late stage of cancer [AHR = 2.32 (95% CI: 1.42, 3.79)] and location of tumor on colorectal [AHR = 1.76 (95% CI: 1.20, 2.55)] were significantly associated with mortality of colorectal cancer. CONCLUSION AND RECOMMENDATION The study highlights significant findings on the survival and mortality of colorectal cancer patients. The overall mortality rate was 2.9 per 100 person-months. Multivariable analysis identified presenting symptoms, low baseline hemoglobin levels, poor performance status, late-stage cancer, and tumor location as significant predictors of mortality. Highlighting the need for early detection and targeted care strategies.
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Affiliation(s)
| | | | - Seteamlak Adane
- School of Public health, College of Health Science, Woldia University, Woldia, Ethiopia
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Toson EA, El-Fallal AA, Oransa MA, El-Gharabawy HM. In vitro antitumor effects of methanolic extracts of three Ganoderema mushrooms. Sci Rep 2025; 15:2274. [PMID: 39824924 PMCID: PMC11748650 DOI: 10.1038/s41598-025-86162-0] [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: 06/05/2024] [Accepted: 01/08/2025] [Indexed: 01/20/2025] Open
Abstract
Ganoderma mushrooms have a variety of pharmacological activities and may have antitumor effects. Therefore, the antitumor activity of the methanolic fruiting body extracts of three Ganoderma spp. will be evaluated by estimating cell viability, cell cycle parameters and the mode of cellular death. In this regard, Sulfo-rhodamine B staining and flow cytometry were used. Hepatocellular carcinoma (HepG2) and breast ductal carcinoma (T-47D) cell lines were used as cancer models, while mouse normal liver (BNL) and oral epithelial cell (OEC) lines were used as respective controls. The results revealed that Ganoderma resinaceum extract decreased the viability of BNL at an IC50 > 100 µg/mL but not that of HepG2 at an IC50 of 72.32 µg/mL. Additionally, Ganoderma australe and Ganoderma mbrekobenum decreased the viability of OEC cell line at an IC50 of 328.29 and 271.56 µg/ mL, respectively. On the other hand, the IC50 of T-47D were 221.95 and 236.45 µg/mL, respectively. The three extracts arrested the cell life cycle at the G1 phase in each case. G. resinaceum extract stimulated total apoptosis (Q2 + Q4) of 19.99% with low necrosis (Q1). However, the percentages of total cell necrosis in the T-47D cell line treated with the other two extracts were 31.10% and 18.28%, respectively while the percentages of total cell apoptosis were 6.83% and 1.78%, respectively. Thus, G. resinaceum significantly inhibited the viability of the HepG2 cell line, while both the G. australe and G. mbrekobenum extracts significantly decreased the viability of the T-47D cell line. These results may encourage speculation about their possible use for the therapeutic management of hepatocellular carcinoma and breast ductal carcinoma after further investigation.
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Affiliation(s)
- Elshahat A Toson
- Chemistry Department, Faculty of Science, Damietta University, New Damietta, 34517, Egypt.
| | - Amira A El-Fallal
- Botany and Microbiology Department, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Marwa A Oransa
- Botany and Microbiology Department, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Hoda M El-Gharabawy
- Botany and Microbiology Department, Faculty of Science, Damietta University, New Damietta, 34517, Egypt.
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50
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Zhao Y, Xue J. Bibliometric analysis of laryngeal cancer treatment literature (2003-2023). Heliyon 2025; 11:e40832. [PMID: 39811326 PMCID: PMC11730226 DOI: 10.1016/j.heliyon.2024.e40832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 11/27/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
Background Despite advancements in medical science, the 5-year survival rate for laryngeal squamous cell carcinoma remains low, posing significant challenges in clinical management. This study explores the evolution of key topics and trends in laryngeal cancer research. Bibliometric and knowledge graph analysis are utilized to assess contributions in treating this carcinoma and to forecast emerging research hotspots that may enhance future clinical outcomes. The findings aim to guide researchers by identifying new areas, providing valuable insights and innovative perspectives. Methods Data were extracted from the Web of Science Core Collection database on December 1, 2023. Bibliometric and knowledge mapping analyses were conducted using software tools such as R-Studio 4.1.3, CiteSpace 6.1.R6, VOSviewer 1.6.18, and http://bibliometre.com.(Both CiteSpace 6.1.R6 and VOSviewer 1.6.18 are widely used bibliometric analysis software tools, each with distinct features and applications. CiteSpace primarily focuses on analyzing literature citation relationships and generating knowledge graphs to visualize research hotspots, trends, and knowledge structures. Its data sources include platforms such as Web of Science. While CiteSpace excels in presenting knowledge structures through its advanced visualization capabilities, it is relatively complex to operate and less efficient in processing large-scale datasets. As a result, it is frequently employed in exploring research trends across multiple disciplines. On the other hand, VOSviewer is designed to construct various types of bibliometric networks and is characterized by its intuitive and user-friendly interface. It supports a wide range of data sources and produces visually appealing and clear visualizations, making it particularly suitable for multi-disciplinary bibliometric research. Additionally, VOSviewer provides valuable insights that can inform scientific research decision-making. Overall, the two tools differ in terms of functionality, data sources, visualization effects, and operational complexity, offering researchers complementary options for bibliometric analysis based on their specific needs.) From this database, 800 papers were extracted using specific criteria. After narrowing the scope to English-language publications, this number was reduced to 775. To ensure data quality, conference papers, letters, and editorial materials were excluded, focusing only on original research papers and review articles. Results The analysis showed that 760 theoretical works and review papers were published in 96 academic journals by 4210 authors from 1148 institutions across 60 countries/regions. The United States emerged as the most significant contributor to laryngeal cancer research. The Croatian Rudjer Boskovic Institute was notable for having the highest publication and citation counts. Among individual researchers, Osmak, M was identified as the most prolific and cited. Predominant international collaborations occurred between European and American countries. The Head and Neck Science Journal was the most frequently co-cited publication. Major research themes encompassed morphological aspects, chemotherapy, and molecular pathway mechanisms in laryngeal cancer treatment. Current research hotspots include disease prognosis, models, clinical trials, tumor recurrence, and surveillance. Notably, targeted therapy and immunotherapy are rapidly advancing fields. Conclusions There is an urgent need to enhance global scholarly communication as the pursuit of effective laryngeal cancer treatment progresses. Focused research on targeting indicators for this type of cancer remains vital. An impending surge in research is driven by investigations into biomarkers, microenvironmental genetic mechanisms, alternatives to systemic chemotherapy, minimally invasive surgery, and herbal medicine explorations.
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Affiliation(s)
- Yan Zhao
- Medical Oncology, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning Province, 110000, China
| | - Jiancheng Xue
- Department of Otolaryngology Head and Neck Surgery, the Second People's Hospital of Shenzhen, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518035, China
- Shenzhen Medical Clinical Research Center for Otolaryngology Diseases, the Second People's Hospital of Shenzhen, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, 518035, China
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