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Zhang S, Miao L, Tian X, Yang B, Luo B. Opportunities and challenges of immuno-oncology: A bibliometric analysis from 2014 to 2023. Hum Vaccin Immunother 2025; 21:2440203. [PMID: 39885669 PMCID: PMC11792843 DOI: 10.1080/21645515.2024.2440203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 11/22/2024] [Accepted: 12/06/2024] [Indexed: 02/01/2025] Open
Abstract
The emergence of immuno-oncology (IO) has led to revolutionary changes in the field of cancer treatment. Despite notable advancements in this field, a thorough exploration of its full depth and extent has yet to be performed. This study provides a comprehensive overview of publications pertaining to IO. Publications on IO from 2014 to 2023 were retrieved by searching the Web of Science Core Collection database (WoSCC). VOSviewer software and Citespace software were used for the visualized analysis. A total of 1,874 articles have been published in the IO domain. The number of publications and citations has been increasing annually. This study also examines the primary research directions within the field of IO. In conclusion, this study offers a comprehensive overview of the opportunities and challenges associated with IO, illuminating the current status of research and indicating potential future trajectories in this rapidly progressing field. This study provides a comprehensive survey of the current research status and hot spots within the field of IO. It will assist researchers in comprehending the current research emphasis and development trends in this field and offers guidance for future research directions.
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Affiliation(s)
- Siqi Zhang
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Oncology, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Department of Oncology, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Lina Miao
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoxia Tian
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Bingxu Yang
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Baoping Luo
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
- Department of Oncology, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China
- Department of Oncology, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
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2
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Mikolaskova I, Gidron Y, Durmanova V, Suchankova M, Bucova M, Hunakova L. Mental distress and inflammation in bladder cancer: The nerve makes things less vague. Brain Behav Immun Health 2025; 46:100995. [PMID: 40343109 PMCID: PMC12059323 DOI: 10.1016/j.bbih.2025.100995] [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: 10/23/2024] [Revised: 03/14/2025] [Accepted: 04/12/2025] [Indexed: 05/11/2025] Open
Abstract
Objectives This study aimed to explore the interaction between perceived stress, life satisfaction, heart rate variability (HRV), and immune-inflammatory markers in bladder cancer patients. We investigated how HRV moderates the relationship between psychological distress and levels of TNF-α and TGF-β cytokines. We hypothesized that high vagal nerve activity, as indicated by higher HRV, mitigates the impact of perceived stress and life dissatisfaction on inflammation. Methods The study included 73 patients with bladder cancer. HRV was determined from a 5-min ECG recording, focusing on the standard deviation of normal-to-normal interbeat intervals (SDNN). Psychological distress was measured using the Perceived Stress Scale (PSS), and life satisfaction was evaluated with the Life Satisfaction Questionnaire (LSQ). Serum concentrations of TNF-α and plasma levels of TGF-β were determined using sandwich ELISA. Results We found evidence that HRV modulates the relation between perceived stress and inflammation. In patients with low HRV (SDNN <20 ms), PSS was positively correlated with serum level of TNF-α and negatively with the level of TGF-β, while life satisfaction was positively correlated with TGF-β. These relationships were not significant in patients with high HRV (SDNN ≥20 ms). Conclusion Our findings suggest that high vagal activity, as indicated by higher HRV, may mitigate the adverse effects of psychological distress on immune-inflammatory responses in patients with bladder cancer. Stress-related inflammation took place under conditions of low HRV, highlighting the potential role of autonomic regulation in cancer prognosis. Future research should further explore these relationships to develop interventions aimed at improving patient outcomes through stress management and enhanced vagal nerve activity to regulate inflammation in cancer.
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Affiliation(s)
- Iveta Mikolaskova
- Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08, Bratislava, Slovakia
| | - Yori Gidron
- Department of Nursing, Faculty of Welfare and Health Sciences, University of Haifa, Haifa, 3498838, Israel
| | - Vladimira Durmanova
- Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08, Bratislava, Slovakia
| | - Magda Suchankova
- Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08, Bratislava, Slovakia
| | - Maria Bucova
- Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08, Bratislava, Slovakia
| | - Luba Hunakova
- Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborarske namestie 14, 811 08, Bratislava, Slovakia
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Issa H, Singh L, Lai KS, Parusheva-Borsitzky T, Ansari S. Dynamics of inflammatory signals within the tumor microenvironment. World J Exp Med 2025; 15:102285. [DOI: 10.5493/wjem.v15.i2.102285] [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: 10/13/2024] [Revised: 12/31/2024] [Accepted: 01/11/2025] [Indexed: 04/16/2025] Open
Abstract
Tumor stroma, or tumor microenvironment (TME), has been in the spotlight during recent years for its role in tumor development, growth, and metastasis. It consists of a myriad of elements, including tumor-associated macrophages, cancer-associated fibroblasts, a deregulated extracellular matrix, endothelial cells, and vascular vessels. The release of proinflammatory molecules, due to the inflamed microenvironment, such as cytokines and chemokines is found to play a pivotal role in progression of cancer and response to therapy. This review discusses the major key players and important chemical inflammatory signals released in the TME. Furthermore, the latest breakthroughs in cytokine-mediated crosstalk between immune cells and cancer cells have been highlighted. In addition, recent updates on alterations in cytokine signaling between chronic inflammation and malignant TME have also been reviewed.
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Affiliation(s)
- Hala Issa
- Division of Health Sciences, Higher Colleges of Technology, Abu Dhabi 25026, United Arab Emirates
| | - Lokjan Singh
- Department of Microbiology, Karnali Academy of Health Sciences, Jumla 21200, Karnali, Nepal
| | - Kok-Song Lai
- Division of Health Sciences, Higher Colleges of Technology, Abu Dhabi 25026, United Arab Emirates
| | - Tina Parusheva-Borsitzky
- Division of Health Sciences, Higher Colleges of Technology, Abu Dhabi 25026, United Arab Emirates
| | - Shamshul Ansari
- Division of Health Sciences, Higher Colleges of Technology, Abu Dhabi 25026, United Arab Emirates
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Feng T, Shen H, Ye S. LncRNA ZFAS1 promotes the transformation from prostatitis to prostate cancer via myddosome assembly-mediated activation of NF-κB signaling. Discov Oncol 2025; 16:1046. [PMID: 40493092 DOI: 10.1007/s12672-025-02488-1] [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: 12/05/2024] [Accepted: 04/24/2025] [Indexed: 06/12/2025] Open
Abstract
BACKGROUND Prostatitis is a critical factor in promoting carcinogenesis, but the key molecular mechanisms remain unknown. Long noncoding RNA (lncRNA) ZFAS1 was reported to be involved in the development of human cancers including prostate cancer and some inflammatory diseases. This research aims at investigating the function of ZFAS1 in regulating prostatitis to prostate cancer transformation and the underlying mechanism. METHODS A prostatitis-cancer transformation cell model RWPE-1/THP-1 was established by co-culturing human prostate epithelial cells RWPE-1 with human acute monocytic leukemia cells THP-1. CCK-8, colony formation, and flow cytometry assays were used to detect the effects of ZFAS1 knockdown or overexpression on the proliferation and apoptosis and malignant transformation ability of the model cells. The influence of ZFAS1 knockdown on the levels of apoptosis-related proteins, MyD88 protein aggregation in cell lysate and pellet fractions, and the phosphorylation of IKKβ, IκBα, and NF-κB p65 in RWPE-1/THP-1 cells. Immunofluorescence staining was used to detect NF-κB p65 nuclear translocation in RWPE-1/THP-1 cells. ST2825 was used to further confirm whether ZFAS1 affects prostatitis to prostate cancer transformation by regulating NF-κB pathway through modulating MYD88 dimerization and the subsequent myddosome assembly. RESULTS ZFAS1 expression was markedly increased in RWPE-1/THP-1 cells. ZFAS1 silencing repressed the proliferation and facilitated the apoptosis of RWPE-1/THP-1 cells. P-IKKβ, p-IκBα and p-p65 protein levels and NF-κB p65 nuclear translocation were significantly enhanced in RWPE-1/THP-1 cells, which were reversed by ZFAS1 knockdown. ZFAS1 knockdown exerted the same inhibitory effects as ST2825 treatment on the degree of MyD88 aggregation and NF-κB pathway activation in RWPE-1/THP-1 cells, suggesting that ZFAS1 knockdown inactivated the NF-κB pathway in RWPE-1/THP-1 cells through suppressing MYD88 dimerization and the subsequent myddosome assembly. In addition, ST2825 treatment overturned the influence of ZFAS1 overexpression on the proliferation and apoptosis of RWPE-1/THP-1 cells. CONCLUSION ZFAS1 promotes prostatitis to cancer transformation by activating the NF-κB signaling through promoting MYD88 dimerization and the subsequent myddosome assembly.
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Affiliation(s)
- Tao Feng
- Department of Urology Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China
| | - Hao Shen
- Department of Medical Administration, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China
| | - Shenglan Ye
- Department of Respiratory Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No.26 Shengli Street, Jiang 'an District, Wuhan, 430014, China.
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Pierce K, Gaskins J, Martin Ii RCG. The Weight of Nutrition on Post-Resection Oncologic Morbidity and Mortality: A Systematic Review and Meta-Analysis of Nutritional Indices. Nutr Rev 2025; 83:988-1005. [PMID: 39405175 DOI: 10.1093/nutrit/nuae138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2025] Open
Abstract
CONTEXT Nutritional status is a critical factor in the selection of patients for solid tumor resection. A variety of indices have been developed to quantify nutritional status, and they have differing degrees of predictive power for various postoperative outcomes. OBJECTIVE This study aimed to comprehensively evaluate the predictive ability of commonly used nutritional indices in relation to postoperative complications (POCs), recurrence-free survival (RFS), and OS. DATA SOURCES We performed a systematic review of 14 established nutritional indices from January 2015 to July 2022. DATA EXTRACTION The primary end point was OS, while the secondary end points were POCs and RFS. A subsequent meta-analysis was performed to further assess the predictive ability of these indices for OS based on general index type, primary tumor site, and the patient's index status. DATA ANALYSIS In this evaluation, 38 articles reporting data on 23 970 patients were analyzed, focusing on 14 nutritional indices. The indices were categorized into phenotypic, metabolic, immunologic, and combined types. Patients within the cut-off range of any index were predicted to have lower OS (hazard ratio [HR] 2.14, 95% CI 1.84-2.49, P < .01). Lower gastrointestinal (GI) and "other" sites were less predictive than upper GI primary tumors (HR 1.63, HR 1.82, and HR 2.54, respectively; all with P < .01). Phenotypic indices were less predictive than combined indices (HR 1.73 vs HR 2.47, P < .01). Within the combined category, there was no significant difference in the predictive ability of Prognostic Nutritional Index (PNI) vs Geriatric Nutritional Risk Index (GNRI) vs Controlling Nutritional Index (CONUT) (HR 2.63 vs HR 2.42 vs HR 2.07, P = .07). CONCLUSION The predictive efficacy of a nutritional index was found to be highly dependent on the index type, the primary tumor site, and the outcome of interest. In the context of upper GI resections, nutritional status appeared to be more of a significant predictor of OS, compared with cases involving lower GI and hepatic malignancies. Indices that integrate phenotypic, metabolic, and immunologic patient factors potentially offer greater clinical utility in forecasting OS.
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Affiliation(s)
- Katherine Pierce
- Division of Surgical Oncology, The Hiram C. Polk, Jr., M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, United States
| | - Jeremy Gaskins
- Department of Bioinformatics and Biostatistics, University of Louisville School of Medicine, Louisville, KY 40292, United States
| | - Robert C G Martin Ii
- Division of Surgical Oncology, The Hiram C. Polk, Jr., M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, United States
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Iaia N, Noviello C, Muscaritoli M, Costelli P. Inflammation in cancer cachexia: still the central tenet or just another player? Am J Physiol Cell Physiol 2025; 328:C1837-C1852. [PMID: 40250836 DOI: 10.1152/ajpcell.00808.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/23/2024] [Accepted: 04/10/2025] [Indexed: 04/20/2025]
Abstract
Cancer cachexia, a multifactorial syndrome characterized by body weight loss, muscle, and adipose tissue wasting, affects patients with cancer. Over time, the definition of cachexia has been modified, including inflammation as one of the main causal factors. Evidence has suggested that a range of proinflammatory mediators may be involved in the regulation of intracellular signaling, resulting in enhanced resting energy expenditure, metabolic changes, and muscle atrophy, all of which are typical features of cachexia. Physiologically speaking, however, inflammation is a response aimed at facing potentially damaging events. Along this line, its induction in the cancer hosts could be an attempt to restore the physiological homeostasis. Interesting observations have shown that cytokines such as interleukins 4 and 6 could improve muscle wasting, supporting the view that the same mediator may exert pro- or anti-inflammatory activity depending on the immune cells involved as well as on the tissue metabolic demand. In conclusion, whether inflammation is crucial to the occurrence of cachexia or just one contributor among others, is still unclear. Indeed, while inflammation is a trigger of cachexia, the alterations of energy and protein metabolism and of the hormonal homeostasis occurring in cachexia likely act as inflammatory stimuli on their own. Whether the causative role prevails over the compensatory one likely depends on the tumor type and stage, patient lifestyle, the presence of comorbidities, and the response to anticancer treatments paving the way to a holistic, personalized approach to cancer cachexia.
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Affiliation(s)
- Noemi Iaia
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
| | - Chiara Noviello
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
| | | | - Paola Costelli
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
- Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
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7
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Russo P, Foschi N, Palermo G, Maioriello G, Lentini N, Iacovelli R, Ciccarese C, Ragonese M, Marino F, Bizzarri FP, Gandi C, Moretto S, Filomena GB, Gavi F, Sacco E, Racioppi M, Pandolfo SD, Sighinolfi MC, Rocco B. SIRI as a biomarker for bladder neoplasm: Utilizing decision curve analysis to evaluate clinical net benefit. Urol Oncol 2025; 43:393.e1-393.e8. [PMID: 39934058 DOI: 10.1016/j.urolonc.2025.01.007] [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: 10/07/2024] [Revised: 01/07/2025] [Accepted: 01/15/2025] [Indexed: 02/13/2025]
Abstract
PURPOSE This analysis aimed to evaluate the clinical relevance of the presurgical systemic inflammation response index (SIRI) in individuals undergoing radical cystectomy (RC). METHODS In this retrospective study, 228 were categorized into 2 cohorts depending on their SIRI levels using the best cut-off determined by the Youden Index. The association between SIRI and lymph node metastasis (N), advanced pT stage (pT3/pT4), and loco-regional extended state were analyzed at the time of surgery. Multivariate Cox regression analysis was performed to evaluate the impact of SIRI on time to relapse, tumor-specific survival, and survival rates. The additional medical advantage was evaluated through decision curve analysis (DCA). RESULTS High and low SIRI group was obtained using the best cut-off value (1.71×109/l). On multivariate logistic regression analysis, elevated SIRI was significantly associated with advanced pT stage (P = 0.003) and loco-regional extended state (P = 0.003). On multivariable Cox regression models based on presurgical clinicopathological factors, an augmented SIRI was linked to poorer relapse-free survival (RFS) (P = 0.035), with the improvement of the concordance index just for RFS. In DCAs, incorporating SIRI yielded results equal to or better than those of the model without SIRI for all outcomes models. It demonstrated improvements in net benefit at probability thresholds up to 50% for the model adjusted with preoperative factors for RFS and for postoperative factors in CSS and OS. CONCLUSIONS SIRI is an innovative prognostic indicator and a potential biomarker that can enhance conventional medical pathological evaluation and improve the personalization of clinical treatment strategies for bladder cancer patients following RC.
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Affiliation(s)
- Pierluigi Russo
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
| | - Nazario Foschi
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Giuseppe Palermo
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Giuseppe Maioriello
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Nicolò Lentini
- Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Roberto Iacovelli
- Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Chiara Ciccarese
- Department of Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Mauro Ragonese
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Filippo Marino
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Francesco Pio Bizzarri
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy; Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy
| | - Carlo Gandi
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Stefano Moretto
- Department of Urology, Humanitas Clinical and Research Institute IRCCS, Milan, Italy
| | | | - Filippo Gavi
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Emilio Sacco
- Department of Urology, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy
| | - Marco Racioppi
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
| | - Savio Domenico Pandolfo
- Department of Urology, University of L'Aquila, L'Aquila, Italy; Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples "Federico II, Naples, Italy
| | | | - Bernardo Rocco
- Department of Urology, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
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Shahbaz S, Sharif A, Akhtar B, Mobashar A, Shazly GA, Metouekel A, Bourhia M. Therapeutic potential of 3-acetyl coumarin against polycystic ovarian syndrome induced by letrozole using female rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:7057-7074. [PMID: 39715882 DOI: 10.1007/s00210-024-03720-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/08/2024] [Indexed: 12/25/2024]
Abstract
Polycystic ovarian syndrome is a heterogeneous endocrine disorder characterized by ovarian cysts, anovulation, endocrine variations, which includes oligo-amenorrhea along with associated subfertility and hyperandrogenism manifested as acne, hirsutism, and male-pattern alopecia. Coumarins are fused benzene and pyrone ring systems that exhibit a wide spectrum of bioactivities. This study aimed to investigate the effects of 3-acetyl coumarin (3-AC) on polycystic ovarian syndrome in female rats. Acute oral toxicity conducted according to OECD guidelines 425 (a test conducted in scenarios where there is information indicating that the test material is non-toxic) exhibited no mortality. In vitro DPPH assay demonstrated anti-oxidant potential of 3-AC. Letrozole, a nonsteroidal aromatase inhibitor was used to induce PCOS (1 mg/kg-21 days). Normal and PCOS control rats were administered a vehicle solution (0.5% CMC), whereas 3-AC (10, 20, and 30 mg/kg) and metformin (300 mg/kg) was administered to treatment groups for 15 days. Vaginal smears were taken to assess estrous cycle. Rats were euthanized at day 37. In vivo analysis included measurement of fasting blood glucose, total-cholesterol, triglycerides, FSH, LH, and testosterone levels. ELISA was used for measurement of inflammatory markers (IL-1β, IL-6, and TNF-α). Oxidative stress markers (SOD, CAT, GSH, MDA, NO) were also evaluated. Expression levels of NF-κB and LHCGR were detected by RT-qPCR. Molecular docking was also performed. One-way analysis of variance was employed followed by Tukey's test for statistical analysis. Treatment with 3-AC led to favorable effects in PCOS rats. Specifically, inflammatory levels, antioxidant status, lipid profile, and glucose concentrations were all improved. These findings suggest that 3-acetyl coumarin (3-AC) may serve as a promising therapeutic agent for alleviating symptoms of PCOS in this animal model.
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Affiliation(s)
- Saliha Shahbaz
- Department of Pharmacology, Faculty of Pharmaceutical and Allied Health Sciences, Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan
| | - Ali Sharif
- Department of Pharmacology, Faculty of Pharmaceutical and Allied Health Sciences, Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan.
| | - Bushra Akhtar
- Department of Pharmacy, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Aisha Mobashar
- Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
- Faculty of Health Sciences, Equator University of Science and Technology, Masaka, Uganda
| | - Gamal A Shazly
- Department of Pharmaceutics, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Amira Metouekel
- University of Technology of Compiègne, EA 4297 TIMR, 60205, Compiègne Cedex, France
| | - Mohammed Bourhia
- Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, Ibn Zohr University, 80060, Agadir, Morocco.
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Li X, Zhao H, Jiang E, Liu P, Chen Y, Wang Y, Li J, Wu Y, Liu Z, Shang Z. ITGB1/FERMT1 mechanoactivation enhances CD44 characteristic stemness in oral squamous cell carcinoma via ubiquitin-dependent CK1α degradation. Oncogene 2025; 44:1530-1544. [PMID: 40044983 DOI: 10.1038/s41388-025-03317-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 01/30/2025] [Accepted: 02/18/2025] [Indexed: 05/15/2025]
Abstract
Cancer stem cells (CSCs) contribute to chemotherapy resistance and poor prognosis, posing significant challenges in the treatment of oral squamous cell carcinoma. The extracellular matrix (ECM)-constructed microenvironment remodels the niche of CSCs. Yet mechanisms by which biophysical properties of ECM relate to CSCs remain undefined. Here, our findings link ECM mechanical stimuli to CSCs phenotype transition, and propose that ECM stiffening mechanoactivates tumor cells to dedifferentiate and acquire CD44+ stem cell-like characteristics through noncanonical mechanotransduction. ITGB1 senses and transduces biomechanical signals, while FERMT1 acts as an intracellular mechanotransduction downstream, activating CSCs. Mechanistically, FERMT1 promotes the proteasomal degradation of CK1α by E3 ubiquitin ligase MIB1, thereby triggering Wnt signaling pathway. Combining targeted ECM softening with mechanotransduction inhibition strategy significantly attenuates tumor stemness and chemoresistance in vivo. Therefore, our findings highlight the role of ECM in regulating CSCs via biomechanical-dependent manner, suggesting the ECM/ITGB1/FERMT1/Wnt axis as a promising therapeutic target for CSCs therapy.
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Affiliation(s)
- Xiang Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Hui Zhao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral and Maxillofacial-Head and Neck Oncology, School of Stomatology-Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Erhui Jiang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral and Maxillofacial-Head and Neck Oncology, School of Stomatology-Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Pan Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yang Chen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yue Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Ji Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Yufei Wu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhenan Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhengjun Shang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
- Department of Oral and Maxillofacial-Head and Neck Oncology, School of Stomatology-Hospital of Stomatology, Wuhan University, Wuhan, China.
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Fernández-Candela A, Barber X, López-Rodríguez-Arias F, Lario-Pérez S, Calero A, Aranaz-Ostáriz V, Caravaca-García I, Lillo-García C, Sánchez-Guillén L, Lacueva FJ. Early prediction of postoperative infection using inflammatory markers after cytoreductive surgery for peritoneal carcinomatosis. World J Gastrointest Surg 2025; 17:101323. [DOI: 10.4240/wjgs.v17.i5.101323] [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: 09/10/2024] [Revised: 12/02/2024] [Accepted: 03/11/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND Major postoperative complications have proved to be an independent adverse prognostic factor for long-term survival in patients undergoing cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). C-reactive protein (CRP) is an inflammatory marker that is reportedly a useful tool for the early prediction of postoperative complications, as is the neutrophil-to-lymphocyte ratio (NLR). In patients with peritoneal carcinomatosis, postoperative CRP levels on days 2 to 4 are predictors of early complications after CRS plus HIPEC.
AIM To determine the usefulness of CRP and NLR for the early detection of overall postoperative infections (OPIs) after CRS +/- HIPEC.
METHODS Patients treated on a peritoneal carcinomatosis program at a tertiary care hospital, in whom complete or optimal cytoreduction was achieved, were analyzed retrospectively. A total of 111 patients were included in this study. CRP and NRL values prior to surgery and during the first four postoperative days (PODs) were recorded, along with immunonutrition intake. Their association with OPI and intra-abdominal infections during the first week after surgery was evaluated.
RESULTS Of the 111 patients included, 19 presented OPI and 8 intra-abdominal infections. Patients with infections had a higher number of digestive anastomoses than those without (1 vs 0.5, P = 0.053 and 1.2 vs 0.6, P = 0.049) and longer length of stay (19 vs 14.9 days, P = 0.022 and 22.3 vs 15.1 days, P = 0.006). CRP values above 118 mg/L on POD3 yielded a sensitivity of 66.7% and a specificity of 74.2% to detect OPI. No differences in NLR values were observed. Patients with immunonutrition intake had higher CRP levels regardless of whether they presented OPI. Subsequently, on POD3 and POD4, patients with OPI presented with higher levels of CRP than patients without infection, regardless of the immunonutrition intake.
CONCLUSION CRP levels are useful to detect early OPI in patients with peritoneal carcinomatosis undergoing CRS. A cut-off value of 118 mg/L on POD3 yields the best sensitivity and specificity.
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Affiliation(s)
- Alba Fernández-Candela
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Xavier Barber
- Joint Research Unit UMH-FISABIO, Center of Operations Research, Universidad Miguel Hernandez, Elche 03202, Valencia, Spain
| | - Francisco López-Rodríguez-Arias
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Sandra Lario-Pérez
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Alicia Calero
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Verónica Aranaz-Ostáriz
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Iban Caravaca-García
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Cristina Lillo-García
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Luis Sánchez-Guillén
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
| | - Francisco-Javier Lacueva
- Department of General Surgery, Peritoneal Carcinomatosis Unit, Elche University General Hospital, Elche 03202, Valencia, Spain
- Department of Pathology and Surgery, Universidad Miguel Hernandez, Elche 03202, Valencia, Spain
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11
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Sakurai K, Nakayama S, Chubachi S, Otake S, Shimada T, Irie H, Tsutsumi A, Kameyama N, Hegab AE, Shimoda M, Hamamoto J, Terai H, Yasuda H, Kanai Y, Fukunaga K. Roflumilast reduces the number of lung adenocarcinomas, inflammation, and emphysema in a smoking-induced mouse model. BMC Pulm Med 2025; 25:262. [PMID: 40420271 PMCID: PMC12105171 DOI: 10.1186/s12890-025-03730-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 05/15/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND The prognosis of lung cancer complicated by chronic obstructive pulmonary disease is poor, and effective prophylactic agents have not been established. Given that inflammation is a shared pathogenic mechanism of both diseases, we aimed to evaluate the efficacy of roflumilast, a novel anti-inflammatory drug, in preventing emphysema and lung cancer using a smoking-induced lung cancer mouse model. METHODS Male A/J mice were exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen, and intermittent mainstream cigarette smoke for 20 weeks. Roflumilast or vehicle was administered via intragastric gavage once daily. Lung tissues were assessed for tumor nodules and emphysema, and bronchoalveolar lavage fluid was collected for cell counting. Emphysema severity and concentrations of inflammatory cytokines (IL-6, IL-1β, and TNF-α) were assessed. RAW 264.7 macrophage cells were used to assess cellular responses to cigarette smoke extract. RESULTS Roflumilast attenuated the increase in total cells and macrophages in bronchoalveolar lavage fluid induced by intermittent smoking exposure and significantly suppressed smoking-induced expressions of IL-6, IL-1β, and TNF-α. Roflumilast also reduced emphysematous changes and the number of lung tumors. In vitro, roflumilast attenuated cigarette smoke extract-induced expression of IL-6, IL-1β, and TNF-α in RAW 264.7 cells. CONCLUSIONS This study highlights the potential use of roflumilast as a chemopreventive agent for patients with chronic obstructive pulmonary disease who are at risk of lung cancer and underscores its relevance for future clinical application and research on phosphodiesterase-4 inhibitors.
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Affiliation(s)
- Kaori Sakurai
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shingo Nakayama
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shotaro Chubachi
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Shiro Otake
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Takashi Shimada
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hidehiro Irie
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Akihiro Tsutsumi
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Naofumi Kameyama
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Ahmed E Hegab
- Medical Education Center, School of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita, Chiba, 286-8686, Japan
| | - Masayuki Shimoda
- Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
- Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Junko Hamamoto
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hideki Terai
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroyuki Yasuda
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yae Kanai
- Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Koichi Fukunaga
- Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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12
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Jin C, Hu B, Liu H, Wang R, Jang J, Su M. Cystathionine gamma-lyase as an inflammatory factor and its link with immune inflammation in hepatitis B virus-related liver disease. Sci Rep 2025; 15:17777. [PMID: 40404804 PMCID: PMC12098708 DOI: 10.1038/s41598-025-98922-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 04/15/2025] [Indexed: 05/24/2025] Open
Abstract
We aimed to explore the effectiveness of CTH as a serum inflammation biomarker for HCC. Enzyme-linked immunosorbent assay was used to detect serum levels of CTH, interleukin-6 (IL-6), C-reactive protein (CRP), and IL-10. The Scheuer scoring system was used to assess the liver inflammation grading (significant liver inflammation: ≥ G2 grade). CTH levels in the HCC group were significantly elevated (P < 0.0001). Of 146 patients, 58.22% exhibited significant liver inflammation. CTH levels in patients with significant liver inflammation were significantly higher than those in patients with no or mild liver inflammation (< G 2) (p < 0.0001). The area under the Receiver Operating Characteristic (ROC) curve for CTH in predicting significant hepatitis was 0.77 (sensitivity, 81.2%; specificity,62.3%). There was a significant positive correlation (r = 0.50, p < 0.05) between serum CTH levels and histopathological parameter G. The area under the ROC curve for CTH in predicting hepatocellular carcinoma was 0.83 (sensitivity, 64.6%; specificity, 83.3%). CTH and AFP improved the diagnostic accuracy of HCC. CTH levels significantly decreased 6 months post-operation (p < 0.05). The recurrence of HCC caused significant increases in CTH levels. Thus, CTH can serve as a serum inflammation marker for HCC.
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Affiliation(s)
- Chao Jin
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Bobin Hu
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Hongyu Liu
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Rongming Wang
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Jianning Jang
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Minghua Su
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China.
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13
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Hutajulu SH, Astari YK, Ucche M, Kertia N, Subronto YW, Paramita DK, Choridah L, Ekaputra E, Widodo I, Suwardjo S, Hardianti MS, Taroeno-Hariadi KW, Purwanto I, Kurnianda J. Prognostic significance of C-reactive protein (CRP) and albumin-based biomarker in patients with breast cancer receiving chemotherapy. PeerJ 2025; 13:e19319. [PMID: 40416620 PMCID: PMC12103165 DOI: 10.7717/peerj.19319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/24/2025] [Indexed: 05/27/2025] Open
Abstract
Background Breast cancer patients with similar clinicopathologic characteristics may experience varied outcomes. This urges an increased effort to investigate other prognostic factors. C-reactive protein (CRP)-to-albumin ratio (CAR) is an inflammatory and nutritional biomarker that has been well studied and reported to have an impact on the survival of patients with diverse types of cancer, but limitedly in breast cancer. Therefore, this study aimed to investigate the prognostic significance of CAR in local patients with breast cancer. Methods This study included 202 stage I-IV breast cancer patients receiving first-line chemotherapy. We calculated inflammatory and nutritional biomarkers including CAR, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and prognostic nutrition index (PNI) before treatment. The Kaplan-Meier with log-rank test and Cox proportional hazard regression were used to analyze the prognostic role of clinicopathologic factors and biomarkers on disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Results The median follow-up period was 46 months (1-77 months). The 3-year DFS and 3-year OS in patients with high CAR (CAR > 1.5) were significantly lower than those with low CAR (CAR ≤ 1.5) (47.0% vs 68.9%, P = 0.022 and 59.5% vs 78.6%, P = 0.009, respectively). Multivariate analysis showed high CAR as prognostic factors for poor DFS (HR 2.10, 95% confidence interval/CI [1.10-3.99], P = 0.023) and OS (HR 2.16, 95% CI [1.27-3.68], P = 0.005), but not for PFS (HR 1.43, 95% CI [0.73-2.80], P = 0.293). In addition, more advanced stage and HER2 positive were correlated with unfavorable DFS and OS, older age predicted poor DFS, and stage was the only prognostic factor of PFS (all P values < 0.05). Conclusion Besides age, stage, and molecular subtypes that have been widely observed to have impact on the survival of breast cancer patients, CAR was demonstrated as a promising prognostic marker in our local patients. A high CAR at diagnosis was associated with unfavorable DFS and OS, which can aid in identifying patients at risk and guide personalized treatment planning.
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Affiliation(s)
- Susanna Hilda Hutajulu
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Yufi Kartika Astari
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Meita Ucche
- Study Program of Subspecialty, Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Nyoman Kertia
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Yanri Wijayanti Subronto
- Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Dewi Kartikawati Paramita
- Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sleman, Yogyakarta Special Region, Indonesia
| | - Lina Choridah
- Division of Radiodiagnosis, Department of Radiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Ericko Ekaputra
- Division of Radiotherapy, Department of Radiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Irianiwati Widodo
- Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sleman, Yogyakarta Special Region, Indonesia
| | - Suwardjo Suwardjo
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Mardiah Suci Hardianti
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Kartika Widayati Taroeno-Hariadi
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Ibnu Purwanto
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
| | - Johan Kurnianda
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Sleman, Yogyakarta Special Region, Indonesia
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14
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Amer H, Flanagan KL, Kampan NC, Itsiopoulos C, Scott CL, Kartikasari AER, Plebanski M. Interleukin-6 Is a Crucial Factor in Shaping the Inflammatory Tumor Microenvironment in Ovarian Cancer and Determining Its Hot or Cold Nature with Diagnostic and Prognostic Utilities. Cancers (Basel) 2025; 17:1691. [PMID: 40427188 PMCID: PMC12109964 DOI: 10.3390/cancers17101691] [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: 03/17/2025] [Revised: 05/05/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Ovarian cancer (OC) remains the leading cause of cancer-related deaths among women, often diagnosed at advanced stages due to the lack of effective early diagnostic procedures. To reduce the high mortality rates in OC, reliable biomarkers are urgently needed, especially to detect OC at its earliest stage, predict specific drug responses, and monitor patients. The cytokine interleukin-6 (IL6) is associated with low survival rates, treatment resistance, and recurrence. In this review, we summarize the role of IL6 in inflammation and how IL6 contributes to ovarian tumorigenesis within the tumor microenvironment, influencing whether the tumor is subsequently classified as "hot" or "cold". We further dissect the molecular and cellular mechanisms through which IL6 production and downstream signaling are regulated, to enhance our understanding of its involvement in OC development, as well as OC resistance to treatment. We highlight the potential of IL6 to be used as a reliable diagnostic biomarker to help detect OC at its earliest stage, and as a part of predictive and prognostic signatures to improve OC management. We further discuss ways to leverage artificial intelligence and machine learning to integrate IL6 into diverse biomarker-based strategies.
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Affiliation(s)
- Hina Amer
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3082, Australia
| | - Katie L. Flanagan
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3082, Australia
- School of Medicine and Health Sciences, University of Tasmania, Launceston, TAS 7250, Australia
- Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Launceston, TAS 7250, Australia
| | - Nirmala C. Kampan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Catherine Itsiopoulos
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3082, Australia
| | - Clare L. Scott
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Parkville, VIC 3052, Australia
- The Royal Women’s Hospital, Parkville, VIC 3052, Australia
| | | | - Magdalena Plebanski
- School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3082, Australia
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15
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Perez-Medina M, Benito-Lopez JJ, Aguilar-Cazares D, Lopez-Gonzalez JS. A Comprehensive Review of Long Non-Coding RNAs in the Cancer-Immunity Cycle: Mechanisms and Therapeutic Implications. Int J Mol Sci 2025; 26:4821. [PMID: 40429961 PMCID: PMC12111859 DOI: 10.3390/ijms26104821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 05/10/2025] [Accepted: 05/16/2025] [Indexed: 05/29/2025] Open
Abstract
Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of the dynamic interplay between cancer progression and immune responses. This review explored their influence on key processes of the cancer-immunity cycle, such as immune cell differentiation, antigen presentation, and tumor immunogenicity. By modulating tumor escape from the immune response, therapeutic resistance, and tumor-stroma interactions, lncRNAs actively shape the tumor microenvironment. Due to their growing knowledge in the area of immune suppression, directly intervening in the induction of regulatory T cells (Tregs), M2 macrophages, and regulating immune checkpoint pathways such as PD-L1, CTLA-4, and others, lncRNAs can be considered promising therapeutic targets. Advances in single-cell technologies and immunotherapy have significantly expanded our understanding of lncRNA-driven regulatory networks, paving the way for novel precision medicine approaches. Ultimately, we discussed how targeting lncRNAs could enhance cancer immunotherapy, offering new avenues for biomarker discovery and therapeutic intervention.
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Affiliation(s)
- Mario Perez-Medina
- Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico; (M.P.-M.); (J.J.B.-L.); (D.A.-C.)
- Asociación Para Evitar la Ceguera en México, I. A. P., Mexico City 04030, Mexico
| | - Jesus J. Benito-Lopez
- Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico; (M.P.-M.); (J.J.B.-L.); (D.A.-C.)
| | - Dolores Aguilar-Cazares
- Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico; (M.P.-M.); (J.J.B.-L.); (D.A.-C.)
| | - Jose S. Lopez-Gonzalez
- Laboratorio de Investigacion en Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico; (M.P.-M.); (J.J.B.-L.); (D.A.-C.)
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16
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Gill GS, Kharb S, Goyal G, Das P, Kurdia KC, Dhar R, Karmakar S. Immune Checkpoint Inhibitors and Immunosuppressive Tumor Microenvironment: Current Challenges and Strategies to Overcome Resistance. Immunopharmacol Immunotoxicol 2025:1-45. [PMID: 40376861 DOI: 10.1080/08923973.2025.2504906] [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: 02/22/2025] [Accepted: 05/06/2025] [Indexed: 05/18/2025]
Abstract
Immune checkpoint inhibitors (ICIs) are shown to improve cancer treatment effectiveness by boosting the immune system of the patient. Nevertheless, the unique and highly suppressive TME poses a significant challenge, causing heterogeneity of response or resistance in a considerable number of patients. This review focuses on the evasive attributes of the TME. Immune evasion mechanism in TME include immunosuppressive cells, cytokine and chemokine signaling, metabolic alterations and overexpression of immune checkpoint molecules such as PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA and their interactions within the TME. In addition, this review focuses on the overcoming resistance by targeting immunosuppressive cells, normalizing tumor blood vessels, blocking two or three checkpoints simultaneously, combining vaccines, oncolytic viruses and metabolic inhibitors with ICIs or other therapies. This review also focuses on the necessity of finding predictive markers for the stratification of patients and to check response of ICIs treatment. It remains to be made certain by new research and intelligent innovations how these discoveries of the TME and its interplay facilitate ICI treatment and change the face of cancer treatment.
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Affiliation(s)
- Gurpreet Singh Gill
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Simmi Kharb
- Department of Biochemistry, Pt. B.D. Sharma Postgraduate Institute of Medical Sciences, Rohtak, India
| | - Gitanjali Goyal
- Department of Biochemistry, All India Institute of Medical Sciences, Bathinda, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Kailash Chand Kurdia
- Department of GI Surgery & Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Ruby Dhar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Subhradip Karmakar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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17
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Jiang X, Zhou T, Liu C, Xu N, Chen X, Wang D. Predicting the prognosis of patients with renal cell carcinoma based on systemic immune inflammatory index and prognostic nutritional index. Int Urol Nephrol 2025:10.1007/s11255-025-04553-8. [PMID: 40353933 DOI: 10.1007/s11255-025-04553-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 04/24/2025] [Indexed: 05/14/2025]
Abstract
PURPOSE This study aimed to evaluate the prognostic value of preoperative systemic immune inflammatory index (SII) and prognostic nutritional index (PNI) in patients with renal cell carcinoma (RCC) undergoing surgery, and to establish a nomogram for predicting overall survival (OS). METHODS We retrospectively analyzed clinical data from 240 RCC patients who underwent surgery. SII and PNI values were calculated, and optimal cutoff value were determined by receiver operating characteristic curves. Patients were classified into high and low SII/PNI groups. Survival outcomes were assessed using Kaplan-Meier analysis and log-rank tests. Univariate and multivariate Cox regression models were used to identify independent prognostic factors, which were incorporated into a nomogram. The model's accuracy and discrimination were evaluated by the consistency index (C-index) and calibration curves. RESULTS The 1-, 3- and 5-year survival rates were significantly higher in low SII group were (98.10%, 92.30%, and 87.20%) compared to the high SII group (90.00%, 72.90%, and 57.40%), and higher in the high PNI group (97.60%, 93.00%, and 87.60%) compared to the low PNI group (86.90%, 67.90%, and 40.80%; P < 0.001). Multivariate Cox regression model analysis showed that SII, PNI, hemoglobin, tumor necrosis, surgical method, pathological type, AJCC stage and Fuhrman grade were independent prognostic factors. The nomogram model demonstrated excellent predictive ability with a C index was 0.915. CONCLUSIONS Preoperative SII and PNI are independent predictors of postoperative prognosis in RCC patients. The constructed nomogram based on multiple factors provides accurate individualized survival predictions.
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Affiliation(s)
- Xi Jiang
- Department of Urology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China
| | - Tingting Zhou
- Department of Urology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China
| | - Chenjing Liu
- Department of Urology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China
| | - Na Xu
- Department of Urology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China.
| | - Xiaobin Chen
- Department of General Surgery, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China
| | - Dong Wang
- Department of Urology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, Fujian, 350025, People's Republic of China.
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Veronez LC, Silveira DSCD, Lopes-Júnior LC, Dos Santos JC, Barbisan LF, Pereira-da-Silva G. Jacalin Attenuates Colitis-Associated Colorectal Carcinogenesis by Inhibiting Tumor Cell Proliferation and Intestinal Inflammation. Inflamm Bowel Dis 2025; 31:1344-1354. [PMID: 39745886 DOI: 10.1093/ibd/izae303] [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: 05/28/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Colorectal cancer (CRC) remains a significant cause of morbidity and mortality worldwide. In patients with inflammatory bowel disease, who have twice the risk of developing CRC, chronic inflammation has been recognized to contribute to colitis-associated cancer (CAC) development. Jacalin, a lectin extracted from jackfruit seeds, has been shown to recognize altered glycosylation and to exert antiproliferative and cytotoxic effects in CRC. However, its activity in CAC remains unknown. Herein, we sought to investigate the effects of jacalin in CAC progression using the dextran sulfate sodium (DSS) and azoxymethane (AOM) mouse model. METHODS Colitis-associated cancer induction was performed in male C57BL/6 mice by an intraperitoneal injection of AOM, followed by 3 cycles of 2.5% DSS diluted in drinking water for 7 days, intercalated by 2 weeks of normal drinking water. After 1 week of daily pretreatment, mice were orally treated with phosphate-buffered saline (control group), 100 or 500 µg of jacalin three times a week for an additional 11 weeks. RESULTS We showed that jacalin-treated mice presented tumors with reduced volumes and mean size compared to the control group. In addition, both doses of jacalin reduced the number of proliferating cells (Ki-67 positive cells) in tumor tissues, while the higher dose (500 µg) showed also a similar effect in "normal-appearing" colonic crypts. Jacalin treatment attenuated the clinical scores of inflammations, which was accompanied by a reduction of intestinal and/or tumoral production of IL-1β, IL-23, and IL-17. CONCLUSIONS Collectively, our findings demonstrated that jacalin suppresses CAC development, highlighting its anti-inflammatory and antitumoral role in the AOM/DSS-induced model.
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Affiliation(s)
- Luciana Chain Veronez
- Graduate Program in Basic and Applied Immunology, Biochemistry and Immunology Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14040-902, Brazil
| | - Denise Sayuri Calheiros da Silveira
- Graduate Program in Basic and Applied Immunology, Biochemistry and Immunology Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14040-902, Brazil
| | - Luis Carlos Lopes-Júnior
- Nursing Department, Health Sciences Center, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil
| | - Jéssica Cristina Dos Santos
- Graduate Program in Basic and Applied Immunology, Biochemistry and Immunology Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14040-902, Brazil
| | - Luis Fernando Barbisan
- Structural and Functional Biology Department, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, São Paulo 18618-689, Brazil
| | - Gabriela Pereira-da-Silva
- Graduate Program in Basic and Applied Immunology, Biochemistry and Immunology Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14040-902, Brazil
- Maternal-Infant and Public Health Nursing Department, Ribeirão Preto School of Nursing, University of São Paulo, Ribeirão Preto, São Paulo 14040-902, Brazil
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19
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Gao Y, Chen J, Du W. Identification of novel potential biomarkers using bulk RNA and single cells to build a neural network model for diagnosis of liver cancer. Discov Oncol 2025; 16:728. [PMID: 40353917 PMCID: PMC12069198 DOI: 10.1007/s12672-025-02420-7] [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: 11/17/2024] [Accepted: 04/17/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND As a common cancer, liver cancer imposes an unacceptable burden on patients, but its underlying molecular mechanisms are still not fully understood. Therefore, there is an urgent need to potential biomarkers and diagnostic models for liver cancer. METHODS In this study, transcriptome and single-cell datasets related to liver cancer were downloaded from the UCSC Xena database and the Mendeley database, and differential analysis and weighted gene co-expression network analysis were used to find differentially expressed genes related to liver cancer. We used multiple machine algorithms to find hub genes related to liver cancer, and constructed new artificial neural network models based on their transcriptome expression patterns to assist in the diagnosis of liver cancer. Subsequently, we conducted survival analysis and immune infiltration analysis to explore the correlation between hub genes and immune cells, and used single-cell data to verify hub genes related to liver cancer. RESULTS This study identified MARCO, KCNN2, NTS, TERT and SFRP4 as central genes associated with liver cancer, and constructed a new artificial neural network model for molecular diagnosis of liver cancer. The diagnostic performance of the training cohort and the validation cohort was good, with the areas under the ROC curves of 1.000 and 0.986, respectively. Immune infiltration analysis determined that these central genes were closely associated with different types of immune cells. The results of immunohistochemistry and the results at the single cell level were consistent with those at the transcriptome level, and also showed obvious differences between different cell types in liver cancer and healthy states. CONCLUSION This study identified MARCO, KCNN2, NTS, TERT, and SFRP4 from multiple dimensions and highlighted their key roles in the diagnosis and treatment of liver cancer from multiple dimensions, providing promising biomarkers for the diagnosis of liver cancer.
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Affiliation(s)
- Yingzheng Gao
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Jiahao Chen
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Weidong Du
- The First Affiliated Hospital of Zhejiang, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Chinese Medical University, Hangzhou, 310006, China.
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20
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Wang B, Li D, Ilnytskyy Y, Khachigian LM, Zhong N, Rodriguez-Juarez R, Kovalchuk I, Kovalchuk O. A Positive Feedback DNA-PK/MYT1L-CXCR1-ERK1/2 Proliferative Signaling Loop in Glioblastoma. Int J Mol Sci 2025; 26:4398. [PMID: 40362634 PMCID: PMC12072392 DOI: 10.3390/ijms26094398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
Glioblastoma is the most common primary brain tumor in adults. Our previous studies revealed a functional interplay of myelin transcription factor 1-like (MYT1L) with the DNA-dependent protein kinase (DNA-PK) in the regulation of p21 transcription. However, the contributing role of this functional interplay in glioblastoma remains largely unknown. Here, we used cell lines with normal DNA-PK (HEK293 and M059K) or deficient DNA-PK (M059J) as a model system to demonstrate the importance of the DNA-PK-dependent activation of MYT1L in controlling the transcription of CXC chemokine receptor 1 (CXCR1) in a positive-feedback proliferative signaling loop in glioblastoma with numerous conventional techniques. In normal DNA-PK cells, MYT1L acted as an oncogene by promoting cell proliferation, inhibiting apoptosis, and shortening a cell cycle S phase. However, in DNA-PK-deficient cells, MYT1L functioned as a tumor suppressor by inhibiting cell proliferation and inducing a G1 arrest. The enforced expression of MYT1L promoted CXCR1 transcription in DNA-PK-normal cells but attenuated transcription in DNA-PK-deficient cells. Bioinformatics analysis predicted a MYT1L-binding sequence at the CXCR1 promoter. The functional dependence of MYT1L on DNA-PK in CXCR1 transcription was validated by luciferase assay. Although the expression of CXCR1 was lower in M059J cells as compared to M059K cells, it was higher than in normal brain tissue. The CXCR1 ligands interleukin 8 (IL-8) and GRO protein alpha (GROα) expressed in M059J and M059K cells may signal through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway that can be blocked by CXCR1 siRNA. Our findings demonstrate the existence of a positive feedback DNA-PK/MYT1L-CXCR1-ERK1/2 proliferation loop in glioblastoma cells that may represent a pharmacological target loop for therapeutic intervention.
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Affiliation(s)
- Bo Wang
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Dongping Li
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Yaroslav Ilnytskyy
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Levon M. Khachigian
- Vascular Biology and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;
| | - Nuanying Zhong
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Rocio Rodriguez-Juarez
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Igor Kovalchuk
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
| | - Olga Kovalchuk
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada; (B.W.); (D.L.); (Y.I.); (N.Z.); (R.R.-J.)
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21
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Huang S, Liu S, Tan F, Chen H, Chen G. Construction and validation of a risk nomogram model for colorectal sessile serrated lesions. J Int Med Res 2025; 53:3000605251337577. [PMID: 40357909 PMCID: PMC12075987 DOI: 10.1177/03000605251337577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 04/09/2025] [Indexed: 05/15/2025] Open
Abstract
ObjectiveThis study aimed to explore the risk factors for colorectal sessile serrated lesions and construct a risk nomogram model.MethodsPatients were enrolled retrospectively from the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University from January 2019 to September 2023 and randomized to the training and validation sets at a ratio of 7:3. The predictors for constructing the nomogram model were screened via univariate analysis and multivariate logistic regression analysis. Subsequently, the performance of the model was evaluated.ResultsMultivariate logistic regression analysis revealed that age, history of smoking, history of alcohol consumption, and triglyceride-glucose index were independent risk factors for colorectal sessile serrated lesions (p < 0.05). The area under the curve values of the nomogram model in the training and validation sets were 0.715 (95% confidence interval: 0.676-0.753) and 0.742 (95% confidence interval: 0.669-0.815), respectively. The calibration curves showed good homogeneity between the predicted and actual values. Decision curve analysis showed that this nomogram model can achieve positive clinical benefits.ConclusionsAge, history of smoking, history of alcohol consumption, and triglyceride-glucose index are independent predictors of colorectal sessile serrated lesions. This nomogram model may predict the risk of colorectal sessile serrated lesions.
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Affiliation(s)
| | | | - Fang Tan
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
| | - Hu Chen
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
| | - Guangxia Chen
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
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22
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Ning Y, Li H, Song Y, He Y, Liu S, Liu Y. Predictive value of CPS combined with inflammatory markers for pathological remission of locally advanced head and neck squamous cell carcinoma after adjuvant immunochemotherapy. Front Mol Biosci 2025; 12:1593742. [PMID: 40376264 PMCID: PMC12078134 DOI: 10.3389/fmolb.2025.1593742] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Accepted: 04/17/2025] [Indexed: 05/18/2025] Open
Abstract
Objective To explore the predictive value of the combined positive score (CPS) and the neutrophil-to- platelet count ratio (NPR) for surgical pathological remission in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) who have undergone neoadjuvant immunotherapy combined with chemotherapy (NICC). Method Patients with LAHNSCC who underwent NICC and surgery from May 2021 to September 2023 were retrospectively analyzed. CPS, NPR and other clinically relevant parameters were collected, which includes gender, age, tumor types, multiple cancer, differentiation, T staging, N staging, immunotherapy cycles and postoperative pathological remission degree. Result Patients with a higher CPS were significantly associated with a higher pathological complete response (PCR) of the primary site (PPCR) (P = 0.034) and a higher PCR of the lymph nodes (LPCR) (P = 0.085). Specifically, patients with a CPS of ≥20 demonstrated a higher rate of severe pathologic tumor response (PTR), with values of 80.8% compared to 66.7% and 50%. Notably, even patients with a CPS <1 had a relatively high severe PTR rate of 66.7%. Moreover, patients with NPR <0.024 exhibited a higher severe PTR, regardless of the CPS subgroups (P < 0.05). Conclusion Higher CPS can be considered a good predictor of higher PCR after NICC in patients with LAHNSCC. Patients with CPS <1 can still achieve a higher PTR. Patients with NPR <0.024 can help achieve a higher severe PTR in patients with LAHNSCC regardless of the CPS.CPS combined with NPR may have a better predicted value for surgical PTR of HNSCC after NICC.
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Affiliation(s)
| | | | | | | | | | - Yang Liu
- *Correspondence: Shaoyan Liu, ; Yang Liu,
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23
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Samoudi A, Abolhasani-Zadeh F, Afgar A, Jalilian E, Zeinalynezhad H, Langroudi L. Treatment of cancer-associated fibroblast-like cells with celecoxib enhances the anti-cancer T helper 1/Treg responses in breast cancer. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:6099-6112. [PMID: 39652176 DOI: 10.1007/s00210-024-03641-3] [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: 08/17/2024] [Accepted: 11/15/2024] [Indexed: 04/11/2025]
Abstract
Tumor inflammation, as one of the hallmarks of cancer, has been the target for anti-cancer treatments. Celecoxib is a selective inhibitor of the enzyme cycloxygenase-2 (COX-2) and inhibits the production of PGE2, which is an important mediator of tumor inflammation produced by cancer cells and cells of the tumor microenvironment. In this study, we aimed at inhibiting COX-2 using celecoxib, expressed in cancer-associated fibroblast (CAF)-like cells isolated from breast cancer and evaluated the alterations in their cytokine profile and gene expression. CAF-like cells were isolated by explant culture from 13 breast cancer tissues. Simultaneously, peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood. CAF-like cells were treated with 10 µM of celecoxib and expression of genes COX-2, smooth muscle actin-alpha (α-SMA), and production of prostaglandin E2 (PGE2), Interleukin 10 (IL10), and transforming growth factor beta1 (TGF-β1) was evaluated. Next, PBMCs were co-cultured with celecoxib-treated CAF-like cells and the expression of genes T-bet, Foxp3, GATA-3; production of cytokines IFN-ɣ, IL-10, IL-4, TGF-β1, and the mediator PGE2 were assessed by real-time-PCR and ELISA, respectively. Isolated CAF-like cells showed expression of fibroblast activation protein (FAP). Treatment with celecoxib was able to efficiently reduce the production of PGE2 and the expression of α-SMA in isolated CAF-like cells. Furthermore, PBMCs in co-culture with these cells showed enhanced Th1 phenotype including T-bet and IFNγ expression and decreased the phenotypical markers of regulatory T cells such as FoxP3 and IL-10 and TGF-β1 production. Our study shows the important role of COX-2 in CAFs by promoting immune suppression. Our results suggested that high expression of COX-2 in CAFs may serve as a new therapeutic, targeting CAFs in enhancing immune responses in breast cancer treatment.
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Affiliation(s)
- Arash Samoudi
- Department of Medical Immunology, School of Medicine, Kerman University of Medical Sciences, Pajoohesh Sq, Kerman, 7616914111, Iran
| | | | - Ali Afgar
- Research center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
| | - Elnaz Jalilian
- Department of Medical Immunology, School of Medicine, Kerman University of Medical Sciences, Pajoohesh Sq, Kerman, 7616914111, Iran
| | - Hamid Zeinalynezhad
- Department of Surgery, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Ladan Langroudi
- Department of Medical Immunology, School of Medicine, Kerman University of Medical Sciences, Pajoohesh Sq, Kerman, 7616914111, Iran.
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Ronchetti L, Terrenato I, Lobascio AM, Iacobelli M, Ferretti M, Setti Boubaker N, Sperati F, Mandoj C, Mancini E, Carosi M, Vizza E, Corrado G. Role of inflammatory blood parameters from complete blood count in predicting ovarian follicular density in cancer patients undergoing ovarian tissue cryopreservation. J Ovarian Res 2025; 18:89. [PMID: 40307845 PMCID: PMC12042306 DOI: 10.1186/s13048-025-01670-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: 01/20/2025] [Accepted: 04/11/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND Inflammation is a key feature of neoplastic diseases, especially cancer. Predicting follicular density (FD) in ovarian cortical tissue is essential for evaluating ovarian tissue cryopreservation (OTC) outcomes in fertility preservation. However, to date, no studies have explored the role of inflammatory markers in predicting FD in OTC patients. This study aims to investigate the relationship between blood inflammatory parameters and FD in this population. METHODS We conducted a retrospective observational study on 101 OTC patients. The primary goal was to assess whether parameters from Complete Blood Count (CBC) that include White Blood Cells (WBC), absolute neutrophil count, absolute lymphocyte count, Neutrophil/Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), Platelet Count (PC), MPV/PC and the Platelet/Lymphocyte Ratio (PLR) could predict FD. We also evaluated the impact of factors such as oncological diagnosis, smoking, Body Mass Index (BMI), and germline BRCA mutations. Spearman's correlation coefficient and the Mann-Whitney test were used for analysis. RESULTS Significant correlations were found in patients aged between 27 and 31. In this group, NLR was inversely correlated with FD (Rho = -0.374, p = 0.032), while lymphocyte count (Rho = 0.371, p = 0.034) and MPV/PC (Rho = 0.365, p = 0.037) were positively correlated with FD. An inverse correlation was also found between PLR and FD (Rho = -0.38, p = 0.028). CONCLUSIONS Our findings suggest that NLR, lymphocyte count, MPV/PC and PLR may be useful in predicting FD in a subgroup of OTC patients. Larger studies are needed to confirm these results.
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Affiliation(s)
- Livia Ronchetti
- Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy.
| | - Irene Terrenato
- Biostatistics & Bioinformatics, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Anna Maria Lobascio
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Marcello Iacobelli
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | | | | | - Francesca Sperati
- UOSD Clinical Trial Center and Biostatistics & Bioinformatics, San Gallicano Dermatological Institute IRCCS, Rome, Italy
| | - Chiara Mandoj
- Clinical Pathology Unit and Cancer Biobank, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Emanuela Mancini
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Mariantonia Carosi
- Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy
| | - Enrico Vizza
- Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Giacomo Corrado
- Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
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Nakatsukasa T, Muraoka D, Deng S, Yasui K, Sawada SI, Shimoda A, Matsushita H, Matsumoto K, Nagayasu T, Harada N, Akiyoshi K, Ikeda H. Antitumor immune response elicited by M2 TAM-specific DDS via C-type lectin CD209b using cholesteryl pullulan nanogel as a protein drug carrier. Biomater Sci 2025; 13:2340-2350. [PMID: 40094910 DOI: 10.1039/d5bm00342c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Many cancer patients develop resistance to immunotherapy, highlighting the urgent need for novel therapeutic strategies. Various factors contribute to tumor resistance to immunotherapy, among which tumor-associated macrophages (TAMs) are critical regulators of tumor sensitivity. Therefore, combining cancer immunotherapies with drug delivery systems (DDSs) targeting TAMs has become an intriguing treatment strategy. However, the target molecules used in DDSs are limited to a few receptors expressed on TAMs. Therefore, the identification of novel target molecules for TAM-specific DDS is urgently needed. The current study evaluated the ability of a cholesteryl pullulan (CHP) nanogel to target TAMs via mDC-SIGN (CD209b). This nanogel encapsulated the cytotoxic protein drug Pseudomonas exotoxin A and was injected into a tumor-bearing mouse model. This treatment significantly reduced the abundance of CD209b-positive M2 TAMs and enhanced antitumor immune responses. Ultimately, tumor growth was suppressed, even in a low-immunogenic tumor model. Hence, CD209b is an effective target molecule for M2 TAM-specific DDSs that can be used to develop novel cancer therapies.
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Affiliation(s)
- Takaaki Nakatsukasa
- Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Daisuke Muraoka
- Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
- Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
| | - Situo Deng
- Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
| | - Kiyoshi Yasui
- Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
| | - Shin-Ichi Sawada
- Synergy Institute for Futuristic Mucosal Vaccine Research and Development (cSIMVa), Chiba University, Chiba 260-8670, Japan
| | - Asako Shimoda
- Department of Immunology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
- The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan
| | - Hirokazu Matsushita
- Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
| | - Keitaro Matsumoto
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Takeshi Nagayasu
- Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | | | - Kazunari Akiyoshi
- Department of Immunology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Hiroaki Ikeda
- Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
- Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8523, Japan
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Liu L, He JH, Xiao Y, Wei D. Prognostic impact of serum interleukin-6 and 17 level in patients with bladder cancer: a systematic review and meta-analysis. PeerJ 2025; 13:e19385. [PMID: 40321822 PMCID: PMC12047212 DOI: 10.7717/peerj.19385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 04/07/2025] [Indexed: 05/08/2025] Open
Abstract
Background Interleukin, a noninvasive biomarker, holds huge potential for providing valuable insights into the management of inflammatory conditions and tumor diseases. This systematic review and meta-analysis aimed to evaluate the prognostic role of interleukin in bladder cancer (BCa) patients. Methods A comprehensive search of six English and Chinese databases (PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Service System) was conducted from inception to July 10, 2024. Studies investigating the association between serum interleukin levels and BCa were included. Outcome measures encompassed disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Statistical analyses were performed using RevMan 5.4.1, employing random or fixed-effects models as appropriate. Sensitivity, subgroup, and descriptive analyses were also conducted. Results A total of seven studies involving 1,505 patients were included. Four studies reported the association between serum interleukin-6/17 (IL-6/17) and OS in BCa. Patients with elevated serum IL levels exhibited a worse OS (HR = 2.28; 95% CI [1.03-5.05]; P = 0.04); however, subgroup analysis revealed that only high serum IL-17 levels were significantly associated with shorter OS, while IL-6 levels showed no association with OS. Six studies examined the relationship between serum IL-6/17 and DFS in BCa. Patients with elevated serum IL levels were associated with poorer DFS (HR = 2.57; 95% CI [1.55-4.26]; P < 0.001). This association remained consistent across subgroup analyses based on interleukin type, publication country, and surgical methods. Only two studies investigated the relationship between serum IL-6/17 and DSS in BCa, with no significant association found (HR = 1.58; 95% CI [1.00-2.51]; P = 0.05). Conclusion This meta-analysis demonstrates a strong association between serum interleukin levels and survival outcomes in BCa, suggesting that serum interleukin testing may be a valuable clinical tool for predicting patient outcomes and guiding treatment decisions.
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Affiliation(s)
- Liang Liu
- Department of Urology, Baoding No.1 Central Hospital, Baoding, Hebei, China
- Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding, Hebei, China
- Prostate and Andrology Key Laboratory of Baoding, Baoding, Hebei, China
| | - Jun-Hui He
- Department of Urology, Heze Municipal Hospital, Heze, Shandong, China
| | - Yu Xiao
- Psychosomatic Medical Center, The Fourth People’s Hospital of Chengdu, Chengdu, Sichuan, China
| | - Dong Wei
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei, China
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Liang H, Pan K, Wang J, Lin J. Association between neutrophil percentage-to-albumin ratio and breast cancer in adult women in the US: findings from the NHANES. Front Nutr 2025; 12:1533636. [PMID: 40357031 PMCID: PMC12066505 DOI: 10.3389/fnut.2025.1533636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 04/08/2025] [Indexed: 05/15/2025] Open
Abstract
Background An increasing number of studies suggests an association between systemic inflammation, nutritional status, and cancer. However, the relationship between the prevalence of breast cancer (BC) and the neutrophil-percentage-to-albumin ratio (NPAR), a recently identified biomarker of inflammation, is not well established. Therefore, this study aims to investigate the relationship between BC risk and the NPAR. Methods This study included 18,726 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018. The NPAR was used to assess inflammation and nutritional status. Statistical methods such as multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) analysis were conducted to investigate the influence of NPAR on the prevalence of BC. In addition, propensity score matching was employed to further validate the findings. Results The logistic regression results showed that the prevalence of breast cancer is significantly associated with the NPAR (OR = 1.05; 95% CI = 1.02-1.09, p = 0.003). In comparison to participants in the lowest quartile, Q1, the prevalence of breast cancer increased by 5% for those in Q2 (p = 0.745), 3% for those in Q3 (p = 0.032), and 38% for those in Q4 (p = 0.018) with a higher NPAR. In addition, subgroup and RCS analyses showed that the NPAR and BC prevalence were positively correlated. Furthermore, a significant association was observed between the NPAR and marital status. The significance of traits was assessed using mean decrease accuracy (MDA) and mean decrease impurity (MDI). These measures of random forest modeling showed that NPAR is one of the major factors affecting the prevalence of BC. Furthermore, linear analysis demonstrated a correlation between a high NPAR and increased total testosterone and sex hormone-binding globulin (SHBG) levels. Conclusion A significant association was observed between a high NPAR and a higher prevalence of breast cancer, which could be attributable to sex hormone levels. This finding suggests that the NPAR may serve as a biomarker for BC in adult women in the US.
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Affiliation(s)
- Huikai Liang
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- The Second Clinical College of Fujian Medical University, Quanzhou, China
| | - Kelun Pan
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jiayi Wang
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- The Second Clinical College of Fujian Medical University, Quanzhou, China
| | - Jianqing Lin
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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Vangala VNP, Uversky VN. Intrinsic disorder in protein interaction networks linking cancer with metabolic diseases. Comput Biol Chem 2025; 118:108493. [PMID: 40319601 DOI: 10.1016/j.compbiolchem.2025.108493] [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: 01/20/2025] [Revised: 04/20/2025] [Accepted: 04/24/2025] [Indexed: 05/07/2025]
Abstract
Complex diseases are usually driven by numerous proteins that operate as intricate network systems. Deciphering of their signals is required for more advanced level understanding of the cellular processes driven by protein interactions. Therefore, placing diseases into a framework, where they can be viewed together, represents an important and fruitful approach. The goal of this study was to assess the intrinsic disorder present in the proteins forming PPI networks linking cancer with different human diseases. To this end, we used a set of bioinformatics tools to explore intrinsic disorder and liquid-liquid phase separation predispositions of 340 proteins reported earlier by Hirsch et al. (Cancer Cell (2010) 17(4), 348-361; doi: 10.1016/j.ccr.2010.01.022) as differently expressed in common chronic diseases, such as cancer, obesity, diabetes, and cardiovascular diseases. We further examined selected proteins from this set for their interactability and intrinsic disorder-based functionality. Our analyses demonstrated that intrinsically disordered proteins and proteins with intrinsically disordered regions may act as active network promoters and operate as highly connected hubs, which further enables them to play key roles in the disease pathways. The study also indicated that differently expressed proteins involved in disease progression could be characterized by diverse degrees of intrinsic disorder and LLPS propensity. We hope that our findings in combination with the outputs of the proteomic and functional genomic analyses contain essential clues that can be used in further medical research leading to the design of better therapies.
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Affiliation(s)
- Veda Naga Priya Vangala
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Vladimir N Uversky
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
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Bekki T, Shimomura M, Yano T, Watanabe A, Ishikawa S, Imaoka K, Ono K, Matsubara K, Mochizuki T, Hattori M, Akabane S, Ohdan H. C-reactive Protein-albumin-lymphocyte Index Is a Useful Indicator for Recurrence and Survival Following Curative Resection of Stage I-III Colorectal Cancer. J Anus Rectum Colon 2025; 9:192-201. [PMID: 40302855 PMCID: PMC12035343 DOI: 10.23922/jarc.2024-070] [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: 07/03/2024] [Accepted: 12/03/2024] [Indexed: 05/02/2025] Open
Abstract
Objectives Recently, several simple inflammation-based prognostic scores that can be calculated easily from serum parameters, have been reported to be related to colorectal cancer prognosis. This study aimed to investigate factors influencing the prognosis of patients, including inflammation-based prognostic scores, with stage I-III colorectal cancer following curative resection. Methods This single-center study included 608 patients with stage I-III colorectal cancer who underwent curative resection between April 2010 and December 2018. A retrospective analysis was performed to identify the prognosis-associated variables in these patients. As a multi-center study, the Hiroshima Surgical study Group of Clinical Oncology database was used to analyze 1659 patients with stage I-III colorectal cancer who underwent curative resection to confirm the results of our single-center study. Results Of the inflammation-based prognostic scores, only preoperative C-reactive protein-albumin-lymphocyte index was revealed to predict a poor prognosis in patients with stage I-III colorectal cancer following curative resection. The low C-reactive protein-albumin-lymphocyte index was associated with poor overall survival and recurrence-free survival, which was similar in patients from multi-center database. The C-reactive protein-albumin-lymphocyte index was found to be associated with patient age, systemic condition, comorbidities, and tumor factors. The time-dependent area under the curve for the postoperative proghosis of the C-reactive protein-albumin-lymphocyte index was superior to those of other inflammation-based prognostic scores in most postoperative observation periods. Conclusions The preoperative C-reactive protein-albumin-lymphocyte index was independently associated with long-term prognosis in patients with stage I-III colorectal cancer following curative resection.
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Affiliation(s)
- Tomoaki Bekki
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Manabu Shimomura
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takuya Yano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Atsuhiro Watanabe
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Sho Ishikawa
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kouki Imaoka
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kosuke Ono
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keiso Matsubara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tetsuya Mochizuki
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Minoru Hattori
- Medical Education Center, Hiroshima University, Hiroshima, Japan
| | - Shintaro Akabane
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Wang Z, Liu S, Zhang M, Liu M. Dual roles of methylglyoxal in cancer. Front Oncol 2025; 15:1557162. [PMID: 40352588 PMCID: PMC12061732 DOI: 10.3389/fonc.2025.1557162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 04/04/2025] [Indexed: 05/14/2025] Open
Abstract
Cancer treatment currently includes a variety of approaches. Chemotherapy, targeted therapy, and immunotherapy are combined based on cancer characteristics to develop personalized treatment plans. However, drug resistance can hinder the progress of treatment over time. Methylglyoxal (MG) is a metabolite with hormesis, exhibiting both pro-tumor and anti-tumor actions depending on its concentration during cancer progression. The MG-related metabolic pathway is being explored in the development of anti-cancer drugs, focusing on reducing MG stress or exploiting its cytotoxic effects to inhibit cancer progression. This article investigates the dual role of MG in cancer, emphasizing its effects on cell metabolism and tumor progression. It proposes MG capture therapy for the pre-cancerous stage and MG toxicity therapy for the cancer stage, contributing to the development of precise and individualized cancer treatments.
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Affiliation(s)
| | | | | | - Min Liu
- Department of Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China
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Zhang Y, Ou G, Li R, Peng L, Shi J. Causal relationship between benign prostatic hyperplasia and prostate cancer: a bidirectional Mendelian randomization analysis. Postgrad Med J 2025; 101:427-434. [PMID: 39547665 DOI: 10.1093/postmj/qgae163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/05/2024] [Accepted: 11/03/2024] [Indexed: 11/17/2024]
Abstract
OBJECTIVE Our aim is to explore the relation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) from a genetic level utilizing Mendelian randomization (MR). METHODS The IEU genome-wide association studies database was surveyed for single nucleotide polymorphisms (SNPs) associated with BPH, PCa, and PCa (validation cohort). Single nucleotide polymorphisms were subjected to stringent quality control based on rigorous screening criteria. BPH and PCa risk were evaluated using the inverse-variance weighted method (IVW), MR-Egger, simple mode, weighted median, and weighted mode. Horizontal pleiotropy of single nucleotide polymorphisms was assessed using the MR-Egger intercept test, while heterogeneity was evaluated using Cochran's Q test. Reverse causality was assessed by evaluating PCa as the exposure and BPH as the outcome. A validation database was used to verify the exposure and outcome. RESULTS The risk of PCa increased significantly with genetically predicted BPH (IVW: OR [95% CI] = 1.3849 × 107 [2330, 8.2294 × 1010], P = 2.0814 × 10-4). In reverse MR analysis, PCa also increased the risk of BPH (IVW: OR [95% CI] = 1.0011 [1.0003, 1.0019], P = 0.0031). The findings were consistent with the MR analysis results of the PCa validation cohort. Sensitivity analyses indicated the presence of heterogeneity but no horizontal pleiotropy. CONCLUSION The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. Key message Three research questions and three bullet points What is already known on this topic? Observational studies suggest a controversial relationship between BPH and PCa. MR allows investigation of causality using genetic variants as instrumental variables (IVs). What does this study add? The study presents proof of a significant bidirectional causal relationship between genetically predicted BPH and an increased risk of PCa. How this study might affect research, practice, or policy? Recognizing the bidirectional relationship between BPH and PCa, men diagnosed with BPH may benefit from more stringent PCa screening protocols.
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Affiliation(s)
- Yi Zhang
- Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, No. 2 Renmin Street, Section 5, Guta District, Jinzhou, 121002, Liaoning, China
- Department of Urology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, No. 2 Heping Road, Section 5, Linghe District, Jinzhou, 121001, Liaoning, China
| | - Guangyang Ou
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, No. 95, Shaoshan Middle Road, Yuhua District, Changsha, 410007, Hunan, China
| | - Rongkang Li
- Department of Urology, Lanzhou University Second Hospital, Lanzhou University, No. 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu, China
| | - Lei Peng
- Department of Urology, Lanzhou University Second Hospital, Lanzhou University, No. 82 Cuiyingmen, Chengguan District, Lanzhou, 730030, Gansu, China
| | - Jianguo Shi
- Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, No. 2 Renmin Street, Section 5, Guta District, Jinzhou, 121002, Liaoning, China
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Barbosa JMG, de Oliveira CG, Soares MFG, Vieira LFM, Filho OC, Cardoso DMM, Beato PMM, Moro CATM, de Oliveira AE, Antoniosi Filho NR. Cerumenogram as an assay for the metabolic diagnosis of precancer, cancer, and cancer remission. Sci Rep 2025; 15:13929. [PMID: 40263376 PMCID: PMC12015372 DOI: 10.1038/s41598-025-97440-2] [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: 12/18/2024] [Accepted: 04/04/2025] [Indexed: 04/24/2025] Open
Abstract
Early diagnosis is crucial for successful cancer treatment. As a mitochondrial metabolic disease, cancer produces volatile organic metabolites that are present in earwax, allowing differentiation between healthy individuals and those with cancer through an assay called cerumenogram. In this case series study, we demonstrated that this assay also enables the diagnosis of precancerous stages, such as hypermetabolic inflammation and dysplasia, which can aid in treatments to prevent cancer progression. Additionally, this assay reveals that oncological metabolism differs from that observed in metaplasias, cysts, and benign tumors, helping to avoid unnecessary oncological procedures due to suspected malignancy. Cerumenogram can also be used to assess cancer remission. Thus, the cerumenogram emerges as an assay that might enable the diagnosis of cancer, monitor remission, and identify precancerous stages, covering key steps of tumorigenesis.
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Affiliation(s)
- João Marcos Gonçalves Barbosa
- Laboratório de Métodos de Extração e Separação (LAMES), Instituto de Química (IQ), Universidade Federal de Goiás (UFG), Campus II - Samambaia, Goiânia, GO, 74690-900, Brazil
| | - Camilla Gabriela de Oliveira
- Laboratório de Métodos de Extração e Separação (LAMES), Instituto de Química (IQ), Universidade Federal de Goiás (UFG), Campus II - Samambaia, Goiânia, GO, 74690-900, Brazil
| | - Marina Ferraz Gontijo Soares
- Laboratório de Métodos de Extração e Separação (LAMES), Instituto de Química (IQ), Universidade Federal de Goiás (UFG), Campus II - Samambaia, Goiânia, GO, 74690-900, Brazil
| | | | - Omar Carneiro Filho
- Insituto de Medicina Nuclear (IMEN), Alameda dos Buritis, 600, St. Central, Goiânia, GO, 74015-080, Brazil
| | | | | | | | - Anselmo Elcana de Oliveira
- Laboratório de Química Teórica e Computacional (LQTC), Instituto de Química (IQ), Universidade Federal de Goiás (UFG), Campus II - Samambaia, Goiânia, GO, 74690-970, Brazil
| | - Nelson Roberto Antoniosi Filho
- Laboratório de Métodos de Extração e Separação (LAMES), Instituto de Química (IQ), Universidade Federal de Goiás (UFG), Campus II - Samambaia, Goiânia, GO, 74690-900, Brazil.
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Song S, Wang J, Ouyang X, Huang R, Wang F, Xie J, Chen Q, Hu D. Therapeutic connections between pyroptosis and paclitaxel in anti-tumor effects: an updated review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04036-8. [PMID: 40257490 DOI: 10.1007/s00210-025-04036-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 03/06/2025] [Indexed: 04/22/2025]
Abstract
As a form of inflammation-associated cell death, pyroptosis has gained widespread attention in recent years. Accumulating evidence indicates that pyroptosis regulates tumor growth and is associated with autoimmune disorders and inflammatory response. Paclitaxel, a traditional Chinese medicine, usually induces death of cancer cells as a chemotherapeutic agent. Previous studies have revealed that paclitaxel can exert an anti-tumor effect through a variety of cell death mechanisms, of which pyroptosis plays a pivotal role in inhibiting tumor growth and enhancing anti-tumor immunity. In this review, we summarize the current advances in therapeutic connections between pyroptosis and paclitaxel in anti-tumor effects.
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Affiliation(s)
- Shuxin Song
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jingbo Wang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaohu Ouyang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Renyin Huang
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fang Wang
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Junke Xie
- Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qianyun Chen
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Sorrenti S, Scerrino G, Lori E, Vassallo F, Saverino S, Amato C, Melfa G, Richiusa P, Mazzola S, Lopes A, Orlando G, Graceffa G. Inflammation and Thyroid Cancer: Deciphering the Role of Blood Immune Indexes. Cancers (Basel) 2025; 17:1363. [PMID: 40282539 PMCID: PMC12025745 DOI: 10.3390/cancers17081363] [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: 03/03/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Inflammation within tumor microenvironments has been correlated to numerous malignancies. This study aims to explore its significance in thyroid cancer (TC). METHODS Retrospective analysis of 157 thyroid carcinomas and 40 benign cases involved initial univariate analysis. The value of neutrophils/value of lymphocytes (NLR), value of platelets/value of lymphocytes (PLR), value of lymphocytes/value of monocytes (LMR), and value of platelets × value of neutrophils/value of lymphocytes (SII) indexes were related to TC characteristics and number and location of involved lymph nodes using χ2 or Fischer's exact tests for categorical variables and Student's t-tests for continuous ones. A 1:1 propensity score matching balanced malignant and benign TC groups based on age, sex, and tumor size was used. Post-matching, a multivariate logistic model integrated sex, age, Central lymph node metastases (CLNM), and SII index. Statistically significant immune index values underwent ROC curve analysis for determining cut-offs. Among the 157 malignant TC, median test and density plots were performed. RESULTS The SII index emerged as a predictor of malignancy in both univariate and multivariate analyses (p-value = 0.0202). The ROC curve indicated a cut-off SII value of 465.71, (specificity = 58% [95% CI: 0.43-0.73]; sensitivity = 80% [95% CI: 0.68-0.93]). Median SII index values for tumor sizes of 1 and >1 were 522.8 and 654.8, respectively (p-value = 0.016). When central lymph nodes metastases(CLNMs) was considered (CLNM = 0 vs. CLNM > 0), median SII values were 530.7 and 1121.7, respectively (p-value = 0.011). CONCLUSIONS The SII index appears to be a valuable tool in the presence of TC, showing correlations with malignancy, tumor size, and CLNMs.
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Affiliation(s)
- Salvatore Sorrenti
- Department of Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy;
| | - Gregorio Scerrino
- Unit of Endocrine Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy;
| | - Eleonora Lori
- Department of Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy;
| | - Fabrizio Vassallo
- Unit of General and Emergency Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy; (F.V.); (C.A.); (G.M.); (G.O.)
| | - Stefania Saverino
- Unit of General and Oncology Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via L. Giuffré, 5, 90127 Palermo, Italy; (S.S.); (A.L.); (G.G.)
| | - Calogera Amato
- Unit of General and Emergency Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy; (F.V.); (C.A.); (G.M.); (G.O.)
| | - Giuseppina Melfa
- Unit of General and Emergency Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy; (F.V.); (C.A.); (G.M.); (G.O.)
| | - Pierina Richiusa
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), Section of Endocrinology, University of Palermo, 90127 Palermo, Italy;
| | - Sergio Mazzola
- Unit of Clinical Epidemiology and Tumor Registry, Department of Laboratory Diagnostics, Policlinico “P. Giaccone”, University of Palermo, Via L. Giuffré, 5, 90127 Palermo, Italy;
| | - Antonella Lopes
- Unit of General and Oncology Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via L. Giuffré, 5, 90127 Palermo, Italy; (S.S.); (A.L.); (G.G.)
| | - Giuseppina Orlando
- Unit of General and Emergency Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via Liborio Giuffré 5, 90127 Palermo, Italy; (F.V.); (C.A.); (G.M.); (G.O.)
| | - Giuseppa Graceffa
- Unit of General and Oncology Surgery, Department of Surgical Oncological and Oral Sciences, Policlinico “P. Giaccone”, University of Palermo, Via L. Giuffré, 5, 90127 Palermo, Italy; (S.S.); (A.L.); (G.G.)
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Lin J, Gong Z, Lu Y, Cai J, Zhang J, Tan J, Huang Z, Chen S. Recent Progress and Potential of G4 Ligands in Cancer Immunotherapy. Molecules 2025; 30:1805. [PMID: 40333779 PMCID: PMC12029830 DOI: 10.3390/molecules30081805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/13/2025] [Accepted: 04/15/2025] [Indexed: 05/09/2025] Open
Abstract
G-quadruplex (G4) structures are non-canonical nucleic acid conformations that play crucial roles in gene regulation, DNA replication, and telomere maintenance. Recent studies have highlighted G4 ligands as promising anticancer agents due to their ability to modulate oncogene expression and induce DNA damage. By stabilizing G4 structures, these ligands affect tumor progression. Additionally, they have been implicated in tumor immunity modulation, particularly through the activation and immunogenic cell death induction of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Moreover, their disruption of telomere maintenance and regulation of key oncogenes, such as c-MYC and KRAS, position them as candidates for immune-based therapeutic interventions. Despite their therapeutic potential, challenges remain in optimizing their clinical applications, particularly in patient stratification and elucidating their immunomodulatory effects. This review provides a comprehensive overview of the mechanisms through which G4 ligands influence tumor progression and immune regulation, highlighting their potential role in future cancer immunotherapy strategies.
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Affiliation(s)
| | | | | | | | | | | | | | - Shuobin Chen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; (J.L.); (Z.G.); (Y.L.); (J.C.); (J.Z.); (J.T.); (Z.H.)
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Theodoulidis V, Kissoudi K, Chatzistamatiou K, Tzitzis P, Zouzoulas D, Theodoulidis I, Anthoulakis C, Moysiadis T, Topalidou M, Timotheadou E, Grimpizis G, Tsolakidis D. Neutrophil-Lymphocyte Ratio and KELIM Score as Prognostic Markers in High-Grade Serous Advanced Ovarian Cancer Patients Treated with Neoadjuvant Chemotherapy. Biomedicines 2025; 13:975. [PMID: 40299674 PMCID: PMC12024925 DOI: 10.3390/biomedicines13040975] [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: 03/22/2025] [Revised: 04/10/2025] [Accepted: 04/13/2025] [Indexed: 05/01/2025] Open
Abstract
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative for patients with extensive disease. Achieving complete cytoreduction is a critical prognostic factor for OS and progression-free survival (PFS). This study evaluated the prognostic value of two biomarkers-the neutrophil-lymphocyte ratio (NLR) and the cancer antigen-125 (CA-125) ELIMination rate constant K (KELIM)-in predicting survival outcomes and recurrence rates in patients with AOC undergoing NACT. Methods: A retrospective, single-center analysis was conducted on 78 patients with high-grade serous AOC (stages III-IV) treated with platinum-based NACT followed by IDS between January 2013 and December 2023. NLR was calculated from prechemotherapy complete blood counts, with a threshold of ≥3 indicating elevated levels. KELIM, a marker of tumor chemosensitivity, was derived from CA-125 kinetics during the first 100 days of chemotherapy, with a cutoff of ≥1 denoting a favorable outcome. Clinical outcomes, including PFS and OS were analyzed using Kaplan-Meier survival curves, log-rank tests, and Cox regression models. Results: Results demonstrated that elevated NLR (≥3) and low KELIM (<1) were associated with poorer PFS and OS. KELIM score was identified as a strong prognostic marker for both PFS and OS, while NLR demonstrated weak association. Complete cytoreduction was achieved in 69.2% of patients, significantly correlating with improved survival outcomes. Postoperative complications, assessed using the Clavien-Dindo classification, were observed in a small subset of patients, with a total median hospital stay of 8 days. Conclusions: This study highlights the potential of NLR and KELIM as prognostic tools in AOC, aiding in patient selection for radical surgical interventions and predicting chemosensitivity. Future multicenter studies with larger cohorts are needed to validate these results and further explore the clinical utility of these biomarkers in optimizing treatment strategies for AOC.
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Affiliation(s)
- Vasilis Theodoulidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Kalliopi Kissoudi
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Kimon Chatzistamatiou
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Panagiotis Tzitzis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Dimitris Zouzoulas
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Iakovos Theodoulidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Christos Anthoulakis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Theodoros Moysiadis
- Department of Computer Science, School of Sciences and Engineering, University of Nicosia, 2417 Nicosia, Cyprus;
| | - Maria Topalidou
- Radiotherapy Department, “Papageorgiou” Hospital, 56429 Thessaloniki, Greece;
| | - Eleni Timotheadou
- Department of Oncology, Aristotle University of Thessaloniki, Genaral Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece;
| | - Grigoris Grimpizis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Dimitris Tsolakidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
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Aneed IK, Luaibi NM, Abdulqader SN. Investigating the clinical significance of immune and thyroid biomarkers in women with breast cancer and Hashimoto's thyroiditis. Reprod Biol 2025; 25:101011. [PMID: 40222067 DOI: 10.1016/j.repbio.2025.101011] [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: 11/25/2024] [Revised: 02/15/2025] [Accepted: 03/19/2025] [Indexed: 04/15/2025]
Abstract
Breast cancer with Hashimoto's thyroiditis (BC-HT) presents a unique immuno-thyroid interplay that remains poorly understood. This study investigates the relationships between thyroid function markers (TSH, T3, T4), immune markers (CD33, CD44), and thyroid autoantibodies (Anti-TPO, Anti-Tg) in BC-HT patients and healthy controls. Normality testing confirmed non-parametric data distribution, necessitating Mann-Whitney U tests for group comparisons. BC-HT patients exhibited significantly elevated TSH, CD33, Anti-TPO, and Anti-Tg levels, alongside reduced T3 and T4, compared to controls, indicating thyroid dysfunction. Spearman's correlation analysis revealed strong negative correlations between TSH and T3/T4 in controls, which were lost in BC-HT, suggesting disruption of normal thyroid feedback mechanisms. Additionally, CD33 and CD44 correlations with thyroid hormones were evident in controls but absent in BC-HT, highlighting altered immune-thyroid interactions. ROC analysis demonstrated high diagnostic performance for TSH, Anti-Tg, and Anti-TPO, with sensitivities exceeding 0.75, whereas CD33 and CD44 showed limited diagnostic utility. These findings suggest a distinct immuno-thyroid dysregulation in BC-HT patients and highlight the potential of thyroid-specific markers for disease stratification. Future research should focus on longitudinal studies and mechanistic investigations to further delineate the role of immune markers in breast cancer pathophysiology within the context of thyroid autoimmunity.
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Affiliation(s)
- Israa Khalaf Aneed
- Department of Biology, Mustansiriyah University, College of Science, Baghdad, Iraq.
| | | | - Sajid Nader Abdulqader
- National center for medical laboratories, Medical City, Ministry of Health, Baghdad, Iraq
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Garlanda C, Dambra M, Magrini E. Interplay between the complement system and other immune pathways in the tumor microenvironment. Semin Immunol 2025; 78:101951. [PMID: 40209638 DOI: 10.1016/j.smim.2025.101951] [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: 01/31/2025] [Revised: 04/01/2025] [Accepted: 04/01/2025] [Indexed: 04/12/2025]
Abstract
Tumor growth and spread are sustained by the tumor microenvironment. Inflammatory cells and pathways have a fundamental role in the tumor microenvironment, driving or conditioning the functional activation of other leukocyte subsets and favoring evasion of anti-tumor immunity. One of the inflammatory pathways contributing to cancer-related inflammation is the complement system. Complement has long been considered an immune mechanism associated with immunosurveillance. More recently it emerged as a tumor promoting pathway, due to direct effects on cancer cells or indirect effects via immunosuppression driven by myeloid cells. The role of complement in cancer is complex and ambiguous, and depends on the tumor type and stage, as well as other factors including oncogenic drivers, leukocyte infiltration, interactions with other tumor microenvironment components or tumor cells. Other factors of complexity include the source of complement molecules, its canonical or non-canonical extracellular functions, its potential intracellular activation, and the interaction with other systems, such as the coagulation or the microbiome. Preclinical studies generally demonstrate the involvement of complement activation in smouldering inflammation in cancer and promotion of an immunosuppressive environment. These studies paved the way for clinical trials aimed at enhancing the potential of immunotherapy, in particular by targeting complement-dependent myeloid-sustained immunosuppression. However, the complex role of complement in cancer and the multiplicity of complement players may represent stumbling blocks and account for failures of clinical trials, and suggest that further studies are required to identify patient subsets who may benefit from specific complement molecule targeting in combination with conventional therapies or immunotherapy. Here, we will discuss the anti- or pro-tumor role of complement activation in cancer, focusing on the interactions of complement with immune cells within the tumor microenvironment, in particular the myeloid compartment. Furthermore, we will examine the potential of complement targeting in cancer treatment, particularly in the context of macrophage reprogramming.
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Affiliation(s)
- Cecilia Garlanda
- Department of Biomedical Sciences, Humanitas University, Milan, Pieve Emanuele 20072, Italy; IRCCS, Humanitas Research Hospital, Milan, Rozzano 20089, Italy.
| | - Monica Dambra
- IRCCS, Humanitas Research Hospital, Milan, Rozzano 20089, Italy
| | - Elena Magrini
- IRCCS, Humanitas Research Hospital, Milan, Rozzano 20089, Italy
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Yincharoen P, Mordmuang A, Techarang T, Tangngamsakul P, Kaewubon P, Atipairin P, Janwanitchasthaporn S, Goodla L, Karnjana K. Microbiome and biofilm insights from normal vs tumor tissues in Thai colorectal cancer patients. NPJ Precis Oncol 2025; 9:98. [PMID: 40185839 PMCID: PMC11971325 DOI: 10.1038/s41698-025-00873-1] [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: 08/18/2024] [Accepted: 03/10/2025] [Indexed: 04/07/2025] Open
Abstract
Colorectal cancer (CRC) is a prevalent global malignancy with complex etiologies, including microbiota alterations. This study investigates gut microbiota and biofilm-producing bacteria in 35 Thai CRC patients, analyzing paired normal and tumor biopsy samples. Bacterial DNA from the V3-V4 region of 16S rRNA was sequenced, and biofilms were visualized via scanning electron microscopy and fluorescence in situ hybridization (FISH). Results revealed Firmicutes as the dominant phylum, followed by Bacteroidota, Proteobacteria, and Fusobacteriota, with Fusobacteriota and Bacteroidota notably enriched in left-sided CRC. Key biofilm producers-Bacteroides fragilis, Fusobacterium nucleatum, and Pasteurella stomatis-showed significantly higher gene expression in tumor tissues. Dense biofilms and higher Fusobacterium abundance, localized within the crypts of Lieberkuhn, were observed in CRC tissues. These findings highlight CRC-associated microbiota alterations and pathogenic biofilm production, emphasizing a spatial relationship between tumor location and microbial distribution, with potential implications for understanding CRC pathogenesis and therapeutic targeting.
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Affiliation(s)
- Pirada Yincharoen
- Department of Clinical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand
| | - Auemphon Mordmuang
- Department of Medical Sciences, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand
| | - Tachpon Techarang
- Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Panus Tangngamsakul
- Walailak University Hospital, Walailak University, Nakhon Si Thammarat, Thailand
| | | | - Paijit Atipairin
- Department of Surgery, Thasala Hospital, Nakhon Si Thammarat, Thailand
| | | | - Lavanya Goodla
- Department of Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, NM, USA
| | - Kulwadee Karnjana
- Department of Medical Sciences, School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.
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Çolak R, Erdem GU, Kapar C, Gültürk İ, Aksu F, Erdal GŞ, Yılmaz M, Tural D. Change in the neutrophil-lymphocyte ratio may predict early recurrence in operated bladder cancer. Asia Pac J Clin Oncol 2025; 21:199-203. [PMID: 38572819 DOI: 10.1111/ajco.14065] [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: 08/30/2023] [Revised: 01/08/2024] [Accepted: 03/20/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND Recurrence develops in 50% of operated bladder cancer patients. It is important to detect recurrence in advance, and there is no prognostic reliable biomarker for bladder cancer. OBJECTIVE The aim of this study is to show that changes in hematological parameters before radiological imaging can predict recurrence. METHODS We performed a retrospective cohort study of patients undergoing radical cystectomy for urothelial carcinoma of the bladder identified using our institutional database (2010-2022). Disease-free survival (DFS) was evaluated as relapse or death due to any cause. Kaplan-Meier analysis was used for DFS according to the follow-up period. DFS was calculated in two groups neutrophil-lymphocyte ratio (NLR) < 3 and NLR ≥ 3. Log-rank test was used for comparison between groups and p < 0.05 was considered statistically significant. RESULTS In the study, 91 patients were examined. The median age was 61.0 (34-79). 57.1% of the patients were T (1-2) and 42.9% were T (3-4). The lymph node (LN) was negative in 78% and positive in 22%. Median follow-up time and DFS were 53.4 months and 54%, respectively. The median NLR was 2.8 (0.8-8.7). For DFS, there was a significant difference according to age, T stage, and LN status (p: 0.048, 0.019, and 0.040). There was no significant difference in the NLR in terms of DFS at the time of diagnosis (p: 0.654). In follow-ups; While there was no difference in the NLR for DFS 12 months before recurrence (p: 0.231), there was a significant difference 6 months before the relapse and at the time of recurrence (p: 0.023 and 0.031). CONCLUSION The change in the NLR before radiological recurrence in bladder cancer is significant in predicting recurrence. Prospective and multi-center research is needed to confirm our findings.
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Affiliation(s)
- Rumeysa Çolak
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Gökmen Umut Erdem
- Department of Medical Oncology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Caner Kapar
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - İlkay Gültürk
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Faruk Aksu
- Department of Medical Oncology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Gülçin Şahingöz Erdal
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Mesut Yılmaz
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Deniz Tural
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
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Carra D, Maas SCE, Seoane JA, Alonso-Curbelo D. Exposomal determinants of non-genetic plasticity in tumor initiation. Trends Cancer 2025; 11:295-308. [PMID: 40023688 DOI: 10.1016/j.trecan.2025.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/07/2025] [Accepted: 01/21/2025] [Indexed: 03/04/2025]
Abstract
The classical view of cancer as a genetically driven disease has been challenged by recent findings of oncogenic mutations in phenotypically healthy tissues, refocusing attention on non-genetic mechanisms of tumor initiation. In this context, gene-environment interactions take the stage, with recent studies showing how they unleash and redirect cellular and tissue plasticity towards protumorigenic states in response to the exposome, the ensemble of environmental factors impinging on tissue homeostasis. We conceptualize tumor-initiating plasticity as a phenotype-transforming force acting at three levels: cell-intrinsic, focusing on mutant epithelial cells' responses to environmental variation; reprogramming of non-neoplastic cells of the host, leading to protumor micro- and macroenvironments; and microbiome ecosystem dynamics. This perspective highlights cell, tissue, and organismal plasticity mechanisms underlying tumor initiation that are shaped by the exposome, and how their functional investigation may provide new opportunities to prevent, detect, and intercept cancer-promoting plasticity.
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Affiliation(s)
- Davide Carra
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
| | - Silvana C E Maas
- Cancer Computational Biology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Jose A Seoane
- Cancer Computational Biology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
| | - Direna Alonso-Curbelo
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
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Zheng H, Zheng H, Du X, Xu B, Hu M, Yu J, Xie R, Wei L, Xue Z, Shen L, Lin J, Xie J, Zheng C, Huang C, Li P. Development of a prognostic oxidative stress-immune-inflammation score and online calculators for predicting survival and recurrence in gastric cancer: a multicenter study. Surg Endosc 2025; 39:2609-2624. [PMID: 40050495 DOI: 10.1007/s00464-025-11596-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/29/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Oxidative stress, immune response, and inflammation play an important role in the occurrence and progression of gastric cancer (GC). This study is to develop a novel prognostic oxidative stress-immune-inflammation score (POSII score) and to explore the clinical value of the novel nomograms incorporating this factor in survival and recurrence risk. METHODS This study included 3612 GC patients who underwent radical gastrectomy at three tertiary hospitals from 2009 to 2020. One hospital formed the training and internal validation cohorts, while the other two constituted the external validation cohort. Twelve hematological markers were collected and analyzed to develop the POSII score via LASSO regression. Two online calculators were developed and validated. RESULTS The POSII score categorized patients into low and high POSII groups, with the low POSII group showing significantly improved 5-year overall survival (OS) and disease-free survival (DFS) rates, as well as a markedly reduced risk of recurrence (all P < 0.05). Multivariate COX regression showed that the POSII score was an independent prognostic factor. Based on the POSII score, two nomograms (OS: AUC = 0.837; DFS: AUC = 0.834, respectively) for individualized prognostic prediction were constructed. To enhance clinical usability, we further developed two user-friendly online calculators. The high-risk group had an earlier, more persistent peak of recurrence and a high incidence of multiple recurrence patterns. CONCLUSION Two novel online calculators based on the POSII score can be used as reliable tools for predicting survival and recurrence after radical gastrectomy. Our findings provide new insights into the role of cancer-related immune dysregulation, inflammation, and oxidative stress imbalances.
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Affiliation(s)
- Hualong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Honghong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Xiaoqiang Du
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Binbin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
- Department of Digestive Endoscopy, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Minggao Hu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Department of General Surgery, The PLA Navy Anqing Hospital, Anqing, 246000, China
| | - Junhua Yu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Department of General Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China
| | - Rongzhen Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Department of General Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 321000, China
| | - Linghua Wei
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Zhen Xue
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Lili Shen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Jia Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Jianwei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Chaohui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China.
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, FuzhouFujian Province, 350000, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350000, China.
- Fujian Province Minimally Invasive Medical Center, Fuzhou, 350000, China.
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Zhang Y, Abousamra S, Hasan M, Torre-Healy L, Krichevsky S, Shrestha S, Bremer E, Oldridge DA, Rech AJ, Furth EE, Bocklage TJ, Levens JS, Hands I, Durbin EB, Samaras D, Kurc T, Saltz JH, Gupta R. Pathomics Image Analysis of Tumor Infiltrating Lymphocytes (TILs) in Colon Cancer. RESEARCH SQUARE 2025:rs.3.rs-6173056. [PMID: 40235501 PMCID: PMC11998795 DOI: 10.21203/rs.3.rs-6173056/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
We developed a deep learning Pathomics image analysis workflow to generate spatial Tumor-TIL maps to visualize and quantify the abundance and spatial distribution of tumor infiltrating lymphocytes (TILs) in colon cancer. Colon cancer and lymphocyte detection in hematoxylin and eosin (H&E) stained whole slide images (WSIs) has revealed complex immuno-oncologic interactions that form TIL-rich and TIL-poor tumor habitats, which are unique in each patient sample. We compute Tumor%, total lymphocyte%, and TILs% as the proportion of the colon cancer microenvironment occupied by intratumoral lymphocytes for each WSI. Kaplan-Meier survival analyses and multivariate Cox regression were utilized to evaluate the prognostic significance of TILs% as a Pathomics biomarker. High TILs% was associated with improved overall survival (OS) and progression-free interval (PFI) in localized and metastatic colon cancer and other clinicopathologic variables, supporting the routine use of Pathomics Tumor-TIL mapping in biomedical research, clinical trials, laboratory medicine, and precision oncology.
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Wu H, Zhou H, Huang C, Yang A, Lau ES, Zhang X, Lui JN, Fan B, Shi M, Ma RC, Kong AP, Chow E, So WY, Chan JC, Luk AO. Identifying and visualising temporal trajectories of hospitalisations for traditional and non-traditional complications in people with type 2 diabetes: a population-based study. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2025; 57:101532. [PMID: 40236266 PMCID: PMC11999218 DOI: 10.1016/j.lanwpc.2025.101532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 03/06/2025] [Accepted: 03/12/2025] [Indexed: 04/17/2025]
Abstract
Background People with type 2 diabetes are increasingly susceptible to complications that are not specific to diabetes. We aimed to examine the temporal trajectories of hospitalisations for traditional and non-traditional complications in people with type 2 diabetes. Methods We included 758,254 people with incident type 2 diabetes between 2002 and 2018 in Hong Kong, followed up until 2019. We included hospitalisations for 72 selected diseases and all-cause deaths. We derived the temporal trajectories of hospitalisations based on pairs of disease associations and identified trajectory clusters using Markov Cluster Algorithm. Findings During a median follow-up of 7.8 (IQR: 4-12) years, 57.6% of people experienced a hospitalisation for any of the 72 selected diseases and 22.6% of people died. Among the 5184 directional disease pairs, 95 were identified as having a significant and directional association. The three most common disease pairs were hospitalisations for urinary tract infection followed by pneumonia, ischemic heart disease followed by heart failure, and ischemic stroke followed by pneumonia. Cardiovascular and kidney diseases were predominant in the hospitalisation trajectories. However, these traditional complications had complex associations both among themselves and with various non-traditional complications across multiple systems. Three distinct trajectory clusters were identified, with heart failure/chronic kidney disease, pneumonia, and urinary tract infection as central diseases. Interpretation Cardiovascular and kidney diseases interacted with a broad set of non-traditional complications to influence the overall patterns of hospitalisation progression in people with diabetes, highlighting the need to broaden diabetes care to consider complications beyond the traditional focus. Funding Direct Grant for Research from The Chinese University of Hong Kong.
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Affiliation(s)
- Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Haobin Zhou
- The First School of Clinical Medicine, Guangzhou Medical University, People's Republic of China
| | - Chuiguo Huang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Eric S.H. Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Xinge Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Juliana N.M. Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Baoqi Fan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Mai Shi
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Ronald C.W. Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Alice P.S. Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Wing-Yee So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Hong Kong Hospital Authority, Hong Kong Special Administrative Region of China
| | - Juliana C.N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Andrea O.Y. Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
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Luo S, Wu X, Wang H, Zhang Y, Xie L. Nitrate induced hepatic fibrosis in tadpoles of Bufo gargarizans by mediating alterations in toll-like receptor signaling pathways. ENVIRONMENTAL RESEARCH 2025; 270:120961. [PMID: 39875068 DOI: 10.1016/j.envres.2025.120961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 01/30/2025]
Abstract
The nitrate pollution has become an increasingly serious environmental problem worldwide, and the toxic effects of elevated nitrate levels in the environment on aquatic animals remain to be elucidated. The purpose of the present study was to investigate the mechanisms of liver injury to tadpoles after exposure to nitrate from embryonic to metamorphic climax and to assess the recovery process of liver function after cessation of exposure. In the group with continuous nitrate exposure, the livers and thyroid of tadpoles showed remarkably histological lesions, of this with structural disorganization of the hepatocytes, cellular atrophy, and fibrosis, as well as significant reduction in the follicular and colloidal area of the thyroid. Meanwhile, the expression levels of genes related to inflammatory signaling pathways, such as TLR2, TLR6 and NF-κB, were significant elevated. After termination of exposure at Gs23, liver damage (histologic, ultrastructural, and molecular levels) was almost completely recovered, whereas thyroid gland damage was irreversible. Overall, this study shed light on the harmful effects of nitrate pollution on amphibian health and emphasizes the importance of controlling nitrate emissions in the environment.
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Affiliation(s)
- Shuangyan Luo
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Xueyi Wu
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China
| | - Hongyuan Wang
- College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Yongpu Zhang
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
| | - Lei Xie
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
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Di Spirito A, Balkhi S, Vivona V, Mortara L. Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2025; 6:1002304. [PMID: 40177538 PMCID: PMC11964778 DOI: 10.37349/etat.2025.1002304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 02/27/2025] [Indexed: 04/05/2025] Open
Abstract
Bladder cancer (BC) is a heterogeneous disease associated with high mortality if not diagnosed early. BC is classified into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), with MIBC linked to poor systemic therapy response and high recurrence rates. Current treatments include transurethral resection with Bacillus Calmette-Guérin (BCG) therapy for NMIBC and radical cystectomy with chemotherapy and/or immunotherapy for MIBC. The tumor microenvironment (TME) plays a critical role in cancer progression, metastasis, and therapeutic efficacy. A comprehensive understanding of the TME's complex interactions holds substantial translational significance for developing innovative treatments. The TME can contribute to therapeutic resistance, particularly in immune checkpoint inhibitor (ICI) therapies, where resistance arises from tumor-intrinsic changes or extrinsic TME factors. Recent advancements in immunotherapy highlight the importance of translational research to address these challenges. Strategies to overcome resistance focus on remodeling the TME to transform immunologically "cold" tumors, which lack immune cell infiltration, into "hot" tumors that respond better to immunotherapy. These strategies involve disrupting cancer-microenvironment interactions, inhibiting angiogenesis, and modulating immune components to enhance anti-tumor responses. Key mechanisms include cytokine involvement [e.g., interleukin-6 (IL-6)], phenotypic alterations in macrophages and natural killer (NK) cells, and the plasticity of cancer-associated fibroblasts (CAFs). Identifying potential therapeutic targets within the TME can improve outcomes for MIBC patients. This review emphasizes the TME's complexity and its impact on guiding novel therapeutic approaches, offering hope for better survival in MIBC.
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Affiliation(s)
- Anna Di Spirito
- Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
| | - Sahar Balkhi
- Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
| | - Veronica Vivona
- Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
| | - Lorenzo Mortara
- Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
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Xue X, Wu D, Yao H, Wang K, Liu Z, Qu H. Mechanisms underlying the promotion of papillary thyroid carcinoma occurrence and progression by Hashimoto's thyroiditis. Front Endocrinol (Lausanne) 2025; 16:1551271. [PMID: 40230479 PMCID: PMC11994412 DOI: 10.3389/fendo.2025.1551271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Accepted: 03/04/2025] [Indexed: 04/16/2025] Open
Abstract
Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) co-occurrence raises significant questions regarding the immune microenvironment and molecular mechanisms in thyroid tumor development. This review synthesizes recent literature to explore the immune microenvironment and molecular characteristics of PTC patients with HT, and to analyze how these characteristics influence disease onset, progression, and treatment. We focused on the immunological and molecular biological mechanisms underlying the interaction between HT and PTC, particularly the recruitment and activation of immune cells and alterations in key signaling pathways. Studies indicate that PTC with HT exhibits distinctive immune microenvironmental features, such as the role of regulatory T cells (Tregs), activation of the IFN-γ-mediated CXCR3A-CXCL10 signaling axis, and NF-κB pathway activation. Additionally, thyroid-stimulating hormone (TSH) stimulation, RET/PTC gene rearrangements, and changes in STAT6 and DMBT1 gene expression levels also play significant roles in PTC development. Notably, while HT may increase the risk of PTC, patients with concurrent HT tend to have better prognoses. Future research should further elucidate the complex interplay between these two diseases to prevent the transformation of HT into PTC and offer more personalized treatment plans for PTC patients, including considerations for preoperative thyroidectomy and lymph node dissection strategies, as well as postoperative TSH suppression therapy risk assessment. This review underscores the importance of a deeper understanding of HT and PTC interactions and offers new perspectives for future research directions and therapeutic strategies.
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Affiliation(s)
- Xiaohui Xue
- School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Thyroid and Breast Diagnosis and Treatment Center, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Deqi Wu
- Department of Thyroid and Breast Diagnosis and Treatment Center, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Hangyu Yao
- Department of Thyroid and Breast Diagnosis and Treatment Center, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Kainan Wang
- School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Thyroid and Breast Diagnosis and Treatment Center, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Zhengtao Liu
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Haijiang Qu
- Department of Thyroid and Breast Diagnosis and Treatment Center, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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Rossi T, Valgiusti M, Puccetti M, Miserocchi G, Zanoni M, Angeli D, Arienti C, Pace I, Bassi C, Vannini I, Melloni M, Bandini E, Urbini M, Negrini M, Bonafè M, Ferracin M, Gallerani G. Gastroesophageal circulating tumor cell crosstalk with peripheral immune system guides CTC survival and proliferation. Cell Death Dis 2025; 16:223. [PMID: 40157906 PMCID: PMC11954855 DOI: 10.1038/s41419-025-07530-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 02/12/2025] [Accepted: 03/12/2025] [Indexed: 04/01/2025]
Abstract
Tumor dissemination is a key event in tumor progression. During this event, a main role is played by circulating tumor cells (CTCs), immune cells, and their interaction. How the immune system supports the survival and proliferation of CTCs is not fully elucidated. In this study we established an in-vitro co-culture system consisting of immune cells and CTCs from the same patient, which increased the success rate in the establishment of CTC-derived long-term cell cultures. In this system, we characterized the immune cells of successful co-cultures and the signals they exchange with cancer cells, including cytokines and extracellular vesicle (EV) content. Using this protocol, we stabilized four CTC-derived cell lines from patients with metastatic gastroesophageal cancer, which were cultured for over a year and characterized from a genetic and molecular point of view. The four cell lines harbor shared chromosomal aberrations including the amplification at 8q24.21 containing MYC and deletion 9p21.3 containing CDKN2A/B and the IFN type I cluster. The transcriptomic profile of CTC cell lines is distinct from primary tumors, and we detected the activation of E2F, G2M and MYC pathways and the downregulation of interferon response pathway. Each cell line shows a degree of invasiveness in zebrafish in-vivo, and the most invasive ones share the same mutation in RAB14 gene. In addition, the four cell lines secrete cell-line specific EVs containing microRNAs that target YAP, BRG1-AKT1, TCF8-HDAC pathways. Overall, we highlight how the immune system plays a key role in the proliferation of CTCs through EV signaling, and how CTC cell line genomic and transcriptomic alterations make these cells less visible from the immune system and likely responsible for the survival advantage in sites distant from the microenvironment of origin.
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Affiliation(s)
- Tania Rossi
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | | | - Giacomo Miserocchi
- Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "DinoAmadori", Meldola, Italy
| | - Michele Zanoni
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Davide Angeli
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Chiara Arienti
- Immuno-Gene Therapy Factory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Ilaria Pace
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Cristian Bassi
- Department of Translational Medicine, Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Centre, University of Ferrara, Ferrara, Italy
| | - Ivan Vannini
- Pathology Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Mattia Melloni
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Erika Bandini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Milena Urbini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Massimo Negrini
- Department of Translational Medicine, Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Centre, University of Ferrara, Ferrara, Italy
| | - Massimiliano Bonafè
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Manuela Ferracin
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giulia Gallerani
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
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Wang Y, Zhou H, Ju S, Dong X, Zheng C. The solid tumor microenvironment and related targeting strategies: a concise review. Front Immunol 2025; 16:1563858. [PMID: 40207238 PMCID: PMC11979131 DOI: 10.3389/fimmu.2025.1563858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 03/12/2025] [Indexed: 04/11/2025] Open
Abstract
The malignant tumor is a serious disease threatening human life. Increasing studies have confirmed that the tumor microenvironment (TME) is composed of a variety of complex components that precisely regulate the interaction of tumor cells with other components, allowing tumor cells to continue to proliferate, resist apoptosis, evade immune surveillance and clearance, and metastasis. However, the characteristics of each component and their interrelationships remain to be deeply understood. To target TME, it is necessary to deeply understand the role of various components of TME in tumor growth and search for potential therapeutic targets. Herein, we innovatively classify the TME into physical microenvironment (such as oxygen, pH, etc.), mechanical microenvironment (such as extracellular matrix, blood vessels, etc.), metabolic microenvironment (such as glucose, lipids, etc.), inflammatory microenvironment and immune microenvironment. We introduce a concise but comprehensive classification of the TME; depict the characteristics of each component in TME; summarize the existing methods for detecting each component in TME; highlight the current strategies and potential therapeutic targets for TME; discuss current challenges in presenting TME and its clinical applications; and provide our prospect on the future research direction and clinical benefits of TME.
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Affiliation(s)
- Yingliang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, China
| | - Huimin Zhou
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuguang Ju
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, China
| | - Xiangjun Dong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, China
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50
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Nishida A, Andoh A. The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis. Cells 2025; 14:488. [PMID: 40214442 PMCID: PMC11987742 DOI: 10.3390/cells14070488] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/14/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Inflammation is an essential component of the immune response that protects the host against pathogens and facilitates tissue repair. Chronic inflammation is a critical factor in cancer development and progression. It affects every stage of tumor development, from initiation and promotion to invasion and metastasis. Tumors often create an inflammatory microenvironment that induces angiogenesis, immune suppression, and malignant growth. Immune cells within the tumor microenvironment interact actively with cancer cells, which drives progression through complex molecular mechanisms. Chronic inflammation is triggered by factors such as infections, obesity, and environmental toxins and is strongly linked to increased cancer risk. However, acute inflammatory responses can sometimes boost antitumor immunity; thus, inflammation presents both challenges and opportunities for therapeutic intervention. This review examines how inflammation contributes to tumor biology, emphasizing its dual role as a critical factor in tumorigenesis and as a potential therapeutic target.
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Affiliation(s)
- Atsushi Nishida
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Shiga, Japan;
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