Background:First-line chemoimmunotherapy has improved outcomes in extensive-stage small-cell lung cancer (ES-SCLC), but survival remains heterogeneous and routine-care prognostic tools are limited. Patients and Methods:We retrospectively analyzed consecutive adults with stage IV ES-SCLC treated with platinum-etoposide plus a programmed death-ligand 1 inhibitor at three Spanish hospitals from August 2021 to December 2024. Outcomes included overall survival (OS), progression-free survival (PFS), objective response, and immune-related toxicity. Baseline Gustave Roussy Immune Score (GRIm) was defined as high-risk when at least two of albumin <35 g/L, lactate dehydrogenase above the upper limit of normal, and neutrophil-to-lymphocyte ratio >6 were present. Baseline Cox models included high-risk GRIm, platelet-to-lymphocyte ratio >180, and Eastern Cooperative Oncology Group performance status ≥2; maintenance exposure was assessed in a 3-month OS landmark analysis. Analyses were exploratory. Results:Among 51 patients, mean age was 64.2 years, 72.5% were men, and 82.3% had ECOG performance status 0-1. During follow-up, 43 deaths and 50 PFS events occurred. Objective response rate was 70.6%, median OS was 11.9 months, and median PFS was 5.7 months. Median OS was 14.2 months with low-risk GRIm and 5.4 months with high-risk GRIm. High-risk GRIm was independently associated with worse OS (hazard ratio [HR] 5.59) and PFS (HR 3.50), while PLR >180 was associated with worse OS (HR 2.37). In the 3-month landmark cohort (n=47), maintenance exposure remained associated with longer OS (HR 0.21), although this analysis remained vulnerable to residual selection bias. Conclusion:Baseline GRIm was the most consistent candidate prognostic marker in this real-world ES-SCLC cohort. The study did not assess prediction of immunotherapy benefit, and prospective validation is warranted before treatment decisions are guided by GRIm.
Introduction:Taxane-induced nail toxicity (TINT) is a relatively common but often underreported adverse effect of docetaxel-based chemotherapy that may significantly impair quality of life and functional status. Severe cases can require structured supportive care involving multiple clinical disciplines. We present a case of high-grade TINT in a patient with breast cancer successfully managed with a multidisciplinary supportive approach. Case Presentation:A 70-year-old woman with HER2-positive breast cancer received neoadjuvant TCH chemotherapy (docetaxel, cyclophosphamide, trastuzumab), followed by surgery and adjuvant trastuzumab emtansine. Nail toxicity developed after the second cycle of docetaxel and progressed to subungual hemorrhages, onycholysis, and marked onychodystrophy associated with pain and functional limitation. The patient underwent podiatric treatment including mechanical nail debridement and topical collagen-based serum therapy. Supportive pharmacologic management, including selective COX-2 inhibitors, was also introduced. Results:Gradual epithelial healing and nail regrowth were observed over a six-month follow-up period. Pain and functional impairment improved, and systemic oncologic therapy was continued without interruption. No recurrence of severe nail complications was noted during subsequent treatment. Conclusion:This case illustrates that severe taxane-induced nail toxicity may be effectively controlled with coordinated multidisciplinary supportive care. Early podiatric intervention combined with pharmacologic symptom management may help maintain treatment continuity and improve patient comfort during taxane-based chemotherapy.
Yingqi Xiong,1 Yaxin Hu,2 Manya Wang,3 Xin Xiong,4 Haishen Zhao31Traditional Chinese Medicine Department, Nanjing West Road Street Community Health Service Center, Shanghai, People’s Republic of China; 2Traditional Chinese Medicine Department, Qingdao Special Servicemen Recuperation Center of PLA Navy, Qingdao, Shandong, People’s Republic of China; 3Department of Rehabilitation Medicine, Nanhui Xincheng Town Community Health Service Center, Shanghai, People’s Republic of China; 4Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Xin Xiong, Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China, Email hljzylsj@126.com Haishen Zhao, Department of Rehabilitation Medicine, Nanhui Xincheng Town Community Health Service Center, Shanghai, People’s Republic of China, Email zhaohaishen666@126.comAbstract: In recent decades, the global incidence of thyroid cancer has risen sharply mainly due to the high detection rate of papillary thyroid microcarcinoma and overdiagnosis, with its overall mortality staying steady. Classic pathogenic drivers encompass childhood radiation exposure, iodine disorder, and hallmark gene alterations including BRAF V600E, RET/PTC, RAS and PAX8/PPARγ. Modern multimodal diagnostic systems integrating artificial intelligence-assisted high-resolution ultrasound, Thyroseq-V2, Afirma, circulating tumor DNA detection and refined pathological examination achieve precise preoperative stratification. Aberrant activation of MAPK/ERK, PI3K/AKT and Wnt/β-catenin cascades, coupled with an immune-suppressive tumor microenvironment dominated by M2-type tumor-associated macrophages, regulatory T cells and PD-L1 overexpression, drives thyroid cancer progression and dedifferentiation. Current comprehensive integrated therapeutic strategies cover robotic surgery, radioactive iodine ablation, external radiotherapy, molecular targeted drugs (sorafenib, lenvatinib, vemurafenib combined with trametinib) and novel immunotherapy. Traditional Chinese Medicine (TCM), based on the TCM pathogenesis of liver qi stagnation, phlegm-blood stasis and qi-blood deficiency for goiter, serves as an adjuvant therapy for thyroid cancer. Active ingredients such as honokiol, artesunate, ginsenoside Rg3, astragalus polysaccharide and curcumin can suppress tumor proliferation, reshape anti-tumor immunity and inhibit metastasis via regulating reactive oxygen species, PI3K/AKT pathway, epithelial–mesenchymal transition and matrix metalloproteinases. Existing clinical observations confirm that TCM can relieve clinical discomfort, improve life quality and lower recurrence risk when combined with conventional radioiodine or anti-tumor treatment. However, the clinical application of TCM for thyroid cancer is greatly restricted by insufficient syndrome differentiation standardization, low-quality clinical evidence and unclear herbal safety risks. Most available studies are small-sample retrospective analyses lacking large-scale, multicenter randomized controlled trials to verify efficacy and safety. Future research should focus on standardized clinical trial design, in-depth pharmacological mechanism exploration, and construction of standardized thyroid cancer integrative diagnosis and treatment regimens combining Western precision therapy and TCM adjuvant intervention, to clarify the definite positioning of TCM in whole-course thyroid cancer management.Keywords: thyroid cancer, BRAF V600E, tumor microenvironment, targeted therapy, traditional Chinese medicine, immunomodulation, overdiagnosis, multimodal imaging
Xiaoying Hong,1 Genqun Wang,2 Li Cai,1 Yuanjiao Lin,2 Yi Zhao21Department of Central Nursing, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Hematology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Genqun Wang, Email 5154151@qq.comAbstract: This case report describes the nursing experience of a patient with ALK‑negative anaplastic large cell lymphoma undergoing autologous hematopoietic stem cell transplantation. A multidisciplinary team model was established, integrating professionals from haematology, rehabilitation, nutrition, psychology to deliver comprehensive peri‑transplant care. An individualized treatment and nursing plan was developed for the peri-transplant period. This plan included pre-transplant physical and psychological preparation, environmental readiness, and management of complications during transplantation, such as infection, bleeding, gastrointestinal symptoms, malnutrition, and depressive mood. Over a 26-day period, successful hematopoietic reconstitution was achieved, and the patient was discharged smoothly from the isolation unit. Post-transplantation, continuous nursing support was provided in infection control, diet, and exercise, along with regular follow-up for two months. The patient’s laboratory parameters returned to normal, and both physical and psychological conditions recovered well.Keywords: multidisciplinary team, ALK negative anaplastic large cell lymphoma, autologous hematopoietic stem cell transplantation, nursing, case report
Recent studies have shown that tumor development and therapeutic resistance are closely linked to the tumor microenvironment (TME), a dynamic ecosystem composed of vascular networks, immune and stromal cells, extracellular matrix components, cytokines, and extracellular vesicles. This review summarizes current mechanistic evidence on how bioactive monomers and purified active fractions derived from traditional Chinese medicine (TCM), including polysaccharides, saponins, alkaloids, terpenoids, flavonoids, and polyphenols, regulate TME-associated processes. These compounds have been reported to modulate macrophage polarization, T-cell and natural killer (NK)-cell surveillance, dendritic-cell maturation, myeloid-derived suppressor cell (MDSC) and neutrophil activities, cancer-associated fibroblast (CAF) activation, angiogenic signaling, cytokine networks, exosome-mediated communication, and extracellular matrix remodeling. However, most available evidence remains derived from cell models and animal experiments, and clinical validation is limited. Therefore, TCM-derived bioactive monomers should currently be interpreted as mechanistic probes, lead structures, or candidate adjunctive agents rather than established TME-directed therapies. Future research should prioritize compound standardization, dose-response relationships, pharmacokinetic and toxicological characterization, reproducible model systems, validated TME biomarkers, and controlled clinical trials.
Background:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with high global morbidity and mortality. Hypericin is a natural photosensitizer that can preferentially accumulate in tumor tissues. Photodynamic therapy (PDT) is an emerging anticancer strategy that eliminates tumor cells through reactive oxygen species (ROS) generation by light-activated photosensitizers in the presence of molecular oxygen. However, PDT-induced oxygen consumption may further aggravate tumor hypoxia. In this study, we evaluated the synergistic antitumor effects of hypericin-mediated PDT combined with siHIF-1α (HYP-siHIF) in TNBC cells. Methods:The MTT assay was performed to evaluate the effects of HYP-PDT alone or in combination with siHIF on TNBC cell viability. Intracellular ROS levels were assessed using the fluorescent probe DCFH-DA. RNA sequencing (RNA-seq) analysis was performed to explore the potential molecular changes induced by HYP-siHIF treatment. Transmission electron microscopy (TEM) and Hoechst staining were used to evaluate cellular morphological alterations, while flow cytometry was performed to assess apoptosis. Western blotting was used to detect the expression levels of proteins associated with cell death pathways. Results:HYP-siHIF significantly inhibited TNBC cell viability, increased intracellular ROS accumulation, and induced morphological and molecular features associated with apoptosis, pyroptosis, and necroptosis. Mechanistically, this study provides evidence that HYP-siHIF activates PANoptosis-related cell death pathways following PDT treatment. For apoptosis, HYP-siHIF increased Bax expression, reduced Bcl-2 expression, and enhanced the cleavage of caspase-9/3/7. For pyroptosis, HYP-siHIF increased NLRP3 expression and promoted the cleavage of GSDMD and GSDME. For necroptosis, HYP-siHIF significantly increased the phosphorylation levels of RIP3 and MLKL. Conclusion:HYP-PDT and siHIF exhibit synergistic antitumor effects, which are associated with the activation of PANoptosis-related cell death pathways. HYP-siHIF may represent a potential therapeutic approach for TNBC that warrants further mechanistic and translational investigation.
Background:Colorectal adenoma recurrence after polypectomy remains an important clinical concern, with current surveillance strategies based primarily on index adenoma characteristics. This study aimed to develop and validate a prediction model integrating clinical and metabolic factors for personalized recurrence risk assessment. Methods:We conducted a retrospective cohort study of 328 patients with colorectal adenomas confirmed by pathology between January 2018 and December 2021. Variable selection was performed using LASSO-penalized Cox regression with 10-fold cross-validation. Model performance was assessed through bootstrap validation (1000 resamples) with calculation of Harrell's C-index, calibration curves, and decision curve analysis. Results:The final model included age (HR 1.28, 95% CI 1.12-1.47), alcohol consumption history (HR 2.12, 95% CI 1.68-2.67), and bile acid levels (mean 3.14 ± 0.85 μmol/L in the recurrence group vs 2.73 ± 0.78 μmol/L in the non-recurrence group). The model demonstrated good discrimination (bootstrap-corrected C-index 0.878, 95% CI 0.843-0.912) and calibration (slope 0.894, 95% CI 0.851-0.937). Conclusion:The developed prediction model integrating age, alcohol history, and bile acid levels provides a practical tool for stratifying recurrence risk after polypectomy, with potential to guide personalized surveillance strategies. External validation is warranted to confirm these findings.
Michał Miciak,1 Krzysztof Jurkiewicz,1,2 Natalia Kalka,1 Maja Reiner,1 Maksymilian Cyprian Szymański,1 Szymon Biernat,1 Dorota Diakowska,3 Krzysztof Kaliszewski11Clinical Department of General Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland; 2Doctoral School, Wroclaw Medical University, Wroclaw, Poland; 3Division of Medical Biology, Department of Midwifery, Faculty of Nursing and Midwifery, Wroclaw Medical University, Wroclaw, PolandCorrespondence: Michał Miciak, Clinical Department of General Surgery, University Centre of General and Oncological Surgery, Faculty of Medicine, Wroclaw Medical University, Borowska Street 213, Wroclaw, 50-556, Poland, Email michal.miciak00@gmail.comPurpose: Ultrasound (US) imaging plays a pivotal role in the preoperative assessment of thyroid cancer (TC). Suspicious US features, including hypoechogenicity, microcalcifications, high vascularity, irregular shape, irregular margins, and the taller-than-wide (TTW) sign, are widely used for preoperative risk stratification of thyroid nodules. This study aimed to investigate the associations between preoperative US features and histopathological indicators of tumor advancement in differentiated thyroid cancer (DTC).Patients and Methods: We conducted a retrospective analysis of 665 patients with DTC who were treated between 2008 and 2024. Preoperative US features, including hypoechogenicity, microcalcifications, high vascularity, irregular shape, irregular margins, and the TTW sign, were correlated with extrathyroidal extension (ETE) and lymph node metastases (LNM). Associations were evaluated using Pearson’s χ2 test, Fisher’s exact test where appropriate, odds ratios (ORs), and Cramér’s V. Statistical significance was defined as p < 0.05.Results: All analyzed US features were significantly associated with histopathological indicators of tumor advancement (p < 0.05). Of all evaluated conventional US features, the strongest associations were observed between microcalcifications and ETE, and between high vascularity and LNM (Cramér’s V = 0.32 and 0.38, respectively). The TTW sign was significantly associated with ETE (OR = 2.96, 95% CI: 1.73– 5.07) and LNM (OR = 9.07, 95% CI: 5.07– 16.24).Conclusion: Among US features, the TTW sign demonstrated particularly strong associations with histopathological indicators of tumor advancement, especially LNM. These findings support the potential value of comprehensive preoperative assessment of US features and warrant further prospective studies with multivariable modelling to better define the role of the TTW sign in preoperative risk stratification of DTC.Keywords: differentiated thyroid cancer, ultrasound imaging, taller-than-wide sign, thyroid surgery, extrathyroidal extension, lymph node metastasis
Xinyu Jia,1 Eerdemutu,2 Yuan Ren,2 Shiduo Yang,1 Chang Yang,1 Qiaochu Ding,1 Yu Lin21First Clinical Medical College, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Yu Lin, Department of Radiation Oncology, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Huimin District, Hohhot, Inner Mongolia, 010010, People’s Republic of China, Email honglanqian@126.comAbstract: Radioresistance and local recurrence remain major barriers to effective radiotherapy in non-small cell lung cancer (NSCLC). Loss-of-function KEAP1 alterations or activating NFE2L2 alterations can stabilize NRF2, but do not alone establish sustained transcriptional activity or functional dependency. This focused narrative review evaluates clinical radiotherapy studies and mechanistically informative preclinical studies linking the KEAP1–NFE2L2/NRF2 axis to NSCLC radioresistance. We prioritized clinical studies reporting radiotherapy-specific outcomes and preclinical studies coupling NRF2-related molecular status or perturbation with radiation-response endpoints; contextual studies informed metabolic, DNA damage response (DDR), immune and normal-lung effects. Evidence most consistently supports NRF2-mediated redox protection through glutathione-dependent defense, cellular reducing capacity and antioxidant enzymes, limiting radiation-induced reactive oxygen species (ROS) accumulation and oxidative injury. Limited studies further suggest that NRF2 may affect DNA-damage signaling, checkpoint control and repair. The detailed RPA32–TOPBP1–ATR–CHK1 model is therefore considered proposed rather than established in NRF2-active NSCLC. Retrospective clinical studies associate pathogenic KEAP1/NFE2L2 alterations with impaired local control in some radiotherapy-treated cohorts, but do not justify treating genomic status, protein abundance, transcriptional activity and functional dependency as equivalent measures or demonstrate treatment-predictive value. NRF2-mediated normal-lung protection also constrains systemic inhibition. Prospective studies integrating molecular classification, radiation-response endpoints, local control and normal-tissue toxicity are required before biomarker-guided radiosensitization can be considered.Keywords: KEAP1, NFE2L2, NRF2, non-small cell lung cancer, radioresistance, redox homeostasis, DNA damage response, radiotherapy
Background:This study evaluated the impact of varying systematic biopsy (SB) core numbers on the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) in men with magnetic resonance imaging (MRI)-suspicious lesions undergoing MRI-ultrasound fusion biopsy; and to assess biopsy-related complications. Methods:This retrospective, non-randomized cohort study included 356 patients who underwent multi-parametric MRI followed by MRI-ultrasound fusion targeted biopsy (TB) combined with SB for suspected PCa (Prostate Imaging Reporting and Data System score ≥ 3). Patients were divided into two groups based on the number of SB cores received: ≤ 6 SB cores (n = 200) and > 6 SB cores (n = 156). Primary outcomes were overall PCa and csPCa (Gleason Grade Group ≥ 2) detection rates. Secondary outcomes included the added diagnostic value of SB for csPCa, SB upgrading rates, and post-biopsy complications. Results:No significant difference was observed in the overall PCa detection rate between the ≤ 6 cores and > 6 cores groups (58.0% vs 50.0%, P = 0.081) or in the overall csPCa detection rate (42.5% vs 37.2%, P = 0.182). The added diagnostic value of SB for csPCa detection (3.0% vs 3.8%, P = 0.439) and SB upgrading rate (7.0% vs 9.6%, P = 0.241) were comparable between the groups. However, the complication rate was significantly lower in the group receiving ≤ 6 SB cores compared to that receiving the > 6 SB cores (15.5% vs 26.3%, P = 0.009). Subgroup analysis indicated that SB provided significantly higher added value for csPCa detection in older patients (≥ 67 years; 5.3% vs 1.6%, P = 0.049). Multivariable logistic regression demonstrated that receiving >6 SB cores was not significantly associated with increased detection of csPCa. Conclusion:These findings seem support optimizing and potentially reducing the systematic component of combined biopsy. Further prospective studies are warranted to confirm these results and refine personalized biopsy protocols.
Natalia Sauer,1 Marta Kowalczuk,2 Adrian Arkada,2 Jacek Calik31Department of Clinical Pharmacology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland; 2AArkada Institute of Podiatry, Wrocław, 50-413, Poland; 3Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, PolandCorrespondence: Natalia Sauer, Email natalia.sauer@umw.edu.plIntroduction: Taxane-induced nail toxicity (TINT) is a relatively common but often underreported adverse effect of docetaxel-based chemotherapy that may significantly impair quality of life and functional status. Severe cases can require structured supportive care involving multiple clinical disciplines. We present a case of high-grade TINT in a patient with breast cancer successfully managed with a multidisciplinary supportive approach.Case Presentation: A 70-year-old woman with HER2-positive breast cancer received neoadjuvant TCH chemotherapy (docetaxel, cyclophosphamide, trastuzumab), followed by surgery and adjuvant trastuzumab emtansine. Nail toxicity developed after the second cycle of docetaxel and progressed to subungual hemorrhages, onycholysis, and marked onychodystrophy associated with pain and functional limitation. The patient underwent podiatric treatment including mechanical nail debridement and topical collagen-based serum therapy. Supportive pharmacologic management, including selective COX-2 inhibitors, was also introduced.Results: Gradual epithelial healing and nail regrowth were observed over a six-month follow-up period. Pain and functional impairment improved, and systemic oncologic therapy was continued without interruption. No recurrence of severe nail complications was noted during subsequent treatment.Conclusion: This case illustrates that severe taxane-induced nail toxicity may be effectively controlled with coordinated multidisciplinary supportive care. Early podiatric intervention combined with pharmacologic symptom management may help maintain treatment continuity and improve patient comfort during taxane-based chemotherapy.Keywords: nails, taxane-induced nail toxicity, breast cancer, ADR
Jingru Xu,1– 3 Yulin Liu,1– 3 Yilin Xiao,1– 3 Yuxing Chen,1– 3 Enqing Meng,1– 3 Min Jin,1– 3 Mengjiao Wu,1– 3 Yan Zong,1– 3 Hongli Liu1– 31Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 2Hubei Key Laboratory of Precision Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 3Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of ChinaCorrespondence: Hongli Liu, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Email hongli_liu@hust.edu.cnAbstract: Radiation enteritis (RE) is the most common complication of pelvic radiotherapy, often manifesting as diarrhea, hematochezia, and tenesmus. In some cases, it progresses to chronic radiation enteritis, leading to intestinal fibrosis and fistula formation, which severely impacts patients’quality of life and prognosis. Current therapeutic strategies for RE include radioprotective agents, surgery, nutritional support, and symptomatic management. However, their efficacy remains limited. The gut microbiota, a complex microbial community residing in the human digestive tract, is closely linked to human health. Numerous studies have identified gut microbiota dysbiosis in the context of RE. This review illustrates the intricate relationship between RE and the gut microbiota, focusing on the underlying mechanisms of their interaction. It also introduces emerging therapeutic strategies targeting the gut microbiota for RE, including engineered probiotics, washed microbiota transplantation (WMT), and ROS-scavenging nanomaterials, offering novel insights for its diagnosis and treatment.Keywords: radiation enteritis, gut microbiota dysbiosis, radiotherapy, gut microbiota metabolites, fecal microbiota transplantation
David Sánchez-García,1 Miguel Borregón-Rivilla,2 Alejandro Moya-Martínez,3,4 María Valero Revert,1 Beatriz Grau-Mirete,1 Mariano Martínez-Marín,1 Elena Navarro-Vicente,1 Cristina Bernabé Martínez,1 María Orengo-López,1 Marta Hernández Sáez,1 Álvaro Muñoz Abad,5 Paula Rodríguez-Payá,2 María Pamies-Ramón,5 María Guirado-Risueño,1 Javier-David Benitez-Fuentes,1 Asia Ferrández-Arias11Department of Medical Oncology, Hospital General Universitario de Elche, Elche, Spain; 2Department of Medical Oncology, Hospital Marina Baixa, Villajoyosa, Spain; 3Biostatistics Service, Hospital General Universitario de Elche, FISABIO, Elche, Spain; 4Department of Statistics, Mathematics and Computer Science, Miguel Hernández University, Elche, Spain; 5Department of Medical Oncology, Hospital Vega Baja, Orihuela, SpainCorrespondence: Javier-David Benitez-Fuentes, Department of Medical Oncology, Hospital General Universitario de Elche, C/ Camí de l’Almazara, 11, Elche, 03203, Spain, Email javierdavidbenitezfuentes@gmail.comBackground: First-line chemoimmunotherapy has improved outcomes in extensive-stage small-cell lung cancer (ES-SCLC), but survival remains heterogeneous and routine-care prognostic tools are limited.Patients and Methods: We retrospectively analyzed consecutive adults with stage IV ES-SCLC treated with platinum-etoposide plus a programmed death-ligand 1 inhibitor at three Spanish hospitals from August 2021 to December 2024. Outcomes included overall survival (OS), progression-free survival (PFS), objective response, and immune-related toxicity. Baseline Gustave Roussy Immune Score (GRIm) was defined as high-risk when at least two of albumin < 35 g/L, lactate dehydrogenase above the upper limit of normal, and neutrophil-to-lymphocyte ratio > 6 were present. Baseline Cox models included high-risk GRIm, platelet-to-lymphocyte ratio > 180, and Eastern Cooperative Oncology Group performance status ≥ 2; maintenance exposure was assessed in a 3-month OS landmark analysis. Analyses were exploratory.Results: Among 51 patients, mean age was 64.2 years, 72.5% were men, and 82.3% had ECOG performance status 0– 1. During follow-up, 43 deaths and 50 PFS events occurred. Objective response rate was 70.6%, median OS was 11.9 months, and median PFS was 5.7 months. Median OS was 14.2 months with low-risk GRIm and 5.4 months with high-risk GRIm. High-risk GRIm was independently associated with worse OS (hazard ratio [HR] 5.59) and PFS (HR 3.50), while PLR > 180 was associated with worse OS (HR 2.37). In the 3-month landmark cohort (n=47), maintenance exposure remained associated with longer OS (HR 0.21), although this analysis remained vulnerable to residual selection bias.Conclusion: Baseline GRIm was the most consistent candidate prognostic marker in this real-world ES-SCLC cohort. The study did not assess prediction of immunotherapy benefit, and prospective validation is warranted before treatment decisions are guided by GRIm.Keywords: small-cell lung cancer, chemoimmunotherapy, maintenance, GRIm, prognostic biomarkers, real-world evidence
Xin Wen,1– 3 Jiangluqi Song,4 Yirui Yu,1– 3 Jinhang Hu,1– 3 Min Cheng1– 31Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi and Education Ministry, Xianyang, 712046, People’s Republic of China; 2Shaanxi Innovative Drug Research Center, Xianyang, 712046, People’s Republic of China; 3State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 4School of Physics, Xidian University, Xi’an, 710071, People’s Republic of ChinaCorrespondence: Jinhang Hu; Min Cheng, Email hujinhanghi@126.com; chengmin_prof@126.comBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with high global morbidity and mortality. Hypericin is a natural photosensitizer that can preferentially accumulate in tumor tissues. Photodynamic therapy (PDT) is an emerging anticancer strategy that eliminates tumor cells through reactive oxygen species (ROS) generation by light-activated photosensitizers in the presence of molecular oxygen. However, PDT-induced oxygen consumption may further aggravate tumor hypoxia. In this study, we evaluated the synergistic antitumor effects of hypericin-mediated PDT combined with siHIF-1α (HYP-siHIF) in TNBC cells.Methods: The MTT assay was performed to evaluate the effects of HYP-PDT alone or in combination with siHIF on TNBC cell viability. Intracellular ROS levels were assessed using the fluorescent probe DCFH-DA. RNA sequencing (RNA-seq) analysis was performed to explore the potential molecular changes induced by HYP-siHIF treatment. Transmission electron microscopy (TEM) and Hoechst staining were used to evaluate cellular morphological alterations, while flow cytometry was performed to assess apoptosis. Western blotting was used to detect the expression levels of proteins associated with cell death pathways.Results: HYP-siHIF significantly inhibited TNBC cell viability, increased intracellular ROS accumulation, and induced morphological and molecular features associated with apoptosis, pyroptosis, and necroptosis. Mechanistically, this study provides evidence that HYP-siHIF activates PANoptosis-related cell death pathways following PDT treatment. For apoptosis, HYP-siHIF increased Bax expression, reduced Bcl-2 expression, and enhanced the cleavage of caspase-9/3/7. For pyroptosis, HYP-siHIF increased NLRP3 expression and promoted the cleavage of GSDMD and GSDME. For necroptosis, HYP-siHIF significantly increased the phosphorylation levels of RIP3 and MLKL.Conclusion: HYP-PDT and siHIF exhibit synergistic antitumor effects, which are associated with the activation of PANoptosis-related cell death pathways. HYP-siHIF may represent a potential therapeutic approach for TNBC that warrants further mechanistic and translational investigation.Keywords: triple-negative breast cancer, TNBC, hypericin, photodynamic therapy, PDT, hypoxia-inducible factor-1α, HIF-1α, PANoptosis
Yunxuan Fei,1,2,* Jiahui Lu,1,2,* Zhexian Yu,2 Chenfei Xu,2 Meilin Tian,2 Qianqian Li,2 Huimin Ye,2 Ying Lu,2 Wenli Shen,2 Qiaohui He,1 Anjing Wang,1 Zhezhong Zhang,1 Haixin Qin,2 Yaping Yu11The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaping Yu, Email yypdaisy@163.comAbstract: Recent studies have shown that tumor development and therapeutic resistance are closely linked to the tumor microenvironment (TME), a dynamic ecosystem composed of vascular networks, immune and stromal cells, extracellular matrix components, cytokines, and extracellular vesicles. This review summarizes current mechanistic evidence on how bioactive monomers and purified active fractions derived from traditional Chinese medicine (TCM), including polysaccharides, saponins, alkaloids, terpenoids, flavonoids, and polyphenols, regulate TME-associated processes. These compounds have been reported to modulate macrophage polarization, T-cell and natural killer (NK)-cell surveillance, dendritic-cell maturation, myeloid-derived suppressor cell (MDSC) and neutrophil activities, cancer-associated fibroblast (CAF) activation, angiogenic signaling, cytokine networks, exosome-mediated communication, and extracellular matrix remodeling. However, most available evidence remains derived from cell models and animal experiments, and clinical validation is limited. Therefore, TCM-derived bioactive monomers should currently be interpreted as mechanistic probes, lead structures, or candidate adjunctive agents rather than established TME-directed therapies. Future research should prioritize compound standardization, dose-response relationships, pharmacokinetic and toxicological characterization, reproducible model systems, validated TME biomarkers, and controlled clinical trials.Keywords: traditional Chinese medicine, bioactive monomers, tumor microenvironment, immunomodulation
Kaili Peng,1 Shuofan Wang,2 Huaqiang You,1 Yangkun Dai11Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou, Zhejiang, 311100, People’s Republic of China; 2Department of Orthopedics, The First People’s Hospital of Linping District, Hangzhou, Zhejiang, 311100, People’s Republic of ChinaCorrespondence: Kaili Peng, Email pengkaili201582@163.comBackground: Colorectal adenoma recurrence after polypectomy remains an important clinical concern, with current surveillance strategies based primarily on index adenoma characteristics. This study aimed to develop and validate a prediction model integrating clinical and metabolic factors for personalized recurrence risk assessment.Methods: We conducted a retrospective cohort study of 328 patients with colorectal adenomas confirmed by pathology between January 2018 and December 2021. Variable selection was performed using LASSO-penalized Cox regression with 10-fold cross-validation. Model performance was assessed through bootstrap validation (1000 resamples) with calculation of Harrell’s C-index, calibration curves, and decision curve analysis.Results: The final model included age (HR 1.28, 95% CI 1.12– 1.47), alcohol consumption history (HR 2.12, 95% CI 1.68– 2.67), and bile acid levels (mean 3.14 ± 0.85 μmol/L in the recurrence group vs 2.73 ± 0.78 μmol/L in the non-recurrence group). The model demonstrated good discrimination (bootstrap-corrected C-index 0.878, 95% CI 0.843– 0.912) and calibration (slope 0.894, 95% CI 0.851– 0.937).Conclusion: The developed prediction model integrating age, alcohol history, and bile acid levels provides a practical tool for stratifying recurrence risk after polypectomy, with potential to guide personalized surveillance strategies. External validation is warranted to confirm these findings.Keywords: colorectal adenoma, recurrence, drinking history, age, alcohol, bile acid
Chung Yi Liu,1,2,* Ying-Hsu Chang,1,2,* Yu-Hsiang Lin,1,3 Po Han Chen,1 Chun Bi Chang,1,4 Li-Jen Wang,1,4 Chun-Te Wu,1,3 See Tong Pang,1,3 Wei Chang Lee,2 Le Wei Fan,2 Yun Ren Li,2 I-Hung Shao1,31College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Division of Urology, Department of Surgery, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan; 3Division of Urology, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: I-Hung Shao, Division of Urology, Department of Surgery, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan, 333423, Taiwan, Tel +8863-3281200 #3698, Fax +886-33979361, Email ehomeshao68@gmail.comBackground: This study evaluated the impact of varying systematic biopsy (SB) core numbers on the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) in men with magnetic resonance imaging (MRI)-suspicious lesions undergoing MRI-ultrasound fusion biopsy; and to assess biopsy-related complications.Methods: This retrospective, non-randomized cohort study included 356 patients who underwent multi-parametric MRI followed by MRI-ultrasound fusion targeted biopsy (TB) combined with SB for suspected PCa (Prostate Imaging Reporting and Data System score ≥ 3). Patients were divided into two groups based on the number of SB cores received: ≤ 6 SB cores (n = 200) and > 6 SB cores (n = 156). Primary outcomes were overall PCa and csPCa (Gleason Grade Group ≥ 2) detection rates. Secondary outcomes included the added diagnostic value of SB for csPCa, SB upgrading rates, and post-biopsy complications.Results: No significant difference was observed in the overall PCa detection rate between the ≤ 6 cores and > 6 cores groups (58.0% vs 50.0%, P = 0.081) or in the overall csPCa detection rate (42.5% vs 37.2%, P = 0.182). The added diagnostic value of SB for csPCa detection (3.0% vs 3.8%, P = 0.439) and SB upgrading rate (7.0% vs 9.6%, P = 0.241) were comparable between the groups. However, the complication rate was significantly lower in the group receiving ≤ 6 SB cores compared to that receiving the > 6 SB cores (15.5% vs 26.3%, P = 0.009). Subgroup analysis indicated that SB provided significantly higher added value for csPCa detection in older patients (≥ 67 years; 5.3% vs 1.6%, P = 0.049). Multivariable logistic regression demonstrated that receiving > 6 SB cores was not significantly associated with increased detection of csPCa.Conclusion: These findings seem support optimizing and potentially reducing the systematic component of combined biopsy. Further prospective studies are warranted to confirm these results and refine personalized biopsy protocols.Keywords: prostate cancer, MRI-fusion biopsy, systemic biopsy
Background:Thyroid cancer incidence is rising globally; however, histopathological data from Somalia are scarce, and no comprehensive characterization of resected thyroid specimens has been reported. Methods:A retrospective review of 438 thyroidectomy specimens reported at a histopathology referral laboratory in Mogadishu, Somalia, between 2022 and 2025 was performed. Each specimen was classified as benign, borderline, or malignant according to the World Health Organization criteria. The associations between malignancy and age and sex were examined using chi-square or Fisher exact tests and unadjusted logistic regression. Results:The cohort was predominantly female (90%), with a median age of 37 years. Benign lesions accounted for 366 specimens, borderline lesions for 8, and malignant lesions for 64, giving an overall malignancy proportion of 14.6%. Nodular and colloid goiters dominated the benign diagnoses, and papillary thyroid carcinoma was the most frequent malignant subtype, accounting for 50 of 64 cases. Malignancy was highest in patients aged 30 years or younger (22.2%), and the variation across age groups was statistically significant. The incidence of malignancy did not differ significantly according to sex. Among malignant tumors, the median size was 3.0 cm, and most were in the early tumor category. Conclusion:Benign goiter dominates thyroid surgical pathology in Mogadishu, while papillary carcinoma leads to a modest malignant burden that is proportionally greatest in younger patients. Strengthening pathology capacity, preoperative cytology, and cancer surveillance is therefore warranted.
Peritoneal metastasis from lung adenocarcinoma is rare and generally associated with poor prognosis. Here, we report two cases of advanced NSCLC with multiple metastases in which the patients developed rare peritoneal metastases during disease progression. Next-generation sequencing (NGS) revealed rare genomic alterations: one patient harbored concurrent EGFR exon 19 deletion and T790M mutation, accompanied by EGFR amplification, TP53 mutation, and STRN::ALK fusion, while the other exhibited EGFR kinase domain duplication and TP53 mutation. Both patients underwent multiple lines of systemic therapy, including targeted treatment guided by NGS results, and achieved survival exceeding six months following the diagnosis of peritoneal metastasis, with ongoing treatment at last follow-up. These observations suggest that more precise molecularly guided targeted therapy may play a crucial role in the clinical management of peritoneal metastasis.
Background:Rab proteins and small GTPase-mediated vesicle trafficking pathways play important roles in tumor progression and the tumor microenvironment. However, the biological function and clinical significance of RAB37 in cutaneous melanoma (CM) remain unclear. This study investigated the expression pattern, prognostic value, biological function, and immune-related characteristics of RAB37 in CM. Methods:RAB37 expression and prognostic significance were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Spearman correlation analysis assessed associations between RAB37 expression and immune cell infiltration, immune checkpoint blockade (ICB)-related signatures, and inflammatory cytokines. Functional roles of RAB37 were validated using loss- and gain-of-function experiments in A375 and WM-115 melanoma cells. CCK-8, EdU, and Transwell assays evaluated cell proliferation and migration. Single-cell functional analysis was performed using CancerSEA. Results:RAB37 expression was significantly higher in metastatic than in primary CM tissues. Elevated RAB37 expression and hypermethylation of the cg26263675 CpG site were associated with favorable survival outcomes. A prognostic nomogram integrating clinicopathological characteristics and RAB37 methylation was established. Functional experiments demonstrated that RAB37 knockdown significantly inhibited, whereas RAB37 overexpression promoted, melanoma cell proliferation and migration in both A375 and WM-115 cells. RAB37 expression was significantly associated with immune cell infiltration, ICB-related signatures, inflammatory cytokines, and immune-related pathways, including T-cell receptor signaling, PD-1 checkpoint signaling, IL-2/STAT5 signaling, and inflammatory responses. Single-cell analysis further revealed a positive association between RAB37 expression and inflammation-related functional states. Conclusion:RAB37 exhibits a context-dependent role in CM by promoting malignant cellular behaviors while being associated with immune-related characteristics and favorable clinical outcomes. These findings suggest that RAB37 may serve as a potential prognostic biomarker and provide new insights into the interplay between CM progression and the tumor immune microenvironment.
