Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by profound molecular heterogeneity and poor clinical outcome. Although current prognostic stratification mainly relies on clinicopathological and molecular features, the contribution of histone modification-related programs to GBM progression and therapeutic vulnerability remains insufficiently defined. In this study, we systematically analyzed histone modification patterns in public GBM transcriptomic cohorts and constructed a histone modification-related prognostic signature (HMS). Based on curated histone modification-related pathways and genes, unsupervised clustering identified distinct histone modification subtypes with different biological characteristics. Prognostic genes shared across TCGA-GBM, GSE74187, and GSE83300 were further screened, and LASSO Cox regression was used to establish a nine-gene HMS model. Patients with high HMS scores consistently showed worse survival across independent cohorts, and the HMS remained an independent prognostic factor. Functional enrichment analyses revealed that high-risk tumors were characterized by enhanced extracellular matrix remodeling, epithelial–mesenchymal transition-related programs, immune activation, and immunosuppressive microenvironmental features. High-HMS tumors also exhibited increased immune-cell infiltration and upregulated immune checkpoint molecules, including PD-L1, CTLA-4, PDCD1, and LAG3. TIDE-based analysis suggested potential relevance of the HMS to immune checkpoint blockade response; however, this finding should be interpreted as hypothesis-generating and requires validation in GBM cohorts treated with immunotherapy. ADAMTS4 was identified as a key risk-associated candidate. Functional experiments demonstrated that ADAMTS4 knockdown suppressed GBM cell proliferation, migration, invasion, EMT-related protein expression, and PD-L1/cell-cycle/anti-apoptotic signaling, whereas ADAMTS4 overexpression promoted malignant phenotypes in vitro and accelerated xenograft tumor growth in vivo. Collectively, this study establishes a histone modification-related risk model for GBM and identifies ADAMTS4 as a functional effector linking epigenetic risk stratification with extracellular matrix remodeling, immune regulation, and tumor aggressiveness.
Background: For patients with unresectable stage III non-small cell lung cancer, consolidation immunotherapy after concurrent or sequential chemoradiotherapy has become the standard treatment paradigm. However, in real-world clinical practice, a considerable proportion of patients are unable to tolerate the standard concurrent chemoradiotherapy regimen due to high tumor burden, advanced age, poor performance status, multiple comorbidities, or early toxicities from chemoradiotherapy. These factors not only limit the safe escalation of radiotherapy doses but also increase the risk of treatment-related mortality and severe complications. Therefore, there is an urgent need to explore alternative treatment strategies. Methods: We retrospectively reviewed patients with histologically or cytologically confirmed stage III unresectable non-small cell lung cancer who received treatment at Sichuan Cancer Hospital between January 2022 and August 2024. The primary endpoints are PFS and OS, while the secondary endpoints are ORR and safety. Results: A total of 87 patients were included. The median follow-up time from the start of induction therapy was 21months. The 1-year PFS rate and OS rate were 70% and 88.5%, respectively. The median PFS and median OS was NR at the time of data cutoff. ORR was 82.8%. Immunotherapy consolidation was associated with both improved PFS and OS. The incidence rate of pneumonia above grade 3 was 8%. Conclusions: The treatment approach of induction ICIs combined with chemotherapy followed by definitive radiotherapy, with or without consolidation immunotherapy, has shown encouraging efficacy and is safe to administer, but further research is still needed to confirm these findings.
Background Cytotoxic chemotherapy adversely affects bone health resulting in poor quality of life (QoL). This study aimed to validate and evaluate the effects of chemotherapy on bone health-specific QoL among postmenopausal women with early and locally advanced breast cancer. Methods One hundred and nine newly diagnosed postmenopausal women with non-metastatic breast cancer aged 45 to 65 years planned for anthracycline and taxane-based chemotherapy were recruited prospectively during the study period (June 2018- December 2021). Bone health-specific QoL using QUALEFFO-31 consisting of three domains: pain, physical function, and mental function, were assessed at baseline, after chemotherapy and six months of follow-up. Results The median age of the study group was 53(45–65) years. Early and locally advanced breast cancer represented 34(31.2%) and 75(68.8%), respectively. A significant worsening of the quality of life was seen at the end of chemotherapy compared to the baseline in the total scores (19.98 ± 8.34 vs. 28.98 ± 7.92 P < 0.001), pain (11.31 ± 11.58 vs. 26.70 ± 15.75 P < 0.001), physical (14.01 ± 9.19 vs. 20.47 ± 10.08, P < 0.001) and mental function (36.10 ± 11.07 vs. 46.37 ± 7.84, P < 0.001). In the subset analysis, the total scores of bone-specific QoL continue to be poor at 6 months of follow-up post-chemotherapy (P < 0.001). Conclusion Our study suggests worsening bone health-related QoL in breast cancer women on chemotherapy and this effect continues to be persistent at six months of follow-up.
Primary mucoepidermoid carcinoma of the liver (MEC-L) is an exceptionally rare malignant tumor characterized by mucinous, epidermoid, and intermediate cells, resembling its salivary gland counterpart. To date, only 24 cases of MEC-L have been reported in the English literature. We present two additional MEC-L cases diagnosed at the Third Affiliated Hospital of Sun Yat-sen University from January 2023 to May 2025, along with a review of 24 published cases. Clinical data, laboratory results, pathological findings, and follow-up information were collected. Thirty-three cases of conventional cholangiocarcinoma (CCA) were included for comparison. Next-generation sequencing (NGS) was performed for all cases. The median age of MEC-L patients was 64 years (range: 35–81 years), with a male-to-female ratio of 16:10, and a median tumor size of 8 cm. MEC-L displayed non-specific clinical and radiological features, with pathology similar to MECs arising in other anatomical sites. Only 16.67% (1/6) of MEC-L cases showed MAML2 rearrangement. Mutations in TP53, CDKN2A and CDKN2B were identified in one case, and mutations in KRAS, PIK3CA, CDK4, MDM2 and MYC were found in another case. The clinicopathological features and mutational profiles of MEC-L closely resembled conventional CCA, but MEC-L had a significantly poorer overall survival (p < 0.05). Age and tumor type were independent prognostic factors for CCA, but no distinct clinicopathological factors were identified for MEC-L. In conclusion, MEC-L is a rare subtype of CCA, who shows similar clinicopathological features and mutational profiles with conventional CCA except for poor prognosis.
Pigment epithelium-derived factor (PEDF) is a potent endogenous immunomodulatory protein with anti-metastatic, anti-angiogenic, and anti-inflammatory properties, and has recently gained attention for its ability to target tumor cells across various cancers. However, the molecular mechanism underlying the effects of PEDF on angiogenesis and metastasis in anaplastic thyroid cancer (ATC), one of the most lethal and aggressive human malignancies, remains poorly understood. In this study, the PEDF coding sequence was cloned into a lentiviral backbone plasmid vector, and its effects on metastasis and epithelial-to-mesenchymal transition (EMT) were assessed in 8305C ATC cells using RT-qPCR, migration, invasion, doubling time, wound healing assays, as well as western blot analysis. Angiogenesis was evaluated using the chicken chorioallantoic membrane (CAM) assay. Overexpression of PEDF in 8305C cells significantly reduced the expression of VEGF and HIF-1α, downregulated angiogenesis-related genes, and was associated with reduced expression of PI3K/AKT-related genes. Additionally, PEDF overexpression markedly decreased MMP-9 and MMP-2 levels, leading to reduced invasion, migration, and EMT-associated phenotype. These findings suggest that PEDF overexpression is associated with reduced angiogenic and metastatic phenotypes in ATC cells and warrants further investigation in additional preclinical models.
Purpose Drug loss in oncology therapies in Japan highlights the need to reduce operational and regulatory uncertainty in drug development. In oncology, regulatory requirements for Japanese Phase 1 studies that primarily assess tolerability in Japanese participants remain unclear. This lack of clarity may discourage sponsors from pursuing drug development in Japan, contributing to drug loss. We (1) characterized current practices of Japanese tolerability assessments through a landscape analysis and (2) identified factors associated with single-dose Japanese tolerability assessments. Methods We analyzed Japanese tolerability assessments among new oncology drugs approved in Japan during fiscal years 2015–2024. Trial characteristics were summarized, including study type, tumor type, and number of dose levels evaluated. Multivariable Firth’s logistic regression was used to identify factors associated with single-dose Japanese tolerability assessments among 71 drugs. Predicted probabilities were estimated for combinations of key factors. Results Single-dose assessments were associated with (1) determination of the recommended phase 2 dose (RP2D) before the Japanese tolerability assessment, although a wide confidence interval suggested instability in this estimate, and (2) regulatory approval supported by multi-regional clinical trials (MRCTs) including Japan. Predicted probabilities showed an increase from 0.2% in the absence of both factors to 61.8% when both were present, although these estimates should be interpreted as exploratory. Conclusion Incorporating a single-dose Japanese tolerability cohort within an MRCT after RP2D determination may represent one potential development strategy. This study may help better understand current Japanese tolerability assessment practices and potential development pathways for integrating Japan into global development programs.
BACKGROUND:Systemic inflammation, immune function, and nutritional status are closely linked to survival in gastric cancer (GC). The C-reactive protein-albumin-lymphocyte (CALLY) index integrates these dimensions; however, its dynamic perioperative changes remain unclear. This study evaluated the prognostic significance of the CALLY recovery ratio in patients undergoing curative gastrectomy. METHODS:We retrospectively analyzed 331 patients who underwent radical gastrectomy for gastric adenocarcinoma between January 2016 and December 2019. Preoperative CALLY (pre-CALLY) was calculated using laboratory values obtained within 7 days before surgery, and postoperative CALLY (POD30-CALLY) was assessed on postoperative day 30. The recovery ratio was defined as POD30-CALLY divided by pre-CALLY. Overall survival (OS) was evaluated using Kaplan-Meier analysis and Cox regression. Predictive performance was assessed by 36-month ROC curves. A nomogram incorporating independent prognostic factors was developed and validated. RESULTS:Preoperative inflammatory markers (NLR, PLR, mGPS, and pre-CALLY) were significantly associated with OS, but showed limited discrimination (36-month AUCs 0.573-0.605). POD30-CALLY alone was not significantly predictive (AUC 0.569, P = 0.087). In contrast, the recovery ratio demonstrated superior prognostic performance (AUC 0.704, P < 0.001). Multivariate analysis identified age (HR 1.022), TNM stage (HR 2.051), adjuvant chemotherapy (HR 0.401), and recovery ratio (HR 0.526) as independent predictors of OS. The nomogram showed good calibration and improved clinical net benefit. CONCLUSIONS:The CALLY recovery ratio is an independent and dynamic prognostic biomarker that improves risk stratification after curative gastrectomy.
BACKGROUND:In sarcoma surgery, a relationship between local complications after tumor resection and the risk of recurrent disease has been suggested. We aimed to investigate the relationship between early wound complications and soft tissue sarcoma (STS) local tumor recurrence (LR) and overall patient survival (OS) in a single Swedish tertiary centre. METHODS:Patients 15 years or older, operated for first time STS in trunk or limbs in one centre during 2010-2022 were considered. Patient files and national- and local registries were used to collect information on comorbidities, adjuvant treatments, tumor characteristics, wound complications, recurrence and death. Only wound complications requiring medication or surgery were considered. An inverse probability weighted model was used to balance for differences between groups. RESULTS:596 patients were included in the study. 186 (31%) developed wound complication within 30 days. 34 (18%) of patients with a complication had LR, compared to 58 (14%) of those without (p= 0.196). Inverse probability weighting and cox regression could not link early wound complications to recurrence. Only patients with no missing data were included in survival analyses, making 575 patients eligible. Local recurrence free survival (LRFS) was 10 months shorter on average (62 vs 72 months, SD=48, p = 0.018) in study participants who developed wound complications compared to those who did not. Regardless of underlying risk profile (malignancy grade, comorbidities and metastatic disease), wound complications remained an independent risk factor for death (HR 1.43 [1.05 1.96] p = 0.024). CONCLUSION:Early wound complications after surgery for STS were associated with reduced LRFS and OS.
BACKGROUND:Breast cancer survival remains markedly unequal across countries, and the determinants of this gap extend beyond tumor biology. This structured narrative review examines how biological characteristics, stage at diagnosis, access to multimodality treatment, survivorship services, and health-system capacity interact in low- and middle-income countries (LMICs), with Indonesia developed as a country case study. METHODS:PubMed/MEDLINE and official World Health Organization (WHO), International Agency for Research on Cancer (IARC), Union for International Cancer Control (UICC), and Indonesian Ministry of Health sources were searched through 20 July 2026. Eligible evidence included international frameworks, systematic reviews, population-based studies, and regionally relevant observational studies addressing epidemiology, diagnosis, pathology, treatment, survivorship, financing, workforce, or cancer-control policy. Evidence was selected and interpreted using a structured narrative approach informed by SANRA principles. RESULTS:GLOBOCAN 2022 estimated 66,271 new female breast cancer cases and 22,598 deaths in Indonesia. Indonesian studies demonstrate substantial diagnostic delay, sociodemographic inequalities in stage at presentation, incomplete access to biomarker-directed care, radiotherapy waiting and completion problems, and financial misalignment between hospital costs and reimbursement. Across LMICs, younger patient age and heterogeneous subtype distributions may modify risk, but late diagnosis and failures across the care pathway frequently exert a larger population-level effect. CONCLUSIONS:Improvement requires an integrated strategy rather than isolated interventions. The WHO Global Breast Cancer Initiative targets->60% of invasive cancers diagnosed at stage I-II, completion of diagnostic evaluation within 60 days, and >80% completion of recommended multimodality treatment-provide measurable anchors. For Indonesia, priorities are symptom-based early detection, rapid referral and tissue diagnosis, quality-assured ER/PR/HER2 testing, resource-stratified treatment pathways, radiotherapy expansion, patient navigation, survivorship integration, and stronger registry-linked accountability.
Background Evidence comparing first-line atezolizumab and pembrolizumab monotherapy in elderly patients with PD-L1-high non-small cell lung cancer (NSCLC) remains limited in routine clinical practice. We compared treatment persistence and clinical outcomes between these two treatment strategies in a real-world setting. Methods We conducted a retrospective single-center study of patients aged ≥75 years with PD-L1 tumor proportion score ≥50% who received first-line atezolizumab or pembrolizumab monotherapy. The primary endpoint was time to treatment failure (TTF). Secondary endpoints included real-world progression-free survival (rwPFS), overall survival (OS), treatment discontinuation patterns, and safety. Results Twenty-nine patients were included (atezolizumab, n = 8; pembrolizumab, n = 21). Patients treated with atezolizumab exhibited greater clinical vulnerability, including older age, a higher burden of comorbidities, and poorer performance status. Despite these less favorable baseline characteristics, time to treatment failure (TTF) appeared broadly similar between the two groups. Similar trends were observed for real-world progression-free survival (rwPFS), while no clear difference in overall survival (OS) was evident. Discontinuation due to immune-related adverse events occurred more frequently in the atezolizumab group, whereas disease progression was the predominant reason for treatment discontinuation in the pembrolizumab group. No treatment-related deaths were observed. Conclusions Despite less favorable baseline characteristics, atezolizumab demonstrated descriptively acceptable treatment persistence in elderly and clinically vulnerable patients. These findings suggest that atezolizumab remains a feasible first-line treatment option for selected older patients with PD-L1-high NSCLC.
The E2F family of transcription factors plays essential roles in cell cycle regulation, DNA damage response, apoptosis, senescence, glucose metabolism, and angiogenesis. Although E2F pathway alterations were identified across multiple cancers, its role in salivary gland tumorigenesis remains elusive. Given the mechanistic role of E2F in cancer stemness, this pathway represents a promising therapeutic target for salivary malignancies. The purpose of this study was to evaluate the function of E2F1 and E2F4 in the stemness of salivary gland mucoepidermoid carcinoma (MEC), and to test whether pharmacologic inhibition of E2F ablates cancer stem cells (CSC) in MEC. Evaluation of a tissue microarray (TMA) of human MEC samples showed that E2F1 and E2F4 were overexpressed in MECs compared with control salivary glands, where their expression was restricted to ductal cells. CSCs showed higher expression of E2F1 and E2F4 compared to non-CSCs in 3 human MEC cell lines (UM-HMC-1,-3A,-3B). Therapeutic inhibition of E2F with HLM006474 induced expression of p53 and p21 while inhibiting expression of the stemness markers Bmi-1 and ALDH. Notably, the fraction of CSC (ALDHhighCD44high) was significantly reduced by HLM006474 in vitro, and in MEC tumor xenografts in vivo. Collectively, these data demonstrate that E2F inhibits stemness in mucoepidermoid carcinoma and suggest that patients with salivary gland malignancies might benefit from therapeutic inhibition of E2F.
BACKGROUND:Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in immune regulation and cancer development. A functional promoter polymorphism in MIF (-173 G>C; rs755622) has been investigated for its association with cancer susceptibility, but results remain inconsistent across populations and tumor types. METHODS:To evaluate the association between the MIF -173 G>C polymorphism and susceptibility to solid cancers, the PubMed, Scopus, and ProQuest databases were searched for case-control studies on MIF and solid cancer risk. Associations between MIF -173 G>C polymorphisms and solid cancer susceptibility were assessed using random-effects models, with subgroup analyses by ethnicity and cancer type. RESULTS:Seventeen studies were identified, contributing 17 independent comparisons with 7678 participants (3680 cases, 3998 controls). The -173C allele was associated with a modest increase in solid cancer susceptibility under the dominant (OR 1.26, 95%CI: 1.02-1.56) and allelic (OR 1.26, 95%CI: 1.04-1.52) models, while the recessive model was not statistically significant. Subgroup analyses revealed stronger and consistent risk associations in Far Eastern populations in all models. Gastrointestinal cancers demonstrated significant associations under all three models, but no significant association was observed in breast cancer. Although formal tests for subgroup differences were not statistically significant CONCLUSIONS: MIF -173 G>C polymorphisms influence cancer susceptibility in a context-dependent manner, with stronger effects in Far Eastern populations and gastrointestinal cancers, though these subgroup patterns warrant confirmation in larger, adequately powered studies. (PROSPERO, ID: CRD420251207775).
Extracellular vesicle (EV)-associated non-coding RNAs (ncRNAs) are increasingly recognized as mediators of intercellular communication within the tumor microenvironment (TME), yet their mechanistic and translational significance varies substantially across gastrointestinal and hepatobiliary cancers. This narrative review, informed by a structured literature search, integrates evidence on EV-associated microRNAs, long non-coding RNAs, and circular RNAs in esophageal, gastric, colorectal, pancreatic, hepatocellular carcinoma, and cholangiocarcinoma. Rather than organizing the literature by RNA class or individual tumor type, we synthesize findings according to major TME functions, including immune remodeling, cancer-associated fibroblast activation, vascular remodeling, paracrine tumor-cell reprogramming, therapy resistance, and tumor-suppressive vesicular signaling. Recurrent mechanisms involve PTEN/PI3K/AKT, JAK/STAT, TGF-β/Smad, Wnt/β-catenin, and immune-checkpoint pathways, but the strength of evidence differs markedly among studies. Accordingly, mechanistic findings are distinguished from animal-model-supported, clinically correlated, preliminary, and biomarker-only evidence using a standardized descriptive framework. The review also highlights cholangiocarcinoma as an underrepresented but increasingly informative hepatobiliary model while avoiding generalization to broader biliary tract cancers when direct evidence is lacking. Major barriers to clinical translation include inconsistent EV isolation and characterization, uncertain vesicle-source attribution, limited validation of recipient-cell transfer and causal targets, small retrospective cohorts, and insufficient prospective validation. Overall, EV-ncRNAs represent promising mechanistic biomarkers and therapeutic targets, but rigorous source-specific validation and standardized analytical workflows are required before clinical implementation.
Background Nottingham histological grading is central to breast cancer prognosis and treatment planning, but conventional pathological assessment is labor-intensive and subject to inter-observer variability. Radiomics and machine learning may support noninvasive preoperative grade prediction. Objective To compare mutual-information, chi-squared, and LASSO feature-selection strategies for binary Nottingham grade classification using tumor- and fibroglandular-tissue (FGT)-derived DCE-MRI features. Methods This retrospective secondary analysis included 576 patients from the Duke-Breast-Cancer-MRI collection in The Cancer Imaging Archive, comprising 288 non-high-grade and 288 high-grade tumors. A total of 529 publicly released precomputed imaging features across 10 categories were analyzed, including volume, morphology, enhancement kinetics, texture, spatial heterogeneity, and temporal variation. No additional segmentation, resampling, normalization, or feature extraction was performed. Feature selection was followed by classifier development and Bayesian hyperparameter optimization. Models were evaluated using stratified 5-fold cross-validation, and SHAP analysis was used for feature interpretation. Because feature selection and model configuration were not embedded within a fully nested cross-validation framework, performance estimates were considered exploratory. Results Chi-squared selection with a neural network achieved the highest mean accuracy (74.78%; AUC 0.77). LASSO provided the strongest discrimination, with a pooled out-of-fold AUC of 0.82 and relatively balanced sensitivity and specificity. Tumor volumetric, morphological, and enhancement-kinetic features were the most influential predictors, while FGT-derived features contributed complementary but more limited information. Conclusion Tumor- and FGT-derived DCE-MRI features showed preliminary potential for binary Nottingham grade classification. Fully nested model development and independent multi-institutional validation are required before clinical application.
Cancer is a major cause of human death. Colon cancer is the fifth leading cause of cancer-related deaths worldwide. Pinkbar, a member of the inverse BAR (I-BAR) domain protein subfamily, is associated with the actin cytoskeleton, leading to cell motility and cell shape changes. We focused on Pinkbar expression in colon cancer patients and explored the therapeutic effects of human amniotic mesenchymal stem cells (hAMSCs) secretome on Pinkbar expression in colon cancer cells through AKT/mTOR and Wnt3a/β-catenin signaling pathways. Thirty colon cancer specimens were collected, and Pinkbar expression was assessed using quantitative real-time PCR (qRT-PCR). A co-culture system with 6-well Transwell plates was utilized to treat HT-29 cells with hAMSCs secretome, followed by analysis of cell proliferation and invasion through qRT-PCR, MTT assay, Western blot, DAPI staining, and wound healing assay. Our results demonstrated up-regulation of Pinkbar in colon cancer patients and inhibition of Pinkbar, p-AKT (Thr308), p-mTOR (Ser2481), Wnt3a, β-catenin, p-P70S6K (Ser411), and cyclin D1 expression along with an increase in E-cadherin levels in hAMSCs-treated HT-29 colon cancer cells. These results suggest that Pinkbar may serve as a potential target for colon cancer therapy, and hAMSCs secretome can effectively inhibit colon cancer cell proliferation and invasion through AKT/mTOR and Wnt3a/β-catenin signaling pathways.
Introduction Avelumab is approved as maintenance therapy after platinum-based chemotherapy in metastatic urothelial carcinoma (mUC). Real-world evidence is needed to validate outcomes and define its role in the era of newly approved agents. Patients and methods This retrospective study included patients with mUC from a Brazilian multicenter oncology network (2021–2026) who received ≥1 cycle of avelumab following chemotherapy. The primary endpoint was overall survival (OS), defined as the time from avelumab initiation to death from any cause. Secondary endpoints included progression-free survival (PFS), treatment-related toxicity, and subsequent therapies after progression. Survival outcomes were estimated using the Kaplan–Meier method. Results Forty-six patients were included (63% male), with a median age of 71 years (range, 55–91). At a median follow-up of 24.4 months, 56.5% were alive, and 43.5% had died. Median treatment duration was 8.48 months, with a median of 19 cycles (range, 1–112). Median OS was not reached. Estimated OS rates at 12 and 36 months were 76.1% (95% CI, 65–89%) and 53% (95% CI, 40–71%), respectively. A PFS event occurred in 67.4% of patients, while 32.6% remained progression-free. After progression, 45.6% received second-line therapy, and 13% received third-line therapy. Median time to next treatment was 5.6 months. Grade 3–4 adverse events occurred in 26%, with no treatment-related deaths. Conclusion Avelumab maintenance demonstrated durable disease control, prolonged survival, and acceptable tolerability in an unselected real-world mUC population. Nearly half of the patients received subsequent therapy after progression.
Three-dimensional (3D) gastric organoids have become valuable experimental models for gastric cancer research, as they closely mirror tumour architecture, molecular features, and treatment responses. Unlike two-dimensional cultures and animal models, gastric organoids capture key physiological and pathological characteristics of the human stomach, allowing more meaningful investigation of tumour development, host–microbe interactions, and epithelial–stromal crosstalk. These systems retain the genetic and phenotypic traits of their tissue of origin, making them suitable for both mechanistic studies and long-term experimentation.This review outlines the development of gastric organoid technology, from early advances in adult stem cell–derived cultures to recent methodological refinements that have expanded their experimental and clinical relevance. We discuss how organoid models have helped address the challenge posed by the marked molecular and histological heterogeneity of gastric cancer, which continues to complicate diagnosis and therapeutics. In this regard, patient-derived gastric organoids and associated biobanks have shown strong potential as predictive tools for drug response, as they reliably preserve tumour structure and gene expression patterns observed in primary tissues. In addition, we highlight recent improvements in culture matrices and experimental approaches that have enhanced organoid robustness and reproducibility. The growing use of gastric organoids as preclinical platforms for drug screening and the study of cancer-related signaling pathways reflects the rapid maturation of the field. We consider current limitations, technical challenges, and future directions for gastric organoid research, emphasizing their role as complementary models that bridge the gap between conventional in vitro systems and in vivo studies in gastric cancer.
Background Ovarian cancer is one of the most common and complicated cancers among women, requiring timely treatment. The treatments and the disease itself can affect the sexual health of sufferers. This research aims to determine the global prevalence of sexual dysfunction (SD) in women with ovarian cancer. Methods For this research, a meticulous search was conducted on each database, including PubMed, ScienceDirect, Scopus WOS, Embase, and the Google Scholar search engine, using keywords related to the title. The scope of searches was unlimited at the time the reviews began until the end of November 2023. Inclusion criteria for this study included observational studies reporting the prevalence of sexual dysfunction (SD) in patients with ovarian cancer. Studies with full text available. Studies published in English. Cross-sectional, cohort, and case-control studies. Exclusion criteria included case studies, interventional studies, replication studies, and articles with full text unavailable, non-English studies, and animal studies. All relevant studies were then transferred to EndNote for reference management. Following data collection, researchers employed the advanced Comprehensive Meta-Analysis software (Version 2) and the random effects model for analysis. The I2 index and tau² and Cochran's Q test was also used to verify the heterogeneity of studies, further enhancing the robustness of the research process. Funnel Plot and Egger test were used to evaluate the publication bias. Results In the review of 17 studies with a sample size of 2018 people, the global prevalence of SD in women with ovarian cancer was found to be 37% (95%CI: 21.7–55.4). The meta-regression results showed a significant trend: as the sample size increased, the global prevalence of SD in ovarian cancer patients decreased (p < 0.05). Additionally, the rise in the year of conducting studies was found to be associated with a decrease in the global prevalence of SD in ovarian cancer patients (p < 0.05). Conclusion Given the high prevalence of sexual dysfunction (SD) in women with ovarian cancer and the associated complications, health systems need to implement timely training and interventions to reduce the incidence of these disorders.
Colorectal cancer (CRC) is the second leading cause of cancer-related death. The tumor immune microenvironment plays a critical role in tumor progression and immune evasion. B7-H3 (CD276), a member of the B7 family of immune checkpoint molecules, is frequently overexpressed in a variety of malignancies, including CRC. A systematic search of the literature was performed to identify studies evaluating B7-H3 in CRC. Data were extracted on study characteristics, B7-H3 expression and detection methods, molecular and signaling pathways, and clinical outcomes. Study quality and risk of bias were assessed using the MASTER scale, and findings were synthesized using a structured narrative approach. Sixty-three studies were included. B7-H3 expression was commonly reported but demonstrated substantial variability, largely driven by differences in detection and scoring methodologies. Preclinical evidence suggests that B7-H3 may contribute to tumor growth, invasion, immune evasion, and resistance to radio- and chemotherapy, potentially through pathways such as PI3K–AKT–mTOR, JAK–STAT, MAPK/ERK, NF-κB, VEGF/hypoxia, and Wnt/β-catenin. Preclinical studies have demonstrated that targeting B7-H3 may improve radiotherapy response and reduce metastatic burden in murine CRC models. However, these findings should be considered preliminary and are not yet supported by clinical evidence in humans. B7-H3 targeting remains an emerging therapeutic approach that requires further clinical validation. However, significant methodological heterogeneity in detection and scoring limits comparability across studies and precludes definitive conclusions regarding its clinical utility. B7-H3 should therefore be considered a candidate biomarker and further standardized. Prospective studies are needed to clarify its diagnostic, prognostic, and therapeutic relevance in CRC.
Purpose: The relationship between the number of initial metastases and metastatic spread in terms of progression-free survival (PFS) and overall survival (OS) in metastatic breast cancer (mBC) remains poorly understood. This study aimed to identify key factors influencing disease progression and survival from the first metastatic manifestation. Methods: This retrospective, single center cohort study included 126 patients with breast cancer and distant metastasis treated at the University Hospital Basel, Switzerland, between 2014 and 2023. We assessed risk factors including metastatic pattern (single metastasis [SM] vs. multiple metastases [MM]), receptor status, histological subtype, and age. Disease progression from the first to second metastatic event was evaluated using the Kaplan-Meier method and log-rank test. Statistical analysis was performed using R software. Results: Patients with SM exhibited significantly better PFS compared to those with MM (HR 2.11, 95% CI 1.38–3.24). Non-triple-negative breast cancer (non-TNBC) patients had superior PFS compared to those with TNBC (HR 2.61, 95% CI: 1.53–4.44). In terms of OS, SM patients had a significantly better outcome compared to MM patients (HR 2.39, 95% CI 1.43–3.99). Additionally, non-TNBC patients showed a significantly better OS than TNBC patients (HR 3.93, 95% CI: 2.2–7). Conclusions: The extent of initial metastasis and TNBC status play a crucial role in determining prognosis in mBC. These factors are essential for predicting disease progression, guiding individualized treatment strategies, and informing ongoing discussions on optimal treatment approaches for patients with oligometastatic breast cancer.
