Cancers最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common and linked to obesity; however, its association with colorectal cancer (CRC) risk in women remains unclear. Materials and Methods: This retrospective cohort study used the Korean National Health Insurance Service health-screening database, including 483,401 women aged 40-59 years examined between 2013 and 2016, followed through 2021. MASLD was defined as hepatic steatosis (hepatic steatosis index ≥ 36 or ICD-10 K76.0) with ≥1 metabolic abnormality and no heavy alcohol use (≥20 g/day). Incident CRC (ICD-10 C18-C20) was analyzed using Cox regression adjusted for demographic, socioeconomic, and metabolic variables. Effect modification was tested across key covariates. Results: MASLD was found in 128,642 participants (26.6%). During a median 7.5-year follow-up, 2432 CRC cases occurred (702 with MASLD). The 7-year cumulative CRC risk was higher in the MASLD group (0.47% vs. 0.43%; p = 0.006). MASLD independently increased CRC risk (adjusted HR 1.10; 95% CI 1.00-1.20). Effect modification was observed for age, dyslipidemia, and waist circumference. MASLD significantly increased CRC risk among women aged 40-49 years (HR 1.26; 95% CI 1.05-1.49), those without dyslipidemia (HR 1.15; 95% CI 1.03-1.28), and with waist < 85 cm (HR 1.15; 95% CI 1.02-1.30). Conclusions: MASLD modestly increases CRC risk in Korean women, particularly among younger, normolipidemic, and non-obese individuals, indicating the need for age- and metabolism-specific risk stratification and suggesting a need for closer clinical attention and metabolic optimization.

Background: While immune checkpoint inhibitors (ICIs) have improved survival in mNSCLC, outcomes may be disparate by age, race, and sex. However, given the limited diversity of trial populations, data are limited. Methods: A systematic review and meta-analysis were conducted of phase III prospective trials of ICIs in mNSCLC initiated after 2015, identified from PubMed and ClinicalTrials.gov in September 2025. Trials that did not report overall survival by race, sex, or age distribution were excluded. Random-effects meta-analyses were used to pool ratios of hazard ratios (RHRs) for overall survival to assess treatment-by-subgroup interactions by sex (men vs. women), race (white vs. Asian), and age (<65 vs. ≥65). Random-effects meta-analyses of odds ratios (ORs) for death were also performed for each subgroup in the investigational treatment arm and across all patients. Heterogeneity across trials was evaluated by Cochran's Q test and I² statistics. Publication bias was assessed by Egger's tests and funnel plots. Results: A total of 21 trials comprising 10,950 patients were included in the meta-analysis. Women have a non-significantly smaller overall survival benefit with the investigational treatment than with control compared with men (RHR 0.91; p = 0.17). On investigational agents, white patients had higher odds of death (OR 1.76; p = 0.0496) compared to Asian patients. Similarly, white patients had higher odds of death across both treatment arms compared to Asian patients (OR 2.35; p < 0.001). No trials reported subgroup analysis for Black patients due to small sample sizes. Patients ≥65 years old have a non-significantly smaller overall survival benefit with investigational agents compared with control (RHR 0.92; p = 0.19). Discussion: This study did not identify significant differences in overall survival benefit on the investigational treatment across race, sex, or age subgroups. Still, it remains unclear whether women and patients ≥65 years old derive less survival benefit from ICIs than men and younger patients. Asian patients had significantly greater survival than white patients on investigational therapies and all therapies, while Black patients were underrepresented in trials. Our results highlight the need for more representative trial populations and standardized reporting of subgroup analysis to ensure equitable benefit and evaluation of ICIs in mNSCLC treatment. Our meta-analysis was limited by inconsistent data reporting across subgroups and by the lack of time-to-event survival data within subgroups.

Background/Objectives: Tumor-induced immune reprogramming is increasingly recognized as a key mechanism by which cancers evade surveillance and promote disease progression. The interaction between cancer and immune cells within the tumor microenvironment (TME) can drive phenotypic and functional changes in immune populations, facilitating metastasis and immune evasion. Methods: In this study, we used co-culture models to expose THP1 monocytes to triple-negative breast cancer (TNBC) cells, MDA-MB-231 and BT-549, either directly or indirectly via tumor-conditioned media, to mimic tumor-immune cell communication. Transcriptomic and pathway analyses revealed that cancer-exposed monocytes adopt a reprogrammed phenotype marked by activation of pro-tumorigenic signaling pathways, enhanced proliferative capacity, and elevated expression of pro-inflammatory cytokines such as IL6. Results: Functional assays confirmed a significant increase in monocyte proliferation under both direct and indirect tumor exposure. Importantly, we demonstrated that this tumor-driven proliferation of THP1 cells could be suppressed by the STAT3 inhibitor STAT3-IN-12. This highlights the critical role of STAT3 signaling in mediating immune cell transformation and supporting a novel immunomodulatory approach for therapeutic intervention. Conclusions: These findings support the potential for targeting tumor-educated transcriptional programs as a novel immunomodulatory strategy in cancer treatment. Restoring immune cell homeostasis and suppressing pro-tumor phenotypes through pharmacological inhibition of the key signaling nodes such as STAT3 may complement existing cancer therapies. This study provides new insights into immune cell plasticity in cancer and identifies actionable strategies to counteract tumor-driven immune dysregulation.

Background and Aims: Diabetes mellitus and chronic hepatitis B/C infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC). This study aimed to evaluate whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) improved liver-related outcomes in patients with chronic viral hepatitis and co-existing diabetes. Methods: Using data from the Korean nationwide cohort, this study included 37,629 patients with concurrent diabetes and chronic hepatitis B/C infection, without prior HCC, who were treated with oral hypoglycemic agents. Patients who were treated with SGLT2is for over 90 days were allocated to the SGLT2i group, whereas those who never received SGLT2is comprised the non-SGLT2i group. The primary outcome was the occurrence of liver-related events, including HCC. Results: After 1:2 propensity score matching, the SGLT2i group comprised 12,543 patients (chronic hepatitis B, CHB: n = 9392; chronic hepatitis C, CHC: n = 4300, CHB & CHC: n = 1149), while the non-SGLT2i group included 25,086 patients (CHB: n = 18,806; CHC: n = 8553, CHB & CHC: 2273). The incidence rate of composite liver-related complications was lower in the SGLT2i group than that in the non-SGLT2i group (6.67 per 1000 vs. 8.99 per 1000). Moreover, SGLT2i therapy was associated with a reduced risk of HCC development (subdistribution hazard ratio [sHR] = 0.77, 95% confidence interval [CI] = 0.66-0.91; p = 0.002) and developing cirrhosis (sHR = 0.67, 95% CI = 0.54-0.83; p < 0.001). Conclusions: SGLT2is should be considered a therapeutic option for controlling diabetes, reducing the metabolic burden, and improving liver outcomes in patients with concurrent diabetes and chronic viral hepatitis.

Background/objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air-liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade.

Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45⁺ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti-PD-1) to assess local immune modulation.

Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC-Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour-immune interactions.

Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour-immune interactions.

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Peritoneal metastases represent one of the most dreadful manifestations of gastric cancer and continue to drive poor outcomes despite significant advances in systemic therapy. Accurate staging-beginning with laparoscopy-remains essential for avoiding non-beneficial surgery and ensuring appropriate allocation to systemic or locoregional treatment pathways. Although modern systemic agents, including immunotherapy and targeted therapies, have transformed the broader management of metastatic disease, their impact in the peritoneal compartment remains limited, reflecting its unique biological and pharmacokinetic constraints. Locoregional approaches such as CRS-HIPEC, PIPAC, and NIPS have expanded the therapeutic armamentarium and have shown encouraging signals in selected populations. Recent randomized studies, including ESTOK01 and PERISCOPE II, emphasize the importance of careful patient selection, technical standardization, and optimal sequencing, while ongoing trials-such as PREVENT, GASTRICHIP, and CONVERGENCE-seek to refine the integration of systemic and intraperitoneal strategies. Yet the field continues to advance without the benefit of validated predictive biomarkers capable of guiding therapeutic decisions. This limitation constrains clinical progress and underscores the need for a stronger translational framework. Future improvement in the management of gastric cancer with peritoneal metastases will depend on the identification of robust biological predictors of response, enabling more rational patient selection and the development of truly personalized multimodal approaches.

Objective: Impairment of the Fas/FasL apoptotic pathway is a mechanism contributing to the malignant transformation of multiple cell types. This study aimed to investigate the clinical and prognostic relevance of serum soluble Fas (sFas) and soluble Fas ligand (sFasL) levels in patients with pancreatic and papilla of Vater adenocarcinomas. Methods: An ELISA was used to determine sFas and sFasL levels. Serum samples were obtained from 53 healthy controls, 82 pancreatic and 14 papilla of Vater carcinoma patients. Sera from carcinoma patients were obtained before surgery and 30 days after surgery. The relationships of preoperative levels with clinicopathological features and patient survival were evaluated. Changes in serum sFas and sFasL levels after surgery were also evaluated. Results: Higher sFas and lower sFasL levels were found in the serum of carcinoma patients in comparison to healthy controls. Serum sFas and sFasL levels correlated significantly with both lymph node and distant metastases and an advanced stage of disease. Elevated sFas and decreased sFasL levels correlated significantly with poor overall survival when the entire study population was considered with sFas being an independent prognostic factor. After patient stratification, their prognostic value was evident in pancreatic carcinoma patients only. Preoperative sFas levels decreased and sFasL levels increased after radical resection of the tumor but remained unchanged in cases of unresectable disease. Conclusions: These findings suggest that serum levels of sFas and sFasL could be useful tumor markers with prognostic value in pancreatic adenocarcinomas. Increased sFas secretion may reflect a mechanism for apoptotic escape of cancer cells.

Background: Immediate breast reconstruction after mastectomy has progressively shifted toward less invasive approaches. The pre-pectoral approach, avoiding muscle dissection, may reduce post-operative pain, surgical trauma, and recovery time. However, concerns regarding surgical complications and their potential impact on the timing of adjuvant treatments still persist.

Methods: A retrospective monocentric study was conducted, including all patients who underwent mastectomy with implant-based breast reconstruction at the Breast Unit of Policlinico Tor Vergata in Rome between January 2014 and March 2024. Patients were classified according to the reconstructive technique as either pre-pectoral or sub-pectoral. Demographic, oncologic, and surgical data were collected and analyzed, with a particular focus on post-operative complications and the timing of adjuvant treatment initiation.

Results: Of 622 patients, 366 (58.9%) underwent sub-pectoral reconstruction and 235 (37.7%) pre-pectoral. Overall, the complication rates were comparable between the two reconstructions (23.8% vs. 20.2%, p = 0.310). Delayed wound healing was higher in the pre-pectoral group (9.0% vs. 4.3%, p = 0.035), whereas post-operative bleeding occurred more often in sub-pectoral cases (4.9% vs. 0.4%, p = 0.057). Operative time was significantly shorter in the pre-pectoral group (p < 0.001). Multivariate analysis identified skin-reducing mastectomy (OR 2.11), smoking (OR 2.89), and diabetes mellitus (OR 3.06) as predictors of delayed adjuvant therapy, whereas the reconstruction technique was not associated with delays.

Acute myeloid leukemia (AML) is an aggressive cancer with rapid progression and a high relapse rate, highlighting the urgent need for effective treatments. While recent advances in drug therapies and combination regimens have improved outcomes, relapsed and refractory (R/R) AML still shows low response rates, poor prognosis, and limited survival. The lack of effective immunotherapies further complicates the management of R/R AML. The bone marrow tumor microenvironment (TME) poses a significant barrier, requiring multifaceted, combined therapeutic strategies for clinical success. This TME creates an immunosuppressive and metabolically challenging environment that limits the expansion, persistence, cytotoxicity, and survival of chimeric antigen receptor (CAR) T cells. Unlike CD19 in B-cell acute lymphoblastic leukemia (B-ALL), AML lacks a truly leukemia-specific antigen. Although clinical trials are ongoing, no CAR-T therapies have received FDA approval for AML. This paper explores the reasons behind these ongoing challenges.