Background: Mesenchymal stem cells (MSCs) therapy is a novel treatment strategy for cancer and a wide range of diseases with an excessive immune response such as ulcerative colitis (UC), due to its powerful immunomodulatory properties and its capacity for tissue regeneration and repair. One of the promising therapeutic options can focus on MSC-secreted exosomes (MSC-Exo), which have been identified as a type of paracrine interaction. In light of a wide variety of recent experimental studies, the present review aims to seek the recent research advances of therapies based on the MSC-Exo for treating UC and colorectal cancer (CRC). Methods: A systematic literature search in MEDLINE, Scopus, and Google Scholar was performed from inception to December 2021 using the terms [(“colorectal cancer” OR “bowel cancer” OR “colon cancer” OR “rectal cancer”) AND (exosome) AND (stem cell) AND (“inflammatory bowel disease” OR “Crohn's disease” OR “colitis”)] in titles and abstracts. Findings: Exosomes derived from various sources of MSCs, including human umbilical cord-derived MSCs (hUC-MSCs), human adipose-derived MSCs (hAD-MSCs), human bone marrow-derived MSCs (hBM-MSCs), and olfactory ecto-MSCs (OE-MSCs), have shown the protective role against UC and CRC. Exosomes from hUC-MSCs, hBM-MSCs, AD-MSCs, and OE-MSCs have been found to ameliorate the experimental UC through suppressing inflammatory cells including macrophages, Th1/Th17 cells, reducing the expression of proinflammatory cytokines, as well as inducing the anti-inflammatory function of Treg and Th2 cells and enhancing the expression of anti-inflammatory cytokines. In addition, hBM-MSC-Exo and hUC-MSC-Exo containing tumor-suppressive miRs (miR-3940-5p/miR-22-3p/miR‐16‐5p) have been shown to suppress proliferation, migration, and invasion of CRC cells via regulation of RAP2B/PI3K/AKT signaling pathway and ITGA2/ITGA6. Key messages: The MSC-Exo can exert beneficial effects on UC and CRC through two different mechanisms including modulating immune responses and inducing anti-tumor responses, respectively.

Colorectal cancer (CRC), one of the most common malignancies worldwide, leads to abundant cancer-related mortalities annually. Pyroptosis, a new kind of programmed cell death, plays a critical role in immune response and tumor progression. Our study aimed to identify a prognostic signature for CRC based on pyroptosis-related genes (PRGs). The difference in PRGs between CRC tissues and normal tissues deposited in the TCGA database was calculated by "limma" R package. The tumor microenvironment (TME) of CRC cases was accessed by the ESTIMATE algorithm. The prognostic PRGs were identified using Cox regression analysis. A least absolute shrinkage and selector operation (LASSO) algorithm was used to calculate the risk scores and construct a clinical predictive model of CRC. Gene Set Enrichment Analysis (GSEA) was performed for understanding the function annotation of the signature in the tumor microenvironment. We found that most PRGs were significantly dysregulated in CRC. Through the LASSO method, three key PRGs were selected to calculate the risk scores and construct the prognostic model for CRC. The risk score was an independent indicator of patient's prognosis. In addition, we classified the CRC patients into two clusters based on risk scores and discovered that CRC patients in cluster 2 underwent worse overall survival and owned higher expression levels of immune checkpoint genes in tumor tissues. In conclusion, our study identified a PRG-related prognostic signature for CRC, according to which we classified the CRC patients into two clusters with distinct prognosis and immunotherapy potential.

Objective/Background: The RNPLS-01 trial aimed to evaluate the efficacy and safety of ramucirumab (a VEGFR2 antagonist) combined with nab-paclitaxel, lobaplatin, and S-1 (RNPLS group) versus nab-paclitaxel, lobaplatin, and S-1 alone (NPLS group) in neoadjuvant therapy for advanced gastric cancer (GC), as part of the RNPLS-01 prospective randomized controlled trial. Methods and analysis: RNPLS-01 trial enrolled 140 patients with advanced GC across two cohorts (neoadjuvant therapy: n = 70; conversion therapy: n = 70). This report focuses on the neoadjuvant cohort where patients were randomized 1:1 to receive either RNPLS (n = 35) or NPLS (n = 35). Primary endpoint was pathological complete response (pCR). Secondary endpoints included R0 resection rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: The RNPLS group demonstrated significant improvements in post-operative T stage ( P = 0.008), N stage ( P = 0.001), and AJCC (American Joint Committee on Cancer) clinical stage ( P = 0.003) compared to controls. The RNPLS group demonstrated significantly higher pCR rates compared to the NPLS group (22.9% vs. 2.9%, P <0.0001). The R0 resection rate was 85.7% in the RNPLS group versus 82.9% in the NPLS group. The RNPLS group achieved a significantly higher ORR compared to the NPLS group (68.6% vs. 25.7%, P = 0.001), while DCRs were comparable between the two groups (94.3% vs. 77.1%, P = 0.055). Treatment-related adverse events (TRAEs) were confined to Grade 1–2 severity, with no Grade 3–4 events reported in either group. The RNPLS group showed a TRAE incidence of 80.0%, versus 88.6% in the NPLS group ( P = 0.324). Neither group exhibited surgical complications during the study period. Conclusion: Ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 significantly enhances the pCR rate and ORR in neoadjuvant therapy of locally advanced GC patients, while maintaining an acceptable safety profile.

Lynch Syndrome (LS) carriers occasionally develop central nervous system (CNS) malignancies or tumors in organs not traditionally linked to the syndrome. These tumors are poorly characterized in the literature, and there is no sufficient consensus on guidelines and management recommendations for these tumors. Here we study LS from the tumor perspective and profile 238 pan-cancer specimens from 228 genetically confirmed LS carriers. Tumors are stratified into CNS LS-related, non-CNS LS-related, and non-CNS LS-unrelated groups according to anatomic site and established LS tumor spectrum. Comparative analyses against TCGA reveal significant alterations in LS incidence within endometrial and hepatic cancers. Across the three groups, we reveal marked heterogeneity in germline pathogenic-variant distribution, age at diagnosis, somatic mutation landscapes, tumor mutational burden, and microsatellite-instability status. This site- and spectrum-based stratification of a large, pan-cancer LS cohort underscores the heterogeneity of the LS and provides a data-driven foundation for refining future disease management strategies.

Background: Colorectal cancer (CRC) is a major global health concern, with obesity rates rising and an observed obesity paradox where higher body mass index (BMI) is linked to better outcomes in certain patient groups. This study aims to explore how age and tumor stage modify the association between BMI and mortality risk in CRC patients.Materials and methods: This retrospective cohort study included 4,114 CRC patients who underwent surgery between December 2013 and December 2019. Patients were categorized by BMI, age, and TNM stage. Multivariate Cox regression models and Kaplan-Meier survival analyses were used to assess the impact of BMI on mortality risk, adjusting for potential confounders such as age, sex, and cancer stage.Results: Higher BMI was associated with lower mortality risk across the study population. Specifically, the protective effect of higher BMI was most pronounced in patients aged 65 and older and in those with Stage III disease. The multivariate Cox regression analysis revealed that each unit increase in BMI was associated with a 7% decrease in mortality risk. The Kaplan-Meier survival analysis showed significant survival benefits for higher BMI in patients aged 65 and older and in Stage III patients.Conclusions: Higher BMI is associated with lower mortality risk in colorectal cancer patients, particularly in those aged 65 and older and those with Stage III disease. These findings highlight the importance of considering BMI, age, and TNM stage jointly in clinical practice for CRC patients.