Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Objectives The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. Methods The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). Results There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. Conclusion TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable (AU)

Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. METHODS: The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. CONCLUSION: TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.

Pan-cancer analysis of the prognostic significance and oncogenic role of GXYLT2.

Growing evidence supports an oncogenic role for glucoside xylosyltransferase 2 (GXYLT2) in a number of malignancies. To evaluate the prognostic value and oncogenic function of GXYLT2 in diverse cancer types, we analyzed sequencing data from public databases on 33 tumor tissues and their corresponding normal tissues. We found that GXYLT2 was overexpressed in a number of tumors, and that its expression was positively correlated with disease progression and mortality in several major cancer types including stomach adenocarcinoma (STAD). GXYLT2 was also linked to tumor size, grade, and the immune and molecular subtypes of STAD. GO and KEGG pathway analyses of GXYLT2 co-expressed genes in STAD suggested that GXYLT2 possibly plays a role in epithelial-mesenchymal transition, extracellular matrix production and degradation, angiogenesis, apoptosis, as well as in tumor inflammation, such as cytokine production and T cell activation. Finally, prognostic nomograms were created and validated for predicting 1, 3, and 5-year survival of patients with STAD. Our findings indicate that GXYLT2 may play a role in tumorigenesis and tumor immunity, and it may serve as a prognostic marker and potential immunotherapeutic target for STAD and some other types of cancer.

Deoxythymidylate kinase (DTYMK) participates in cell cycle arrest to promote pancreatic adenocarcinoma progression regulated by miR-491-5p through TP53 and is associated with tumor immune infiltration.

Background: This study aimed to understand the mechanism of action of deoxythymidylate kinase (DTYMK) and its effect on the prognosis of patients with pancreatic cancer. So as to provide better reference value for improving the clinical management of pancreatic cancer patients. Methods: First, The Cancer Genome Atlas (TCGA) database was employed to identify DTYMK as a differentially expressed gene and to further confirm its expression and its association with the prognosis of pancreatic adenocarcinoma (PAAD) patients. Furthermore, Cox Law of Return is used for multi factor analysis. By constructing a multi factor regression model, a nomogram is constructed according to the contribution of each influencing factor in the model to the outcome variables, The GeneMania and STRING databases served as the basis for investigating the protein-gene interaction network. Moreover, to understand the correlation between DTYMK and immune cells, the TIMER and TCGA databases were explored. Then, Gene Set Enrichment Analysis (GSEA) was performed to investigate potential mechanisms of action. TargetScan was used to identify the miRNAs binding to the 3'UTR of DTYMK mRNA, and starBase was used to verify a possible link between candidate miRNAs and DTYMK. In parallel, the expression of these potential miRNAs in PAAD and their correlation with prognosis was validated through the TCGA database. Results: PAAD patients were observed to have high overall survival (OS), progression free interval (PFI), and disease-specific survival (DSS) with reduced DTYMK expression. Data from the TIMER database show that DTYMK expression inversely correlated with the infiltration levels of most immune cells. GSEA results suggested that DTYMK has a role in cell senescence, DNA repair, pyrimidine metabolism, MYC activation, TP53 control of cell cycle arrest, apoptosis, and the MAPK6/MAPK4 pathway, all of which might influence the biological processes of PAAD. Conclusions: Reduced DTYMK expression may be considered a novel prognostic biomarker for PAAD patients, associated with improved OS, DSS, and PFI. Immune escape may play an important facilitative role. Moreover, we found that miR-491-5p may negatively regulate DTYMK and participate in cell cycle arrest through TP53 to promote pancreatic cancer progression.

SOX combined with intraperitoneal perfusion of docetaxel compared with DOS regimen in the first-line therapy for advanced gastric cancer with malignant ascites: a prospective observation.

OBJECTIVE: This study aimed to verify the survival superiority of the combination of intraperitoneal perfusion and systemic chemotherapy over standard systemic chemotherapy. METHODS: A total of 78 advanced gastric cancer patients with malignant ascites were randomly divided into D-SOX group (intraperitoneal infusion of docetaxel 30 mg/m2 on d1 and d8, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14) and DOS group (intravenous docetaxel 60 mg/m2 on d1, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14). Efficacy of both groups was evaluated every 2 cycles with 21 days as a cycle. The primary endpoint was overall survival, and the secondary endpoints were objective response rate, ascites control rate, negative conversion rate of ascites cytology, and side effects. RESULTS: The median overall survival in D-SOX group was significantly higher than that in the DOS group (11.7 vs 10.3 months, HR 0.52, 95%CI 0.31-0.86, P = 0.005). The ascites control rate in the D-SOX group was 58.9% and 30.8% in DOS group (95%CI 42.8-75.1% vs 95%CI 15.6-45.9%, P = 0.012). Besides, the adverse reactions were tolerable in both groups, and patients in the D-SOX group had lower grade 3/4 blood toxicity than that in the DOS group (26% vs 54%, P = 0.01). CONCLUSION: Compared with traditional systemic chemotherapy, docetaxel intraperitoneal infusion combined with chemotherapy has better therapeutic effect on gastric cancer ascites, with better survival benefit and tolerance and less hematological toxicity, which is worthy of further research and clinical application.

The expression of Slit2 and Robo1 increased during retinoic acid syndrome in acute promyelocytic leukemia and impacted differentiated cell migration.

Retinoic acid syndrome (RAS) is a serious complication developed during the induction therapy of acute promyelocytic leukemia (APL). Cytokines and differentiated cells migration play important roles in the development of RAS. Slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) involve in cell migration. Our study aimed to investigate the expression of Slit2 and Robo1 in APL and check whether they affected promyelocytes migration. 62 cases of newly diagnosed APL patients were involved and received all-trans retinoic acid (ATRA) and arsenic trioxide as induction therapy. Bone marrow cells (BMCs) were obtained on days 0 and 28, and promyelocytes and plasma were collected from day 1 to day 21. The expression of Robo1 in promyelocytes, and that of Slit2 and cytokines, including IL-8,IL-1ß and others, in serum were monitored. 20 healthy individuals donated their cells as control. Of the 62 APL patients, 16 (25.81%) patients developed RAS. The expression of Robo1, Slit2 and IL-8 increased significantly with the development of RAS. In the 16 patients with RAS, levels of Slit2, Robo1 and IL-8 were higher during the development of RAS than before or after the RAS (P < 0.05). RhSlit2-N and rhIL-8 induced cells migration, and the migration induced by IL-8 was not inhibited by rhSlit2-N. Elevated Slit2 and Robo1 levels might be useful markers for the diagnosis and treatment of RAS. The levels of Slit2, Robo1 and IL-8 showed a positive correlation with the severity of RAS. Slit2 and IL-8 promoted the migration of differentiated cells.

The expression and biological information analysis of miR-375-3p in head and neck squamous cell carcinoma based on 1825 samples from GEO, TCGA, and peer-reviewed publications.

BACKGROUND: The specific expression level and clinical significance of miR-375-3p in HNSCC had not been fully stated, as well as the overall biological function and molecular mechanisms. Therefore, we purpose to carry out a comprehensive meta-analysis to further explore the clinical significance and potential function mechanism of miR-375-3p in HNSCC. METHODS: HNSCC-related data was gained from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and peer-reviewed journals. A meta-analysis was carried out to comprehensively explore the relationship between miR-375-3p expression level and clinicopathological features of HNSCC. And summary receiver operating characteristic (SROC) curve analysis was applied for evaluating disease diagnosis value of miR-375-3p. In addition, a biological pathway analysis was also performed to assess the possible molecular mechanism of miR-375-3p in HNSCC. RESULTS: A total of 24 available records and references were added into analysis. The overall pooled meta-analysis outcome revealed a relatively lower expression level of miR-375-3p in HNSCC specimens than that in non-cancerous controls (P < 0.001). And SROC curve analysis showed that the pooled area under the SROC curve (AUC) was 0.90 (95%CI: 0.88-0.93). In addition, biological pathway analysis indicated that LAMC1, EDIL3, FN1, VEGFA, IGF2BP2, and IGF2BP3 maybe the latent target genes of miR-375-3p, which were greatly enriched in the pathways of beta3 integrin cell surface interactions and the binding of RNA via the insulin-like growth factor-2 mRNA-binding protein (IGF2BPs/IMPs/VICKZs). CONCLUSION: MiR-375-3p expression clearly decreased in HNSCC samples compared with non-cancerous controls. Meanwhile, miR-375-3p may serve as a tumor suppressor via regulating tumor-related genes LAMC1, EDIL3, FN1, VEGFA, IGF2BP2, and IGF2BP3 in HNSCC.