Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

RhoB expression associated with chemotherapy response and prognosis in colorectal cancer

Abstract Purpose To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. Materials and methods The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. Results All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. Conclusion RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival

Additional file 1 of RhoB expression associated with chemotherapy response and prognosis in colorectal cancer

Additional file 1: Figure S1. Figure showing the protein level of RhoB in all the selected cell lines. Figure S2. Figure showing the statistical differences of RhoB WT vs KO/OE cell lines. Figure S3. KEGG pathway analysis of DEGs in HCT116 and SW480 cells after treatment with 5-fluorouracil (5-FU) and oxaliplatin (OXL). Figure S4. KEGG pathway network analysis of DEGs in HCT116 cells after treatment with 5-fluorouracil (5-FU). Figure S5. KEGG pathway network analysis of DEGs in HCT116 cells after treatment with oxaliplatin (OXL). Figure S6. The overall haddock score of all clusters generated for the RhoB and caspase 3 interaction. Figure S7. Gene ontology (GO) biological process and KEGG pathway analysis of overlapping RhoB OE up-regulated and KO down-regulated genes

Podoplanin: An emerging cancer biomarker and therapeutic target

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.Funding Agencies|Proteintech; Fox Rothschild; VWR; Sentrimed; Rowan University; Osteopathic Heritage Foundation; New Jersey Health Foundation; JSPS KAKENHI [25461674, 24659185, 16H05311, 2617H06356]; National Cancer Center Research and Development Fund [23-A-12]; Foundation for the Promotion of Cancer Research; 3rd Term Comprehensive 10-Year Strategy for Cancer Control; Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO); British Heart Foundation [RG/13/18/30563]; Project for Cancer Research and Therapeutic Evolution (P-CREATE) [17cm0106205 h0002]; Medical Research and Development Programs Focused on Technology Transfer, Acceleration Transformative Research for Medical Innovation (ACT-MS) from the Japan Agency for Medical Research and Development (AMED) [17im0210607 h0002]</p