Background: Hyperthermia is used as an adjunctive treatment for gastric cancer; however, the corresponding antitumor mechanism remains unclear.
Objective: To investigate the expression of PLEK2 in gastric cancer and the mechanism by which hyperthermia inhibits gastric cancer progression and participating in immunomodulation.
Methods: PLEK2 was screened by combining microarray analysis with gene knockdown and proliferation assays. Analysis based on the TCGA database, GEPIA website, and detection of clinical samples was employed to investigate the expression and correlation of PLEK2 and PD-L1. Knockdown of the expression PLEK2, subsequent experiments including western blotting, RT-qPCR, cell functional assays, and flow cytometry were used to assess the effects on cell migration, invasion, viability, and apoptosis. Intervention with hyperthermia to explore its effects. To evaluate the impact on immunity by detecting T cell proliferation and the release of IFNγ, activated T cells were co-cultured with the target cells.
Results: Hyperthermia significantly reduced the expression of PLEK2 and PD-L1, while both were increased in gastric cancer. Knockdown of PLEK2 inhibited PD-L1 expression and significantly inhibited the proliferation, invasion, migration, and viability of gastric cancer cells. A decrease in PLEK2 expression promotes cell apoptosis. Although it cannot affect the proliferation of activated T cells, it can partially reverse IFNγ suppression.
Conclusion: PLEK2 plays a promoting role in gastric cancer, and hyperthermia downregulates PLEK2/PD-L1, which further inhibits cell proliferation, invasion, and migration, promotes cell apoptosis, and possibly participates in immune regulation.
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http://dx.doi.org/10.1016/j.gene.2023.148111 | DOI Listing |
J Cancer
January 2025
Department of Gastroenterology and Respiratory Internal Medicine & Endoscopy Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, P.R. China.
While previous studies have established the role of exosomal miR-552-5p in promoting gastric cancer (GC) progression, the exact mechanisms through which it modulates the PD-1/PD-L1 axis to affect NK cell function and subsequently influence GC epithelial-mesenchymal transition (EMT) remain to be elucidated. Western blot, transmission electron microscopy (TEM), and nanoparticle tracking analysis were used to characterize exosomes that were isolated from GC cell supernatants. Subcutaneous AGS cell injections expressing either Lv-miR-552-5p or Lv-NC were administered to nude BALB/C mice.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Gastric Cancer Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Chemoresistance severely deteriorates the prognosis of advanced gastric cancer (GC) patients. Several studies demonstrated that (HP)-positive GC patients showed better outcomes after receiving chemotherapy than HP-negative ones. This study aims to confirm the role of HP in GC chemotherapy and to study the underlying mechanisms.
View Article and Find Full Text PDFCureus
December 2024
Digestive Surgery, Cho Ray Hospital, Ho Chi Minh City, VNM.
The management of gastrointestinal anastomotic leaks post surgery is a considerable challenge, characterized by elevated morbidity and mortality, particularly in cases of esophageal-jejunal anastomotic leaks. Diverse endoscopic intervention techniques have been utilized with enhanced success. We present a case where a 57-year-old patient with Siewert type II esophageal cardia cancer underwent endoscopic deployment of a fully covered stent into a fistula resulting from anastomotic leakage, following a laparoscopic proximal gastrectomy with Roux-en-Y and double tract reconstruction.
View Article and Find Full Text PDFFront Pharmacol
December 2024
State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Aim: Programmed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.
Methods: We analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses.
Front Oncol
December 2024
Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Background: Gastric cancer (GC) is a significant public health concern in the USA, and its burden is on the rise.
Methods: This study utilized the latest data from the Global Burden of Disease (GBD) study. We provided descriptive statistics on the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) of GC across the USA and states.
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