ABSTRACT
BACKGROUND: Na+/K+-ATPase α1 subunit (ATP1A1) exhibits aberrant expression in various types of cancer. Moreover, its levels in specific tissues are associated with the development of cancer. Nevertheless, the mechanism and signaling pathways underlying the effects of ATP1A1 in colon cancer (CC) have not been elucidated, and its prognostic impact remains unknown. METHODS: Knockdown of ATP1A1 expression was performed in human CC cell lines HT29 and Caco2 using small interfering RNA. The roles of ATP1A1 in various biological processes of cells (i.e., proliferation, cell cycle, apoptosis, migration, and invasion) were assessed. Microarray analysis was utilized for gene expression profiling. Samples obtained from 200 patients with CC who underwent curative colectomy were analyzed through immunohistochemistry. RESULTS: ATP1A1 knockdown suppressed cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that the upregulated or downregulated gene expression in ATP1A1-depleted cells was related to the extracellular signal-regulated kinase 5 (ERK5) signaling pathway [epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase 5 (MAP2K5), mitogen-activated protein kinase 7 (MAPK7), FOS, MYC, and BCL2 associated agonist of cell death (BAD)]. Immunohistochemical analysis demonstrated a correlation between ATP1A1 expression and pathological T stage (p = 0.0054), and multivariate analysis identified high ATP1A1 expression as an independent predictor of poor recurrence-free survival in patients with CC (p = 0.0040, hazard ratio: 2.807, 95% confidence interval 1.376-6.196). CONCLUSIONS: ATP1A1 regulates tumor progression through the ERK5 signaling pathway. High ATP1A1 expression is associated with poor long-term outcomes in patients with CC.
Subject(s)
Clinical Relevance , Colonic Neoplasms , Humans , Caco-2 Cells , Sodium-Potassium-Exchanging ATPase/genetics , Sodium-Potassium-Exchanging ATPase/metabolism , Sodium-Potassium-Exchanging ATPase/pharmacology , Cell Proliferation , Colonic Neoplasms/genetics , Cell Line, TumorABSTRACT
BACKGROUND: Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. METHODS: We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. RESULTS: We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CONCLUSIONS: CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.
Subject(s)
Blood Glucose Self-Monitoring/methods , Blood Glucose/analysis , Dumping Syndrome/diagnosis , Gastrectomy/adverse effects , Hypoglycemia/diagnosis , Quality of Life , Stomach Neoplasms/surgery , Aged , Dumping Syndrome/etiology , Dumping Syndrome/metabolism , Dumping Syndrome/pathology , Female , Follow-Up Studies , Humans , Hypoglycemia/etiology , Hypoglycemia/metabolism , Hypoglycemia/pathology , Male , Middle Aged , Prognosis , Stomach Neoplasms/pathology , Surveys and QuestionnairesABSTRACT
Anal canal adenocarcinoma with pagetoid spread has different a treatment strategy and prognosis from extramammary perianal Paget disease. We report two cases of anal canal adenocarcinoma with pagetoid spread along with a literature review. Case 1: A 69-year-old woman complained of perianal pain, redness, and erosion. Biopsy revealed adenocarcinoma with pagetoid spread. Laparoscopic abdominoperineal resection was performed, which resulted in 12 months' survival without postoperative recurrence. Case 2: A 62-year-old man complained of fecal occult blood and hemorrhoid. Under the diagnosis of anal canal cancer, transanal tumor resection was performed. Five years after surgery, he underwent endoscopic submucosal dissection for anal canal cancer. Ten years after surgery, he complained of anal tumor and perianal redness. Biopsy revealed adenocarcinoma with pagetoid spread. Laparoscopic abdominoperineal resection was performed, which resulted in 10 months' survival without postoperative recurrence.
