Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.
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http://dx.doi.org/10.1158/1940-6207.CAPR-12-0249 | DOI Listing |
Mol Biol Rep
January 2025
Department of Molecular Biology Vadi Kampüsü, Istanbul Atlas University, Anadolu Cd., No 40, Kağıthane, Istanbul, 34408, Turkey.
Background: Modulation of protein synthesis according to the physiological cues is maintained through tight control of Eukaryotic Elongation Factor 2 (eEF2), whose unique translocase activity is essential for cell viability. Phosphorylation of eEF2 at its Thr56 residue inactivates this function in translation. In our previous study we reported a novel mode of post-translational modification that promotes higher efficiency in T56 phosphorylation.
View Article and Find Full Text PDFEgypt J Immunol
January 2025
Department of Clinical Pathology, Faculty of Medicine Ain Shams University, Cairo, Egypt.
The worldwide incidence of colorectal cancer (CRC) is roughly two million new instances each year throughout the world, according to the World Health Organization 2022. CRC is the third most prevalent disease and the second most common cancer in terms of fatality. People diagnosed with colorectal cancer in the early stages have a five-year survival rate of roughly 95%, but people identified with the disease in the later stages have a survival rate of approximately 12%.
View Article and Find Full Text PDFCureus
December 2024
Upper Gastrointestinal Surgery, North Manchester General Hospital, Manchester, GBR.
Non-Meckel small bowel diverticula, particularly ileal diverticula, are rare, especially when incarcerated within an inguinal hernia sac. This case involves an 80-year-old man who presented with a newly noticed tender, irreducible lump in his left groin, accompanied by symptoms of bowel obstruction such as inability to pass flatus and vomiting. His medical history included a previous right inguinal hernia repair.
View Article and Find Full Text PDFCureus
December 2024
Comprehensive Colorectal Center, Department of Surgery, Children's Mercy Kansas City, Kansas City, USA.
Long-segment Hirschsprung disease (HSCR) presents significant challenges in surgical management, often requiring extensive bowel mobilization and creative techniques to achieve tension-free anastomosis. Colonic derotation offers a viable solution for preserving bowel length and maintaining the ileocecal valve, which is crucial for postoperative bowel function. The procedure involves extensive colonic mobilization and strategic vascular divisions of the right and middle colic vessels while preserving the ileocolic and marginal arteries, followed by a 180° counterclockwise rotation of the colon around the ileocolic vascular axis.
View Article and Find Full Text PDFAnn Gastroenterol
December 2024
Gastroenterology Unit, Nuovo Regina Margherita Hospital, Rome, (Sabrina Berardi, Angelo Zullo); Italy.
Background: Data on the potential association between diverticulosis and colonic neoplastic lesions are still controversial. We investigated this issue in subjects who underwent screening colonoscopy.
Methods: We reviewed the data of subjects with a positive fecal immunological test who underwent a first colonoscopy in the national colorectal screening program.
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