التفاصيل البيبلوغرافية
| العنوان: |
A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index |
| المؤلفون: |
Zell, Jason A, McLaren, Christine E, Morgan, Timothy R, Lawson, Michael J, Rezk, Sherif, Albers, C Gregory, Chen, Wen-Pin, Carmichael, Joseph C, Chung, Jinah, Richmond, Ellen, Rodriguez, LM, Szabo, Eva, Ford, Leslie G, Pollak, Michael N, Meyskens, Frank L |
| المصدر: |
Cancer Prevention Research, vol 13, iss 2 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2020 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Nutrition, Colo-Rectal Cancer, Clinical Research, Cancer, Prevention, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adenoma, Administration, Oral, Aged, Biomarkers, Tumor, Biopsy, Body Mass Index, Colonic Polyps, Colonoscopy, Colorectal Neoplasms, Female, Humans, Intestinal Mucosa, Intestine, Large, Male, Metformin, Middle Aged |
| جغرافية الموضوع: |
203 - 212 |
| الوصف: |
Obesity is associated with risk of colorectal adenoma (CRA) and colorectal cancer. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps. We hypothesized that metformin would affect colorectal tissue S6Ser235 among obese patients with recent history of CRA. A phase IIa clinical biomarker trial was conducted via the U.S. National Cancer Institute-Chemoprevention Consortium. Nondiabetic, obese subjects (BMI ≥30) ages 35 to 80 with recent history of CRA were included. Subjects received 12 weeks of oral metformin 1,000 mg twice every day. Rectal mucosa biopsies were obtained at baseline and end-of-treatment (EOT) endoscopy. Tissue S6Ser235 and Ki-67 immunostaining were analyzed in a blinded fashion using Histo score (Hscore) analysis. Among 32 eligible subjects, the mean baseline BMI was 34.9. Comparing EOT to baseline tissue S6Ser235 by IHC, no significant differences were observed. Mean (SD) Hscore at baseline was 1.1 (0.57) and 1.1 (0.51) at EOT; median Hscore change was 0.034 (P = 0.77). Similarly, Ki-67 levels were unaffected by the intervention. The adverse events were consistent with metformin's known side-effect profile. Among obese patients with CRA, 12 weeks of oral metformin does not reduce rectal mucosa pS6 or Ki-67 levels. Further research is needed to determine what effects metformin has on the target tissue of origin as metformin continues to be pursued as a colorectal cancer chemopreventive agent. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt2sp0q0gm; https://escholarship.org/uc/item/2sp0q0gmTest |
| الإتاحة: |
https://escholarship.org/uc/item/2sp0q0gmTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.7CCA8FFE |
| قاعدة البيانات: |
BASE |
