Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients

S. Yamagishi, K. Nakamura, Hiroyoshi Inoue, S. Kikuchi, M. Takeuchi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Colorectal cancer is a major public health problem, being the second most common cause of cancer in developed countries. Several epidemiological studies have reported moderately increased risks of colorectal cancer in diabetic patients compared with general population. However, the underlying molecular link between diabetes and colorectal cancer remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs-RAGE interactions stimulated the growth of human pancreatic cancer cells through the autocrine induction of platelet-derived growth factor-B. Furthermore, we have recently found that AGEs stimulated the growth and migration of cultured human melanoma cells and that anti-RAGE antibodies inhibited tumor formation and lung metastasis of melanoma cell xenografts and subsequently improved survival in athymic mice. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and colorectal cancer. In this paper, we would like to propose the possible ways of testing our hypotheses. Is elevation of serum AGE levels a risk factor for colorectal cancer in patients with diabetes? Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for colorecetal cancer in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for colorectal cancer as well? Furthermore, are increased levels of AGEs and RAGE in colorectal cancer associated with poor prognosis in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and colorectal cancer.

Original languageEnglish
Pages (from-to)1208-1210
Number of pages3
JournalMedical Hypotheses
Volume64
Issue number6
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Colorectal Neoplasms
Metformin
Melanoma
Pyridoxamine
Proto-Oncogene Proteins c-sis
Diabetic Angiopathies
Neoplasms
Growth
Pancreatic Neoplasms
Developed Countries
Heterografts
Nude Mice
Epidemiologic Studies
Anti-Idiotypic Antibodies
Atherosclerosis
Diabetes Mellitus
Public Health
Neoplasm Metastasis
Lung

ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)
  • Drug Discovery

Cite this

Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients. / Yamagishi, S.; Nakamura, K.; Inoue, Hiroyoshi; Kikuchi, S.; Takeuchi, M.

In: Medical Hypotheses, Vol. 64, No. 6, 2005, p. 1208-1210.

Research output: Contribution to journalArticle

Yamagishi, S. ; Nakamura, K. ; Inoue, Hiroyoshi ; Kikuchi, S. ; Takeuchi, M. / Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients. In: Medical Hypotheses. 2005 ; Vol. 64, No. 6. pp. 1208-1210.
@article{1d26093443c043c09470a0e3b1b068bb,
title = "Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients",
abstract = "Colorectal cancer is a major public health problem, being the second most common cause of cancer in developed countries. Several epidemiological studies have reported moderately increased risks of colorectal cancer in diabetic patients compared with general population. However, the underlying molecular link between diabetes and colorectal cancer remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs-RAGE interactions stimulated the growth of human pancreatic cancer cells through the autocrine induction of platelet-derived growth factor-B. Furthermore, we have recently found that AGEs stimulated the growth and migration of cultured human melanoma cells and that anti-RAGE antibodies inhibited tumor formation and lung metastasis of melanoma cell xenografts and subsequently improved survival in athymic mice. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and colorectal cancer. In this paper, we would like to propose the possible ways of testing our hypotheses. Is elevation of serum AGE levels a risk factor for colorectal cancer in patients with diabetes? Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for colorecetal cancer in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for colorectal cancer as well? Furthermore, are increased levels of AGEs and RAGE in colorectal cancer associated with poor prognosis in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and colorectal cancer.",
author = "S. Yamagishi and K. Nakamura and Hiroyoshi Inoue and S. Kikuchi and M. Takeuchi",
year = "2005",
doi = "10.1016/j.mehy.2005.01.015",
language = "English",
volume = "64",
pages = "1208--1210",
journal = "Medical Hypotheses",
issn = "0306-9877",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients

AU - Yamagishi, S.

AU - Nakamura, K.

AU - Inoue, Hiroyoshi

AU - Kikuchi, S.

AU - Takeuchi, M.

PY - 2005

Y1 - 2005

N2 - Colorectal cancer is a major public health problem, being the second most common cause of cancer in developed countries. Several epidemiological studies have reported moderately increased risks of colorectal cancer in diabetic patients compared with general population. However, the underlying molecular link between diabetes and colorectal cancer remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs-RAGE interactions stimulated the growth of human pancreatic cancer cells through the autocrine induction of platelet-derived growth factor-B. Furthermore, we have recently found that AGEs stimulated the growth and migration of cultured human melanoma cells and that anti-RAGE antibodies inhibited tumor formation and lung metastasis of melanoma cell xenografts and subsequently improved survival in athymic mice. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and colorectal cancer. In this paper, we would like to propose the possible ways of testing our hypotheses. Is elevation of serum AGE levels a risk factor for colorectal cancer in patients with diabetes? Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for colorecetal cancer in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for colorectal cancer as well? Furthermore, are increased levels of AGEs and RAGE in colorectal cancer associated with poor prognosis in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and colorectal cancer.

AB - Colorectal cancer is a major public health problem, being the second most common cause of cancer in developed countries. Several epidemiological studies have reported moderately increased risks of colorectal cancer in diabetic patients compared with general population. However, the underlying molecular link between diabetes and colorectal cancer remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs-RAGE interactions stimulated the growth of human pancreatic cancer cells through the autocrine induction of platelet-derived growth factor-B. Furthermore, we have recently found that AGEs stimulated the growth and migration of cultured human melanoma cells and that anti-RAGE antibodies inhibited tumor formation and lung metastasis of melanoma cell xenografts and subsequently improved survival in athymic mice. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and colorectal cancer. In this paper, we would like to propose the possible ways of testing our hypotheses. Is elevation of serum AGE levels a risk factor for colorectal cancer in patients with diabetes? Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for colorecetal cancer in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for colorectal cancer as well? Furthermore, are increased levels of AGEs and RAGE in colorectal cancer associated with poor prognosis in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and colorectal cancer.

UR - http://www.scopus.com/inward/record.url?scp=17044434656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17044434656&partnerID=8YFLogxK

U2 - 10.1016/j.mehy.2005.01.015

DO - 10.1016/j.mehy.2005.01.015

M3 - Article

VL - 64

SP - 1208

EP - 1210

JO - Medical Hypotheses

JF - Medical Hypotheses

SN - 0306-9877

IS - 6

ER -