ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Many important advances have been made in the phenotypic and genetic characterization of malignant tumors since the publication of Peter Nowell’s seminal article on the origin of cancer, but there has been no consistent effort to incorporate this wealth of knowledge into a general model of carcinogenesis. Current theoretical discussions on cancer are frequently dominated by attempts to categorize genetic alterations and phenotypic characteristics and establish correspondences between them. In this article, I argue, on the basis of recent data as well as “old” observations, that a developmental error leading to the acquisition of a unique cell character (de-differentiation) underlies all phenotypic characteristics of cancer cells and discuss how this notion can be reconciled with Nowell’s model of carcinogenesis as a microevolutionary process into an updated theoretical description of cancer.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Environment or genetic constitutions can lead to an increase of genetic or epigenetic events and increase the risk for malignancy. Genomic instability is seen in most types of malignancies. Two forms of genetic instability have been described in colorectal cancer: chromosomal instability (CIN), and microsatellite instability (MIN). Almost all sporadic MIN tumors occur in the proximal colon, whereas most sporadic CIN tumors are distributed in the distal colon. The two familial syndromes, familial adenomatous polyposis and Lynch syndrome, constitute models for the different carcinogenic mechanisms in CIN and MIN tumors, respectively. This article reviews the principal differences between CIN and MIN tumors, evidence for a proximal and distal route in carcinogenesis, gender differences, and aspects of methylation in CIN and MIN colorectal tumorigenesis.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Transforming growth factor-β is believed to play a dual role in carcinogenesis. Through its ability to inhibit cellular proliferation it suppresses tumor development in its early stages, but in the course of tumor progression malignant cells often acquire resistance to growth inhibition by transforming growth factor-β and themselves secrete large amounts of this cytokine. Transforming growth factor-β furthers malignant progression in two ways: for one, it acts on nontransformed cells present in the tumor mass to suppress antitumor immune responses and to augment angiogenesis. Secondly, it promotes invasion and the formation of metastases in a cell-autonomous manner that requires transforming growth factor-β signaling activity, albeit at reduced levels, to be present in the tumor cells themselves.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Peroxisome proliferator-activated receptors are nuclear receptors that were isolated for their ability to modulate lipid metabolism. Similar to other members of the nuclear receptor family, peroxisome proliferator-activated receptors bind ligand as heterodimers and exert their effects via transcriptional regulation through their DNA binding domains. During the past decade, it has become clear that peroxisome proliferator-activated receptors also contribute to a variety of different biologic processes, including atherosclerosis, insulin resistance, and more recently, cancer. In this review, we discuss the evidence for the different peroxisome proliferator-activated receptors’ roles in tumorigenesis and also their potential application for the treatment and prevention of neoplastic diseases.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID