Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The emergence of hepatocellular carcinoma (HCC) is thought to be a stepwise process, with high-grade dysplastic nodules (HGDN) representing premalignant lesions arising in a background of cirrhosis. Earlier studies have revealed altered expression of transforming growth factor-alpha (TGF-alpha) (a mitogen capable of inducing hepatocarcinogenesis in mice) in HCC and its surrounding parenchyma. DNA topoisomerase II-alpha (Topo II-alpha) is a nuclear protein targeted by several chemotherapeutic agents and is overexpressed in HCC. The expression of both TGF-alpha and Topo II-alpha in putative preneoplastic hepatocytic lesions, however, has not been extensively studied. We examined the patterns of TGF-alpha and Topo II-alpha expression in noncirrhotic liver, liver cirrhosis, low-grade dysplastic nodules (LGDN), HGDN, and HCC to define the possible relationships of these markers to tumor progression. Paraffin sections from formalin-fixed material were immunostained with antibodies against TGF-alpha, Topo II-alpha, and Ki-67. Forty-six HCC, 17 HGDN, and 12 low-grade dysplastic nodules were identified in 52 cirrhotic livers from explanted or resected specimens. Nuclear staining for Ki-67 and Topo II-alpha was significantly increased in the progression from cirrhosis, through HGDN, to HCC, whereas the scores for TGF-alpha in these lesions showed an inverse relationship. In comparison with 18 HCC arising in noncirrhotic livers, the expression of TGF-alpha is significantly stronger in cirrhotic liver than in noncirrhotic parenchyma and its expression is also stronger in HCC arising in cirrhosis than in HCC arising in noncirrhotic parenchyma. The increased expression of Topo II-alpha and Ki-67 from HGDN to HCC, when compared with cirrhosis, suggests that HGDN is a precursor lesion in hepatocarcinogenesis. The inverse relationship between these proliferative markers and TGF-alpha expression in these lesions and stronger expression of TGF-alpha in HCC arising in cirrhosis suggest that TGF-alpha may play an important role in the early events of liver carcinogenesis.
 ...
PMID:The expression of transforming growth factor-alpha in cirrhosis, dysplastic nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases. 1746 Apr 50

The ADAMs (a disintegrin and metalloproteinase) comprise a family of multidomain transmembrane and secreted proteins. One of their best-established roles is the release of biologically important ligands, such as tumor necrosis factor-alpha, epidermal growth factor, transforming growth factor-alpha, and amphiregulin. Because these ligands have been implicated in the formation and progression of tumors, it might be expected that the specific ADAMs involved in their release would also be involved in malignancy. Consistent with this hypothesis, emerging data from model systems suggest that ADAMs, such as ADAM-9, ADAM-12, ADAM-15, and ADAM-17, are causally involved in tumor formation/progression. In human cancer, specific ADAMs are up-regulated, with levels generally correlating with parameters of tumor progression and poor outcome. In preclinical models, selective ADAM inhibitors against ADAM-10 and ADAM-17 have been shown to synergize with existing therapies in decreasing tumor growth. The ADAMs are thus a new family of potential targets for the treatment of cancer, especially malignancies that are dependent on human epidermal growth factor receptor ligands or tumor necrosis factor-alpha.
 ...
PMID:Role of ADAMs in cancer formation and progression. 1922 19


<< Previous 1 2 3