Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic artery ligation (HAL), transarterial embolization (TAE), and transarterial chemoembolization (TACE) have been treatment choices for unresectable hepatocellular carcinoma (HCC). Obstruction of tumor blood supply is one of the most important mechanisms of these therapeutics measures. Here we introduced HAL into a metastatic human HCC orthotopic nude mouse model (using MHCC97L and HepG2 cell lines) to examine the effects of hepatic blood flow obstruction on the metastatic potential of hepatic tumor cells, and to investigate the mechanisms underlying these effects. Our results indicated that HAL inhibited tumor growth but concomitantly elicited tumor adaptation and progression, with increased potential for invasion and distant metastases. The underlying proinvasive mechanism of HAL appeared to be associated with enhanced intratumoral hypoxia and epithelial-mesenchymal transition (EMT) due to hypoxia. This was in accord with the in vitro response of MHCC97L and HepG2 cells to hypoxia. The therapeutic effects of HAL could be enhanced by the phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002, through arrest of EMT in hepatic tumor cells. It could be useful in the development of mechanism-based combination therapies to enhance the initial antitumor response.
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PMID:Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: relevance of epithelial-mesenchymal transition. 1983 42

The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway mediates the effects of a variety of extracellular signals in a number of cellular processes including cell growth, proliferation, and survival. The alteration of integrants of this pathway through mutation of its coding genes increases the activation status of the signaling and can thus lead to cellular transformation. The frequent dysregulation of the PI3K/Akt pathway in breast cancer (BC) and the mediation of this pathway in different processes characteristically implicated in tumorigenesis have attracted the interest of this pathway in BC; however, a more comprehensive understanding of the signaling intricacies is necessary to develop clinical applications of the modulation of this pathway in this pathology. We review a series of experiments examining the contribution of alteration of integrants of this signaling network to human BC and we make an update of the information about the effect of the modulation of this pathway in this cancer.
Cancer Metastasis Rev 2010 Dec
PMID:The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. 2092 61

Mouse Kit L575P, the ortholog of human KIT L576P, a common KIT mutation found in human melanoma was expressed in an immortalized but non-transformed mouse Ink4a-Arf-deficient melanocyte cell line. The resultant Ink4a-Arf-deficient Kit L575P-expressing melanocytes exhibited increased proliferation, the ability to grow in soft agar, and increased migration. When these cells were injected subcutaneously into NOD/SCID/gamma(c) mice, melanomas arose in 5 of 7 (71%) mice. One of seven mice (14%) injected with these cells developed metastatic disease. Evaluation of signal transduction pathways downstream of constitutively activated Kit L575P revealed striking activation of the phosphatidyl inositol 3-kinase (PI3K) pathway. Inhibition of the PI3K pathway pharmacologically or genetically abolished the transformation phenotypes gained by the L575P single mutant. These studies validate this Kit L575P-activated model of melanoma and establish the PI3K pathway as a dominant signaling pathway downstream of Kit in melanoma.
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PMID:The phosphatidyl inositol 3-kinase pathway is central to the pathogenesis of Kit-activated melanoma. 2159 58