Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer, which is responsible for >90% of exocrine pancreatic tumours, is typically a disease of the elderly (> or =70 years of age). However, older patients are less likely to be staged than younger patients despite having a worse overall 5-year survival rate than their younger counterparts. Various radiological, ultrasonographic and endoscopic investigations are used not only as diagnostic tools but also to accurately stage the cancer for possible surgery. Many patients with pancreatic cancer have mutations of the K-ras oncogene, and various tumour suppressor genes are also inactivated. Pancreas resection can be performed in elderly resectable patients without excess mortality, even in those >80 years of age. However, treatment for locally advanced, unresectable and metastatic pancreatic cancer is palliative. Fluorouracil-based chemoradiation for locally advanced or unresectable cancer, and gemcitabine for patients with metastatic disease, can result in clinical benefits. Placement of a stent in the biliary tract has been shown to improve symptoms of obstructive jaundice or ascites, as well as quality of life. As molecular targets are identified, interventions with targeted specific agents may improve tumour control. However, further studies will be needed to demonstrate whether or not various agents targeting signal transduction pathways or nuclear transcription factors are useful for elderly patients with advanced pancreatic cancer.
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PMID:Current treatment strategies for pancreatic cancer in the elderly. 1682 93

Smad4 is a tumour suppressor gene frequently deleted in pancreatic cancer. To investigate the roles of Smad4 deficiency in invasive and matastatic capabilities of pancreatic cancer, we examined the effects of Smad4 deficiency on regulation of the invasion suppressor E-cadherin in pancreatic cancer cell line PANC-1. TGF-beta decreased expression of E-cadherin and beta-catenin proteins at the plasma membrane, increased Snail and Slug mRNA expression, and induced fibroblastoid morphology in PANC-1 cells. These effects of TGF-beta were abrogated in Smad4-knocked-down PANC-1 cells. We also found that TGF-beta-induced down-regulation of E-cadherin expression was partially inhibited in Snail- and Slug-knocked-down PANC-1 cells. Thus, Smad4 mediates down-regulation of E-cadherin induced by TGF-beta in PANC-1 cells, at least in part, through Snail and Slug induction. These results suggest that Smad4 deficiency observed in invasive and metastatic pancreatic cancer might not be linked to the loss of E-cadherin.
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PMID:Smad4 is essential for down-regulation of E-cadherin induced by TGF-beta in pancreatic cancer cell line PANC-1. 1730 Oct 79