Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Programmed cell death 4 gene (PDCD4), an in vivo repressor of transformation, was originally isolated from a human glioma library by screening it with an antibody against a nuclear antigen in proliferating cells. PDCD4 functions as a transformation repressor by inhibiting the activity of the RNA helicase, eIF4A. We previously showed that retinoids, anti-estrogens and HER2/neu antagonist induce PDCD4 expression in human breast cancer cell lines. Very little is known about the expression of PDCD4 in human breast cancer tissues or the significance of the PDCD4 expression in breast cancer. To gain insight into the pattern of the PDCD4 expression in breast tissues, we performed an immunohistochemical analysis of the PDCD4 expression in 80 archived, normal and ductal breast carcinoma tissues (invasive and carcinoma in situ) (DCIS) and correlated PDCD4 expression with expression of known prognostic markers in breast cancer (ER, PR and HER2/neu). To assess the role of methylation on PDCD4 expression in breast cancer cells, breast cancer cell lines were treated with the demethylating agent 5-deoxy-azacytidine and analyzed for PDCD4 expression. We observed primarily nuclear localization of PDCD4 in ductal carcinoma in situ compared to normal breast tissues where the PDCD4 expression was predominantly cytoplasmic. This was seen more frequently in DCIS cases that were ER positive and HER2/neu negative samples. PDCD4 expression was markedly decreased in the invasive ductal carcinoma. We did not observe any significant relationship between PDCD4 expression and the expression of RAR or PR. In T-47D, MDA-MB-435 and MDA-MB-231 cells, treatment with 5-deoxy-azacytidine did not result in an increased expression of PDCD4. The present study demonstrated altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissues. In addition, there was a decreased expression of PDCD4 in breast cancer when compared with normal breast tissue. A loss of the PDCD4 expression in breast cancer cell lines does not appear to result from hypermethylation of the PDCD4 promoter.
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PMID:Alterations in the expression of PDCD4 in ductal carcinoma of the breast. 1798 21

The selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene exert their estrogen agonist and antagonist actions depending on the target organ and individual circumstances. For instance, tamoxifen increases bone mineral density in postmenopausal patients, but decreases it in premenopausal patients when it is used as the adjuvant therapy for breast cancer in both populations. Due to positive results from recent large clinical trials for early breast cancer, the aromatase inhibitors (AIs) are the agent of first choice for postmenopausal patients. However, the veteran SERM tamoxifen is still the primary drug for premenopausal breast cancer patients, patients with ductal carcinoma in situ and subset of postmenopausal women. Recent accumulated data suggest that both raloxifene and tamoxifen could be useful in chemoprevention. Further investigation should be made into the development of a systematic strategy for application to a suitable target population, i.e., one more likely to develop hormone receptor-positive breast cancer. Unlike the AIs, SERMs have a distinct function that does not directly relate to hormone receptors when used in higher pharmacological concentration. The attempt to overcome chemo-drug resistance using high-dose SERMs would be one approach to developing such a strategy. There were several reports showing the antiproliferative effect of SERMs for estrogen receptor-negative cells, such as glioma. There are still numerous possible applications for SERMs when their intrinsic nature is utilized.
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PMID:Application of selective estrogen receptor modulators for breast cancer treatment according to their intrinsic nature. 1865 29