Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen is known to stimulate endothelial nitric oxide production and attenuate endothelial dysfunction after ischemia and reperfusion. However, estrogen therapy increases the risk of breast and endometrial cancer. The present study was designed to determine whether idoxifene, a selective estrogen receptor modulator without adverse effects on reproductive organs, may stimulate nitric oxide release and protect endothelial function. In U-46619 precontracted superior mesenteric arterial (SMA) segments isolated from ovariectomized rats, idoxifene and 17 beta-estradiol resulted in a comparable dose-dependent vasorelaxation (maximal relaxation: 75.3 +/- 4.9 and 71 +/- 4.7%, respectively). Treatment of the rings with N(omega)-nitro-L-arginine methyl ester completely blocked idoxifene- and 17 beta-estradiol-induced vasorelaxation. In vitro incubation of SMA rings with TNF alpha significantly reduced vasorelaxation to an endothelium-dependent vasodilator, acetylcholine (maximal relaxation: 73 +/- 3.7 versus 95 +/- 2.9% pre-TNF alpha, P <.01). Idoxifene, but surprisingly not 17 beta-estradiol, prevented TNF alpha-induced endothelial dysfunction (maximal relaxation: 86 +/- 2.6% in idoxifene-treated rings and 77 +/- 5.1% in 17beta-estrogen-treated rings). In vivo ischemia and reperfusion resulted in significant endothelial dysfunction as evidenced by decreased vasorelaxation to acetylcholine (maximal relaxation: 48 +/- 5.5 versus 92 +/- 3.9% in normal SMA rings), but a normal relaxation response to an endothelium-independent vasodilator, acidified NaNO(2) (95 +/- 3.2%). Treatment with idoxifene at either 1 or 2 mg/kg/day, or 17beta-estrogen at 1 mg/kg/day for 4 days significantly preserved endothelial function (P <.01 versus vehicle). Taken together, these results demonstrate that idoxifene is an endothelium-dependent vasodilator and exerts significant endothelial protective effects against TNF alpha- and ischemia-reperfusion-induced endothelial injury. These results suggest that selective estrogen receptor modulators have therapeutic potential in diseases where endothelial dysfunction plays an important role.
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PMID:Nitric oxide stimulatory and endothelial protective effects of idoxifene, a selective estrogen receptor modulator, in the splanchnic artery of the ovariectomized rat. 1104 19

Heat shock proteins (Hsp) are cytoplasmic proteins that act as molecular chaperones for protein molecules in various intra-cellular processes. They play an important role in protein-protein interactions, including folding and conformation, and prevention of inappropriate protein aggregation. They are called "heat shock proteins" since they were first discovered in cells exposed to high temperatures. However, their synthesis is also accentuated under other stress conditions, such as exposure of the cell to inflammation, infection, ischemia, toxins, cytotoxic drugs and malignant transformation. Hsp have been classified into families according to their molecular weight. In ovarian carcinoma, over-expression of Hsp27 was associated with increased resistance to chemotherapy and a worse prognosis. In endometrial carcinoma, over-expression of Hsp70 was associated with poorly differentiated tumors and a worse prognosis, whereas over-expression of Hsp27 and Hsp90 were associated with well-differentiated tumors and better prognosis. The association between increasing expression of Hsp90 and better differentiation and prognosis seems to reflect high levels of sex steroid receptors in well-differentiated endometrial carcinomas. In cervical carcinoma, the presence of Hsp70 was associated with a worse outcome. Since Hsp are highly antigenic, their property to bind with tumor proteins and proteins produced by viruses may be used for the development of vaccines against cancers and viral diseases. It is speculated that examination of the lower genital tract secretions for IgA antibodies against Hsp will contribute to early detection of malignancies. Since Hsp may affect the growth of the tumor and its response to chemotherapy, it is speculated that using drugs that inhibit Hsp in combination with conventional chemotherapy may contribute to the improvement of the treatment results.
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PMID:[Heat shock proteins and malignancies of the female genital tract]. 1247 32