Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better disease-free survival (P= 0.004) and actuarial survival (P= 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.
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PMID:Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a marker for potential molecularly targeted treatment? 1644 68

Preeclampsia is a complication of pregnancy manifested as hypertension-in-pregnancy (HTN-Preg) and often intrauterine growth restriction (IUGR). Placental ischemia could be an initiating event, but the molecular mechanisms are unclear. To test the hypothesis that dimerization of matrix metalloproteinases (MMPs) plays a role in HTN-Preg and IUGR, the levels/activity of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1), and their dimerization forms were measured in the placenta, uterus, and uterine artery of normal pregnant (Preg) rats and a rat model of reduced uteroplacental perfusion pressure (RUPP). Consistent with our previous report, blood pressure (BP) was higher, pup weight was lower, and gelatin zymography showed different gelatinolytic activity for pro-MMP-9, MMP-9, pro-MMP-2 and MMP-2 in RUPP vs Preg rats. Careful examination of the zymograms showed additional bands at 200 and 135kDa. Western blots with MMP-9 antibody suggested that the 200kDa band was a MMP-9 homodimer. Western blots with TIMP-1 antibody as well as reverse zymography suggested that the 135kDa band was a MMP-9/TIMP-1 complex. The protein levels and gelatinase activity of MMP-9 homodimer were decreased while MMP-9/TIMP-1 complex was increased in placenta, uterus and uterine artery of RUPP vs Preg rats. The epidermal growth factor (EGF) receptor blocker erlotinib and protein kinase C (PKC) inhibitor bisindolylmaleimide decreased MMP-9 homodimer and increased MMP-9/TIMP-1 complex in placenta, uterus and uterine artery of Preg rats. EGF and the PKC activator phorbol-12,13-dibutyrate (PDBu) reversed the decreases in MMP-9 homodimer and the increases in MMP-9/TIMP-1 complex in tissues of RUPP rats. Thus, the increased BP and decreased pup weight in placental ischemia model of HTN-Preg are associated with a decrease in MMP-9 homodimer and an increase in MMP-9/TIMP-1 complex in placenta, uterus, and uterine artery, which together would cause a net decrease in MMP-9 activity and reduce uteroplacental and vascular remodeling in the setting of HTN-Preg and IUGR. Enhancing EGFR/PKC signaling may reverse the MMP-9 unfavorable dimerization patterns and thereby promote uteroplacental and vascular remodeling in preeclampsia.
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PMID:Decreased homodimerization and increased TIMP-1 complexation of uteroplacental and uterine arterial matrix metalloproteinase-9 during hypertension-in-pregnancy. 2850 58


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