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)

GHRH is produced in a variety of extrahypothalamic tissues, including some neoplasms. We have previously reported that GHRH antagonists can inhibit the growth of various human cancers xenografted into nude mice. These observations suggest that locally produced GHRH might directly affect tumor cell proliferation. To investigate this possibility, we have examined the local production of GHRH in human endometrial, ovarian, and breast cancers obtained after surgery or grown in nude mice as xenografts. We have also examined whether the GHRH produced in these tumors is biologically active. RT-PCR and Southern blotting showed expression of messenger ribonucleic acid for GHRH in 17 of 22 endometrial and 17 of 22 ovarian cancer specimens and in all of the human endometrial, ovarian, and breast cancer xenografts studied. Acid extracts of endometrial cancer specimens and breast cancer xenografts that expressed the GHRH gene contained immunoreactive GHRH peptide, as assessed by RIA for GHRH. The level of immunoreactive GHRH detected was equivalent to 2.7-6.4 ng GHRH-(1-29)/g tissue. Purified extract from one of these tumor samples induced a powerful stimulation of GH release from rat pituitary cells. The presence of biologically and immunologically active GHRH and messenger ribonucleic acid for GHRH in human breast, endometrial, and ovarian cancers supports the hypothesis that locally produced GHRH may play a role in the proliferation of these tumors.
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PMID:Expression of growth hormone-releasing hormone (GHRH) messenger ribonucleic acid and the presence of biologically active GHRH in human breast, endometrial, and ovarian cancers. 1002 20

Antagonists of GHRH are being developed for the treatment of various cancers. In this study we investigated in vivo and in vitro the effects of the GHRH antagonist MZ-J-7-118 and its mechanism of action in HEC-1A human endometrial cancer. Treatment of nude mice bearing HEC-1A xenografts with 10 mug/d MZ-J-7-118 for 6 wk significantly inhibited the volume of HEC-1A tumors by 43%, tumor weight by 40% compared with controls and prolonged the tumor doubling time from 18.7 +/- 1.4 to 25.4 +/- 3.8 d. Administration of 20 mug MZ-J-7-118, sc, twice a day significantly (P < 0.05) decreased HEC-1A growth, as evidenced by a 57.9% decrease in tumor volume, a 50.7% reduction in tumor weight, and the extension of tumor doubling time from 17.5 +/- 2.8 to 36.4 +/- 6.5 d. Therapy with GHRH antagonists significantly decreased serum IGF-I levels in experiment 1, and significantly increased tumoral IGF-I levels in experiment 2 in treated mice. Levels of IGF-II and vascular endothelial growth factor-A in tumors were not changed. Specific high affinity binding sites for GHRH were found on HEC-1A tumor membranes using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-118 displaced radiolabeled JV-1-42 with an IC(50) of 0.13 +/- 0.04 nm. The expression of mRNA for GHRH and splice variants of the GHRH receptor in HEC-1A tumors was demonstrated by real-time RT-PCR analysis. HEC-1A cells cultured in vitro secreted GHRH into the medium. The GHRH antagonist MZ-J-7-118 inhibited the growth of HEC-1A cells in vitro. Our results indicate that GHRH antagonists can reduce the growth of human endometrial cancer and could be used as an alternative adjuvant therapy for the management of endometrial cancer.
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PMID:Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone. 1578 1

More than 25% of patients diagnosed with endometrial carcinoma have invasive primary cancer accompanied by metastases. Growth hormone-releasing hormone (GHRH) plays an important role in reproduction. Here, we examined the effect of a GHRH antagonist on the motility of endometrial cancer cells and the mechanisms of action of the antagonist in endometrial cancer. Western blotting and immunohistochemistry (IHC) were used to determine the expression of the GHRH receptor protein. The activity of Twist and N-cadherin was determined by Western blotting. Cell motility was assessed by an invasion and migration assay. GHRH receptor siRNA was applied to knockdown the GHRH receptor in endometrial cancer cells. The GHRH antagonist inhibited cell motility in a dose-dependent manner. The GHRH antagonist inhibited cell motility and suppressed the expression of Twist and N-cadherin, and the suppression was abolished by GHRH receptor siRNA pretreatment. Moreover, the inhibition of Twist and N-cadherin with Twist siRNA and N-cadherin siRNA, respectively, suppressed cell motility. Our study indicates that the GHRH antagonist inhibited the cell motility of endometrial cancer cells through the GHRH receptor via the suppression of Twist and N-cadherin. Our findings represent a new concept in the mechanism of GHRH antagonist-suppressed cell motility in endometrial cancer cells and suggest the possibility of exploring GHRH antagonists as potential therapeutics for the treatment of human endometrial cancer.
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PMID:Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression. 2803 99