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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1997-6-19
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pubmed:abstractText |
In view of evidence that growth hormone (GH) and insulin-like growth factors (IGF) may play a role in the development of renal cell carcinoma (RCC), we investigated the effects of growth hormone-releasing hormone (GH-RH) antagonist MZ-4-71 on the proliferation of the human renal adenocarcinoma cell line Caki-I in vitro and in vivo. Male nude mice bearing xenografts of human Caki-I RCC were treated for 4 weeks with MZ-4-71 injected s.c. twice daily at a dose of 20 microg per animal. Tumor growth, serum, liver, and tumor IGF levels and IGF-I receptor concentrations in Caki-I cell membranes were measured. After 4 weeks of therapy, the final volume of Caki-I tumors in nude mice treated with MZ-4-71 was significantly (P < 0.01) decreased to 52.6 +/- 12.3 mm3 as compared with controls that measured 504.2 +/- 104.1 mm3. Treatment with GH-RH antagonist also significantly reduced tumor weight, serum levels of GH and IGF-I, liver concentrations of IGF-I, and tumor levels of IGF-I and IGF-II. High-affinity binding sites for IGF-I were detected in the cell membranes of Caki-I tumors. IGF-I and IGF-II stimulated the proliferation of Caki-I cells in tissue cultures. Antagonist MZ-4-71 could inhibit in vitro growth of Caki-I cells, but only at high concentrations. Our findings demonstrate that GH-RH antagonist MZ-4-71 can significantly inhibit the growth of Caki-I RCC. MZ-4-71 may exert its suppressive effect on tumor growth through a reduction in GH release from the pituitary and the subsequent decrease in the production of IGF-I in the liver and IGF-I and II by the tumors. The efficacy of MZ-4-71 suggests that this compound could be considered for the therapy of recurrent or metastatic RCC.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-1313689,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-1332849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-1394233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-1707433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-2543641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-2839083,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-2986538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-3018703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-3530441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-6254391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-6583688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-6998997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7473836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7518352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7628369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7665217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7834629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-7991622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-8044804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-8200618,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-833871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-8493752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9159156-8548526
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/MZ 4-71,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Sermorelin,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5810-3
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9159156-Animals,
pubmed-meshheading:9159156-Carcinoma, Renal Cell,
pubmed-meshheading:9159156-Cell Division,
pubmed-meshheading:9159156-Cell Membrane,
pubmed-meshheading:9159156-DNA, Neoplasm,
pubmed-meshheading:9159156-Growth Hormone,
pubmed-meshheading:9159156-Growth Hormone-Releasing Hormone,
pubmed-meshheading:9159156-Hormone Antagonists,
pubmed-meshheading:9159156-Humans,
pubmed-meshheading:9159156-Insulin-Like Growth Factor I,
pubmed-meshheading:9159156-Insulin-Like Growth Factor II,
pubmed-meshheading:9159156-Kidney Neoplasms,
pubmed-meshheading:9159156-Liver,
pubmed-meshheading:9159156-Male,
pubmed-meshheading:9159156-Mice,
pubmed-meshheading:9159156-Mice, Nude,
pubmed-meshheading:9159156-Receptor, IGF Type 1,
pubmed-meshheading:9159156-Sermorelin,
pubmed-meshheading:9159156-Thymidine,
pubmed-meshheading:9159156-Transplantation, Heterologous,
pubmed-meshheading:9159156-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo proliferation of Caki-I renal adenocarcinoma.
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pubmed:affiliation |
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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