Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones

T. W. Redding, Andrew V Schally

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Abstract

The Swarm chondrosarcoma is a hormone-responsive tumor growth whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp6]LH-RH, which lowers blood levels of LH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of SS-14, [p-NH2-Phe4]SS, ]D-5-F-Trp8]SS, and [D-5-MeO-Trp8]SS, in doses of 30 μg once or twice daily for 14-30 days, there was a significant reduction in tumor volume and/or weight as compared with control rats. The longer acting SS-28 or its analog Val-Gly-Tyr-Val-Ile-Leu-Gly-SS-28, given in doses of 30 μg/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp6]LH-RH (30-60 μg/day), administered alone or together with analogs of SS-14, decreased tumor weight and/or volume. Serum growth hormone and prolactin levels in rats bearing the tumors were significantly decreased after treatment with [D-5-F-Trp8]SS or with [D-Trp6]LH-RH. The inhibition of growth of the Swarm chondrosarcoma in rats by these analogs suggests that they might lead to a new endocrine therapy for chondrosarcomas, osteosarcomas, and related hormone-dependent neoplasias.

Original languageEnglish
Pages (from-to)1078-1082
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number4 I
StatePublished - Jan 1 1983
Externally publishedYes

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Hypothalamic Hormones
Chondrosarcoma
Somatostatin
Tumor Burden
Somatostatin-28
Gonadotropin-Releasing Hormone
Growth
Growth Hormone
Prolactin
Adrenocorticotropic Hormone
Neoplasms
Hormones
Hypophysectomy
Follicle Stimulating Hormone
Somatomedins
Osteosarcoma
Subcutaneous Injections
Serum
Glucocorticoids
Sprague Dawley Rats

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones",
abstract = "The Swarm chondrosarcoma is a hormone-responsive tumor growth whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp6]LH-RH, which lowers blood levels of LH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of SS-14, [p-NH2-Phe4]SS, ]D-5-F-Trp8]SS, and [D-5-MeO-Trp8]SS, in doses of 30 μg once or twice daily for 14-30 days, there was a significant reduction in tumor volume and/or weight as compared with control rats. The longer acting SS-28 or its analog Val-Gly-Tyr-Val-Ile-Leu-Gly-SS-28, given in doses of 30 μg/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp6]LH-RH (30-60 μg/day), administered alone or together with analogs of SS-14, decreased tumor weight and/or volume. Serum growth hormone and prolactin levels in rats bearing the tumors were significantly decreased after treatment with [D-5-F-Trp8]SS or with [D-Trp6]LH-RH. The inhibition of growth of the Swarm chondrosarcoma in rats by these analogs suggests that they might lead to a new endocrine therapy for chondrosarcomas, osteosarcomas, and related hormone-dependent neoplasias.",
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AU - Schally, Andrew V

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N2 - The Swarm chondrosarcoma is a hormone-responsive tumor growth whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp6]LH-RH, which lowers blood levels of LH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of SS-14, [p-NH2-Phe4]SS, ]D-5-F-Trp8]SS, and [D-5-MeO-Trp8]SS, in doses of 30 μg once or twice daily for 14-30 days, there was a significant reduction in tumor volume and/or weight as compared with control rats. The longer acting SS-28 or its analog Val-Gly-Tyr-Val-Ile-Leu-Gly-SS-28, given in doses of 30 μg/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp6]LH-RH (30-60 μg/day), administered alone or together with analogs of SS-14, decreased tumor weight and/or volume. Serum growth hormone and prolactin levels in rats bearing the tumors were significantly decreased after treatment with [D-5-F-Trp8]SS or with [D-Trp6]LH-RH. The inhibition of growth of the Swarm chondrosarcoma in rats by these analogs suggests that they might lead to a new endocrine therapy for chondrosarcomas, osteosarcomas, and related hormone-dependent neoplasias.

AB - The Swarm chondrosarcoma is a hormone-responsive tumor growth whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp6]LH-RH, which lowers blood levels of LH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of SS-14, [p-NH2-Phe4]SS, ]D-5-F-Trp8]SS, and [D-5-MeO-Trp8]SS, in doses of 30 μg once or twice daily for 14-30 days, there was a significant reduction in tumor volume and/or weight as compared with control rats. The longer acting SS-28 or its analog Val-Gly-Tyr-Val-Ile-Leu-Gly-SS-28, given in doses of 30 μg/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp6]LH-RH (30-60 μg/day), administered alone or together with analogs of SS-14, decreased tumor weight and/or volume. Serum growth hormone and prolactin levels in rats bearing the tumors were significantly decreased after treatment with [D-5-F-Trp8]SS or with [D-Trp6]LH-RH. The inhibition of growth of the Swarm chondrosarcoma in rats by these analogs suggests that they might lead to a new endocrine therapy for chondrosarcomas, osteosarcomas, and related hormone-dependent neoplasias.

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