Horm Metab Res 2008; 40(5): 315-322
DOI: 10.1055/s-2008-1073142
Review

© Georg Thieme Verlag KG Stuttgart · New York

New Approaches to the Therapy of Various Tumors Based on Peptide Analogues

A. V. Schally 1 , 2
  • 1Veterans Affairs Medical Center, and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL, USA
  • 2Department of Pathology and Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
Further Information

Publication History

received 04.10.2007

accepted 22.10.2007

Publication Date:
19 May 2008 (online)

Abstract

The discovery of hypothalamic hormones was briefly reviewed. The development of new hormonal methods for the therapy of various cancers based on analogues of hypothalmic hormones is then presented. My group isolated luteininzing hormone-releasing hormone (LH-RH), also known as Gn-RH, from pig hypothalmi, elucidated its amino acid sequence, and synthesized it in 1971. The interest in medical applications of LH-RH led to the synthesis of LH-RH analogues by various groups. LH-RH agonists substituted in positions 6 or 10 including Decapeptyl, Leuprolide and Zoladex are much more active than LH-RH and on continuous administration produce inhibition of pituitary and gonads. Chronic administration of LH-RH agonists is being utilized for the treatment of prostate and breast cancer. Octapeptide analogues of somatostatin have various applications in Oncology. In 1980 we developed a new endocrine therapy for advanced prostate cancer based on agonists of LH-RH, which is now preferred by 70-90% of prostate cancer patients for primary treatment. LH-RH antagonists such as Cetrorelix can be used for therapy of BPH. On the basis of the presence of specific receptors for hypothalamic peptides on human cancers, we developed targeted cytotoxic analogues of LH-RH, somatostatin, and bombesin/GRP linked to doxorubicin or 2-pyrrolinodoxorubicin. These analogues inhibit the growth of experimental human prostate, breast, ovarian and endometrial cancer, renal cell carcinoma, pancreatic, colorectal and gastric cancers, small cell lung carcinoma (SCLC) and non-SCLC, brain tumors, melanomas, and lymphomas. Cytotoxic LH-RH analogues are now in clinical trials. Recently we demonstrated that growth hormone-releasing hormone (GH-RH) also serves as an autocrine growth factor in many cancers. Antagonistic analogues of GH-RH synthesized in our laboratory inhibit the growth of diverse tumors. The discovery of LH-RH and somatostatin has led to clinical use of their analogues in the field of cancer treatment and GH-RH antagonists also show a great promise.

References

  • 1 Schally AV, Comaru-Schally AM, Nagy A, Kovacs M, Szepeshazi K, Plonowski A, Varga JL, Halmos G. Hypothalamic hormones and cancer.  Front Neuroendocrinol. 2001;  22 248-291
  • 2 Schally AV, Comaru-Schally AM. Hypothalamic and other peptide hormones. In: Kufe DW, Pollock RE, Weichselbaum RR, Bast Jr RC, Gansler TS, Holland JF, Frei III E (Eds). Cancer Medicine. 7th Edition. Hamilton, Ontario: B. C. Dekker Publishers 2006: 802-816
  • 3 Schally AV. Aspects of hypothalamic regulation of the pituitary gland.  Science. 1978;  202 18-28
  • 4 Green JD, Harris GW. The neurovascular link between the neurohypophysis and adenohypophysis.  J Endocrinol. 1947;  5 136-147
  • 5 Saffran M, Schally AV. The release of corticotrophin by anterior pituitary tissue in vitro.  Can J Biochem Physiol. 1955;  33 408-415
  • 6 Schally AV, Bowers CY, Redding TW, Barrett JF. Isolation of thyrotropin releasing factor (TRF) from porcine hypothalamus.  Biochem Biophys Res Commun. 1966;  25 165-169
  • 7 Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV. The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidine-proline amide.  Biochem Biophys Res Commun. 1969;  37 705-710
  • 8 Anderson MS, Bowers CY, Kastin A, Schalch DS, Schally AV, Snyder PJ, Utiger RD, Wilber JF, Wise AJ. Synthetic thyrotropin releasing hormone (TRH): A potent stimulator of thyrotropin secretion in man.  N Engl J Med. 1971;  285 1279-1283
  • 9 Kastin AJ, Schally AV, Gual C, Midgley  Jr  AR, Bowers CY, Diaz-Infante  Jr  A. Stimulation of LH release in men and women by LH-Releasing hormone purified from porcine hypothalami.  J Clin Endocrinol Metab. 1969;  29 1040-1050
  • 10 Schally AV, Arimura A, Baba Y, Nair RMG, Matsuo H, Redding TW, Debeljuk L, White WF. Isolation and properties of the FSH and LH-releasing hormone.  Biochem Biophys Res Commun. 1971;  43 393-399
  • 11 Schally AV, Nair RMG, Redding TW, Arimura A. Isolation of the LH and FSH-releasing hormone from porcine hypothalami.  J Biol Chem. 1971;  246 7230-7236
  • 12 Matsuo H, Baba Y, Nair RMG, Arimura A, Schally AV. Structure of the porcine LH- and FSH-releasing hormone I, the proposed amino acid sequence.  Biochem Biophys Res Commun. 1971;  43 1334-1339
  • 13 Matsuo H, Arimura A, Nair RMG, Schally AV. Synthesis of the porcine LH- and FSH-releasing hormone by the solid-phase method.  Biochem Biophys Res Commun. 1971;  45 822-827
  • 14 Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, Nair RMG, Debeljuk L, White WF. The gonadotropins-releasing hormone: One polypeptide regulates the secretion of luteinizing and follicle-stimulating hormone.  Science. 1971;  173 1036-1038
  • 15 Schally AV, Kastin AJ, Arimura A. Hypothalamic FSH and LH-regulating hormone: structure, physiology and clinical studies.  Fertil Steril. 1971;  22 703-721
  • 16 Karten MJ, Rivier JE. Gonadotropin-releasing hormone analog design. Structure-function studies toward the development of agonists and antagonists: rationale and perspective.  Endocr Rev. 1986;  7 44-66
  • 17 Hall R, Besser GM, Schally AV, Coy DH, Evered D, Goldie DJ, Kastin AJ, MacNeilly AS, Mortimer CH, Phenekos C, Turnbridge WMG, Weightman D. Action of growth-hormone-release inhibitory hormone in healthy men and in acromegaly.  Lancet. 1973;  ii 581-584
  • 18 Redding TW, Schally AV. Inhibition of prostate tumor growth in two rat models by chronic administration of d-Trp-6LH-RH.  Proc Natl Acad Sci USA. 1981;  78 6509-6512
  • 19 Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas A, Comaru-Schally AM, Schally AV. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.  Proc Natl Acad Sci USA. 1982;  79 1658-1662
  • 20 Redding TW, Schally AV, Tice TR, Meyers WE. Long acting delivery system for peptides: Inhibition of rat prostate tumors by controlled release of (d-Trp-6) luteinizing hormone-releasing hormone from injectable microcapsules.  Proc Natl Acad Sci USA. 1984;  81 5845-5848
  • 21 Schally AV. Luteinizing hormone releasing-hormone analogues: Their impact on the control of tumorigenesis.  Peptides. 1999;  20 1247-1262
  • 22 Gonzalez-Barcena D, Vadillo-Buenfil M, Gomez-Orta F, Fuentes GM, Cardenas-Carnejo I, Graef-Sanchez A, Comaru-Schally AM, Schally AV. Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer.  Prostate. 1994;  24 84-92
  • 23 Schally AV, Nagy A. Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors.  Eur J Endocrinol. 1999;  141 1-14
  • 24 Ehrlich P. The relationship existing between chemical constitution, distribution, and pharmacological action. In: Himmelweite F, Marquardt M, Dale H (Eds). The Collected Papers of Paul Ehrlich. New York: Pergamon 1956: 596-618
  • 25 Halmos G, Arenciba JM, Schally AV, Davis R, Bostwick DG. High incidence of receptors for luteinizing hormone-releasing hormone (LH-RH) and LH-RH receptor gene expression in human prostate cancers.  J Urol. 2000;  163 623-629
  • 26 Schally AV, Nagy A. Chemotherapy targeted to cancers through tumoral hormone receptors.  Trends Endocrinol Metab. 2004;  15 300-310
  • 27 Nagy A, Schally AV, Armatis P, Szepeshazi K, Halmos G, Kovacs M, Zarandi M, Groot K, Miyazaki M, Jungwirth A, Horvath J. Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxoruvicin, a derivative 500-1000 times more potent.  Proc Natl Acad Sci USA. 1996;  93 7269-7273
  • 28 Letsch M, Schally AV, Szepeshazi K, Halmos G, Nagy A. Preclinical evaluation of targeted cytotoxic luteinizing hormone-releasing hormone analog AN-152 in androgen sensitive and insensitive prostate cancers.  Clin Cancer Res. 2003;  9 4505-4513
  • 29 Plonowski A, Schally AV, Nagy A, Groot K, Krupa M, Navone NM, Logothetis C. Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207.  Cancer Lett. 2002;  176 57-63
  • 30 Stangelberger A, Schally AV, Nagy A, Szepeshazi K, Kanashiro CA, Halmos G. Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207.  Prostate. 2006;  66 200-210
  • 31 Fekete M, Wittliff JL, Schally AV. Characteristics and distribution of receptors for d-Trp-6luteinizing hormone-releasing hormone, somatostatin, epidermal growth factor and sex steroids in 500 biopsy samples of human breast cancer.  J Clin Lab Anal. 1989;  3 137-147
  • 32 Chatzistamou I, Schally AV, Nagy A, Armatis P, Szepeshazi K, Halmos G. Effective treatment of metastatic MDA-MD-435 human estrogen independent breast carcinomas with a targeted cytotoxic analog of luteinizing hormone-releasing hormone, AN-207.  Clin Cancer Res. 2000;  6 4158-4165
  • 33 Kahan Z, Nagy A, Schally AV, Halmos G, Arencibia JM, Groot K. Complete regression of MX- I human breast carcinoma xenografts after targeted chemotherapy with a cytotoxic analog of luteinizing hormone-releasing hormone, AN-207.  Cancer. 1999;  85 2608-2615
  • 34 Bajo AM, Schally AV, Halmos G, Nagy A. Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers.  Clin Cancer Res. 2003;  9 3742-3748
  • 35 Miyazaki M, Nagy A, Schally AV, Lamharzi N, Halmos G, Szepeshazi K, Groot K, Armatis P. Growth inhibition of human ovarian cancers by cytotoxic analogues of luteinizing hormone-releasing hormone.  J Natl Cancer Inst. 1997;  89 1803-1809
  • 36 Arencibia JM, Bajo AM, Schally AV, Krupa M, Chatzistamou I, Nagy A. Effective treatment of experimental ES-2 human ovarian cancers with a cytotoxic analog of luteinizing hormone-releasing hormone AN-207.  Anti Cancer Drugs. 2002;  13 949-956
  • 37 Miyazaki M, Schally AV, Nagy A, Lamharzi N, Halmos G, Szepeshazi K, Armatis P. Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits growth of OV-1063 human epithelial ovarian cancers in nude mice.  Am J Obstet Gynecol. 1999;  180 1095-1103
  • 38 Engel JB, Keller G, Schally AV, Nagy A, Chism DD, Halmos G. Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207.  Fertil Steril. 2005;  83 1125-1133
  • 39 Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Halmos G, Engel JB. Receptors for luteinizing hormone releasing hormone (LHRH) expressed in human non-Hodgkin's lymphomas can be targeted for therapy with the cytotoxic LHRH analogue AN-207.  Eur J Cancer. 2005;  41 2196-2202
  • 40 Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Westphal G, Halmos G, Engel JB. Human malignant melanomas express receptors for luteinizing hormone releasing hormone allowing targeted therapy with cytotoxic luteinizing hormone releasing hormone analogue.  Cancer Res. 2005;  65 5857-5863
  • 41 Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Halmos G, Engel JB. Receptors for luteinizing hormone releasing hormone expressed on human renal cell carcinomas can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone analogues.  Clin Cancer Res. 2005;  11 5549-5557
  • 42 Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone.  Science. 1973;  179 77-79
  • 43 Schally AV, Dupont A, Arimura A, Redding TW, Nishi N, Linthicum GL, Schlesinger DH. Isolation and structure of growth hormone-release inhibiting hormone (somatostatin) from porcine hypothalami.  Biochemistry. 1976;  15 509-514
  • 44 Schally AV, Huang WY, Chang RCC, Arimura A, Redding TW, Millar RP, Hunkapiller MW, Hood LE. Isolation and structure of pro-somatostatin: A putative somatostatin precursor from pig hypothalamus.  Proc Natl Acad Sci USA. 1980;  77 4489-4493
  • 45 Bauer W, Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher TJ, Pless J. SMS 201-995: A very potent and selective octapeptide analogue of somatostatin with prolonged action.  Life Sci. 1982;  31 1133-1140
  • 46 Cai RZ, Szoke B, Lu R, Fu D, Redding TW, Schally AV. Synthesis and biological activity of highly potent octapeptide analogs of somatostatin.  Proc Natl Acad Sci USA. 1986;  83 1896-1900
  • 47 Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, Hagen M Van, Postema PT, Jong M de, Reubi JC, Visser TJ, Reijs AEM, Hofland LJ, Koper JW, Lamberts SWJ. Somatostatin receptor scintigraphy with (111In-DTPA-D-Phe1)- (123I-Tyr3)octreotide: The Rotterdam experience with more than 1,000 patients.  Eur J Nucl Med. 1993;  20 716-731
  • 48 Nagy A, Schally AV, Halmos G, Armatis P, Cai R-Z, Csernus V, Kovacs M, Koppan M, Szepeshazi K, Kahn Z. Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative 2- pyrrolinodoxonubicin.  Proc Natl Acad Sci USA. 1988;  95 1794-1799
  • 49 Plonowski A, Schally AV, Nagy A, Sun B, Szepeshazi K. Inhibition of PC-3 human androgen-independent prostate cancer and its metastases by cytotoxic somatostatin analogue AN-238.  Cancer Res. 1999;  59 1947-1953
  • 50 Plonowski A, Schally AV, Nagy A, Sun B, Halmos G. Effective treatment of experimental DU-145 prostate cancers with targeted cytotoxic somatostatin analog AN-238.  Int J Oncology. 2002;  20 397-402
  • 51 Letsch M, Schally AV, Szepeshazi K, Halmos G, Nagy A. Effective treatment of experimental models of androgen-sensitive and androgen-independent prostate cancer metastatic to the bone with targeted cytotoxic somatostatin analog AN-238.  J Urol. 2004;  171 911-915
  • 52 Kahan Z, Nagy A, Schally AV, Hebert F, Sun B, Groot K, Halmos G. Inhibition of growth of MX- I, MCF-7, MIII and MDA-MB-23I human breast cancer xenografts after administration of a targeted cytotoxic analog of somatostatin, AN-238.  Int J Cancer. 1999;  82 592-598
  • 53 Plonowski A, Schally AV, Koppan M, Nagy A, Arencibia JM, Csernus B, Halmos G. Inhibition of the UCI-107 human ovarian carcinoma cell line by a targeted cytotoxic analog of somatostatin, AN-238.  Cancer. 2001;  92 1168-1176
  • 54 Engel JB, Schally AV, Halmos G, Baker B, Nagy A, Keller G. Targeted therapy with a cytotoxic somatostatin analog, AN-238, inhibits growth of human experimental endometrial carcinomas expressing multidrug resistance protein MDR-1.  Cancer. 2005;  104 1312-1321
  • 55 Plonowski A, Schally AV, Nagy A, Kiaris H, Hebert F, Halmos G. Inhibition of metastatic renal cell carcinomas expressing somatostatin receptors by a targeted cytotoxic analog of somatostatin AN-238.  Cancer Res. 2000;  60 2996-3001
  • 56 Kiaris H, Schally AV, Nagy A, Sun B, Szepeshazi K, Halmos G. Regression of U-87MG human glioblastomas in nude mice after treatment with a cytotoxic somatostatin analog AN-238.  Clin Cancer Res. 2000;  6 709-717
  • 57 Kiaris H, Schally AV, Nagy A, Szepeshazi K, Hebert F, Halmos G. A targeted cytotoxic somatostatin (SST) analogue AN-238 inhibits the growth of H-69 small cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice.  Eur J Cancer. 2001;  37 620-628
  • 58 Szereday Z, Schally AV, Szepeshazi K, Bajo AM, Hebert F, Halmos G, Nagy A. Effective treatment of H838 human non-small cell lung carcinoma with a targeted cytotoxic somatostatin analog, an-238.  Int J Oncol. 2003;  22 1141-1146
  • 59 Szepeshazi K, Schally AV, Halmos G, Sun B, Hebert F, Csernus B, Nagy A. Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancer.  Clin Cancer Res. 2001;  7 2854-2861
  • 60 Szepeshazi K, Schally AV, Halmos G, Armatis P, Hebert F, Sun B, Feil A, Kiaris H, Nagy A. Targeted cytotoxic somatostatin analogue AN-238 inhibits somatostatin receptor-positive experimental colon cancers independently of their p53 status.  Cancer Res. 2002;  62 781-788
  • 61 Szepeshazi K, Schally AV, Nagy A, Wagner BW, Bajo AM, Halmos G. Preclinical evaluation of therapeutic effects of targeted cytotoxic analogs of somatostatin and bombesin on human gastric carcinomas.  Cancer. 2003;  98 1401-1410
  • 62 Keller G, Engel JB, Schally AV, Nagy A, Hammann B, Halmos G. Growth inhibition of experimental non-Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN-238.  Int J Cancer. 2005;  114 831-835
  • 63 Keller G, Schally AV, Nagy A, Baker B, Halmos G, Engel JB. Effective therapy of experimental human malignant melanomas with a targeted cytotoxic somatostatin analogue without induction of multi-drug resistance proteins.  Int J Oncol. 2006;  28 1507-1513
  • 64 Cai RZ, Reile H, Armatis P, Schally AV. Potent bombesin antagonists with C-terminal Leu ψ(CH2N) Tac-NH2 or its derivatives.  Proc Natl Acad Sci USA. 1994;  91 12664-12668
  • 65 Nagy A, Armatis P, Cai R-Z, Szepeshazi K, Halmos G, Schally AV. Design, synthesis and in vitro evaluation of cytotoxic analogs of bombesin-like peptides containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin.  Proc Natl Acad Sci USA. 1997;  94 652-656
  • 66 Schally AV, Varga JL. Antagonistic analogs of growth hormone-releasing hormone: New potential antitumor agents.  Trends Endocrinol Metab. 1999;  10 383-391
  • 67 Schally AV, Varga JL. Antagonists of growth hormone-releasing hormone.  Comb Chem High Throughput Screen. 2006;  9 163-170
  • 68 Varga JL, Schally AV. Analogues of growth hormone-releasing hormone (GH-RH) in cancer. In: Kastin A (Ed). Handbook of Peptides. London: Elsevier/Academic Press 2006: 483-489
  • 69 Szepeshazi K, Schally AV, Groot K, Armatis P, Hebert F, Halmos G. Antagonists of growth hormone-releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic cancers and decrease IGF-II levels in tumors.  Eur J Cancer. 2000;  36 128-136
  • 70 Szepeshazi K, Schally AV, Groot K, Armatis P, Halmos G, Hebert F, Szende B, Varga JL, Zarandi M. Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers.  Br J Cancer. 2000;  82 1724-1731
  • 71 Plonowski A, Schally AV, Krupa A, Hebert F, Groot K, Varga JL. Inhibition of proliferation of PC-3 human prostate cancer by antagonists of growth hormone-releasing hormone; lack of correlation with the levels of serum IGF-I and expression of IGF-II and vascular endothelial growth factor.  Prostate. 2002;  52 173-182
  • 72 Kahan Z, Varga JL, Schally AV, Rekasi Z, Armatis P, Chatzistamou I, Czompoly T, Halmos G. Antagonists of growth hormone Releasing hormone arrest the growth of MDA-MB-468 estrogen-independent human breast cancers in nude mice.  Breast Cancer Res Treat. 2000;  60 71-79
  • 73 Halmos G, Schally AV, Varga JL, Plonowski A, Rekasi Z, Czompoly T. Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone.  Proc Natl Acad Sci USA. 2000;  12 10555-10560
  • 74 Kiaris H, Schally AV, Varga JL. Antagonists of growth hormone-releasing hormone inhibit the growth of U-87MG human glioblastoma in nude mice.  Neoplasia. 2000;  2 242-250
  • 75 Kiaris H, Schally AV, Varga JL, Groot K, Armatis P. Growth hormone-releasing hormone: an autocrine growth factor for small cell lung carcinoma.  Proc Natl Acad Sci USA. 1999;  96 14894-14898
  • 76 Engel JB, Keller G, Schally AV, Toller GL, Groot K, Havt A, Armatis P, Zarandi M, Varga JL, Halmos G. Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone.  J Clin Endocrinol Metab. 2005;  90 3614-3621
  • 77 Halmos G, Schally AV, Czompoly T, Krupa M, Varga JL, Rekasi Z. Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer.  J Clin Endocrinol Metab. 2002;  87 4707-4714
  • 78 Busto R, Schally AV, Varga JL, Garcia-Fernandez MO, Groot K, Armatis P, Szepeshazi K. The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas.  Proc Natl Acad Sci USA. 2002;  99 11866-11871
  • 79 Kanashiro CA, Schally AV, Varga JL, Havt A, Hammann BD, Groot K, Halmos G, Zarandi M. Alterations of EGFR/HER, angiogenesis and apoptosis pathways after therapy with antagonists of growth hormone releasing hormone and bombesin in non-small cell lung cancer.  Int J Oncology. 2007;  30 1019-1028
  • 80 Keller G, Schally AV, Groot K, Toller GL, Havt A, Koster F, Armatis P, Halmos G, Zarandi M, Varga JL, Engel JB. Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone.  Proc Natl Acad Sci USA. 2005;  102 10628-10633
  • 81 Rekasi Z, Czompoly , Schally AV, Halmos G. Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers.  Proc Natl Acad Sci USA. 2000;  12 10561-10566
  • 82 Havt A, Schally AV, Halmos G, Varga JL, Toller GL, Horvath JE, Szepeshazi K, Koster F, Kovitz K, Groot K, Zarandi M, Kanashiro CA. The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues.  Proc Natl Acad Sci USA. 2005;  102 17424-17429

Correspondence

A. V. Schally

Veterans Affairs Medical Center

Research Service (151)

Room 2A103

1201 NW 16th Street

Miami

33125 FL

USA

Phone: +1/305/575 34 77

Fax: +1/305/575 31 26

Email: Andrew.Schally@va.gov

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