Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function

References

• Slipicevic A, Herlyn M. Narrowing the knowledge gaps for melanoma. Upsala J Med Sci 2012; 117:237-43; PMID:22339359; http://dx.doi.org/10.3109/03009734.2012.658977
   PubMed Web of Science ®Google Scholar
• Usher-Smith JA, Emery J, Kassianos AP, Walter FM. Risk Prediction Models for Melanoma: A Systematic Review. Cancer Epidemiol Biomarkers Prev 2014; 23:1450-63; PMID:24895414; http://dx.doi.org/10.1158/1055-9965.EPI-14-0295
   PubMed Web of Science ®Google Scholar
• Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med 2004; 351:998-1012; PMID:15342808; http://dx.doi.org/10.1056/NEJMra041245
   PubMed Web of Science ®Google Scholar
• Lee B, Mukhi N, Liu D. Current management and novel agents for malignant melanoma. J Hematol Oncol 2012; 5:3; PMID:22333219; http://dx.doi.org/10.1186/1756-8722-5-3
   PubMed Web of Science ®Google Scholar
• Schally AV, Varga JL, Engel JB. Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab 2008; 4:33-43; PMID:18084344; http://dx.doi.org/10.1038/ncpendmet0677
   PubMedGoogle Scholar
• Rick FG, Schally AV, Szalontay L, Block NL, Szepeshazi K, Nadji M, Zarandi M, Hohla F, Buchholz S, Seitz S. Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases. Proc Natl Acad Sci USA 2012; 109:1655-60; PMID:22307626; http://dx.doi.org/10.1073/pnas.1120588109
   PubMed Web of Science ®Google Scholar
• Cai R, Schally AV, Cui T, Szalontay L, Halmos G, Sha W, Kovacs M, Jaszberenyi M, He J, Rick FG, et al. Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities. Peptides 2014; 52:104-12; PMID:24373935; http://dx.doi.org/10.1016/j.peptides.2013.12.010
   PubMed Web of Science ®Google Scholar
• Fahrenholtz CD, Rick FG, Garcia MI, Zarandi M, Cai RZ, Block NL, Schally AV, Burnstein KL. Preclinical efficacy of growth hormone-releasing hormone antagonists for androgen-dependent and castration-resistant human prostate cancer. Proc Natl Acad Sci USA 2014; 111:1084-9; PMID:24395797; http://dx.doi.org/10.1073/pnas.1323102111
   PubMed Web of Science ®Google Scholar
• Kiaris H, Chatzistamou I, Papavassiliou AG, Schally AV. Growth hormone-releasing hormone: not only a neurohormone. Trends Endocrinol Metab 2011; 22:311-7; PMID:21530304; http://dx.doi.org/10.1016/j.tem.2011.03.006
   PubMed Web of Science ®Google Scholar
• Rick FG, Saadat SH, Szalontay L, Block NL, Kazzazi A, Djavan B, Schally AV. Hormonal manipulation of benign prostatic hyperplasia. Curr Opin Urol 2013; 23:17-24; PMID:23202285; http://dx.doi.org/10.1097/MOU.0b013e32835abd18
   PubMed Web of Science ®Google Scholar
• Rick FG, Schally AV, Block NL, Abi-Chaker A, Krishan A, Szalontay L. Mechanisms of synergism between antagonists of growth hormone-releasing hormone and antagonists of luteinizing hormone-releasing hormone in shrinking experimental benign prostatic hyperplasia. Prostate 2013; 73:873-83; PMID:23280565; http://dx.doi.org/10.1002/pros.22633
   PubMed Web of Science ®Google Scholar
• Rick FG, Szalontay L, Schally AV, Block NL, Nadji M, Szepeshazi K, Vidaurre I, Zarandi M, Kovacs M, Rekasi Z. Combining growth hormone-releasing hormone antagonist with luteinizing hormone-releasing hormone antagonist greatly augments benign prostatic hyperplasia shrinkage. J Urol 2012; 187:1498-504; PMID:22341819; http://dx.doi.org/10.1016/j.juro.2011.11.081
   PubMed Web of Science ®Google Scholar
• Jaszberenyi M, Rick FG, Szalontay L, Block NL, Zarandi M, Cai RZ, Schally AV. Beneficial effects of novel antagonists of GHRH in different models of Alzheimer's disease. Aging 2012; 4:755-67; PMID:23211425
   PubMedGoogle Scholar
• Kanashiro-Takeuchi RM, Takeuchi LM, Rick FG, Dulce R, Treuer AV, Florea V, Rodrigues CO, Paulino EC, Hatzistergos KE, Selem SM, et al. Activation of growth hormone releasing hormone (GHRH) receptor stimulates cardiac reverse remodeling after myocardial infarction (MI). Proc Natl Acad Sci USA 2012; 109:559-63; PMID:22203988; http://dx.doi.org/10.1073/pnas.1119203109
   PubMed Web of Science ®Google Scholar
• Lucas R, Sridhar S, Rick FG, Gorshkov B, Umapathy NS, Yang G, Oseghale A, Verin AD, Chakraborty T, Matthay MA, et al. Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema. Proc Natl Acad Sci U S A 2012; 109:2084-9; PMID:22308467; http://dx.doi.org/10.1073/pnas.1121075109
   PubMed Web of Science ®Google Scholar
• Lucas R, Czikora I, Sridhar S, Zemskov E, Gorshkov B, Siddaramappa U, Oseghale A, Lawson J, Verin A, Rick FG, et al. Mini-review: novel therapeutic strategies to blunt actions of pneumolysin in the lungs. Toxins 2013; 5:1244-60; PMID:23860351; http://dx.doi.org/10.3390/toxins5071244
   PubMed Web of Science ®Google Scholar
• LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003; 195:127-37; PMID:12767520; http://dx.doi.org/10.1016/S0304-3835(03)00159-9
   PubMed Web of Science ®Google Scholar
• Schally AV. New approaches to the therapy of various tumors based on peptide analogues. Horm Metab Res 2008; 40:315-22; PMID:18491250; http://dx.doi.org/10.1055/s-2008-1073142
   PubMed Web of Science ®Google Scholar
• Havt A, Schally AV, Halmos G, Varga JL, Toller GL, Horvath JE, Szepeshazi K, Koster F, Kovitz K, Groot K, et al. 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; 102:17424-9; PMID:16299104; http://dx.doi.org/10.1073/pnas.0506844102
   PubMed Web of Science ®Google Scholar
• Pozsgai E, Schally AV, Hocsak E, Zarandi M, Rick F, Bellyei S. The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines. Int J Oncol 2011; 39:1025-32; PMID:21701777; http://dx.doi.org/10.3892/ijo.2011.1098
   PubMed Web of Science ®Google Scholar
• Hohla F, Buchholz S, Schally AV, Seitz S, Rick FG, Szalontay L, Varga JL, Zarandi M, Halmos G, Vidaurre I, et al. GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells. Cell Cycle 2009; 8:3149-56; PMID:19755849; http://dx.doi.org/10.4161/cc.8.19.9698
   PubMed Web of Science ®Google Scholar
• Chatzistamou I, Volakaki AA, Schally AV, Kiaris H, Kittas C. Expression of growth hormone-releasing hormone receptor splice variant 1 in primary human melanomas. Regul Peptides 2008; 147:33-6; PMID:18255167; http://dx.doi.org/10.1016/j.regpep.2007.12.008
   PubMedGoogle Scholar
• Jaszberenyi M, Schally AV, Block NL, Zarandi M, Cai RZ, Vidaurre I, Szalontay L, Jayakumar AR, Rick FG. Suppression of the proliferation of human U-87 MG glioblastoma cells by new antagonists of growth hormone-releasing hormone in vivo and in vitro. Targeted Oncol 2013; 8:281-90; PMID:23371031; http://dx.doi.org/10.1007/s11523-013-0264-y
   PubMed Web of Science ®Google Scholar
• Papadia A, Schally AV, Halmos G, Varga JL, Seitz S, Buchholz S, Rick F, Zarandi M, Bellyei S, Treszl A, et al. Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer. Horm Metab Res 2011; 43:816-20; PMID:22009378; http://dx.doi.org/10.1055/s-0031-1287766
   PubMed Web of Science ®Google Scholar
• Perez R, Schally AV, Vidaurre I, Rincon R, Block NL, Rick FG. Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers. Oncotarget 2012; 3:988-97; PMID:22941871
   PubMed Web of Science ®Google Scholar
• Rick FG, Seitz S, Schally AV, Szalontay L, Krishan A, Datz C, Stadlmayr A, Buchholz S, Block NL, Hohla F. GHRH antagonist when combined with cytotoxic agents induces S-phase arrest and additive growth inhibition of human colon cancer. Cell Cycle 2012; 11:4203-10; PMID:23095641; http://dx.doi.org/10.4161/cc.22498
   PubMed Web of Science ®Google Scholar
• Seitz S, Rick FG, Schally AV, Treszl A, Hohla F, Szalontay L, Zarandi M, Ortmann O, Engel JB, Buchholz S. Combination of GHRH antagonists and docetaxel shows experimental effectiveness for the treatment of triple-negative breast cancers. Oncol Rep 2013; 30:413-8; PMID:23624870
   PubMed Web of Science ®Google Scholar
• Stangelberger A, Schally AV, Rick FG, Varga JL, Baker B, Zarandi M, Halmos G. Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild-type p53 and decrease in p21 and mutant p53 proteins. Prostate 2012; 72:555-65; PMID:21796649; http://dx.doi.org/10.1002/pros.21458
   PubMed Web of Science ®Google Scholar
• Kovacs M, Schally AV, Hohla F, Rick FG, Pozsgai E, Szalontay L, Varga JL, Zarandi M. A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides 2010; 31:1839-46; PMID:20633588; http://dx.doi.org/10.1016/j.peptides.2010.07.006
   PubMedGoogle Scholar
• Abdel-Wahab M, Schally AV, Rick FG, Szalontay L, Block NL, Jorda M, Mahmoud O, Markoe A, Shi Y-F, Reiner T, et al. Antagonists of growth hormone releasing hormone (GHRH) given before whole body radiation lead to modulation of radiation response and organ-specific changes in the expression of angiogenesis. J Radiat Oncol 2012; 1:389-96; http://dx.doi.org/10.1007/s13566-012-0031-1
   Google Scholar
• Rick FG, Schally AV, Block NL, Nadji M, Szepeshazi K, Zarandi M, Vidaurre I, Perez R, Halmos G, Szalontay L. Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia. Proc Natl Acad Sci U S A 2011; 108:3755-60; PMID:21321192; http://dx.doi.org/10.1073/pnas.1018086108
   PubMed Web of Science ®Google Scholar
• Klukovits A, Schally AV, Szalontay L, Vidaurre I, Papadia A, Zarandi M, Varga JL, Block NL, Halmos G. Novel antagonists of growth hormone-releasing hormone inhibit growth and vascularization of human experimental ovarian cancers. Cancer 2012; 118:670-80; PMID:21751186; http://dx.doi.org/10.1002/cncr.26291
   PubMed Web of Science ®Google Scholar
• Slingerland J, Pagano M. Regulation of the cdk inhibitor p27 and its deregulation in cancer. J Cell Physiol 2000; 183:10-7; PMID:10699961; http://dx.doi.org/10.1002/(SICI)1097-4652(200004)183:1<10::AID-JCP2>3.0.CO;2-I
   PubMed Web of Science ®Google Scholar
• Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer 2008; 8:253-67; PMID:18354415; http://dx.doi.org/10.1038/nrc2347
   PubMed Web of Science ®Google Scholar
• Chen G, Cheng Y, Zhang Z, Martinka M, Li G. Prognostic significance of cytoplasmic p27 expression in human melanoma. Cancer Epidemiol Biomar Prev: A Pub Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 2011; 20:2212-21; http://dx.doi.org/10.1158/1055-9965.EPI-11-0472
   Google Scholar
• Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 2006; 6:729-34; PMID:16915295; http://dx.doi.org/10.1038/nrc1974
   PubMed Web of Science ®Google Scholar
• Hong F, Larrea MD, Doughty C, Kwiatkowski DJ, Squillace R, Slingerland JM. mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation. Mol Cell 2008; 30:701-11; PMID:18570873; http://dx.doi.org/10.1016/j.molcel.2008.04.027
   PubMed Web of Science ®Google Scholar
• Siejka A, Barabutis N, Schally AV. GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells. Cell Cycle 2011; 10:3714-8; PMID:22041656; http://dx.doi.org/10.4161/cc.10.21.17904
   PubMed Web of Science ®Google Scholar
• Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4:E131-6; PMID:11988758; http://dx.doi.org/10.1038/ncb0502-e131
   PubMed Web of Science ®Google Scholar
• Rutberg SE, Goldstein IM, Yang YM, Stackpole CW, Ronai Z. Expression and transcriptional activity of AP-1, CRE, and URE binding proteins in B16 mouse melanoma subclones. Mol Carcin 1994; 10:82-7; PMID:8031468; http://dx.doi.org/10.1002/mc.2940100205
   PubMed Web of Science ®Google Scholar
• Scheibenbogen C, Mohler T, Haefele J, Hunstein W, Keilholz U. Serum interleukin-8 (IL-8) is elevated in patients with metastatic melanoma and correlates with tumour load. Melanoma Res 1995; 5:179-81; PMID:7640519; http://dx.doi.org/10.1097/00008390-199506000-00006
   PubMed Web of Science ®Google Scholar
• Brennecke S, Deichmann M, Naeher H, Kurzen H. Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma. Melanoma Res 2005; 15:515-22; PMID:16314737; http://dx.doi.org/10.1097/00008390-200512000-00006
   PubMed Web of Science ®Google Scholar
• Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000; 6(Suppl 1):S11-4; PMID:10685652
   PubMed Web of Science ®Google Scholar
• Sacca R, Cuff CA, Lesslauer W, Ruddle NH. Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol 1998; 160:485-91
   PubMed Web of Science ®Google Scholar
• Cuff CA, Schwartz J, Bergman CM, Russell KS, Bender JR, Ruddle NH. Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. J Immunol 1998; 161:6853-60; PMID:9862717
   PubMed Web of Science ®Google Scholar
• Schrama D, thor Straten P, Fischer WH, McLellan AD, Brocker EB, Reisfeld RA, Becker JC. Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity 2001; 14:111-21; PMID:11239444; http://dx.doi.org/10.1016/S1074-7613(01)00094-2
   PubMed Web of Science ®Google Scholar
• Zarandi M, Horvath JE, Halmos G, Pinski J, Nagy A, Groot K, Rekasi Z, Schally AV. Synthesis and biological activities of highly potent antagonists of growth hormone-releasing hormone. Proc Natl Acad Sci U S A 1994; 91:12298-302; PMID:7991622; http://dx.doi.org/10.1073/pnas.91.25.12298
   PubMed Web of Science ®Google Scholar