A. V. Schally
Louisiana State University
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Featured researches published by A. V. Schally.
Cellular and Molecular Life Sciences | 2004
A. V. Schally; Karoly Szepeshazi; Attila Nagy; Ana Maria Comaru-Schally; Gabor Halmos
Cancers of the stomach, colon and exocrine pancreas are major international health problems and result in more than a million deaths worldwide each year. The therapies for these malignancies must be improved. The effects of gastrointestinal (GI) hormonal peptides and endogenous growth factors on these cancers were reviewed. Some GI peptides, including gastrin and gastrin-releasing peptide (GRP) (mammalian bombesin), appear to be involved in the growth of neoplasms of the GI tract. Certain growth factors such as insulin-like growth factor (IGF)-I, IGF-II and epidermal growth factor and their receptors that regulate cell proliferation are also implicated in the development and progression of GI cancers. Experimental investigations on gastric, colorectal and pancreatic cancers with analogs of somatostatin, antagonists of bombesin/GRP, antagonists of growth hormone-releasing hormone as well as cytotoxic peptides that can be targeted to peptide receptors on tumors were summarized. Clinical trials on peptide analogs in patients with gastric, colorectal and pancreatic cancers were reviewed and analyzed. It may be possible to develop new approaches to hormonal therapy of GI malignancies based on various peptide analogs.
Proceedings of the National Academy of Sciences of the United States of America | 2009
Christian G. Ziegler; Jacqueline Brown; A. V. Schally; A Erler; Linda Gebauer; Andrea Treszl; Louise Young; L M Fishman; J B Engel; Holger S. Willenberg; S Petersenn; Graeme Eisenhofer; Monika Ehrhart-Bornstein; Stefan R. Bornstein
Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4–71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.
British Journal of Cancer | 2002
Zoltan Szereday; A. V. Schally; Attila Nagy; Artur Plonowski; Ana M. Bajo; Gabor Halmos; Karoly Szepeshazi; Kate Groot
Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-215 to U-87MG tumours was characterised by an IC50 value of 4.0±0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P<0.05) extended tumour doubling time from 4.54±0.2 days to 8.18±1.8 days and inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P<0.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215.
Proceedings of the National Academy of Sciences of the United States of America | 1999
Hippokratis Kiaris; A. V. Schally; Jozsef L. Varga; Kate Groot; Patricia Armatis
Proceedings of the National Academy of Sciences of the United States of America | 1994
Marta Zarandi; Judit Horvath; Gabor Halmos; Jacek Pinski; Attila Nagy; Kate Groot; Zoltan Rekasi; A. V. Schally
Proceedings of the National Academy of Sciences of the United States of America | 1996
Gabor Halmos; A. V. Schally; Jacek Pinski; Manuel Vadillo-Buenfil; Kate Groot
Proceedings of the National Academy of Sciences of the United States of America | 1994
Renzhi Cai; Herta Reile; Patricia Armatis; A. V. Schally
International Journal of Oncology | 1998
Najib Lamharzi; Gabor Halmos; Patricia Armatis; A. V. Schally
Receptor | 1993
Gabor Halmos; Zoltan Rekasi; Balazs Szoke; A. V. Schally
International Journal of Oncology | 1994
Y Shirahige; Cb Cook; J Pinski; Gabor Halmos; R Nair; A. V. Schally