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1.

001-es BibID:BIBFORM033539
035-os BibID:WOS:000239069400046
Első szerző:Buchholz, Stefan
Cím:Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations / Stefan Buchholz, Gunhild Keller, Andrew V. Schally, Gabor Halmos, Florian Hohla, Elmar Heinrich, Frank Koester, Benjamin Baker, Jörg B. Engel
Dátum:2006
ISSN:0027-8424
Megjegyzések:The aim of this study was to investigate the effect of treatment of experimental ovarian cancers with targeted cytotoxic analogs as single compounds and in combination. Targeted cytotoxic analogs of bombesin (AN-215), somatostatin (AN-238), and luteinizing hormone-releasing hormone (AN-207) consisted of 2-pyrrolinodoxorubicin (AN-201) linked to the respective peptide carrier. AN238 at 200 nmol/kg significantly inhibited growth of UCI-107, ES-2 and OV-1063 ovarian cancers. AN-215 alone at 200 nmol/kg and its combination with AN-238 at one-half of the dose were also able to inhibit the growth of UCI-107 tumors. A combination of AN-238 with AN-207at 50% of the dose strongly suppressed the proliferation of ES-2 and OV-1063 ovarian tumors. Cytotoxic radical AN-201 was toxic and had no significant effect on tumor growth. In contrast, the toxicity of the conjugated peptide analogs was low. Because ovarian cancers tend to acquire chemoresistance, we used real-time PCR to measure the mRNA expression of multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein after treatment. Low or no induction of multidrug resistance protein 1, multidrug resistance-related protein, and breast cancer resistance protein occurred after treatment with AN-238, AN-215, and the combination of AN-238 with AN-207 or AN-215. These results demonstrate that a therapy with cytotoxic analogs such as single agents and combinations is effective and nontoxic. Our work suggests that cytotoxic peptide analogs of luteinizing hormone-releasing hormone, somatostatin, and bombesin could be used for the therapy of ovarian cancers, considering the lack of induction of chemoresistance.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 103 : 27 (2006), p. 10403-10407. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hohla, Florian Heinrich, Elmar Koester, Frank Baker, Benjamin Engel, Jörg B.
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2.

001-es BibID:BIBFORM002242
Első szerző:Buchholz, Stefan
Cím:Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel / Stefan Buchholz, Andrew V. Schally, Jörg B. Engel, Florian Hohla, Elmar Heinrich, Frank Koester, Jozsef L. Varga, Gabor Halmos
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Proceedings of the National Academy of Sciences of the United States of America. - 104 (2007), p. 1943-1946. -
További szerzők:Schally, Andrew Victor Engel, Jörg B. Hohla, Florian Heinrich, Elmar Koester, Frank Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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3.

001-es BibID:BIBFORM004056
Első szerző:Heinrich, Elmar
Cím:Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138 / Elmar Heinrich, Andrew V. Schally, Stefan Buchholz, Ferenc G. Rick, Halmos Gábor, Mile Melinda, Kate Groot, Florian Hohla, Zarandi Márta, Jozsef L. Varga
Dátum:2008
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers and affect tumoral growth factors. Methods: We investigated the effect of a new GHRH antagonist MZ-J-7-138 at doses of 1.25, 2.5, 5 and 10 mű g/day s.c. on the growth of PC-3 human androgen independent prostate cancers xenografted s.c. into nude mice. Binding assays were used to investigate GHRH receptors. The levels of IGF-II and VEGF in tumors were measured by radioimmunoassays. Results: Treatment with 2.5, 5, and 10 mű g/day MZ-J-7-138 caused a significant dose-dependent growth reduction of PC-3 tumors. The greatest inhibition of 78% was obtained with 10 mű g/day. The suppression of IGF-II protein levels in tumors was seen at all doses of MZ-J-7-138, but only 10 microg dose induced a significant inhibition. MZ-J-7-138 also reduced VEGF protein levels, the inhibition being significant at doses of 5 and 10 microg. Specific high affinity binding sites for GHRH were found on PC-3 tumors using 125I-labeled GHRH antagonist JV-1-42. MZ-J-7-138 displaced radiolabeled JV-1-42 with an IC50 of 0.32 nM indicating its high affinity to GHRH receptors. Real-time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH-R) as well as pituitary type of GHRH-R and GHRH ligand. Conclusion: Our results demonstrate the efficacy of GHRH antagonist MZ-J-7-138 in suppressing growth of PC-3 prostate cancer at doses lower than previous antagonists. The reduction of levels of growth factors such as VEGF and IGF-II in tumors by GHRH antagonist was correlated with the suppression of tumor growth.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The Prostate. - 68 : 16 (2008), p. 1763-1772. -
További szerzők:Schally, Andrew Victor Buchholz, Stefan Rick Ferenc G. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Mile Melinda (1983-) (gyógyszerész) Groot, Kate Hohla, Florian Zarándi Márta Varga József L.
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4.

001-es BibID:BIBFORM033538
035-os BibID:WOS:000240968100047
Első szerző:Hohla, Florian
Cím:Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel / Florian Hohla, Andrew V. Schally, Karoly Szepeshazi, Jozsef L. Varga, Stefan Buchholz, Frank Köster, Elmar Heinrich, Gabor Halmos, Ferenc G. Rick, Chandrika Kannadka, Christian Datz, Celia A. Kanashiro
Dátum:2006
ISSN:0027-8424
Megjegyzések:We investigated the effect of antagonists of growth hormone-releasing hormone (GHRH) MZ-J-7-138 and JV-1-92 on H460 human non-small cell lung carcinoma (NSCLC) xenografted orthotopically into nude mice. Treatment with MZ-J-7-138 or JV-1-92 inhibited orthotopic growth of H460 NSCLC by 52-65% (P < 0.001) and was associated with a significant decrease in protein expression of K-Ras, cyclooxygenase-2 (Cox-2) and phospho-Akt (pAkt). in other experiments, treatment with MZ-J-7-138 or docetaxel reduced tumor volume of s.c. xenografted H460 human NSCLC by 30-36% (P < 0.01). The combination of MZ-J-7-138 and docetaxel resulted in a synergistic growth inhibition of H460 NSCLC xenografts of 63%. MZ-J-7-138 alone or in combination with docetaxel significantly reduced protein levels of K-Ras, Cox-2, and pAkt by 56-63%. Docetaxel given singly diminished the protein levels only of Cox-2 and did not affect K-Ras and pAkt. High-affinity binding sites, mRNA, and protein expression of pituitary GHRH receptors and its splice variant (SV) 1 were found in H460. H460 NSCLC cells contained GHRH peptide, and its growth was significantly inhibited in vitro by 10 mu M MZ-J-7-138 (P < 0.001). Serum insulin-like growth factor 1 (IGF1) was not reduced by either GHRH antagonists. These findings suggest that antiproliferative effects of GHRH antagonists in H460 NSCLC are associated with down-regulation of K-Ras, Cox-2, and pAkt. In conclusion, GHRH antagonists in combination with docetaxel synergistically inhibit growth of H460 NSCLC and the expression of K-ras, Cox-2, and pAkt, which might abrogate the signal transduction pathways for cell growth stimulation and therapeutic resistance.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 103 : 39 (2006), p. 14513-14518. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Varga József L. Buchholz, Stefan Köster, Frank Heinrich, Elmar Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Rick Ferenc G. Kannadka, Chandrika Datz, Christian Kanashiro, Celia A.
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5.

001-es BibID:BIBFORM019785
Első szerző:Hohla, Florian
Cím:Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells / Hohla Florian, Buchholz Stefan, Schally Andrew V., Krishan Awtar, Rick Ferenc G., Szalontay Luca, Papadia Andrea, Halmos Gabor, Koster Frank, Aigner Elmar, Datz Christian, Seitz Stephan
Dátum:2010
ISSN:0304-3835
Megjegyzések:The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and high affinity binding sites for SST were detected in all CRC cell lines and in P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In vivo, AN-162 reduced the volume of CRC xenografts more effectively than its unconjugated components. Our results suggest that AN-162 inhibits growth of experimental CRC more effectively than DOX and increases sensitivity of DOX resistant human leukemia cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cancer Letters. - 294 : 1 (2010), p. 35-42. -
További szerzők:Buchholz, Stefan Schally, Andrew Victor Krishan, Awtar Rick Ferenc G. Szalontay Luca Papadia, Andrea Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Koster, Frank Aigner, Elmar Datz, Christian Seitz, Stephan
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6.

001-es BibID:BIBFORM011626
Első szerző:Hohla, Florian
Cím:GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells / Florian Hohla, Stefan Buchholz, Andrew V. Schally, Stefan Seitz, Ferenc G. Rick, Luca Szalontay, Jozsef L. Varga, Marta Zarandi, Gabor Halmos, Irving Vidaurre, Awtar Krishan, Metin Kurtoglu, Sudhir Chandna, Elmar Aigner, Christian Datz
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cell Cycle. - 8 : 19 (2009), p. 3149-3156. -
További szerzők:Buchholz, Stefan Schally, Andrew Victor Seitz, Stephan Rick Ferenc G. Szalontay Luca Varga József L. Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Vidaurre, Irving Krishan, Awtar Kurtoglu, Metin Chandna, Sudhir Aigner, Elmar Datz, Christian
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7.

001-es BibID:BIBFORM002243
Első szerző:Hohla, Florian
Cím:Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt / Hohla F., Schally A. V., Kanashiro C. A., Buchholz S., Baker B., Kannadka C., Moder A., Aigner E., Datz C., Halmos G.
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Proceedings of National Academy of Sciences of the United States of America. - 104 : 47 (2007), p. 18671-18676. -
További szerzők:Schally, Andrew Victor Kanashiro, Celia A. Buchholz, Stefan Baker, Benjamin Kannadka, Chandrika Moder, Angelika Aigner, Elmar Datz, Christian Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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8.

001-es BibID:BIBFORM040825
Első szerző:Papadia, Andrea
Cím:Growth Hormone-Releasing Hormone Antagonists Inhibit Growth of Human Ovarian Cancer / Papadia, A., Schally, A., Halmos, G., Varga, J., Seitz, S., Buchholz, S., Rick, F., Zarandi, M., Bellyei, S., Treszl, A., Szalontay, L., Lucci, J. A.
Dátum:2011
ISSN:0018-5043
Megjegyzések:Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 gammaM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Hormone And Metabolic Research. - 43 : 11 (2011), p. 816-820. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Varga J. (orvos) Seitz, S. Buchholz, Stefan Rick Ferenc G. Zarándi Márta Bellyei Szabolcs Treszl Andrea (1974-) (molekuláris biológus) Szalontay Luca Lucci III, J. A.
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9.

001-es BibID:BIBFORM015979
Első szerző:Papadia, Andrea
Cím:Experimental therapy of ES-2 human platinum resistant ovarian cancer with growth hormone-releasing hormone antagonist JMR-132 or with targeted cytotoxic analog somatostatin AN-162 / A. Papadia, A. Schally, S. Seitz, S. Buchholz, F. Rick, L. Szalontay, G. Halmos, A. Treszl, J. A. Lucci
Dátum:2004
ISSN:0090-8258
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:Gynecologic Oncology. - 112 : 2 (2004), p. S128-S129. -
További szerzők:Schally, Andrew Victor Seitz, Stephan Buchholz, Stefan Rick Ferenc G. Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Treszl Andrea (1974-) (molekuláris biológus) Lucci III, J. A.
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10.

001-es BibID:BIBFORM004789
Első szerző:Papadia, Andrea
Cím:Experimental therapy of ES-2 human platinum resistant ovarian cancer with targeted cytotoxic somatostatin and LHRH analogues / A. Papadia, A. V. Schally, S. Seitz, S. Buchholz, A. Treszl, L. Szalontay, G. Halmos, J. A. Lucci III
Dátum:2008
Megjegyzések:New methods are needed for treatment of platinum resistant ovarian cancers. It has been shown that ovarian cancers express receptors for LHRH and somatostatin. The aim of the study is to test targeted cytotoxic analogue of somatostatin AN-162 [AEZS-124] and of LHRH AN-152 [AEZS-108] consisting of Doxorubicin (DOX) conjugated respectively to somatostatin octapeptide RC-121 and to [D-Lys6] LHRH analogue, which act as a carrier. Methods. The expression of mRNA for somatostatin and LHRH receptors in ES-2 platinum resistant human ovarian cancer cell line was investigated by RT-PCR. Somatostatin and LHRH receptor proteins were measured by ligand competitive assays. Nude mice bearing ES-2 tumors were randomized into five groups, which received weekly intravenous injections of AN-162, DOX, somatostatin analogue (RC-160), combination of RC-160 and DOX or solvent, respectively. Mean tumor volumes measured weekly were compared with ANOVA test. Subsequently, the effect of AN-162 and AN-152 versus DOX was tested in a similar model. The doses of AN-162, AN-152 and RC-160 were equivalent to 1.45 mg/kg DOX (2.5 ?mol/kg). Results. ES-2 expressed mRNA for sstr1, sstr2, sstr3, sstr4 and also for LHRH receptors. High affinity binding sites for LHRH (Kd = 3.84 nM; Bmax = 287.9 fmol/mg protein) and somatostatin (Kd = 6.71 nM; Bmax = 375.9 fmol/mg protein) were demonstrated in ES-2 cancer samples. Tumor volume of mice treated with AN-162 was significantly smaller than that of the other groups (p < 0.001). Tumor volumes of mice treated with RC-160 and with the combination of RC160 and DOX were also smaller than those of the control and DOX groups (p < 0.001). Final tumor growth expressed as percent of the starting volume was as follows: 1991% ? 19.4% for control, 1469% ? 29.7% for DOX, 1268% ? 23.5% for the combination of RC-160 and DOX, 1077% ? 13% for RC-160, and 813% ? 21.6% for AN-162. Tumor growth inhibition was similar with AN-162 and AN-152 and greater as compared to DOX or control (P < 0.005). Conclusion. Targeted somatostatin and LHRH cytotoxic analogues AN-162 and AN-152 produce a greater inhibition of tumor growth than DOX in somatostatin and LHRH receptor positive platinum resistant human ovarian cancer. These findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of gynecological cancers and other cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idézhető absztrakt
Megjelenés:Gynecologic Oncology. - 111 : 2 (2008), p. 376. -
További szerzők:Schally, Andrew Victor Seitz, S. Buchholz, Stefan Treszl Andrea (1974-) (molekuláris biológus) Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Lucci III, J. A.
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11.

001-es BibID:BIBFORM011473
Első szerző:Seitz, Stephan
Cím:Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition / Seitz S., Schally A. V., Treszl A., Papadia A., Rick F., Szalontay L., Szepeshazi K., Ortmann O., Halmos G., Hohla F., Buchholz S.
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Anti-Cancer Drugs. - 20 : 7 (2009), p. 553-558. -
További szerzők:Schally, Andrew Victor Treszl Andrea (1974-) (molekuláris biológus) Papadia, Andrea Rick Ferenc G. Szalontay Luca Szepesházi Károly Ortmann, Olaf Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hohla, Florian Buchholz, Stefan
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