Westphalen, Anne

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Endocrinology"],["dc.bibliographiccitation.lastpage","14"],["dc.bibliographiccitation.volume","146"],["dc.contributor.author","Grundker, Carsten"],["dc.contributor.author","Gunthert, Andreas R."],["dc.contributor.author","Westphalen, S."],["dc.contributor.author","Emons, G."],["dc.date.accessioned","2018-11-07T10:33:02Z"],["dc.date.available","2018-11-07T10:33:02Z"],["dc.date.issued","2002"],["dc.description.abstract","The expression of GnRH and its receptor as a part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors; including cancers of the breast, ovary and endometrium. Dose-dependent antiproliferative effects of GnRH agonists in cell lines derived from these cancers have been observed by various investigators. GnRH antagonists also have marked antiproliferative activity in most breast, ovarian and endometrial cancer cell lines tested, indicating that the dichotomy of GnRH agonists and antagonists might not apply to the GnRH system in cancer cells. The classical GnRH receptor signal-transduction mechanisms, known to operate in the pituitary, are not involved in the mediation of antiproliferative effects of GnRH analogs in cancer cells. Rather, the GnRH receptor interacts with the mitogenic signal transduction of growth factor receptors and related oncogene products associated with tyrosine kinase activity; via activation of a phosphotyrosine phosphatase, resulting in downregulation of cancer cell proliferation. In addition, GnRH activates nuclear factor kappaB and protects the cancer cells from apoptosis. Furthermore, GnRH induces activation of the c-Jun N-terminal kinase/activator protein-1 (AP-1) pathway independent of the known AP-1 activators, protein kinase or mitogen activated protein kinase."],["dc.identifier.doi","10.1530/eje.0.1460001"],["dc.identifier.isi","000178742700001"],["dc.identifier.pmid","11751060"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44505"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bioscientifica Ltd"],["dc.relation.issn","1479-683X"],["dc.relation.issn","0804-4643"],["dc.title","Biology of the gonadotropin-releasing hormone system in gynecological cancers"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","291"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Endocrine Related Cancer"],["dc.bibliographiccitation.lastpage","299"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Grundker, Carsten"],["dc.contributor.author","Gunthert, Andreas R."],["dc.contributor.author","Westphalen, S."],["dc.contributor.author","Kavanagh, J."],["dc.contributor.author","Verschraegen, C."],["dc.date.accessioned","2018-11-07T10:38:30Z"],["dc.date.available","2018-11-07T10:38:30Z"],["dc.date.issued","2003"],["dc.description.abstract","Approximately 80% of human ovarian and endometrial cancers and 50% of breast cancers express GnRH and its receptor as part of an autocrine regulatory system. After binding of its ligand the tumor GnRH receptor couples to G-protein alphai and activates a variety of intracellular signaling mechanisms. (1) Through activation of a protein tyrosine phosphatase, autophosphorylation of growth factor receptors is reverted leading to an inhibition of mitogenic signaling and reduced cell proliferation. (2) Through activation of nuclear factor kappa B antiapoptotic mechanisms are induced protecting tumor cells from apoptosis induced, for example, by doxorubicin. (3) Through activation of the Jun kinase pathway AP-1 is induced, leading to cell cycle arrest in the G(0)/G(1) phase. It seems reasonable to speculate that this system enables the tumor cell to reduce proliferation and to activate repair mechanisms while being protected simultaneously from apoptosis. Interestingly, GnRH antagonists show the same activity in this system as agonists, indicating that the dichotomy GnRH agonist-GnRH antagonist defined in the pituitary gonadotrope is not valid for the tumor GnRH system. Recently, a second type of GnRH receptor, specific for GnRH-II, has been identified in ovarian and endometrial cancers, which transmits significantly stronger antiproliferative effects than the GnRH-I receptor. GnRH antagonists have agonistic effects on this type II receptor. In animal models of human cancers, GnRH antagonists had stronger antitumor effects than GnRH agonists. Therefore, we performed a phase II clinical trial with the GnRH antagonist, cetrorelix (10 mg/day), in patients with ovarian or mullerian carcinoma refractory to platinum chemotherapy. Of 17 evaluable patients treated with cetrorelix, 3 obtained a partial remission (18%) which lasted for 2 to 6 months. Furthermore, 6 patients experienced disease stabilization (35%) for up to 1 year. In this very refractory patient population (median number of prior chemotherapies = 3) these results are quite remarkable when compared with palliative chemotherapy. In addition, cytotoxic GnRH analogs have been developed, where for example doxorubicin was covalently coupled to GnRH analogs. These compounds have superior antitumor effects in cancers expressing GnRH receptors as compared with native doxorubicin and allow for a targeted cytotoxic chemotherapy of gynecologic and breast cancers."],["dc.identifier.doi","10.1677/erc.0.0100291"],["dc.identifier.isi","000184151400018"],["dc.identifier.pmid","12790790"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45828"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Endocrinology"],["dc.publisher.place","Bristol"],["dc.relation.conference","11th International Congress on Hormonal Steroids/7th International Congress on Hormones and Cancer"],["dc.relation.eventlocation","FUKUOKA, JAPAN"],["dc.relation.issn","1351-0088"],["dc.title","GnRH antagonists in the treatment of gynecological and breast cancers"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1063"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.lastpage","1069"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Westphalen, S."],["dc.contributor.author","Kotulla, G."],["dc.contributor.author","Kaiser, Armin Florian"],["dc.contributor.author","Krauss, W."],["dc.contributor.author","Werning, G."],["dc.contributor.author","Elsasser, H. P."],["dc.contributor.author","Nagy, A."],["dc.contributor.author","Schulz, Klaus-Dieter"],["dc.contributor.author","Grundker, Carsten"],["dc.contributor.author","Schally, Andrew V."],["dc.contributor.author","Emons, G."],["dc.date.accessioned","2018-11-07T11:24:26Z"],["dc.date.available","2018-11-07T11:24:26Z"],["dc.date.issued","2000"],["dc.description.abstract","Eighty percent of human ovarian and endometrial cancers express receptors for luteinizing hormone-releasing hormone (LHRH). These receptors might be used for targeted chemotherapy with cytotoxic LHRH analogs such as AN-152, in which doxorubicin is linked to agonist carrier [D-Lys(6)]LHRH. The antiproliferative effects of doxorubicin and AN-152 were assessed in LHRH receptor-positive ovarian (EFO-21, EFO-27) and endometrial (HEC-1A, Ishikawa) cancer cell lines as well as in LHRH receptor negative ovarian SKOV-3 and endometrial MFE-296 lines. The mechanism of action of AN-152 was investigated by a blockage of receptors using an excess of the LHRH agonist [D-Trp(6)]LHRH. In some cases, confocal laser-scanning microscopy was used to visualize the accumulation of AN-152 or doxorubicin within the cells. In 3 of 4 LHRH receptor-positive cell lines (EFO-21, HEC-1A, Ishikawa) AN-152 was more effective than doxorubicin in inhibiting cell proliferation. The effect of AN-152 was shown to be receptor-mediated because it could be reduced by competitive blockade of the LHRH receptors with [D-Trp(6)]LHRH. In contrast, AN-152 was less active than doxorubicin in LHRH receptor-negative lines. Confocal laser-scanning microscopy showed an intranuclear accumulation of AN-152 and competitive inhibition thereof by [D-Trp(6)]LHRH in LHRH receptor-positive cell lines, but no intracellular accumulation of AN-152 could be detected in the receptor-negative SKOV-3 line. These results suggest a selective receptor-mediated action of AN-152 in receptor-positive cell lines."],["dc.identifier.isi","000089825300028"],["dc.identifier.pmid","11029513"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56405"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Professor D A Spandidos"],["dc.relation.issn","1019-6439"],["dc.title","Receptor mediated antiproliferative effects of the cytotoxic LHRH agonist AN-152 in human ovarian and endometrial cancer cell lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]