Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I).

Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I). Research Abstract Details 

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Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I). Abstract Text:

Helena Jernberg-Wiklund,Kenneth Nilsson,

Human multiple myeloma (MM) is characterized by the expansion of neoplastic plasmablasts/plasma cells with complex genetic aberrations and high dependence for survival and growth on cytokines produced in the bone marrow microenvironment. As tools in the study of MM about 80 authentic MM cell lines and a few relevant in vivo mouse models are available. The dependence on insulin-like growth factor receptor (IGF-IR) signaling in the development and maintenance of the malignant phenotype in a variety of cancers is a rationale for attempts to improve tumor treatment by selectively inhibiting the IGF-IR in malignant cells by neutralizing antibodies, dominant negative IGF-IR, and IGF-IR siRNA. Testing the hypothesis that abrogating IGF-IR-mediated signaling of survival should make MM cells more susceptible to apoptosis, our studies have so far provided proof-of-principle by the demonstration that inhibition of a signaling pathway stimulating survival renders cells susceptible to drug-induced apoptosis when the drug (dexamethasone) and inhibitor (rapamycin) converge on the same target, that is p70(S6K). The recent publication of the three-dimensional structure of the IGF-IR kinase domain has facilitated the development of IGF-IR inhibitors of the cyclolignan family, that is picropodophyllin, with capacity to distinguish also in vivo between the IGF-IR and the insulin receptor. Studies in vitro and in vivo with picropodophyllin show promising effects, that is apoptosis induction and growth arrest, and have made it possible to evaluate the biological and therapeutic effects of inhibition of the IGF-IR signaling in MM.

Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I). Publishing Authors By Initials

H Jernberg-Wiklund,K Nilsson,

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Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I). Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Advances in cancer research

VOLUME: 97

Page Numbers: 139-65

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ISSN: 0065-230X

DAY: 10

MONTH: 04

YEAR: 2007

Control of Apoptosis in Human Multiple Myeloma by Insulin-like Growth Factor I (IGF-I). Information

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LANGUAGE: eng

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AFFILIATION: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.

Country: United States

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MEDLINETA: Adv Cancer Res

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