17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and Multiple-Endocrine-Neoplasia-Type-1

17-(dimethylaminoethylamino)-17-demethoxygeldanamycin has been researched along with Multiple-Endocrine-Neoplasia-Type-1* in 1 studies

Other Studies

1 other study(ies) available for 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and Multiple-Endocrine-Neoplasia-Type-1

ArticleYear
Expression and therapeutic relevance of heat-shock protein 90 in pancreatic endocrine tumors.
    Endocrine-related cancer, 2012, Volume: 19, Issue:3

    Pancreatic endocrine tumors (PET) represent a heterogenous group of neoplasms. Although surgical resection is considered a safe and effective treatment for many PET, therapeutic options for inoperable and progressive PET are limited. The expression of heat-shock protein (HSP) 90 was investigated in 120 clinically and pathomorphologically well-characterized PET from 84 patients using immunohistochemistry. In addition, in 19 snap-frozen PET and in three healthy pancreatic tissues, we performed immunoblot analyses, and in 15 snap-frozen PET and in three healthy pancreatic tissues, we investigated the expression of HSP90 isoforms by means of semiquantitative RT-PCR. Functional tests were conducted using the human pancreas carcinoid cell line BON and the mouse insulinoma cell line β-TC-3. HSP90 was expressed in 95% of the PET patients. The transcript levels of the HSP90 isoforms HSP90α, HSP90β, glucose-related protein 94, and TNF receptor-associated protein 1 were significantly increased in PET compared with non-neoplastic pancreatic tissues. The treatment of the cell lines BON and β-TC-3 with the HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin resulted in significant, dose-dependent reduction of cell viability, cell cycle arrest, and increased apoptosis. Furthermore, HSP90 inhibition induced the degradation and inactivation of several oncogenetic HSP90 client proteins in a time- and dose-dependent manner. HSP90 inhibitors increased the therapeutic effects of doxorubicin and 5-fluorucacil in BON and β-TC-3 cells. HSP90 is expressed in the vast majority of PET and its inhibition reveals significant treatment effects in vitro. Thus, HSP90 qualifies as a promising new target.

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Apoptosis; Benzoquinones; Cell Line, Tumor; Cell Survival; Doxorubicin; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Male; Mice; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; RNA, Messenger; Young Adult

2012
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