Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention.

Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Research Abstract Details 

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Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Abstract Text:

Axel J Baumgarten,Heinz-Herbert Fiebig,Angelika M Burger,

Approximately 50% of all cancer patients develop cachexia, a paraneoplastic syndrome that is characterized by wasting of adipose tissue and skeletal muscle mass. Cytokines, including TNF-alpha, interleukins-1, -6, and interferon-A are known mediators of the cachectic process. The latter however represent only one of many imbalanced systems in cancer cachexia. The aim of this study was to further delineate the pathogenesis of cachexia by molecular profiling. Human renal cancer xenografts that do and do not induce cachexia in mice were used as disease models. Cachexia-associated gene expression was studied on Human Genome U95 Affymetrix arrays and revealed several new genes such as TNF-alpha ligand superfamily protein, interferon-A treatment inducible protein, and DKFZ5641I1922. The expression of the IL-8 gene was also elevated in cachexia inducing xenografts (CIX). At the protein level, TNF-alpha was found expressed only in CIX, whereas IL-1 and IL-6 were not cachexia specific. Levels of parathyroid hormone-related protein were elevated in CIX and accompanied by hypercalcemia. COX-2 and prostaglandin E2 were also found to be over expressed. By using the COX-2 inhibitors rofecoxib and nimesulide, we were able to delay tumor-mediated wasting in vivo. Overall, our results suggest that cachexia is a multigenetic disease that will require complex combinations of drugs for an effective therapeutic intervention.

Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Publishing Authors By Initials

AJ Baumgarten,HH Fiebig,AM Burger,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

PUBMED ID PMID:

MEDLINE DATE: 2007 May-Jun

Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer genomics & proteomics

VOLUME: 4

Page Numbers: 223-31

Journal Abbreviation:

ISSN: 1109-6535

DAY: 28

MONTH: 11

YEAR: 2007

Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101188791

Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention. Information

Substance Name: PTGS2 protein, human

Registry Number: EC 1.14.99.1

Grant and Affiliation Information for Molecular analysis of xenograft models of human cancer cachexia--possibilities for therapeutic intervention.

AFFILIATION: Institute for Experimental Oncology, Oncotest GmbH, Am Flughafen 12-14, D-79108 Freiburg, Germany.

Country: Greece

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MEDLINETA: Cancer Genomics Proteomics

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