Journal article
Architectural Heterogeneity in Tumors Caused by Differentiation Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound
Journal of oncology, Vol.2010, pp.396286-13
01/01/2010
DOI: 10.1155/2010/396286
PMCID: PMC2860580
PMID: 20445750
Abstract
Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.
Details
- Title: Subtitle
- Architectural Heterogeneity in Tumors Caused by Differentiation Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound
- Creators
- Youcef M. Rustum - Roswell Park Cancer InstituteKaroly Toth - Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USAMukund Seshadri - Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USAArindam Sen - Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USAFarukh A. Durrani - Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USAEmily Stott - Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USACarl D. Morrison - Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USAShousong Cao - Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USAArup Bhattacharya - Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA
- Resource Type
- Journal article
- Publication Details
- Journal of oncology, Vol.2010, pp.396286-13
- DOI
- 10.1155/2010/396286
- PMID
- 20445750
- PMCID
- PMC2860580
- NLM abbreviation
- J Oncol
- ISSN
- 1687-8450
- eISSN
- 1687-8450
- Publisher
- Hindawi Publishing Group
- Number of pages
- 13
- Grant note
- R21CA133682 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA016056 / National Cancer Institute, Bethesda, Md, USA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 1R21 CA133682-01A2 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 01/01/2010
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359919502771
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