Logo image
Back
Inhibition of Colon Cancer Growth by Methylselenocysteine-Induced Angiogenic Chemomodulation Is Influenced by Histologic Characteristics of the Tumor
Journal article   Open access   Peer reviewed

Inhibition of Colon Cancer Growth by Methylselenocysteine-Induced Angiogenic Chemomodulation Is Influenced by Histologic Characteristics of the Tumor

Arup Bhattacharya, Károly Tóth, Arindam Sen, Mukund Seshadri, Shousong Cao, Farukh A. Durrani, Erik Faber, Elizabeth A. Repasky and Youcef M. Rustum
Clinical colorectal cancer, Vol.8(3), pp.155-162
2009
DOI: 10.3816/CCC.2009.n.025
PMCID: PMC2823082
PMID: 19632930
url
https://www.ncbi.nlm.nih.gov/pmc/articles/2823082View
Open Access

Abstract

Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.
 Antiangiogenesis Differentiated tumor Drug delivery Hypoxia Selenium Vascular maturation

Details

Metrics

13 Record Views
27 Times Cited - Web of Science
Logo image