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The effects of behavioral stress and endothelin receptor antagonists on cancer

Citation

Montgomery, Jennifer Pielstick (2007) The effects of behavioral stress and endothelin receptor antagonists on cancer. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05222007-105207

Abstract

This work examines two potential mediators of cancer. Section one considers the putative link between behavioral stress and cancer. We developed a stress paradigm of alternating established stressors that dramatically increases serum corticosterone and causes thymus involution. When this stress paradigm was applied to mice implanted with either melanoma or lymphosarcoma tumors we observed no alteration in the growth of either tumor. In addition, we applied a protocol established in another laboratory that demonstrated a dramatic enhancement of lymphosarcoma tumors following rotational stress (Riley V. (1981). Psychoneuroendocrine influences on immunocompetence and neoplasia. Science 212, 1100-1109). We find no significant effect on lymphosarcoma progression. Therefore, under the conditions used in our studies, strong behavioral stress does not influence tumor growth.

Section two considers the effects of endothelin receptor (ETR) antagonists on cancer progression. Their ability to inhibit growth of many cancers is well documented, but similar research on glioma has been limited. We find that two ETRB-specific antagonists, BQ788 and A-192621, reduce the number of viable cells in glioma and melanoma cell lines in a dose- and time-dependent manner. In glioma cells, A-192621 induces a G2/M arrest, decreases the mean number of cell divisions and enhances apoptosis. BQ123, an ETRA-specific antagonist, has no effect on cell viability. A-192621 also up-regulates several DNA damage-inducible genes. Interestingly, reducing ETRB expression with small interfering RNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Thus, while ETRB antagonists are effective against glioma, it appears unlikely that their therapeutic effects are mediated by ETRB. Further investigation is needed to define the mechanism by which these compounds decrease cell viability.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:6C3HED; A375; B16F10; LN-229; SW1088; WM35
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Patterson, Paul H.
Thesis Committee:
  • Zinn, Kai George (chair)
  • Rothenberg, Ellen V.
  • Patterson, Paul H.
  • Fraser, Scott E.
Defense Date:15 May 2007
Record Number:CaltechETD:etd-05222007-105207
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-05222007-105207
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1954
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:29 May 2007
Last Modified:26 Dec 2012 02:44

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