In Vitro Assays for Methionine-Dependent Chemotherapy

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$50,000.00
Award Year:
1993
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Agency Tracking Number:
22007
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
Anticancer, Inc.
7917 Ostrow Street, San Diego, CA, 92111
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Hui-yan Guo
(619) 654-2555
Business Contact:
() -
Research Institution:
n/a
Abstract
We are developing a new tumor selective treatment termed antimethionine chemotherapy. Many tumor types have been shown to exhibit an absolute requirement for methionine in vitro in order to proliferate. Normal cells and tissues can utilize homocysteine in place of methionine in order to proliferate. Methionine dependence causes methionine-dependent tumor cells to synchronously arrest in the late-S/G2 phase of the cell cycle. The selective synchronization of tumor cells by methionine deprivation allows the tumor cells to be selectively killed by antitumor drugs such as vincristine when the cell cycle block is alleviated with methionine. In order to bring methionine-dependent chemotherapy closer to the clinic, we will develop assays of methionine dependence with actual tumor specimens put into Collagen sponge-matrix supported histoculture. These assays will be based on biochemical parameters, which involve measurements of S-adenosylmethionine to S-adenosylhomocysteine ratios, and on cell cycle parameters which involve measuring arrest in the cell-cycle as late S/G2 in methionine-free homocysteine-containing medium. These assays will be compared in Phase I to their ability to predict in vitro susceptibility of the tumors to antimethionine chemotherapy based on methionine depletion and subsequent methionine repletion with chemotherapeutic drugs. In Phase II, we will compare the assays ability to predict sensitivity to antimethionine therapy in vivo with the purified methioninase currently produced in our laboratory.

* information listed above is at the time of submission.

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