IN VITRO ANTINEOPLASTIC DRUG TOXICOLOGY CHARACTERIZATION

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$332,369.00
Award Year:
1987
Program:
SBIR
Phase:
Phase II
Contract:
n/a
Award Id:
3055
Agency Tracking Number:
3055
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
Hipple Cancer Research Center (Currently Hipple Cancer Research)
4100 South Kettering Boulevard, Dayton, OH, 45439
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Francis Aliosman
Principal Investigator
(513) 293-8508
Business Contact:
() -
Research Institution:
n/a
Abstract
AMONG THE MAJOR DOSE-LIMITING TOXICITIES OF CURRENTLY USED ANTICANCER DRUGS ARE THOSE AFFECTING THE BONE MARROW, CARDIOVASCULAR SYSTEM, LUNGS, GASTROINTESTINAL TRACT AND THE NERVOUS SYSTEM. HOWEVER, HEMATOTOXICITIES CONSTITUTE THE MOST COMMON AND OFTEN MOST SIGNIFICANT SIDE EFFECT OF THE MAJORITY OF AGENTS. WE PROPOSE THE FURTHER DEVELOPMENT AND CHARACTERIZATION OF IN VITRO SYSTEMS FOR HUMAN MYELOPOIESIS (CFU-GM), ERYTHROPOIESIS (CFU-E/BFU-E) AND MEGAKARYOPOIESIS (CFU-MEG) WITH WHICH TO QUANTIFY AND CHARACTERIZE MYELOTOXICITIES INDUCED AT CLINICALLY ACHIEVABLE DRUG EXPOSURES FOR CIS-PLATINUM, METHOTREXATE, BCNU, VINCRISTINE AND CHLOROZOTOCIN. SURVIVING COLONIES WILL BE STAINED AND ASSESSED MORPHOLOGICALLY AND CYTOCHEMICALLY. OBSERVED IN VITRO TOXICITIES WILL BE CORRELATED WITH THE KNOWN CLINICAL TOXICITIES OF THESE AGENTS. IN PHASE II OF THE CONTRACT A WIDER RANGE OF ANTICANCER AGENTS WILL BE EVALUATED USING THESE SYSTEMS AND THE KINETICS OF TOXICITY INDUCTION INVESTIGATED IN GREATER DETAIL. DELAYED AND CUMULATIVE TOXICITY WILL BE INVESTIGATED USING LONG-TERM BONE MARROW CULTURES. IN ORDER TO IMPROVE THE THERAPEUTIC INDICES OF THE MOST SIGNIFICANTLY MYELO-SUPPRESSIVE AGENTS, CYTO- AND CHEMOPROTECTIVE AGENTS WILL BE EVALUATED FOR THEIR ABILITY TO SELECTIVELY PROTECT BONE MARROW CELLS AGAINST DRUG-INDUCED DAMAGE.

* information listed above is at the time of submission.

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