Tumor or cancer cell killing therapy and agents useful therefor

Drug – bio-affecting and body treating compositions – Identification or warning feature – Taste or smell or chemical irritation to the eye – nose – or...

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424649, A61K 4900, G01N 3315

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active

053405650

ABSTRACT:
The effectiveness of cytostatic and/or cytotoxic drugs and/or radiation in the killing of tumor and/or cancer cells is increased by the administration, along with said drugs and radiation, of an effective activating or inhibiting amount of a compound or agent which activates or inhibits the chromatin-bound enzyme adenosine diphosphate ribosyl transferase (ADPRT) or the administration of an effective intracellular free Ca.sup.++ -increasing amount of a compound which induces cellular or oxidative stress or which acts as an inhibitor or antagonist or calmodulin or Ca.sup.++ -calmodulin binding. Suitable such compounds or agents include the phenothiazines, antihistamines, butyrophenones, cannabinoids and corticosteriods and particularly metoclopramide when employed in combination with cisplatin.

REFERENCES:
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S. Lybak et al., "Dose schedule evaluation of metoclopramide . . . ," Anti-Cancer Drugs 2: 375-82 (1991).
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L. A. Zwelling et al., "DNA-Protein and DNA Interstrand Cross-Linking . . . ," Cancer Research 39: 365-69 (1979).
C. A. Perez et al., "Impact of Irradiation Technique and Tumor Extent . . . ," Cancer 50: 1091-99 (1982).
E. Kjellen et al., "Metoclopramide enhances the effect of cisplatin . . . ," Br. J. Cancer 59: 247-50 (1989).
E. Kjellen et al., "A therapeutic benefit from combining normobaric carbogen . . . ," Radiotherapy and Oncology 22: 81-91 (1991).
S. Lybak, Metoclopramide: A representative of a new class of drugs for potentiation of cytotoxicity, University of Lud, Sweden (1991), p. 115.

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