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Titolo:
FLAVONE ACETIC-ACID INCREASES THE CYTOTOXICITY OF MITOMYCIN-C WHEN COMBINED WITH HYPERTHERMIA
Autore:
TAKEUCHI H; BABA H; MAEHARA Y; SUGIMACHI K; NEWMAN RA;
Indirizzi:
KYUSHU UNIV HOSP,CTR CANC,HIGASHI KU,3-1-1 MAIDASHI FUKUOKA 812 JAPAN KYUSHU UNIV,FAC MED,DEPT SURG 2,HIGASHI KU FUKUOKA 812 JAPAN UNIV TEXAS,MD ANDERSON CANC CTR HOUSTON TX 77030
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 1, volume: 38, anno: 1996,
pagine: 1 - 8
SICI:
0344-5704(1996)38:1<1:FAITCO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; CELLS INVITRO; HYPOXIC CONDITIONS; ACTIVATION; MICE; CARBOQUONE; RADIATION; NSC-347512; DEFICIENT; CARCINOMA;
Keywords:
FLAVONE ACETIC ACID; MITOMYCIN C; HYPERTHERMIA; TUMOR BLOOD FLOW; HYPOXIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
H. Takeuchi et al., "FLAVONE ACETIC-ACID INCREASES THE CYTOTOXICITY OF MITOMYCIN-C WHEN COMBINED WITH HYPERTHERMIA", Cancer chemotherapy and pharmacology, 38(1), 1996, pp. 1-8

Abstract

Flavone acetic acid (FAA, NSC 347512) is known to selectively reduce tumor blood flow. Taking advantage of this pharmacodynamic effect, we have previously shown that FAA in combination with hyperthermia (HT) can produce a marked improvement in antitumor response in mice. In the present study, we investigated whether FAA could increase the cytotoxicity of mitomycin C (MMC), a bioreductive drug with selective cytotoxicity against hypoxic cells, under either normothermic or hyperthermic conditions. In vitro, the cytotoxicity of MMC against B16 melanoma cells was not enhanced with exposure to FAA at concentrations less than 100 mu g/ml, even when combined with HT (43 degrees C, 60 min). The cytotoxicity of MMC (1 mu g/ml) at pH 6.5, however, was enhanced by exposure of cells to hypoxia in combination with HT. In vivo, the tumor growth time, calculated as the time required to double the initial tumor volume, was 5.2, 6.8, 8.5, and 15.0 days with FAA (150 mg/kg) alone, MMC (4 mg/kg) alone, FAA + MMC, or FAA + MMC + HT (43 degrees C, 15 min) treatment groups, respectively. Antitumor response obtained in animals treated with FAA plus MMC with HT was clearly better than that obtained in any of the other groups. Scheduling of FAA, MMC, and HT was found to be important in producing optimal antitumor response. Administration of MMC (4 mg/kg) prior to FAA (150 mg/kg) and subsequent HT treatment was superior to administration of FAA before MMC. In an attempt to explain these findings, the influence of FAA on blood flow in skeletal muscle and in tumor was examined using a laser blood flowmeter. FAA administration to mice produced a 75% reduction in blood flow to thetumor for up to 2 h but had no detectable effect on normal skeletal blood flow. Our current explanation of the increased antitumor responseachieved with the combination of MMC, FAA, and HT is as follows. The FAA-mediated decrease in blood flow to the tumor, when combined with HT, may produce sufficiently hypoxic conditions to significantly increase the antitumor efficacy of the bioreductive drug, MMC. We believe that clinical testing of this combined drug treatment with hyperthermia is warranted.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 07:36:30