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Titolo:
IMMUNOMODULATORY ACTIONS OF XANTHENONE ANTICANCER AGENTS
Autore:
BAGULEY BC; CHING LM;
Indirizzi:
UNIV AUCKLAND,SCH MED,CANC RES LAB,PRIVATE BAG 92019 AUCKLAND 1000 NEW ZEALAND
Titolo Testata:
Biodrugs
fascicolo: 2, volume: 8, anno: 1997,
pagine: 119 - 127
Fonte:
ISI
Lingua:
ENG
Soggetto:
FLAVONE ACETIC-ACID; TUMOR-NECROSIS-FACTOR; POTENTIAL ANTITUMOR AGENTS; KILLER CELL-ACTIVITY; MURINE RENAL-CANCER; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID; FLAVONE-8-ACETIC ACID; COLON-38 TUMORS; FACTOR-ALPHA; 9-OXO-9H-XANTHENE-4-ACETIC ACID;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
63
Recensione:
Indirizzi per estratti:
Citazione:
B.C. Baguley e L.M. Ching, "IMMUNOMODULATORY ACTIONS OF XANTHENONE ANTICANCER AGENTS", Biodrugs, 8(2), 1997, pp. 119-127

Abstract

Derivatives of xanthenone-4-acetic acid (XAA) were developed as analogues of flavone-8-acetic acid (FAA), a drug with excellent activity against experimental tumours in mice but no clinical activity. XAA derivatives were found to differ from conventional cytotoxic agents try having little direct cytotoxic activity against cultured cells. However, they exhibit pronounced immunomodulatory activity, inducing natural killer activity in mice and stimulating peritoneal macrophages to kill cultured tumour cells. They also induce selective reduction in tumour blood flow, leading to tumour haemorrhagic necrosis. The key to these actions appears to be the induction of cytokines, including tumour necrosis factor (TNF) and interferons. Cytokines are thought to mediate the increase in natural killer activity, the in vitro killing of tumour cells, and, through effects on vascular endothelial cells, the reduction of tumour blood flow and consequent onset of tumour necrosis. Although the target of XAA derivatives is not known, there is evidence for species differences. In particular, FAA induces messenger RNA for TNF in cultured mouse cells but not in cultured human cells, whereas one of the XAA derivatives, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces it in both murine and human cells. DMXAA is also more active and 12 times more dose potent than FAA in the mouse, and on this basis has been selected for clinical trials as a novel low molecular weight immunomodulatory antitumour agent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 02:51:00