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Titolo:
THE EFFECT OF PACLITAXEL ON THE PROGRESSION OF POLYCYSTIC KIDNEY-DISEASE IN RODENTS
Autore:
MARTINEZ JR; COWLEY BD; GATTONE VH; NAGAO S; YAMAGUCHI T; KANETA S; TAKAHASHI H; GRANTHAM JJ;
Indirizzi:
UNIV KANSAS,MED CTR,DEPT MED,DIV NEPHROL & HYPERTENS,3901 RAINBOW BLVD KANSAS CITY KS 66160 UNIV KANSAS,MED CTR,DEPT BIOCHEM & MOL BIOL KANSAS CITY KS 66160 UNIV KANSAS,MED CTR,DEPT ANAT & CELL BIOL KANSAS CITY KS 66160 HOKKAIDO COLL PHARM OTARU HOKKAIDO JAPAN FUJITA HLTH UNIV,SCH MED TOYOAKE AICHI 47011 JAPAN
Titolo Testata:
American journal of kidney diseases
fascicolo: 3, volume: 29, anno: 1997,
pagine: 435 - 444
SICI:
0272-6386(1997)29:3<435:TEOPOT>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAN-SPRD RAT; PROTOONCOGENE EXPRESSION; MURINE MODEL; PATHOGENESIS; MOUSE;
Keywords:
PACLITAXEL; KIDNEY; HEREDITARY DISEASE; RENAL CYSTS; RENAL THERAPY; EPITHELIAL CELL PROLIFERATION; RENAL INSUFFICIENCY; APOPTOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
J.R. Martinez et al., "THE EFFECT OF PACLITAXEL ON THE PROGRESSION OF POLYCYSTIC KIDNEY-DISEASE IN RODENTS", American journal of kidney diseases, 29(3), 1997, pp. 435-444

Abstract

Woo et al (Nature 368:750-753) reported that parenteral administration of paclitaxel arrested the striking renal enlargement and prolonged life in C57BL/6J-cpk/cpk mice with a rapidly progressive form of polycystic kidney disease (PKD), In the current study, we sought to determine whether paclitaxel could alter the progression of other forms of hereditary PKD in rodents, Paclitaxel was administered by intraperitoneal injection to C57BL/6J-cpk/cpk mice and Han:SPRD-Cy/Cy rats with rapidly progressive PKD and to DBA/2FG-pcy/pcy mice and Han:SPRD-Cy/+ ratswith slowly progressive PKD, Paclitaxel (150 mu g/wk) prolonged the survival of cpk/cpk mice from 24.5 days to more than 65 days and decreased kidney weight relative to body weight from 16.5% at 21 days of ageto 8.2% at more than 65 days of age, Mortality attributable to paclitaxel was 12%, By contrast, the administration of paclitaxel (0.1 to 15mg/kg/wk) to 7- to 10-day-old Han:SPRD-Cy/Cy rats with rapidly progressive PKD had no effect on the course of the disease; moreover, paclitaxel caused severe side effects and premature death in all the Cy/Cy animals, Heterozygous male Cy/+ rats develop slowly progressive renal enlargement and azotemia. Paclitaxel, administered at 7, 15, or 27 mg/kg/wk to male Cy/+ rats from 4 until 10 weeks of age, reduced body weight gain, had an inconsistent effect on kidney weight relative to body weight, and had no effect on the serum urea nitrogen concentration. Mortality associated with the 7, 15, and 27 mg/kg/wk doses of paclitaxelwas 0%, 15.4%, and 28.5%, respectively, DBA/2FG-pcy/pcy mice of either sex developed slowly progressive renal enlargement and azotemia. Theadministration of paclitaxel (100 to 150 mu g/wk) from 2 to 10 weeks of age to DBA/2FG-pcy/pcy mice with cystic disease had no effect on the increase in kidney weight or on the level of serum urea nitrogen in comparison to untreated cystic animals, Mortality associated with 100-and 150-mu g/wk doses of paclitaxel was 0% and 20%, respectively. We conclude that paclitaxel diminished the rate of renal enlargement and increased the life span of cpk/cpk mice but not Cy/Cy rats with rapidly progressive forms of PKD. Paclitaxel had no apparent benefit in Cy/rats nor pcy/pcy mice with slowly progressive PKD. On the basis of these studies in rodents, it appears that paclitaxel has limited potential usefulness as a therapeutic agent in the treatment of PKD. (C) 1997by the National Kidney Foundation, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 00:55:21