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Titolo:
Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth
Autore:
Hotz, HG; Reber, HA; Hotz, B; Sanghavi, PC; Yu, T; Foitzik, T; Buhr, HJ; Hines, OJ;
Indirizzi:
Univ Calif Los Angeles, Sch Med, Div Gen Surg, Dept Surg, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Free Univ Berlin, Benjamin Franklin Med Ctr, D-1000 Berlin, Germany Free Univ Berlin Berlin Germany D-1000 n Med Ctr, D-1000 Berlin, Germany
Titolo Testata:
JOURNAL OF GASTROINTESTINAL SURGERY
fascicolo: 2, volume: 5, anno: 2001,
pagine: 131 - 138
SICI:
1091-255X(200103/04)5:2<131:AITRHP>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-GROWTH; CELLS; METASTASIS; INDUCTION; CARCINOMA; AGM-1470; MICE;
Keywords:
pancreatic cancer; TNP-470; angiogenesis; endothelial cell; vascular endothelial growth factor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Hines, OJ Univ Calif Los Angeles, Sch Med, Div Gen Surg, Dept Surg, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA Univ Calif Los Angeles 10833 LeConte Ave,72-215 CHS Los Angeles CA USA 90095
Citazione:
H.G. Hotz et al., "Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth", J GASTRO S, 5(2), 2001, pp. 131-138

Abstract

In this study we investigated the effects of the angiogenesis inhibitor TNP-470 on human pancreatic cancer cells in vitro and in vivo. The action of TNP-470 on vascular endothelial growth factor (VEGF) was also assessed. In vitro human pancreatic cancer cells (MIAPaCa-2, AsPC-1, and Capan-1), and human umbilical vein endothelial cells (HUVEC) were exposed to increasing concentrations (1 pg/ml to 100 mug/ml) of TNP-470. Cell proliferation uas assessed after 3 days by cell count and MTT assay. In vivo, 5 x 10(6)' pancreatic cancer cells were injected subcutaneously into nude mice. Four weeks later, 1 mm(3) fragments of the resulting tumors were implanted into the pancreas of other mice. Animals received either TNP-470 (30 mg/kg every other day) or vehicle subcutaneously for 14 weeks. The volume of the primary tumorand metastatic spread were determined at autopsy Concentrations of VEGF were determined in serum (VEGF(S)) and ascites (VEGF(A)) by enzyme-linked immunosorbent assay. Microvessel density was analyzed by immunohistochemistry in CD31-stained tumor sections. In vitro, proliferation and viability of the human pancreatic cancer cell lines were significantly inhibited at high concentrations of TNP-470 (> 1 mug/ml). In contrast, TNP -470 effectively decreased the grow th of HUVEC at 100 pg/ml. In vivo, tumor volume and dissemination scores were significantly lower in all three pancreatic cancer celllines. VEGF(S) and VEGF(A) were not different between treated groups. Treatment with TNP-470 significantly reduced neoangiogenesis in tumors of all three human pancreatic cancer cell lines: MIAPaCa-2 = 74.8 +/- 7.8/0.74mm(2)vs. 24.8 +/- 3.7/0.74 mm(2); AsPC-1 = 65.3 +/- 5.0/0.74 mm(2) vs. 26.0 +/-3.4/0.74 mm(2); and Capan-1 = 82.2 +/- 5.8/0.74 mm(2) vs. 26.9 +/- 2.5/0.74 mm(2) (P <0.001). However, survival was not statistically different between groups. TNP-470 reduced tumor growth and metastatic spread of pancreaticcancer in vivo. This was probably due to the antiproliferative effect of the agent on endothelial cells rather than to the direct inhibition of pancreatic cancer cell growth. TNP-470 activity was not associated with alteration of VEGF secretion.

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Documento generato il 04/04/20 alle ore 02:12:20