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Titolo:
Bryostatin 1 induces differentiation and potentiates the antitumor effect of Auristatin PE in a human pancreatic tumor (PANC-1) xenograft model
Autore:
Mohammad, RM; Adsay, NV; Philip, PA; Pettit, GR; Vaitkevicius, VK; Sarkar, FH;
Indirizzi:
Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA Wayne State Univ Detroit MI USA 48201 os Canc Inst, Detroit, MI 48201 USA Wayne State Univ, Sch Med, Dept Internal Med, Karmanos Canc Inst,Div Hematol & Oncol, Detroit, MI 48201 USA Wayne State Univ Detroit MI USA 48201 atol & Oncol, Detroit, MI 48201 USA Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA Arizona State UnivTempe AZ USA 85287 Canc Res Inst, Tempe, AZ 85287 USA
Titolo Testata:
ANTI-CANCER DRUGS
fascicolo: 9, volume: 12, anno: 2001,
pagine: 735 - 740
SICI:
0959-4973(200110)12:9<735:B1IDAP>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC LYMPHOCYTIC-LEUKEMIA; WALDENSTROM MACROGLOBULINEMIA; PRECLINICAL EVALUATION; CELL-LINES; AGENTS; CANCER; DOLASTATIN-10; P21(WAF1); LYMPHOMA; INVITRO;
Keywords:
Auristatin PE; bryostatin 1; PANC-1; pancreatic tumor line; SCID mice; xenograft;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Sarkar, FH Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, 9374 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA Wayne State Univ 9374 Scott Hall,540 E Canfield Ave Detroit MI USA 48201
Citazione:
R.M. Mohammad et al., "Bryostatin 1 induces differentiation and potentiates the antitumor effect of Auristatin PE in a human pancreatic tumor (PANC-1) xenograft model", ANTI-CANC D, 12(9), 2001, pp. 735-740

Abstract

Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Hence, there is a tremendous need for development of newand effective therapy for this tumor. In an earlier study we reported a potent antitumor activity of Auristatin PE (AuriPE) against pancreatic tumor. In addition, we have also reported that bryostatin 1 (bryo1) induces differentiation of leukemia cells, but the effect of bryo1 has not been investigated in pancreatic tumors. This is the first report where we demonstrate that bryo1 induces differentiation and potentiates the antitumor effect of AuriPE in a human pancreatic tumor (PANC-1) xenograft model. A xenograft model was established by injecting the PANC-1 cells s.c. in severe combined immune deficient (SCID) mice. After development of the s.c. tumors, tumors were dissected and small fragments were transplanted in vivo to new SCID mice,with a success rate of 100% and a doubling time of 4.8 days. The SCID mouse xenograft model was used to test the in vivo differentiation effect of bryo1 and its efficacy when given alone or in combination with AuriPE. Sections from paraffin-embedded tumors excised from untreated (control) SCID micerevealed typical poorly differentiated adenocarcinoma of the pancreas. Interestingly, sections of s.c. tumors taken from bryo1-treated mice revealed carcinomas that were much lower grade and less aggressive, and displayed prominent squamous and glandular differentiation. In this study, the tumor growth inhibition (T/C), activity score and cure rate for bryo1, AuriPE and bryo1+AuriPE were 80%, (+) and 0/4; 0.0%, (++++) and 3/5; and 0.0%, (++++) and 3/4, respectively. Mice treated with either AuriPE or bryo1+AuriPE were free of tumors for more than 150 days and were considered cured. The use ofbryo1 as a novel differentiating agent and its combination with AuriPE should be further explored for the treatment of adenocarcinoma of the pancreas. [(C) 2001 Lippincott Williams & Wilkins.].

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 09:49:41