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Titolo:
ADMINISTRATION OF INTERLEUKIN-12 WITH PULSE INTERLEUKIN-2 AND THE RAPID AND COMPLETE ERADICATION OF MURINE RENAL-CARCINOMA
Autore:
WIGGINTON JM; KOMSCHLIES KL; BACK TC; FRANCO JL; BRUNDA MJ; WILTROUT RH;
Indirizzi:
NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM FREDERICK MD 21702 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM FREDERICK MD 21702 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS &DEV PROGRAM FREDERICK MD 21702 HOFFMANN LA ROCHE INC,DEPT ONCOL NUTLEY NJ 00000
Titolo Testata:
Journal of the National Cancer Institute
fascicolo: 1, volume: 88, anno: 1996,
pagine: 38 - 43
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; T RESPONSES INVITRO; RECOMBINANT INTERLEUKIN-2; IMMUNE-RESPONSES; INTERFERON-GAMMA; IL-12; CANCER; PROLIFERATION; INDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Wigginton et al., "ADMINISTRATION OF INTERLEUKIN-12 WITH PULSE INTERLEUKIN-2 AND THE RAPID AND COMPLETE ERADICATION OF MURINE RENAL-CARCINOMA", Journal of the National Cancer Institute, 88(1), 1996, pp. 38-43

Abstract

Background: Interleukin 2 (IL-2) and interleukin 12 (IL-12) are potent immunoregulatory cytokines that exhibit antitumor activity. Preliminary evidence suggests that combined administration of IL-2 and IL-12 may yield greater antitumor activity than that observed with either agent alone. Purpose: We evaluated the ability of combination regimens ofIL-2 and IL-12 to induce regression of established primary and metastatic murine renal carcinoma (Renca) tumors. Methods: BALB/c mice were given either subcutaneous or intrarenal injections of 10(5) Renca cells; tumor cell injections were given to 10-12 mice for each treatment group. Mice bearing subcutaneous primary tumors were treated with chronic IL-2 (300 000 IU given on a daily basis) or pulse 1L-2 (300 000 IU given twice daily one day per week) alone, IL-12 alone (0.5 mu g givenon a daily basis), or IL-12 in combination with either chronic or pulse IL-2. Mice with metastatic tumors (arising from intrarenal implants; animals were nephrectomized to remove the primary tumors) were treated with IL-12 plus or minus pulse IL-2; in these experiments, IL-12 was given at doses of either 0.5 or 1.0 mu g. In most experiments, treatment was continued for at least 3 weeks. Two-sided statistical tests were used to evaluate the data. Results: Most mice with subcutaneous Renca tumors treated with the combination of IL-12 and chronic IL-2 diedof treatment-related toxic effects within 7-14 days. In contrast, treatment with IL-12 plus pulse IL-2 was well tolerated, and six of 10 mice experienced complete tumor regression; none of the mice treated with either IL-12 alone or pulse IL-2 alone experienced a curative response. Seven of eight and nine of nine mice with metastatic tumors experienced complete tumor regression after treatment with 0.5 mu g IL-12 plus pulse IL-2 or 1.0 mu g IL-12 plus pulse IL-2, respectively; two of 12 mice treated with pulse IL-2 alone and 10% or less of mice treated with IL-12 alone were cured of metastatic tumors (with 0.5 mu g IL-12,none of 10 mice; with 1.0 mu g IL-12, one of 10 mice). Five of 10 mice with metastatic tumors treated with a short-course regimen of IL-12 and pulse IL-2 (two pulses of IL-2 flanking 5 days of 0.5 mu g IL-12) experienced complete tumor regression, while only one of the 12 mice treated with IL-2 alone and none of the mice treated with IL-12 alone experienced complete tumor regression. Virtually ail curative response frequencies obtained with IL-12 and pulse IL-2 combination regimens differed significantly (P<.05) from those obtained with corresponding single-agent treatments. Conclusions: IL-12 administered in combination with pulse IL-2 induced rapid and complete regression of primary and metastatic Renca tumors and displayed greater antitumor activity than that observed with either IL-12 or IL-2 alone.

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Documento generato il 08/07/20 alle ore 08:03:23