picibanil and Thymoma

Sixty-seven patients with thymoma were surgically treated during the past 19 years in our department. The 5-year, 10-year and 15-year survival rates of total cases with thymomas were 69.2%, 59.6% and 59.6%, respectively. Survival rates of thymoma with MG and without MG were not significantly different. According to clinical stages in Masaoka's classification, there were significant difference between Stage I and Stag III (p < 0.05), Stage I and Stage IV a (p < 0.01), and Stage I and Stage IV b (p < 0.01). We can conclude that complete resection of thymomas lead to better prognosis, and immunochemotherapy using cyclophosphamide, vincristine and OK-432 are effective.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Humans; Male; Middle Aged; Picibanil; Prognosis; Survival Rate; Thymoma; Thymus Neoplasms; Vincristine

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Drug Synergism; Female; Fibrosarcoma; Immunity; In Vitro Techniques; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Picibanil; Recombinant Proteins; Spleen; T-Lymphocytes, Cytotoxic; Thymoma

The present study was designed to examine whether cyclophosphamide augmented induction of antitumor cells and antitumor resistance in C57BL/6 mice pretreated with mitomycin-C-treated EL4 cells (EL4MMC) plus OK-432, a streptococcal preparation. C57BL/6 mice were pretreated with EL4MMC (10(7] plus OK-432 (2.5 KE) i.p. twice at 1-week intervals. When the mice received an i.p. injection of cyclophosphamide at 200 mg/kg 2 days before the last treatment, the antitumor activity of their spleen cells and peritoneal exudate cells (PEC) was effectively augmented 7-8 days after the last treatment. Splenic antitumor activity disappeared 15 days after the last treatment whereas augmented antitumor activity of the PEC was detected even 28 days after the last treatment. This cyclophosphamide effect was dose-dependent and 200 mg/kg was the most effective among the doses tested. If the EL4MMC plus OK-432 treatment was injected at a s.c. site, it was also effective in combination with cyclophosphamide. The antitumor activity of the PEC from s.c.-pretreated mice, however, was lower than that from i.p.-pretreated mice. Despite the fact that cyclophosphamide effectively augmented induction of antitumor cells in C57BL/6 mice pretreated with EL4MMC plus OK-432, it diminished rather than augmented, under all conditions tested, the ability of the mice to resist a challenge of live EL4 cells. Reduction of antitumor resistance by cyclophosphamide was also observed in an experimental system of a semi-syngeneic host (BDF1) tumor (EL4). These results indicate that augmentation of in vivo induction of certain kinds of antitumor cells does not necessarily result in a beneficial augmentation of the host's ability to resist tumor growth.

Topics: Animals; Cyclophosphamide; Dose-Response Relationship, Drug; Immunity, Cellular; Immunotherapy; In Vitro Techniques; Mice; Mice, Inbred C57BL; Mitomycin; Mitomycins; Picibanil; Thymoma; Thymus Neoplasms; Tumor Cells, Cultured

Murine spleen cells cultured for 3 or more days in medium with streptococcal preparation OK-432 became cytotoxic in vitro against several allogeneic and syngeneic tumor cells. These cytotoxic cells were designated OK-432-induced killer (OIK) cells. This study examined the in vivo antitumor efficacy of OIK cells in adoptive immuno- and immunochemo-therapy in mice bearing syngeneic tumors, such as EL-4 lymphoma, Meth-A fibrosarcoma, and MOPC-31C plasmacytoma. OIK cells neutralized these tumor cells, as shown by Winn-type tests, and the cell transfer prolonged the survival of mice inoculated intraperitoneally (ip) with EL-4 or Meth-A cells. Concomitant administration of OK-432 plus recombinant interleukin 2 (rIL-2) significantly improved the therapeutic efficacy of the transferred OIK cells. In mice inoculated with 1 x 10(4) EL-4 cells, chemoimmunotherapy consisting of ip administration of 200 mg/kg cyclophosphamide on day 3 followed by treatment with OIK cell (1 x 10(7)) transfer and with OK-432 (50 KE/kg) plus rIL-2 (50 units/mouse) 6 hr later and on day 6, prolonged the survival. Therefore, the immunotherapy with OIK-cell transfer followed by administration of OK-432 and rIL-2 may be clinically useful as an adjunct of cytoreductive chemotherapy for cancer.

Topics: Animals; Biological Products; Fibrosarcoma; Immunization, Passive; Interleukin-2; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms, Experimental; Picibanil; Plasmacytoma; Thymoma

Sensitization with mitomycin C-treated L1210 or EL-4 tumor cells followed by intraperitoneal injection of a streptococcal preparation OK-432 rendered histocompatible or syngeneic mice immune to the corresponding tumor cells. The antitumor immunity, which was more potent than that induced by attenuated tumor cells alone, was manifested by transplantation resistance to challenge tumor cells, and by cytotoxic activity of spleen cells from the primed mice. The former activity was closely related to the latter, which was found to be mainly due to tumor-specific cytotoxic T lymphocytes. The in vivo immunoaugmentation by OK-432 was susceptible to macrophage toxins such as trypan blue and carragheenins, and was partly dependent on the activity of noncytotoxic Ia-positive peritoneal macrophages. OK-432-mediated enhancement of Ia-positive macrophage functions was confirmed by concanavalin A-blastogenesis and T cell-dependent antibody formation. Allo-reactive cytotoxicity induced in allogeneic or semiallogeneic mice, which had been primed with clonogenic or attenuated tumor cells, was also augmented by concomitant administration of OK-432. These results suggest that OK-432 augments induction of antitumor immunity and alloreactive cytotoxicity, associated with stimulation of noncytotoxic Ia-positive accessory macrophage activity.

Topics: Animals; Biological Products; Graft Rejection; Histocompatibility Antigens Class II; Leukemia L1210; Leukemia P388; Leukemia, Experimental; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Picibanil; T-Lymphocytes, Cytotoxic; Thymoma; Thymus Neoplasms; Transplantation, Homologous