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N Kan

Publications and source records attributed to N Kan.

82 records · Page 5Linked to original sources

Antitumor and therapeutic effects of spleen cells from tumor-bearing mice cultured with T cell growth factor and soluble tumor extract.

Spleen cells of BALB/c mice that had been inoculated with syngeneic plasmacytoma MOPC 104E were cultured for 11 days in T-cell growth factor (TCGF) and ultrasonicated tumor extract (USE). Cultured lymphocytes (MOPC-CL) possessed three-fold more lytic units than normal spleen cells cultured in TCGF without USE (N-CL). Moreover, the in vivo neutralization assay suggested that MOPC-CL were composed of at least two populations, one possessing tumor-specific and the other nonspecific antitumor activity. When 2 X 10(7) of MOPC-CL were administered IP to mice that had been inoculated IP with 10(5) MOPC 104E cells 5 days previously marginal prolongation of survival was observed. This effect was not augmented by the single injection of a larger number (5 X 10(7] of CL, but was augmented by the repeated daily administration for 4 days (from day 5 to day 8 after the inoculation) of the same total number (5 X 10(7] of CL. In addition, IP injection of the streptococcal preparation OK432 before the transfer of CL significantly enhanced the therapeutic efficacy, and resulted in a cure rate of 20%. The mechanism of this combined effect appears to involve the effect of OK432 on interleukin 2 (IL-2) regulation systems in vivo. Our culture system with TCGF and USE and our therapy system with OK432 and CL allow the clinical application of adoptive immunotherapy for the many types of solid cancers.

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[Tumor-specific cytotoxicity of tumor infiltrating lymphocytes (TIL) induced with TCGF in murine mammary carcinoma].

A medullary carcinoma with lymphocytic infiltration is associated with relatively good prognosis following radical mastectomy in breast cancer. This suggests that tumor infiltrating lymphocytes (TIL) play an important role in the immunological resistance of the host against cancer. The cytotoxic activities of TIL in murine mammary carcinoma SC42 and SC115 of syngeneic DS mice were assessed with 51Cr release assay in this study. The tumor masses were minced and trypsinized, and lymphoid cell rich fraction was separated with Percoll discontinuous gradient centrifugation. During 10 days culture with T cell growth factor (TCGF) obtained from Con A stimulated rat spleen cells, the tumor cells were collapsed and lymphocytes were expanded. The cultured TIL from SC42 tumor had stronger cytotoxicity against SC42 tumor cells than the cultured TIL from SC115 tumor and the cultured spleen cells of SC42 tumor bearer, and the cultured TIL from SC115 tumor showed predominant activity against SC115 tumor cells. Nonspecific cytotoxic activity and natural killer (NK) activity of these TIL were weaker than the cultured spleen cells. The culture of the spleen cells with the tumor cells and TCGF failed to induce tumor-specific cytotoxic lymphocytes. Moreover, the tumor-specific cytotoxicity was reduced by the treatment of anti thy-1, 2 and complement, and NK activity was reduced by the treatment of anti-asialo GM1 and complement. These results indicate that the tumor-specific cytotoxicity is latent in the T cell population of TIL and is induced by the culture with TCGF.

Animals↗

Sequential immunotherapy using interleukin-1 followed by interleukin-2 of ascitic MOPC104E-bearing mice.

This study shows that intraperitoneal injection of interleukin-1 (IL-1), followed by interleukin-2 (IL-2), can effectively eradicate murine ascitic tumor cells. This antitumor effect of IL-1 and IL-2 was abolished when administration of IL-2 preceded that of IL-1. Solid tumors inoculated subcutaneously (s.c.) into the back of mice were also sensitive to this combined i.p. therapy, indicating a systemically-operating antitumor mechanism. Splenocytes from tumor-bearing mice treated with IL-1 followed by IL-2 showed a strong tumor-neutralizing activity. The population responsible proved to be Lyt2.2 (CD8)-positive cells.

Animals↗

Anticancer chemosensitivity profiles of human breast cancer cells assessed by in vitro DNA synthesis inhibition assay.

The present study was designed to assess the profile of the chemosensitivity of breast cancer cells and to screen effective agents for combination regimens. Chemosensitivity to anticancer agents was assessed by the 3H-thymidine incorporation assay, as the rate of inhibition of DNA synthesis in 145 samples (88 primary and 57 metastatic or recurrent lesions) from 136 patients with breast cancer. The correlations of the anticancer agents with various clinicopathological factors were analysed. The effectiveness of the agents was classified as a rate of inhibition on log scale as follows: highly sensitive (> or = 30%), moderately sensitive (25-30%), slightly sensitive (20-25%), resistant (< 20%). The chemosensitivity of breast cancer showed variations according to tumor location: primary lesions seemed to be slightly sensitive to carboquone (CQ), adriamycin (ADR), and cytosine arabinoside (Ara-C); nodal involvement was moderately sensitive to CQ and slightly sensitive to Ara-C, 5-FU, ADR, mitomycin-C (MMC), and cisplatin (CDDP); malignant effusions were highly sensitive to ADR, moderately sensitive to CQ, and slightly sensitive to Ara-C and CDDP; local recurrences were slightly sensitive to Ara-C, CQ and 5-FU; vincristine (VCR) and nimustine chloride (ACNU), however, seemed to be ineffective against breast cancer. There were significant correlations in chemosensitivity between most agents, but no correlation was found between 5-FU and CDDP, 5-FU and ACNU, MMC and VCR, ADR and CDDP, ADR and VCR, and ADR and ACNU. There were no differences in chemosensitivity between stages of primary lesions or between estrogen receptor-positive and -negative tumors. In 10 patients, simultaneous nodal involvement was more sensitive to the agents than were primary lesions, and the correlation of chemosensitivity to ADR and CQ between such lesions was significant. On the other hand, there was no significant difference or correlation of chemosensitivity between the original lesions and recurrent ones after chemotherapy. The heterogeneity and homogeneity in the chemosensitivity of breast cancer suggested not only the necessity of patient-specific chemotherapy based on a sensitivity assay, but also the usefulness of choosing agents for widely-applicable combination regimens against breast cancer.

Adult↗