[The oral administration of OK-432. The 5th report: the effects on the lymphoproliferative response and natural killer cell activity in mice with transplanted cecal tumors].
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Biomedical subjects
Publications and source records attributed to T Inamoto.
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In order to evaluate the clinical usefulness of an electronic real-time linear array scanner in breast diseases, ultrasonography was performed in 148 cases of histologically confirmed palpable breast masses. The real-time images were observed on a television monitor while moving the hand-held transducer probes over the masses. It took only a few minutes to examine and diagnose a palpable mass. Among 45 carcinomas, 39 lesions were correctly diagnosed, four lesions were not detected by ultrasound and two were misdiagnosed as fibroadenomas. On the other hand, ten benign lesions were falsely diagnosed as breast cancers: seven mastopathies (including four sclerosing adenosis), two fibroadenomas and one abscess. The sensitivity and specificity for diagnosing breast cancer were 0.87 and 0.90 respectively. Real-time sonography is a simple, time-saving and useful tool for examining palpable breast masses. However, it should be realised that some breast cancers are difficult to image and differentiate from benign lesions.
In this paper, we demonstrated a selection system of anti-cancer agents (ACA) using discontinuous Ficoll density gradient method (DFDGM) for purification of tumor cells and 3H-Thymidine for evaluation of DNA synthesis of tumor cells. The tumor cells, purified to more than 80% by DFDGM, were contacted with ACAs for 3 days from the culture initiation and tumor suppression rate (TSR) by ACAs were calculated by following formula; TSR = ACA(-)cpm-ACA(+)cpm-background cpm divided by ACA(-)cpm-background cpm X 100% 7 ACAs; Mitomycin C (MMC), Adriamycin (ADM), 5-Fluorouracil (5-FU), Cytosine Arabinoside (Ara-C), Carbazilquinone (CQ), ACNU and Cis-platinum (CDDP) were examined in 106 cancers; 60 breast cancers, 18 gastric cancers, 23 colorectal cancers and 5 others. ADM and CQ showed high TSR against breast cancers, CQ against gastric cancers, and 5-FU and CQ against colorectal cancers, respectively. The reliability of this ACA selection system should be evaluated by future clinical studies, however, we stress that ACA should be selected by not only the effect on tumor cells but also the effect on immunity of the host, in future.
Clinical efficacy and safety of SM-4300, a newly developed human immunoglobulin, have been studied in 7 episodes of severe infections complicated with advanced cancer. Clinical effect of SM-4300 was good in 1 case, fair in 5 and poor in 1. The efficacy rate was summarized as 14.35%, and the rate including fair response was 85.7%. No subjective and objective clinical side effect was observed and abnormal laboratory findings were not noted. In conclusion, combination therapy with SM-4300 and antibiotics was considered to be safe and effective against the patients with severe infections complicated with advanced cancer.
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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.
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.