PubMed Health⌕ Search

Biomedical subjects

N Kan

Publications and source records attributed to N Kan.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effect of vitamin E on toxicity and antitumor activity of adriamycin in mice.

The use of vitamin E as a protective agent against adriamycin-induced toxicity in CDF1 and BDF1 mice resulted in potentiation of the chemotherapeutic index of adriamycin. A single dose of 15 mg of adriamycin per kg body weight produced a significantly reduced mean survival time. A dosage of adriamycin of 15 mg per kg body weight was employed in the following experiments. In P388 ascites tumor-bearing mice, four consecutive injections of several doses of vitamin E before injection of adriamycin produced a significant prolongation of the mean survival. In concomitant studies of serum tocopherol content, 7 to 10 micrograms/ml appeared to be an appropriate serum concentration, in accordance with the result of our previous report on its immunopotentiation effect. alpha-tocopherol seemed to have a two- to three-fold greater physiological activity than alpha-tocopheryl acetate. Dietary vitamin E treatments offered no protection against adriamycin toxicity, because the serum tocopherol content reached only 4.39 micrograms/ml in mice given the vitamin E-sufficient feed in this study. The results suggested that an increase of the serum tocopherol level to about two to three times the untreated control would be required before the adriamycin treatment to reduce its toxicity.

Animals↗
PubMed1986

[Augmentation of the anti-tumor activity of regional lymph node lymphocytes and spleen cells of tumor-bearing mice by culture with T cell growth factor in vitro--a comparison of the intestinal cancer model and footpad cancer model].

The anti-tumor activity of regional lymph node lymphocytes (RLNL) of DS mice bearing syngeneic carcinoma SC42 was observed both in intestinal cancer model and in footpad cancer model, while neither spleen cells (SPLC) nor distant lymph node lymphocytes showed any activity in Winn's tumor neutralizing test. This anti-tumor activity of RLNL was tumor specific examining between SC42 and SC115. RLNL in both cancer models did not show any cytotoxic activity against SC42 measured by 51Cr release test. However, after 9 days of culture with lectin-free T cell growth factor (LF-TCGF), the cytotoxic activity against SC42 of RLNL was induced in both cancer models. Cultured SPLC showed the cytotoxic activity against SC42 only in intestinal cancer model. Any lymphocytes from normal mice showed no cytotoxic activity against SC42 after culture with LF-TCGF. Moreover, the cytotoxic activity of cultured RLNL was tumor specific between SC42 and SC115, while that of cultured SPLC was non-specific. These results indicated that RLNL was immunologically important in tumor bearing host and the immunological significance of spleen was different between intestinal cancer and cancer of other sites.

Animals↗
PubMed1986

[Effect of combined immunotherapy using two different BRMs; OK-432 and IL-2-cultured lymphocytes].

We have developed an adoptive immunotherapy (AIT) system using syngeneic tumor-bearer-spleen cells cultured with interleukin-2 (IL-2) and soluble tumor extract. The therapeutic effect of the AIT was significantly augmented by in vivo local preadministration of a streptococcal preparation, OK-432. The previous report demonstrated a mechanism in which OK-432 augments the effect of AIT. That is, OK-432 induces IL-2 in vivo and prolongs the in vivo life span of cultured, IL-2-dependent lymphocytes (CL). This paper describes another mechanism, that is, the synergism between CL and OK-432-induced host lymphocytes. Fresh spleen cells (FSC) obtained from mice in complete remission after chemotherapy (cyclophosphamide, 100 mg/kg) showed a clear synergistic anti-tumor effect on CL, when both were injected i.p. into MOPC104E-bearing BALB/c mice which had been inoculated i.p. with 1 X 10(5) tumor cells 5 days previously. The effect was greatest when the FSC: CL ratio was 4:1, whereas the administration of either FSC or CL alone had little effect. The effector population of CL that exhibited synergism on FSC was Lyt 2+, cytotoxic T cells. FSC and CL both needed a tumor-specific combination. In addition, OK-432-induced tumor-infiltrating, intraperitoneal lymphocytes had a similar synergistic effect on CL as assessed by the transplantability of intraperitoneal cells. Probably because of this mechanism, OK-432 showed a much higher augmenting effect on AIT using CL than in vivo administration of IL-2. This therapy system using OK-432 and CL is a proper model which, through combined use of different, correlated BRMs, may bring a great effect whereas the effect of single BRM is weak.

Animals↗
PubMed1985

Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts.

Avian carcinoma virus MH2 contains two potential transforming genes, delta gag-mht and delta gag-myc. Thus, MH2 may be a model for two-gene carcinogenesis in which transformation depends on two synergistic genes. Most other directly oncogenic viruses contain single, autonomous transforming (onc) genes and are models for single-gene carcinogenesis. To determine which role each potential onc gene of MH2 plays in oncogenesis, we have prepared deletion and frameshift mutants of each of the two MH2 genes by in vitro mutagenesis of cloned proviral DNA and have tested transforming function and virus production in cultured primary quail cells. We have found that mht deletion mutants and wild-type virus transform primary cells and that myc deletion and frameshift mutants do not. The morphologies of cells transformed by the mht deletion mutants and by wild-type MH2 are similar yet vary considerably. Nevertheless, typical mutant transformed cells can often be distinguished from cells transformed by wild-type MH2. We conclude that the delta gag-myc gene transforms primary cells by itself, without the second potential onc gene. This myc-related gene is the smallest that has direct transforming function. delta gag-mht is without detectable transforming function but may affect transformation by delta gag-myc. Thus, MH2 behaves like a virus with a single onc gene, although it expresses two potential onc genes, and it appears not to be a model for two-gene carcinogenesis. Further work is necessary to determine whether the delta gag-mht gene possibly enhances oncogenic function of delta gag-myc or has independent oncogenic function in animals.

Animals↗
PubMed1985

[An in vitro sensitivity assay of anti-cancer agents by measuring the inhibition rate of DNA synthesis (3H-thymidine uptake) of cancer cells--clinical study].

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.

Antineoplastic Agents↗