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N Kumano

Publications and source records attributed to N Kumano.

At least 19 recordsLinked to original sources
PubMed1999

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Expression of nucleolar protein p120 in human lung cancer: difference in histological types as a marker for proliferation.

The function of proliferation-associated nucleolar protein p120 is unclear. A recent report that a yeast protein, NOP2, 67% homologous to human p120, is up-regulated during the onset of growth and influences the morphology of the nucleolus supports the notion that this protein could serve as a marker for proliferation in neoplastic cells. Lung cancer is characteristic in that different histological types show different biological features. We attempted to evaluate the levels of p120 expression in resected human lung cancer tissues of different histological types and the relation of p120 expression and cell proliferation using human lung cancer cell lines. When 37 frozen specimens of human lung cancer and normal lung were stained with a p120 monoclonal antibody, the nucleoli of cancer cells were positively stained, whereas a few macrophages in normal lung revealed only weak staining. The labeling index of p120 in squamous cell carcinoma (67.7 +/- 12.4%) was significantly higher than that in adenocarcinoma (35.3 +/- 12.6%) or in large cell carcinoma (30.1 +/- 17.3%; P < 0.01). In six human lung cancer cell lines and one normal lung fibroblast cell line cultured in vitro, there was a significant correlation between S-phase fraction and p120 mRNA (r = 0.851, P < 0.02)/p120 protein (r = 0.869, P < 0.01) or between doubling time and p120 protein (r = -0.928, P < 0.01). In the context of the reports that indicate higher [3H]thymidine incorporation and shorter doubling time in the squamous cell carcinoma, these results indicate that p120 can be a marker for proliferation in human lung cancer cells in vivo and in vitro, and that it has an important function in the cell cycle of tumor proliferation.

Adenocarcinoma↗
PubMed1992

Protein kinase C activity in human leukemia cell lines with reference to sensitivity to antineoplastic agents.

Protein kinase C (PKC) regulates many cellular processes. In view of its possible relevance to the drug resistance, the levels of PKC activity were assessed in human leukemia cell lines with reference to the sensitivity to antineoplastic agents. K562/ADM exhibited approximately 2-fold higher levels of PKC activity as compared with the parental K562. After a 1-hr preincubation with Adriamycin (ADM) (0.5, 1, 10 microM), PKC activity in K562 tended to increase dose-dependently, while no substantial alteration was found in K562/ADM. Cisplatin (CDDP) or etoposide was of no effect. The activity in THP-1/E was slightly lower than THP-1, and the basal level stayed unchanged with any one of the above drugs. These results suggest that in K562 increase in PKC activity with ADM may play a role in the process of acquisition of resistance.

Antineoplastic Agents↗
PubMed1989

Conversion of Lewis lung carcinoma into ascitic form.

Lewis lung carcinoma (3LL), which has been most frequently used for various investigations of cancer, was converted to an ascitic form designated 3LL-SA. Ascites tumor cells showed a mixed population of single cells and about 10% islands which were made up of 2 to about 50 cells. Transplantability was 100%. The biological and metastatic capacities were preserved in this line as shown by its ability to form hemorrhagic and necrotic tumors, and by its multiple lung metastases. Moreover, histological and ultrastructural characteristics of this tumor line were identical to those of the parental 3LL. Thus, it can be seen that 3LL-SA will be a useful tool for the study of cancer.

Animals↗
PubMed1989

Establishment of an etoposide (VP-16)-resistant subline of THP-1 human monocytic leukemia cell line.

A VP-16-resistant subline was established from THP-1 human monocytic leukemia cells by subculturing in stepwise increasing concentrations of the drug. The resistant cells (THP-1/E) were capable of sustaining continuous growth in 1.0 microgram/ml VP-16. The 50% inhibition dose (IC50) was 1.4 micrograms/ml or a 35-fold of the parent cells. A more than 18-fold IC50 was also obtained with teniposide (VM-26). However, no substantial cross-resistance was observed with 5 other antineoplastic drugs, IC50 values being limited below several times of THP-1.

Cell Division↗
PubMed1989

Characterization of resistance to VP-16 in human leukemic cell line.

Resistance mechanism was studied in the VP-16-resistant human leukemic cell line (THP-1/E) which was developed by continuous drug exposure. The drug uptake and efflux studies revealed no decrease in net cellular drug accumulation. VP-16-induced DNA single- and double-strand breaks in the whole THP-1/E cells decreased significantly compared to the sensitive counterpart as assessed by alkaline elution methods. Decrease in DNA SSBs was also observable in the isolated nuclei from the THP-1/E cells. The resistance to VP-16 in THP-1/E appeared to be independent of altered membrane permeability, and more likely to be associated with decreased VP-16-mediated DNA cleavage.

Cell Line↗
PubMed1987

Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Antitumor effects of cyclophosphamide (CY) and lipopolysaccharide (LPS) were investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and were inoculated subcutaneously with syngeneic mouse hepatoma and mastocytoma P815 respectively. A subsequent injection of LPS caused hemorrhagic necrosis and retarded growth of tumor. When mice were treated with LPS plus suboptimal dose of CY, tumor growth was retarded and survival time was prolonged. The antitumor effects were more remarkable when mice were treated with CY prior to the injection of LPS. Without BCG pretreatment, LPS showed no antitumor activity in mice. Sera from mice treated with BCG plus LPS was cytotoxic for cultured tumor cells. However treatment of mice with CY did not increase the in vitro cytotoxicity. In this experimental condition, CY had no effect on delayed type hypersensitivity when evaluated by the footpad reaction to purified protein derivative (PPD). These results seem to indicate that the antitumor effects of the treatment with CY and LPS in BCG-treated mice are mediated by the reduction of tumor burden by CY and a serum factor induced by LPS.

Animals↗
PubMed1986

cis-Diamminedichloroplatinum (CDDP)-fosfomycin (FOM) combination in lung cancer patients with respect to the peripheral T lymphocyte subsets.

An antibiotic FOM was found to be preventive of the side effect of an antineoplastic drug CDDP on the peripheral T lymphocytes in lung cancer patients. Whereas finding a significant decrease in T3+ cells (p less than 0.01) and T4+ subset (p less than 0.05) with CDDP alone, the initial levels of these cell populations were kept unchanged in combination with FOM. T8+ subset showed no substantial change. A protective effect of FOM on T4+ subset was suggested to be an additional aspect of its action at least in combination with CDDP.

Aged↗
PubMed1986

Antitumor activity of lipopolysaccharide in tumor-bearing mice pretreated with BCG.

The antitumor activity of lipopolysaccharide (LPS) was investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and then were inoculated with syngeneic mouse hepatoma MH134 and mastocytoma P815 respectively. Hemorrhagic necrosis and retarded growth of tumor were observed after an intravenous (i.v.) injection of LPS, when tumor cells had been inoculated subcutaneously (s.c.). However an intraperitoneal (i.p.) injection of BCG plus LPS did not increase the mean survival time of mice that had been inoculated with tumor cells i.p. Sera from mice that had been treated with BCG plus LPS i.v. were cytotoxic for cultured tumor cells. These results seemed to indicate that growth-inhibitory effects of LPS on tumors inoculated s.c. were mediated by a humoral factor.

Animals↗
PubMed1986

Tumor histology and the immunoregulatory T lymphocyte subsets in lung cancer patients.

The immunoregulatory T lymphocyte subsets (CD4+, CD8+) in 39 patients with primary lung cancer were analyzed as for the possible correlation with tumor histology. Compared to the healthy controls (n = 36), cancer lymphocytes were generally characterized by a higher proportion of CD8+ subset (p less than 0.01) with no difference in either CD4+ subset or CD3+ cells. There was, however, a significant difference (p less than 0.05) between one extreme of epidermoid carcinoma with the highest CD8+ and the lowest ratio (CD4+/8+) and the other end of adenocarcinoma with the lowest CD8+ and the highest ratio. Large cell and small cell carcinomas were of the intermediate values. A spectrum of the subset marker profiles was thus found in associated with tumor histology. A diversity in the host immune status was suggested in primary lung cancer, although clinical implication remains to be clarified.

Adenocarcinoma↗
PubMed1985

Changes in the immunological parameters after a single dose of forphenicinol, a new small molecular immunomodifier.

Forphenicinol [L-2-(3-hydroxy-4-hydroxymethyl-phenyl) glycine, M.W. 197.19] is a derivative of forphenicine, an inhibitor of alkaline phosphatase discovered by Umezawa. In order to find an optimal dose, a single dose of the drug ranging from 10 to 600 mg per body was orally administered to a total of 55 patients (36 cancer, 13 tuberculosis, and 6 others). The possible changes in the percentages of the peripheral T and B lymphocytes, natural killer (NK) activity, and the proliferative response to phytohemaglutinin (PHA) were studied as immunological parameters. A significant effect of forphenicinol was demonstrated in restoring the normal proportion of T and B cells, especially in those who had 'low'-T and/or 'high'-B before administration of the drug. No difference was found between cancer and tuberculosis. The mean percentage of T cells increased from the low initial level of 68.0 to 75.6 in cancer (n = 12, p less than 0.05) or from 63.1 to 78.5 in tuberculosis (n = 7, p less than 0.05), while that of B cells decreased from the high initial level of 34.6 to 26.9 in cancer (n = 7) or from 34.9 to 14.3 in tuberculosis (n = 6, p less than 0.025). The effect of a single dose of the drug tended to disappear by day 8, a peak response being found on day 3 in most cases. With respect to this parameter, an optimal dose was found in a range from 60 to 100 mg. Forphenicinol was rather inhibitory on the NK activity, while it exerted diverse effect on the lymphocyte proliferation. No evidence of adverse effect was observed.

Adjuvants, Immunologic↗
PubMed1985

Antitumor effect of the yeast polysaccharide preparation in syngeneic mouse tumor models.

Antitumor effect of our Candida utilis glucomannan preparation (YPS) was evaluated in two syngeneic transplantable tumors; the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice and the 3-methylcholanthrene (MCA)-induced fibrosarcoma in C3H/He mice. YPS inhibited preferentially the 3LL pulmonary metastases only when optimal dosage was given at an earlier stage; 7 daily intraperitoneal (i.p.) doses of 100 mg/kg per dose from the next day of tumor inoculation (1 X 10(5)/mouse, subcutaneously, s.c.) substantially reduced the number of metastatic nodules, yielding the inhibition ratio 54% on day 21. However, the same treatment delayed until day 8 markedly facilitated the metastatic spread (-105%). Postsurgical-adjuvant therapy with YPS (10 daily i.p. doses of 100 mg/kg per dose from the next day of surgery) was effective in improving the survival rate with no evidence of metastatic growth on day 200, even though the amputation of the tumor-bearing legs was performed after the pulmonary metastases had been established (on day 20). In the MCA-fibrosarcoma model, YPS treatment from day 3 (10 daily doses of 100 mg/kg per dose) was effective in prolonging the survival period. The 3LL local tumor was affected only marginally and temporarily, while the MCA-tumor was not at all.

Animals↗
PubMed1985

Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice.

Effects of the organogermanium compound Ge-132 (i.p.) were examined on the 3LL local tumor (1 X 10(5)/mouse, s.c.) and its pulmonary metastases in B6 mice. A characteristic feature of its action was the preferential antimetastatic effect under strictly defined conditions. Either inhibition or facilitation was observed depending on the treatment schedules; 7 daily doses of 100 mg/kg yielded the inhibition ratio 49% when started from day 1, whereas the treatment from day 8 resulted in the ratio -99%. The maximum inhibition was obtained at 100 mg/kg. The postsurgical-adjuvant treatment with Ge-132 was of no beneficial effect. The local tumor growth was affected only marginally and temporarily. When inoculum size was minimized (1 X 10(4)), a single dose of 300 mg/kg on day 1, but not on day 8, was effective in prolonging the latency before tumor take. The antitumor action of Ge-132 was discussed with reference to its interferon (IFN)-inducing activity.

Adjuvants, Immunologic↗
PubMed1985

Imbalance of T cell subsets in cancer patients and its modification with bestatin, a small molecular immunomodifier.

The peripheral T lymphocyte subsets and natural killer (NK) cells of patients with cancer were studied by monoclonal antibody assays in comparison with those of non-cancer individuals. An imbalance of immunoregulatory T cell subsets was frequently found in the group of cancer patients (n = 26), being characterized by a relatively high proportion of OKT8+ cells (45.0 +/- 12.0%, p less than 0.01) and a low OKT4+/OKT8+ ratio (1.29 +/- 0.56, p less than 0.05). T cell level showed no significant difference as assessed by either OKT3 or rosette formation with sheep erythrocytes (E). The effect of bestatin was examined in 10 of these cancer patients. The relative proportion of T cell subsets tended to normalize 2 to 6 weeks after starting the daily doses of 30 mg per body. The mean percentage of OKT8+ cells decreased from 47.2 to 33.4 (p less than 0.01), while the helper to suppressor ratio increased from 1.18 to 1.79 (p less than 0.01). A significant increase was also found in the percentage and number of OKT4+ cells and HNK-1+ cells after the drug administration, while T cell level tended to converge to a normal range.

Adjuvants, Immunologic↗