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T Kunimoto

Publications and source records attributed to T Kunimoto.

At least 19 recordsLinked to original sources
PubMed1999

Cross-country comparisons suggest shared risk factors for carcinomas, including male lung adenocarcinoma and colon cancer development.

Smoking is clearly the major risk factor for both squamous cell carcinomas (SCCs) and adenocarcinomas (ACs) of the lung, although less so for the latter, where other influences appear to be important. In order to determine whether cross-country comparisons might provide evidence of shared risk factors with cancers in other organs of males, an examination of IARC/WHO data for cancer incidence was made for countries/registries in Europe, North America, Australia and Asia. Significant simple correlations, which persisted on partial analysis, were observed between lung SCCs and tumors of the larynx (P < 0.001), but not the buccal cavity or oesophagus, along with a link to rectal ACs (P < 0.001). Incidences of lung ACs also correlated with those for colon ACs (P < 0.001) but not lung SCCs. Oesophageal ACs were only related to colon cancers at the simple correlation level, this not persisting on partial analysis or separation into Asian and Western groups. The results suggest that blood borne factors, like hormones, may be important as determinants for the increasingly prevalent lung AC.

Adenocarcinoma↗
PubMed1999

Cross-country comparisons of colon and rectal cancer mortality suggest the existence of differences in risk factors in eastern and western Europe.

A comparison of relative mortality rates from colon and rectal cancers in World Health Organization data for various countries in Europe was undertaken to determine whether the two sites demonstrate a direct link. A significant correlation between figures for colon and rectal cancers was found throughout Europe but limited to males and only at the p < 0.05 level. Cluster analysis revealed marked differences between countries of the former west and east European blocks, the latter having much higher values for rectal cancers. Separation of countries on this basis gave rise to significant correlation between the two sites for both sexes (p < 0.05 and p < 0.001, respectively, for western and eastern males; and p < 0.05 and p < 0.001 for females). In order to assess the possible contribution of factors associated with squamous cell cancers (SCCs), data for buccal and cervical cancers, both more prevalent in eastern than in western Europe, were also compared. Whereas a significant correlation was evident between female rectal and cervical cancers overall and in the western countries (p < 0.05) this was not the case for the eastern countries. The results suggest that the observed excess of rectal cancer mortality in eastern European countries may not be simply due to factors contributing to SCCs, but that country level comparisons of individual harmful and beneficial influences, alone and in combination, might allow the underlying reasons to be explained.

Analysis of Variance↗
PubMed1998

European country comparisons provide evidence of a link between colon cancer and adenocarcinoma development in the lung but not the oesophagus.

Relative incidence rates of lung cancers demonstrate marked international variation in values for the different histological sub-types. In order to determine whether adenocarcinomas (ACs) in this site might share risk factors with other ACs, for example, in the breast, prostate, oesophagus and colon, a comparison of data in the IARC/WHO Cancer Incidence in Five Continents (Volume VII) was made for selected registries in Europe. Significant correlations were found between lung AC incidences/100,000 population and prostate and colon cancers in males (P < 0.005 and P < 0.05, respectively) and for breast and colon in females (P < 0.05 for both). Partial correlation coefficients were significant for lung and colon (P < 0.001) and prostate and colon (P < 0.005) in men, and for breast and colon in women (P < 0.005). A significant negative correlation with prostate cancer was noted for lung ACs in men. The results provide support for shared risk factors between lung Acs and colon cancers but do not indicate any link with AC development in the oesophagus. Data from registries in the UK and Italy were remarkable for high incidences of oesophageal and lung ACs, respectively, pointing to major differences in environmental risk factor or beneficial influence acting on these sites between the two countries.

Adenocarcinoma↗
PubMed1997

Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities.

In order to determine the effects of single unsaturated fatty acids (UFAs) or combinations on establishment of lung metastatic colonies, UFAs were administered orally to CDF1 mice bearing s.c. implants of the highly metastatic colon carcinoma 26. Oleic acid (OA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrated significant inhibition. In the case of DHA, this inhibitory potential was markedly reduced by co-administration of linoleic acid (LA) or EPA. Furthermore, while tumor cells treated with DHA showed a very low potential for lung colony formation when injected i.v., this again being partially reversed by co-administration of EPA. UFAs were found to be well absorbed into tumor tissues after oral administration, causing marked changes in relative levels, the arachidonic acid (AA) content, in particular, being markedly decreased by treatment with DHA or EPA, but not with DHA plus EPA or with DHA plus LA. Investigation of the gelatinolytic activity of the 57-kDa and 92-kDa isoforms of type-IV collagenase (MMP-2 and MMP-9, respectively) showed a clear reduction in the former by treatment with OA, while DHA, but not DHA plus LA or EPA, caused a decrease in the 92-kDa isoform, which was well correlated with AA content in tumor tissues (r = 0.900, p < 0.001). These results suggest that inhibition of metastasis due to treatment with OA and DHA might be due to depressed type-IV collagenase activity.

Animals↗
PubMed1997

Evaluation of synergism by a novel three-dimensional model for the combined action of cisplatin and etoposide on the growth of a human small-cell lung-cancer cell line, SBC-3.

Although the combination of cisplatin and etoposide has been used as standard therapy for small-cell lung cancer, it is difficult to demonstrate combination effects between cisplatin and etoposide in vitro. We therefore adopted a 3-dimensional (3-D) model to analyze the combination effects of anticancer drugs, and compared the results of analysis by the new 3-D model with those obtained from traditional 2-D models for the cisplatin-etoposide combination. In this study, using a human small-cell lung-cancer cell line (SBC-3), 3-D model analysis clearly identified a relationship depending on the concentrations of both drugs, and demonstrated that peak synergy occurred at the higher concentrations of cisplatin and etoposide. Antagonistic interactions were noted with a nadir at low concentrations of etoposide and cisplatin. In contrast, 2-D models such as combination index and isobologam analysis fail to characterize the complex interactions between cisplatin and etoposide, since their joint effects are concentration-dependent. Combination index (CI) plots show that synergy is evident only for molar ratios of cisplatin: etoposide of 2:1 to 1:5. On isobologram analysis, synergy could be detected when great inhibitory effects on cell growth were present (high endpoint), but not with small inhibitory effects (lower endpoints). Thus, either synergy or antagonism may occur, but depend on the selection of variables, such as the molar ratios or the endpoints chosen for the experiments. This could explain the inconsistency in the in vitro combination effects reported to date. The 3-D model, which compensates for the above deficiencies of 2-D models, can facilitate rigorous analysis of drug interactions over the entire clinical dose range, using microcomputers and sophisticated graphics programs. This direct and pragmatic method offers investigators a practical new tool with which to analyze drug combinations for cancer chemotherapy.

Antineoplastic Agents↗
PubMed1991

Antitumor activity of polymorphonuclear leukocytes activated by a beta-1,3-D-glucan.

The antitumor activity of mouse polymorphonuclear leukocyte (PMN) treated with a beta-1,3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK-N) and its carboxymethylated derivative (CM-TAK) was investigated in vitro and in vivo. ICR mouse PMN showed strong cytotoxicity against sarcoma 180 cells and inhibition of the growth of the tumor cells in vitro in the presence of TAK-N but not in the presence of CM-TAK. Since the cytotoxicity induced by TAK-N was almost completely inhibited by catalase, it seems to be mediated by H2O2 production by PMN. On the other hand, TAK-N induced no cytotoxicity in macrophages and neither did CM-TAK in PMN or in macrophage. Intraperitoneal injection of TAK-N into ICR mice induced a large number of PMN and macrophages in the peritoneal cavity. The peritoneal exudate PMN which were harvested at 10 to 72 h after TAK-N injection showed cytotoxicity against sarcoma 180 cells, but the peritoneal exudate macrophages did not. Treatment of sarcoma 180 ascites tumor-bearing ICR mice with TAK-N at a dose of 100 mg/kg prolonged significantly the survival time over that of the control. These results indicate that TAK-N induces PMN cytotoxicity against sarcoma 180 cells not only in vitro but also in vivo. The antitumor effect of TAK-N on sarcoma 180 ascites tumor seems to be derived from PMN stimulated with TAK-N.

Animals↗
PubMed1990

[Tumor-regressing factor induced by antitumor polysaccharide in the serum of tumor-bearing mice].

A potent tumor-regressing activity was found in the serum of mice with S180 tumor undergoing rapid regression caused by antitumor polysaccharides. Beta (1-3) glucan including CM-TAK and lentinan and mannoglucan MGA induced such activity. It causes a rapid decrease in the number of tumor cells accompanied with a marked increase in neutrophiles in solid tumors. The entity of the activity was named as tumor-regressing factor (TRF) and was partially purified revealing a proteinaceous nature with an approximate molecular weight of 250,000. The factor was induced in a serum of tumor-bearing mice in various host-tumor combinations after the tumor growth had been established but only weakly in normal mice. The sensitivity of tumors to the factor was also dependent on the stage of tumor growth. The serum of normal mice or tumor-bearing mice without polysaccharide treatment exhibited similar activity as TRF after definite chromatographic step. The chromatographic behavior of the revealed activity was closely similar to that of the induced factor. It was postulated that a TRF-like activity exists in normal serum in a inactivated form being bound by antagonist(s) and the appropriate chromatography might remove the antagonist resulting in the active form of the factor. The concept was confirmed by reconstituting the chromatographic fractions, the revealed activity was again obscured after mixing with a certain fraction.

Animals↗
PubMed1987

Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.

Animals↗
PubMed1987

Antitumor activity of a new camptothecin derivative, SN-22, against various murine tumors.

The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.

Animals↗
PubMed1987

[Antitumor activity of new derivatives of camptothecin].

With the purpose of obtaining more potent and less toxic camptothecin (CPT) analogs, we prepared many derivatives of CPT. Among them, 7-ethyl-CPT (SN 22) and 7-ethyl-10-hydroxy-CPT (SN 38) showed strong antitumor activity with less toxicity. They were, however, insoluble and when they were made soluble, their activity was markedly diminished, as a result of cleavage of the delta-lactone ring. We therefore attempted to make soluble derivatives without breaking the delta-lactone ring and obtained 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-CPT (CPT-11), which showed very strong antitumor activity by i.p., i.v. or p.o. administration against the ascites type of L1210 leukemia, P388 leukemia, sarcoma 180, Meth A fibrosarcoma, B16 melanoma, Ehrlich carcinoma and MH134 hepatoma and the solid type of sarcoma 180, Meth A fibrosarcoma, Lewis lung carcinoma, C3H/HeN mammary carcinoma, Ehrlich carcinoma and MH134 hepatoma. The antileukemic activity of CPT-11 against L1210 was much higher than that of adriamycin. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration, the LD50 being 765.3 mg/kg, 22 times greater than that of CPT-Na.

Animals↗
PubMed1986

Rapid tumor regression and induction of tumor-regressing activity in serum by various immune-modulating agents.

A rapid decrease in the number of tumor cells from S180 tumors was caused by several antitumor polysaccharides including the beta (1-3)glucans lentinan and TAK-N and a mannoglucan MGA, but not by those lacking antitumor activity. MGA was demonstrated to induce potent tumor-regressing activity in the serum of tumor-bearing mice similar to that reported previously to be induced after an injection of CM-TAK, a carboxymethylated beta (1-3)glucan. It is probable that the induction of rapid regression of established tumors is a phenomenon common to antitumor polysaccharides and some microbiological products and that the tumor-regressing factor in the serum underlies a common mechanism.

Animals↗
PubMed1986

Antitumor polysaccharide-induced tumor-regressing factor in the serum of tumor-bearing mice: purification and characterization.

Marked tumor-regressing activity was induced in the serum of S180 tumor-bearing mice by injection of an antitumor polysaccharide, CM-TAK [carboxymethylated beta(1-3)glucan]. Maximal activity was induced 7-14 days after the tumor transplantation and 10-12 h after CM-TAK treatment. A quantitative assay for the activity was established on the basis of the initial decrease in the number of the tumor cells within 24 h. The factor with tumor-regressing activity was purified 10,000-fold by the series of hydroxylapatite chromatography, ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, and boronate-mediated affinity chromatography. The molecular weight was estimated to be 250,000 by gel filtration. The activity was proteinase K sensitive, but relatively resistant to trypsin. Neuraminidase did not affect the activity. It is believed that the tumor-regressing factor is different from the tumor necrosis factor.

Alcaligenes↗
PubMed1986

Rapid tumor regression caused by antitumor polysaccharide and induction of tumor-regressing factor in the serum of tumor-bearing mice.

The antitumor polysaccharide CM-TAK [carboxymethylated beta(1-3)glucan] caused immediate and rapid loss of viable tumor cells from S180 solid tumors in ICR mice if it was given after a week of tumor growth. We found marked tumor-regressing activity in the serum of mice with S180 tumors undergoing CM-TAK-induced regression. When injected intravenously into S180-bearing mice, 0.1 ml of serum/mouse induced complete regression of day-14 tumors. However, in vitro cytotoxic activity against L929 and S180 cells was not detected. After the injection of CM-TAK or serum, along with the rapid decrease in tumor cells there was a marked increase in polymorphonuclear leukocytes. The serum was also active against fibrosarcoma Meth A in BALB/c mice, inducing partial regression or significant decrease in growth of the tumor. The properties of the factor in the serum seem to be different from those reported for tumor-necrotizing factor and other endogenous cytotoxic substances.

Animals↗
PubMed1985

The therapeutic effects of orally administered 5'-deoxy-5-fluorouridine, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil on experimental murine tumors.

The antitumor effects of three 5-fluorouracil-related compounds, 5'-deoxy-5-fluorouridine (5'-DFUR), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-fluorouracil (5-FU) itself, on several experimental murine tumors were compared after oral administration. 5'-DFUR showed strong antitumor activity against the solid type of four kinds of tumors tested with a wide range of effective doses, and also showed moderate antitumor activity against three kinds of solid tumors with a narrow range of effective doses. 5'-DFUR was effective against a few kinds of ascites tumors. In general, the antitumor activity of FT-207 was not very strong, with narrow ranges of effective doses under the present conditions. 5-FU showed strong toxicity but at lower doses its antitumor effectiveness was almost the same as that of FT-207. When the doses were divided into three and the divided dose was given orally three times a day for five consecutive days to mice bearing L1210 leukemia, this modality (with any of the three drugs) enhanced the ILS of the mice by two to three times in the case of the ascites type but not the solid type of L1210. The chemotherapeutic index in oral treatment of the solid type of tumors was higher for 5'-DFUR than for FT-207 or 5-FU. The minimum lethal doses in oral administration for five consecutive days were about 3, 1.5 and 0.5 mmol/kg/day for 5'-DFUR, FT-207 and 5-FU, respectively. In conclusion, 5'-DFUR appeared to have stronger antitumor activity and less toxicity than FT-207 and 5-FU, and it is therefore expected to be clinically useful.

Animals↗
PubMed1984

Separation of macrophages from mouse peritoneal exudate cells with substrata coated with chemically modified collagens.

A cell-separation technique was designed on the basis of specific interaction between macrophages and chemically modified collagens in the presence of serum. When unseparated mouse peritoneal exudate cells containing approximately 50% macrophages and 50% lymphocytes were incubated in dishes coated with unmodified and chemically modified collagens, only macrophages adhered more rapidly and in greater numbers to succinylated and methylated collagen than to unmodified collagen. The adherent macrophages could be easily detached from the substrata by divalent cation chelating agents. The purity and recovery of macrophages separated by this method were approximately 92-94% and 41-48%, respectively.

Animals↗