研究者総覧

早田 邦康 (ソウダ クニヤス)

  • 循環器病臨床医学研究所 教授
Last Updated :2020/06/18

研究者情報

学位

  • 医学博士(自治医科大学(JMU))

学位

    早田 邦康

J-Global ID

研究キーワード

  • 発癌抑制   老化抑制   遺伝子メチル化   寿命延長   スペルミン   ポリアミン   悪液質   Gastroenterological Surgery   Surgery in General   

研究分野

  • ライフサイエンス / 外科学一般、小児外科学
  • ライフサイエンス / 免疫学

経歴

  • 2007年  - 自治医科大学 准教授
  • 2001年  - Jichi Medical School, Assistant Professor
  • 1996年 - 1997年  The Picower Institute for Medical Research, Study investigator
  • 1994年 - 1996年  Jichi Medical School, Assistant Professor
  • 1989年 - 1994年  Jichi Medical School, Assistant
  • 1994年  - 自治医科大学 講師
  • 1989年  - 自治医科大学 助手

学歴

  •         - 1980年   自治医科大学(JMU)   医学部
  •         - 1980年   自治医科大学   Faculty of Medicine

所属学協会

  • 日本消化器外科学会   日本消化器病学会   日本外科学会   日本バイオセラピィ   日本ポリアミン学会   

研究活動情報

論文

  • Fumihiro Chiba, Kuniyasu Soda, Shigeki Yamada, Yuka Tokutake, Shigeru Chohnan, Fumio Konishi, Toshiki Rikiyama
    INTERNATIONAL JOURNAL OF ONCOLOGY 44 1 177 - 186 2014年01月 [査読有り][通常論文]
     
    The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation of the mechanisms involved in cachexia of cancer patients.
  • Kuniyasu Soda, Yoshihiko Kano, Fumihiro Chiba, Kei Koizumi, Yuichiro Miyaki
    PLOS ONE 8 5 e64357  2013年05月 [査読有り][通常論文]
     
    Polyamines (spermine and spermidine) play many important roles in cellular function and are supplied from the intestinal lumen. We have shown that continuous high polyamine intake inhibits age-associated pathologies in mice. The mechanism by which polyamines elicit these effects was examined. Twenty-four week old Jc1:ICR male mice were fed one of three experimental chows containing different polyamine concentrations. Lifetime intake of high polyamine chow, which had a polyamine content approximately three times higher than regular chow, elevated polyamine concentrations in whole blood, suppressed age-associated increases in pro-inflammatory status, decreased age-associated pathological changes, inhibited age-associated global alteration in DNA methylation status and reduced the mortality in aged mice. Exogenous spermine augmented DNA methyltransferase activity in Jurkat and HT-29 cells and inhibited polyamine deficiency-induced global alteration in DNA methylation status in vitro. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration; 12 mice (60%) in the low polyamine group developed tumors, compared with only 5 mice (25%) in the high polyamine group (Fisher's exact probability = 0.027, p = 0.025). However, increased polyamine intake accelerated the growth of established tumors; maximal tumor diameter in the Low and High groups was 3.85 +/- 0.90 mm and 5.50 +/- 1.93 mm, respectively (Mann-Whitney test, p = 0.039). Spermine seems to play important roles in inhibiting age-associated and polyamine-deficient induced abnormal gene methylation as well as pathological changes including tumorigenesis.
  • Kuniyasu Soda, Yoshihiko Kano, Fumihiro Chiba, Kei Koizumi, Yuichiro Miyaki
    PLOS ONE 8 5 e64357  2013年05月 [査読有り][通常論文]
     
    Polyamines (spermine and spermidine) play many important roles in cellular function and are supplied from the intestinal lumen. We have shown that continuous high polyamine intake inhibits age-associated pathologies in mice. The mechanism by which polyamines elicit these effects was examined. Twenty-four week old Jc1:ICR male mice were fed one of three experimental chows containing different polyamine concentrations. Lifetime intake of high polyamine chow, which had a polyamine content approximately three times higher than regular chow, elevated polyamine concentrations in whole blood, suppressed age-associated increases in pro-inflammatory status, decreased age-associated pathological changes, inhibited age-associated global alteration in DNA methylation status and reduced the mortality in aged mice. Exogenous spermine augmented DNA methyltransferase activity in Jurkat and HT-29 cells and inhibited polyamine deficiency-induced global alteration in DNA methylation status in vitro. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration; 12 mice (60%) in the low polyamine group developed tumors, compared with only 5 mice (25%) in the high polyamine group (Fisher's exact probability = 0.027, p = 0.025). However, increased polyamine intake accelerated the growth of established tumors; maximal tumor diameter in the Low and High groups was 3.85 +/- 0.90 mm and 5.50 +/- 1.93 mm, respectively (Mann-Whitney test, p = 0.039). Spermine seems to play important roles in inhibiting age-associated and polyamine-deficient induced abnormal gene methylation as well as pathological changes including tumorigenesis.
  • Yoshihiko Kano, Kuniyasu Soda, Fumio Konishi
    PLOS ONE 8 2 e56056  2013年02月 [査読有り][通常論文]
     
    Spermine and spermidine, natural polyamines, suppress lymphocyte function-associated antigen 1 (LFA-1) expression and its associated cellular functions through mechanisms that remain unknown. Inhibition of ornithine decarboxylase, which is required for polyamine synthesis, in Jurkat cells by 3 mM D,L-alpha-difluoromethylornithine hydrochloride (DFMO) significantly decreased spermine and spermidine concentrations and was associated with decreased DNA methyltransferase (Dnmt) activity, enhanced demethylation of the LFA-1 gene (ITGAL) promoter area, and increased CD11a expression. Supplementation with extracellular spermine (500 mu M) of cells pretreated with DFMO significantly increased polyamine concentrations, increased Dnmt activity, enhanced methylation of the ITGAL promoter, and decreased CD11a expression. It has been shown that changes in intracellular polyamine concentrations affect activities of -adenosyl-L-methioninede-caroboxylase, and, as a result, affect concentrations of the methyl group donor, S-adenosylmethionine (SAM), and of the competitive Dnmt inhibitor, decarboxylated SAM. Additional treatments designed to increase the amount of SAM and decrease the amount of decarboxylated SAM-such as treatment with methylglyoxal bis-guanylhydrazone (an inhibitor of S-adenosyl- L-methionine-decaroboxylase) and SAM supplementation-successfully decreased CD11a expression. Western blot analyses revealed that neither DFMO nor spermine supplementation affected the amount of active Ras-proximate-1, a member of the Ras superfamily of small GTPases and a key protein for regulation of CD11a expression. The results of this study suggest that polyamine-induced suppression of LFA-1 expression occurs via enhanced methylation of ITGAL.
  • Shingo Tsujinaka, Kuniyasu Soda, Yoshihiko Kano, Fumio Konishi
    INTERNATIONAL JOURNAL OF ONCOLOGY 38 2 305 - 312 2011年02月 [査読有り][通常論文]
     
    Polyamine levels are elevated in the organs and tissues of cancer patients due to increased synthesis and active intercellular transport in cancer cells. Because increased polyamine levels are associated with poor prognosis, the effect of polyamines on the malignant potential of cancer cells was investigated. Highly metastatic colon cancer cells (HT-29) were cultured under either normoxia (21% O(2)) or hypoxia (2% O(2)) for 48 h with 0, 100, or 500 mu M spermine, one of the natural polyamines with the strongest biological activity. Spermine supplementation ameliorated MTT metabolism of hypoxic cancer cells in a dose-dependent manner, but had no effect on cells cultured under normoxia. Hypoxia decreased cancer cell CD44 and E-cadherin expression, while CD44 expression further decreased by spermine in a dose-dependent manner. By comparing cells cultured under normoxia with increasing amounts of spermine, we found that CD44 expression decreased by 11% (0 mu M spermine), 14% (100 mu M), and 18% (500 mu M), and was accompanied by comparable decreases in CD44 mRNA levels. Martigel invasion assay showed that hypoxia increased the number of invading cells, and spermine further enhanced the hypoxia-induced increase in the number of invading cells in a dose-dependent manner. The numbers of invading cells cultured with 0, 100, and 500 mu M spermine under hypoxia were 2.3, 2.8, and 3.2 times greater, respectively, compared to cells with 0 mu M spermine under normoxia. Increased extracellular spermine enhances the invasion potential of cancer cells under hypoxia.
  • Mediterranean diet and polyamine intake –possible contribution of increased polyamine intake to inhibition of age-associated disease.
    SODA Kuniyasu
    Nutrition and Dietary Supplements 3 1 - 7 2011年 [査読有り][通常論文]
  • Kuniyasu Soda
    MEDICAL HYPOTHESES 75 3 299 - 301 2010年09月 [査読有り][通常論文]
     
    In addition to general lifestyle, a number of foods and dietary patterns, such as the Mediterranean diet (MD), are associated with lower incidences of chronic, age-related diseases, and mortality. We have shown that increased polyamine intake decreases age-associated pathology and increases longevity in mice. Several foods in the MD, such as fruits and legumes, are foods containing high amount of polyamines. Among age-associated conditions, cardiovascular diseases (CVD) are the leading cause of mortality worldwide, and individuals who adhere to a MD have a lower incidence of CVD. The possible contribution of increased polyamine intake to CVD prevention is discussed in this manuscript. Polyamines from food are distributed to all organs and tissues, and long-term intake increases polyamine concentration in blood. Because most polyamines are associated with red and white blood cells, they act to suppress synthesis of pro-inflammatory cytokines and of leukocyte function-associated antigen-1. Foods with anti-inflammatory properties such as n-3 polyunsaturated fatty acids are known to help prevent CVD. Additionally, suppression of de novo polyamine synthesis results from increased polyamines intake, normally synthesized from arginine. This in turn increases availability of arginine for synthesis of nitric oxide, which plays an important role in preserving normal vascular physiology. (C) 2010 Elsevier Ltd. All rights reserved.
  • Gross domestic product and dietary pattern among 49 Western countries with a focus on polyamine intake.
    SODA Kuniyasu
    Health 2 1327 - 1334 2010年 [査読有り][通常論文]
  • Kuniyasu Soda, Yoh Dobashi, Yoshihiko Kano, Shingo Tsujinaka, Fumio Konishi
    EXPERIMENTAL GERONTOLOGY 44 11 727 - 732 2009年11月 [査読有り][通常論文]
     
    The purpose of this study was to test whether oral intake of foods rich in polyamines (spermine and spermidine) suppresses age-associated pathology in aged mice. Synthetic polyamines were mixed into experimental chows, and 24-week-old Jc1:ICR male mice were fed one of three chows containing differing polyamine concentrations. The spermine and spermidine concentrations in the low, normal, and high polyamine chows were 143 and 224 nmol/g, 160 and 434 nmol/g, and 374 and 1540 nmol/g, respectively. An increase in concentration of polyamine in the blood was found only in mice fed the high polyamine chow at 50 weeks of age. While the body weights of mice in all three groups were similar, the survival rate of mice fed high polyamine chow was significantly higher than those in the other two groups (p = 0.011). Mice fed the high polyamine chow analyzed at 88 weeks of age, corresponding to the end of the study, demonstrated lower incidence of glomerulosclerosis and increased expression of senescence marker protein-30 in both kidney and liver compared to those fed the low polyamine chow. As these pathological changes are associated with senescence, oral polyamine appears to inhibit the progression of age-associated pathologies. (C) 2009 Elsevier Inc. All rights reserved.
  • Kuniyasu Soda, Yoshihiko Kano, Masako Sakuragi, Koichi Takao, Alan Lefor, Fumio Konishi
    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 55 4 361 - 366 2009年08月 [査読有り][通常論文]
     
    Although the intracellular de novo synthesis of the polyamines decreases with age. there is no similar trend in blood polyamine levels. but rather there is wide individual variability. We hypothesized that dietary polyamines attenuate a decrease in blood polyamine levels with age and augment the previously observed individual variability. The effect of a polyamine rich diet, in both mice and humans, on blood polyamine concentrations was examined in this study. Jc1:ICR male mice were fed test diets containing 3 different polyamine concentrations. Healthy human male volunteers added 50 to 100 g of the polyamine-rich fermented soybean product. natto, to their daily intake. After 26 wk. the mean blood spermine concentration in mice receiving the test diet with high polyamine concentrations was 10.1 +/- 2.4 mu mol/L while the mean concentrations found in mice fed with a diet with normal or low polyamine concentrations were 5.2 +/- 0.9 and 4.7 +/- 0.5 mu mol/L, respectively (p < 0.05). A mean daily intake of 66.4 +/- 3.7 g (range = 46.4-89.3 g) of natto for 2 mo by human volunteers increased the mean blood spermine concentration by a factor of 1.39 (n = 10) (p < 0.01), while in control volunteers (n = 7), asked to exclude polyamine-rich foods from their diet, blood spermine concentration remained unchanged. The individual variability of blood polyamine levels was enhanced after polyamine intake in mice and, to a lesser extent, in humans. The long-term oral intake of enhanced polyamine diets increases blood polyamine levels in both mice and humans.
  • Alper Celik, Yoshihiko Kano, Shingo Tsujinaka, Sinichirou Okada, Koichi Takao, Masakazu Takagi, Shigeru Chohnan, Kuniyasu Soda, Masanobu Kawakami, Fumio Konishi
    ONCOLOGY REPORTS 21 4 1105 - 1111 2009年04月 [査読有り][通常論文]
     
    The alterations of enzymatic activities involved in lipid degradation in cancer cachexia have not been fully elucidated. One of the two subclones of colon 26 adenocarcinoma, clone 20, with a potent ability to induce cachexia, or clone 5, without such an activity, was transplanted in to CDF-1 male mice. Murine livers were extirpated for analyses on the 14th day after tumor inoculation. The body weights and food intake of mice bearing clone 20 were all significantly lower than those of non-tumor bearing mice and mice bearing the clone 5 tumor. The decline of body weight was accompanied by a shrinkage of epididymal fat pads. Expression of spermidine/spermine N-1 acetyl transferase (SSAT) assessed by real-time PCR was significantly increased in cachectic mice. Conversely, acetyl-CoA carboxylase (ACC) measured by Western blotting and malonyl-CoA levels determined by malonyl-CoA:acetyl-CoA cycling procedures were decreased in cachectic mice. Indomethacin in drinking water reversed the clone 20 induced decrease in body and fat weight and food intake, and simultaneously negated the clone 20 induced increase of SSAT expressions and decrease of ACC and malonyl-CoA amounts. Because malonyl-CoA inhibits the rate-limiting step in the beta-oxidation of fatty acids, the decreased malonyl-CoA and the background metabolic alterations may contribute to the accelerated lipolysis of cancer cachexia.
  • Yoshihiko Kano, Kuniyasu Soda, Takeshi Nakamura, Masaaki Saitoh, Masanobu Kawakami, Fumio Konishi
    CANCER IMMUNOLOGY IMMUNOTHERAPY 56 6 771 - 781 2007年06月 [査読有り][通常論文]
     
    Increased blood polyamine levels, often observed in cancer patients, have negative impacts on patient prognosis and are associated with tumor progression. The purpose of our study was to examine the effects of polyamines on cellular immune function. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were cultured with the human natural polyamines spermine, spermidine, or putrescine, and the effects on immune cell function were examined. The correlation between post-operative changes in blood polyamine levels and lymphokine-activated killer (LAK) activity was also examined in cancer patients. Spermine decreased the adhesion of non-stimulated PBMCs to tissue culture plastic in a dose- and a time-dependent manner without affecting cell viability or activity. This decrease in adhesion capacity was accompanied by a decrease in the number of CD11a bright-positive and CD56 bright-positive cells. Upon stimulation with interleukin 2 to activate LAK cytotoxicity, PBMCs cultured overnight with 100 or 500 mu M spermine showed decreased cytotoxic activity against Daudi cells (91.5 +/- 1.7 and 84.9 +/- 3.0%, respectively (n = 6) compared to PBMC cultured without polyamines). In a group of 25 cancer patients, changes in blood spermine levels after surgery were negatively correlated with changes in LAK cytotoxicity after surgery (r = -0.510, P = 0.008: n = 25). Increased blood spermine levels may be an important factor in the suppression of anti-tumor immune cell function.
  • M Kanzaki, K Soda, PT Gin, T Kai, F Konishi, M Kawakami
    CYTOKINE 32 5 234 - 239 2005年12月 [査読有り][通常論文]
     
    In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the clay after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic (nice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6. (c) 2005 Elsevier Ltd. All rights reserved.
  • Spermine, a natural polyamine, suppresses LFA-1 expression on human lymphocyte
    K Soda, Y Kano, T Nakamura, K Kasono, M Kawakami, F Konishi
    JOURNAL OF IMMUNOLOGY 175 1 237 - 245 2005年07月 [査読有り][通常論文]
     
    Natural polyamines, spermine, spermidine, and putrescine, play a pivotal role in the regulation of gene expression; therefore, the age-dependent decreases and the disease-dependent increases in polyamine synthesis suggest a possible contribution of polyamines to the age-related and disease-associated changes in cellular function. In this study, we examined the effects of polyamines on the cellular function and the expression of adhesion molecules on human PBMCs from healthy volunteers. Flow cytometry revealed that PBMCs cultured with spermine decreased mean fluorescent intensities (MFIs) of CD11a and CD18 in the lymphocyte light-scattered region, but not in the monocyie region. This suppression was observed in a dose- and time-dependent manner and found nonspecifically on all cell subsets we tested (CD3(+), CD4(+), CD8(+), CD19(+), CD45RA(+), CD45RO(+), CD4(+)CD45RA(+), CD4(+)CD45RO(+), CD8(+)CD45RA(+), CD8(+)CD45RO(+)). The decreases of CD11a and CD18 MFIs were accompanied by the decrease in adherent capacity of PBMCs to HUVECs. Spermine did not hinder cell activities or cell viability. Among 42 healthy volunteers (mean, 49.5 years old; from 26 to 69), blood spermine levels inversely correlated with the CD11a MFIs of cells in the lymphocyte region (r = -0.48; p = 0.001), but not with those in the monocyte region. The effects of spermidine seemed weaker than those of spermine, and blood spermidine levels had no correlation with CD11a MFIs of the lymphocyte region. Putrescine had no effect on the expressions of membrane molecules. Polyamines, especially spermine, decrease LFA-1 (CD11a/CD18) expression on human lymphocyte and adhesion capacity of PBMCs to HUVECs.

書籍

  • The role of cytokines and the effect of modifications of host's immune system on cancer cachexia
    ()
    cytokines, cholera, and the gut 1996年

MISC

  • Fetuin protects the fetus from TNF
    HC Wang, MH Zhang, K Soda, A Sama, KJ Tracey LANCET 350 (9081) 861 -862 1997年09月 [査読無し][通常論文]
  • MH Zhang, T Caragine, HC Wang, PS Cohen, G Botchkina, K Soda, M Bianchi, P Ulrich, A Cerami, B Sherry, KJ Tracey JOURNAL OF EXPERIMENTAL MEDICINE 185 (10) 1759 -1768 1997年05月 [査読無し][通常論文]
     
    The local production of proinflammatory cytokines mediates the host response to inflammation, infection, and injury, whereas an overexpression of these mediators can injure or kill the host. Recently, we identified a class of multivalent guanylhydrazone compounds that are effective inhibitors of proinflammatory cytokine synthesis in monocytes/macrophages. The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection. Here, we addressed the hypothesis that spermine might counter regulate the innate immune response by downregulating the synthesis of potentially injurious cytokines. When spermine was added to cultures of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, MIP-1 alpha, and MIP-1 beta. The inhibition of cytokine synthesis was specific and reversible, with significant inhibition of TNF synthesis occurring even when spermine was added after LPS. The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity. Local administration of spermine in vivo protected mice against the development of acute footpad inflammation induced by carrageenan. These results identify a distinct molecular counterregulatory role for spermine in downregulating the monocyte proinflammatory cytokine response.
  • Peroral cholangioscopy using a new fine-caliber flexible scope for detailed examination without papillotomy
    K Soda, K Shitou, Y Yoshida, T Yamanaka, A Kashii, M Miyata GASTROINTESTINAL ENDOSCOPY 43 (3) 233 -238 1996年03月 [査読無し][通常論文]
  • SPLENECTOMY BEFORE TUMOR INOCULATION PROLONGS THE SURVIVAL-TIME OF CACHECTIC MICE
    K SODA, M KAWAKAMI, S TAKAGI, A KASHII, M MIYATA CANCER IMMUNOLOGY IMMUNOTHERAPY 41 (4) 203 -209 1995年10月 [査読無し][通常論文]
     
    The effects of splenectomy on the development of cachexia, tumor growth and animal survival were studied in tumor-bearing CDF1 mice. Mice were inoculated with two subclones of colon 26 adenocarcinoma, clone 20 (with a potent capacity to induce cachexia) and clone 5 (without such activity), and underwent splenectomy before or after tumor inoculation. Splenectomy significantly prolonged the survival of mice bearing clone 20 when it was performed prior to tumor inoculation, although the progression of cachexia and tumor growth were not affected. The survival rate was higher in splenectomized than it was in nonsplenectomized mice 20-40 days after tumor inoculation. Such effects on survival were not observed, however, in mice splenectomized after inoculation with clone 20 or in mice that underwent splenectomy either before or after inoculation with clone 5. The decrease of peripheral blood lymphocyte count observed in mice bearing clone 20 was magnified when splenectomy was performed before tumor inoculation, but the serum levels of tumor necrosis factor and interleukin-6 were comparable. These results indicate that cancer death from cachexia is not directly attributable to enhanced catabolism. The mechanism by which splenectomy ameliorates the survival of cachectic mice remains to be studied, although several changes observed in the splenectomized mice after inoculation, including decreases in the peripheral blood L3T4(+) cells and Lyt-2(+) cells on the 9th day and 15th day respectively, and increase in the L3T4(+)/Lyt-2(+) cell ratio on the 15th day suggest the involvement of the modified host's immune response.
  • K SODA, M KAWAKAMI, A KASHII, M MIYATA INTERNATIONAL JOURNAL OF CANCER 62 (3) 332 -336 1995年07月 [査読無し][通常論文]
     
    In order to further clarify the role of interleukin 6 (IL-6) in the pathogenesis of cachexia, recombinant human IL-6 (hIL-6) was administered s.c. by osmotic pump for 9 days at a dose of 1 or 10 mu g/day into CDF1 mice inoculated with a non-cachexia-inducing subclone of colon 26 adenocarcinoma (clone 5), or with a cachexia-inducing subclone (clone 20) of this malignancy, The serum level of IL-6 in non-cachectic mice with clone-5 tumors was 35% lower than in cachectic mice bearing clone 20 of colon 26 adenocarcinoma on the 19th day after tumor inoculation. IL-6 administration induced anemia, thrombocytosis and visceral organ hypertrophy not only in mice with clone-5 tumors but also in control mice with no tumor burden. Lipolysis and proteolysis became conspicuous when a large dose (10 mu g/day) of IL-6 was infused into mice with clone-5 tumors. However, IL-6 supplementation did not induce loss Of body weight, a decline in food intake or lymphocytopenia, which were characteristically observed in cachectic mice with clone-20 tumors. In conclusion, IL-6 appears to be a permissive factor for the development of cachexia but, while it can induce some of the symptoms typical of cachexia, it cannot in itself induce the full cachectic syndrome. (C) 1995 Wiley-Liss, Inc.
  • Surgery Today 25 (5) 444 -446 1995年 [査読無し][通常論文]
  • CHARACTERIZATION OF MICE BEARING SUBCLONES OF COLON-26 ADENOCARCINOMA DISQUALIFIES INTERLEUKIN-6 AS THE SOLE INDUCER OF CACHEXIA
    K SODA, M KAWAKAMI, A KASHII, M MIYATA JAPANESE JOURNAL OF CANCER RESEARCH 85 (11) 1124 -1130 1994年11月 [査読無し][通常論文]
     
    A subclone (clone 20) of chemically induced, murine colon adenocarcinoma with a potent ability to induce cachexia and another subclone (clone 5) without such an activity were transplanted to syngeneic mice (CDR) and their tissue weights, blood components and cytokine levels in sera were compared. Mice transplanted with clone 20 showed a profound body-weight loss by 15 days after inoculation when the tumor accounted for less than 1% of the body weight, along with marked reduction of food and water intakes. Thereafter, they transiently gained in body weight with restoration of food and water intakes. Thus, the change in body weight was biphasic and not proportional to the tumor size. Body fat was lost preferentially, accompanied with a decrease in plasma triglyceride levels. The thymus contracted remarkably, and the peripheral lymphocyte count decreased extensively. Mice transplanted with clone 5, in contrast, did not show any of these changes characteristic of cachexia. Serum concentration of interleukin-6, which has been proposed as the principal inducer of cachexia in mice with colon 26, increased in mice with clone 5 to levels comparable to those in mice with clone 20. The changes in mice bearing clone 20 could not all be explained in terms of known biological activities of interleukin-6. Additional unknown factors, therefore, are presumed to contribute to cachexia in mice with clone 20. Identification of them should be helpful in the care of cachectic patients.
  • A NEWLY DEVELOPED FINE-CALIBER ENDOSCOPE FOR PERORAL CHOLANGIOPANCREATOSCOPY
    K SODA, T YAMANAKA, Y YOSHIDA, K SHITOU, A KASHII, M MIYATA ENDOSCOPY 26 (8) 671 -675 1994年10月 [査読無し][通常論文]
     
    We have developed a new fine-caliber (2.09 mm outer diameter) endoscope for peroral cholangiopancreatos-copy. The endoscope contains one image transmission fiber, 12 light guide fibers (the transmitter of light from the light source) and a working channel (a lumen for the guide wire and rinsing). The working channel, whose bore is 0.72 mm, is located centrally within the endoscope. The endoscope can be introduced reliably into the bile and pancreatic ducts using the same techniques as those for endoscopic nasobiliary drainage through the instrumental channel of a duodenoscope for examination without pretreatment of the papilla of Vater. Two patients with lesions of the pancreatic duct and seven patients with lesions of the bile duct suspected or detected by endoscopic retrograde cholangiopancreatography (ERCP) were examined. Direct inspection of the biliopancreatic duct not only provided enough information to make a definite diagnosis, but also revealed lesions that were not detectable by ERCP or other examinations.
  • SERUM LIDOCAINE AND MEGX CONCENTRATIONS AFTER PHARYNGEAL ANESTHESIA FOR GASTROSCOPY
    K SODA, K SHIMANUKI, Y YOSHIDA, N SEO, T YAMANAKA, SAKURABAYASHI, I, M MIYATA ENDOSCOPY 26 (4) 347 -351 1994年05月 [査読無し][通常論文]
     
    In 20 patients undergoing topical anesthesia for gastroscopic examination, serum concentrations of lidocaine and its metabolite, monomethylglycinexylidide (MEGX), were measured. Patients were divided randomly into two groups: a gel group, in which 5 ml of 2 % lidocaine gel was applied to the throat for 20 minutes; and a solution group, in which 40 ml of 2 % lidocaine solution was administered by gargling for rive minutes. The effect of oropharyngeal anesthesia was comparable in both groups. In the gel group, the serum levels of lidocaine and MEGX were not elevated at 15 minutes after application of the anesthetic. However, in the solution group, a rise in both serum lidocaine and MEGX at 15 minutes after anesthesia was detected in some of the patients (40 %). Increased serum MEGX concentrations, which correlated well with serum lidocaine concentrations, were associated with the age of the patient (r = 0.606; p < 0.05), but not with height or weight. As a topical anesthetic for endoscopic examination, we prefer lidocaine gel to lidocaine solution, because the latter might be absorbed more rapidly and unpredictably in some, especially aged patients.
  • Cancer cachexia : pathogenesis and possible role of cytokines
    Annals of Cancer Research and Therapy 3 (2) 73 -81 1994年 [査読無し][通常論文]
  • Gastroenterological Endoscopy 35 (12) 2883 -2891 1993年 [査読無し][通常論文]
  • Gastroenterological Endoscopy 35 (3) 505 -510 1993年 [査読無し][通常論文]
  • Effects of β-glucon (Lentinen) on activity of mice with cancer cachexia
    BIOTHERAPY 6 (6) 969 -975 1992年 [査読無し][通常論文]
  • Splenctomy Protect the mice from cochectic death (Preliminary Study) : Preliminary report.
    339,93/3 1992年 [査読無し][通常論文]
  • K SOUDA, T SHIRAMIZU, N OKA, H TSURUMARU, Y MIYAMOTO JAPANESE JOURNAL OF SURGERY 14 (6) 505 -509 1984年 [査読無し][通常論文]

共同研究・競争的資金等の研究課題

  • ポリアミンの臨床応用
    研究期間 : 1996年 
    ポリアミンによる各種疾患の予防および治療法の開発
  • 術後免疫機能のコントロール
    手術や侵襲が免疫機能へおよぼす影響とその制御
  • 癌悪液質の病態解明
    癌悪液質の病態の解明、とくにサイトカインとの関連
  • Polyamine
  • Control of post-operative immune change
  • Patho physiology of Cancer Cachexia

委員歴

  • 日本バイオセラピィ   評議員   日本バイオセラピィ
  • 日本ポリアミン学会   評議員   日本ポリアミン学会


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