Hiroshi Koyama

Universitas Padjadjaran, Bandung, East Java, Indonesia

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Publications (41)48.53 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer has become a leading cause of mortality in humans. Previous studies have shown the potential anticancer properties of kaempferol‑3‑O‑rhamnoside in breast cancer cell lines. In the present study, the anticancer potential of kaempferol‑3‑O‑rhamnoside was investigated in LNCaP human prostate cancer cell lines. The inhibition of cell proliferation was investigated using MTT assays, whereas its ability to induce the caspase‑cascade pathway was investigated by western blotting. The results showed that kaempferol‑3‑O‑rhamnoside inhibits the proliferation of LNCaP cells in a dose‑dependent manner by upregulating the expression of caspase‑8, caspase‑9, caspase‑3 and poly (ADP‑ribose) polymerase proteins. Although further studies are required, the results of the present study indicate the potential application of kaempferol‑3‑O‑rhamnoside in cancer treatment.
    Biomedical Reports. 01/2015; 3(1):115-117.
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    ABSTRACT: Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate?consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 µg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine?resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 µg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 µg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC50 of 106 µM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.
    Biomedical Reports. 07/2014; 2(4):579-583.
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    ABSTRACT: To establish guidelines for the selenium supplementation in radiotherapy we assessed the benefits and risks of selenium supplementation in radiotherapy. Clinical studies on the use of selenium in radiotherapy were searched in the PubMed electronic database in January 2013. Sixteen clinical studies were identified among the 167 articles selected in the initial search. Ten articles were observational studies, and the other 6 articles reported studies on the effects of selenium supplementation in patients with cancer who underwent radiotherapy. The studies were conducted worldwide including European, American and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium levels were common parameters used to assess the effects of radiotherapy and the selenium supplementation status. Selenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200-500 mug/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of selenium supplementation.
    Radiation Oncology 05/2014; 9:125. · 2.11 Impact Factor
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    ABSTRACT: Selenium is an essential nutrient for human health, and maternal selenium concentration has been reported to be associated with pregnancy outcome. To further investigate the possible role of selenium (Se) in miscarriage, we conducted a case-control study to evaluate the correlations among selenium status, glutathione peroxidase activity, and spontaneous abortion. A total of 46 subjects with normal pregnancies and 25 subjects with spontaneous abortion were recruited, and their serum selenium concentrations and serum glutathione peroxidase activities were analyzed. The total serum selenium concentrations in subjects with normal pregnancies were significantly higher than those of subjects with spontaneous abortion; however, the glutathione peroxidase activities were similar in both groups. We further separated the subjects into smoking and nonsmoking groups, and the logistic regression analysis suggested that total serum selenium concentration, but not serum glutathione peroxidase activity or smoking, was significantly correlated with the incidence of miscarriage. The present study thus reaffirms that low serum selenium levels are associated with miscarriage and that selenium plays an important role in pregnancy maintenance.
    Biological trace element research 05/2013; · 1.92 Impact Factor
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    ABSTRACT: The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 μg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2013; 68(1):1-10.
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    ABSTRACT: BACKGROUND AND AIM: Previous evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity. METHODS: Plasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n=78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group. RESULTS: In the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r=0.390, P<0.05) and with fatty acid binding protein-4 (FABP4) (r=0.474, P<0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r=-467, P<0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r=0.413, P<0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r=-0.429, P<0.05). CONCLUSIONS: These results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.
    Journal of Trace Elements in Medicine and Biology 11/2012; · 1.96 Impact Factor
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    ABSTRACT: Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.
    Oncology letters 05/2012; 3(5):1069-1072. · 0.24 Impact Factor
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    ABSTRACT: Primate-consumed plants are assumed to be a promising source of therapeutic agents since primates can survive and be cured from any disease by their daily consumed food. In the course of our study to search for anticancer agents, we evaluated 42 species of plants usually consumed by primates for their antiproliferative activity against cell lines of human breast adenocarcinoma (MCF-7). In this study, crude ethanol extracts of the plants were tested using MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay. The results showed that four extracts of Dysoxylum caulostachyum, Eugenia aquea, Garcinia celebica, and Psychotria valentonic leaves strongly inhibited the MCF-7 cell proliferation with IC50 values of 12, 58, 87, and 87 μg/ml, respectively. Further examination on the fractions of the four extracts indicated that the ethyl acetate fraction of D. caulostachyum, the n-hexane fractions of E. aquea and G. celebica, and the water fraction of P. valentonic were the most active fractions with the IC50 of 78 , 24, 60, and 23 μg/ml, respectively. These results suggest that primate-consumed plants might have potential as a source of anticancer agents.
    E3 Journal of Medical Research. 05/2012; 1(4):38-43.
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    E3 Journal of Medical Research. 02/2012;
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    ABSTRACT: SUMMARYPlasmodium falciparum has for some time been developing resistance against known anti-malarial drugs, and therefore a new drug is urgently needed. Selenium (Se), an essential trace element, in the form of inorganic Se, selenite (SeO32-), has been reported to have an anti-plasmodial effect, but its mechanism is still unclear. In the present study, we evaluated the anti-plasmodial effect of several Se compounds against P. falciparum in vitro. The anti-plasmodial effect of several Se compounds was analysed and their apoptosis-inducing activity was evaluated by morphological observation, DNA fragmentation assay and mitochondrial function analysis. SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial effects with 50% inhibition concentration at 9, 10, 45, and 65 μm, respectively, while selenate and methylselenocysteine up to 100 μm have no effect on parasite growth. The effective Se compounds caused the parasites to become shrunken and pyknotic and significantly increased mitochondrial damage against P. falciparum compared to the untreated control. In conclusion, SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial activities that induce apoptosis-like cell death in P. falciparum, and the anti-plasmodial effects of Se seem to be based on its chemical forms. The apoptosis-like cell-death mechanism in P. falciparum can be beneficial to respond to the growing problem of drug resistance.
    Parasitology 08/2011; · 2.36 Impact Factor
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    ABSTRACT: Prostate cancer is one of the leading causes of cancer-related deaths among males. Although use of the micro-nutrient selenium in prostate cancer clinical trials is limited, the outcomes indicate that selenium is a promising treatment. Furthermore, selenium inhibits prostate cancer through multiple mechanisms, and it is beneficial in controlling the development of this disease. This review highlights the latest epidemiological and biomolecular research on selenium in prostate cancer, as well as its prospects for future clinical use.
    International Journal of Oncology 08/2011; 39(2):301-9. · 2.66 Impact Factor
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    ABSTRACT: Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p < 0.05) and decreases in the plasma Se concentration (p < 0.05) and in serum albumin (p < 0.05) after surgery were observed. Since albumin is a Se-containing protein and represents a negative acute phase protein that provides amino acids for the production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.
    Biological trace element research 06/2011; 144(1-3):388-95. · 1.92 Impact Factor
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    ABSTRACT: Depression is a common mental disorder. Several studies suggest that lifestyle and health status are associated with depression. However, only a few large-scale longitudinal studies have been conducted on this topic. The subjects were middle-aged and elderly Japanese adults between the ages of 40 and 69 years. A total of 9,650 respondents completed questionnaires for the baseline survey and participated in the second wave of the survey, which was conducted 7 years later. We excluded those who complained of depressive symptoms in the baseline survey and analyzed data for the remaining 9,201 individuals. In the second-wave survey, the DSM-12D was used to determine depression. We examined the risks associated with health status and lifestyle factors in the baseline survey using a logistic regression model. An age-adjusted analysis showed an increased risk of depression in those who had poor perceived health and chronic diseases in both sexes. In men, those who were physically inactive also had an increased risk of depression. In women, the analysis also showed an increased risk of depression those with a BMI of 25 or more, in those sleeping 9 hours a day or more and who were current smokers. A multivariate analysis showed that increased risks of depression still existed in men who had chronic diseases and who were physically inactive, and in women who had poor perceived health and who had a BMI of 25 or more. These results suggest that lifestyle and health status are risk factors for depression. Having a chronic disease and physical inactivity were distinctive risk factors for depression in men. On the other hand, poor perceived health and a BMI of 25 or more were distinctive risk factors for depression in women. Preventive measures for depression must therefore take gender into account.
    BMC Psychiatry 01/2011; 11:20. · 2.23 Impact Factor
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    ABSTRACT: Broccoli is a Brassica vegetable that is believed to possess chemopreventive properties. Selenium also shows promise as an anticancer agent. Thus, selenium enrichment of broccoli has the potential to enhance the anticancer properties of broccoli sprouts. Selenium-enriched broccoli sprouts were prepared using a sodium selenite solution. Their anticancer properties were evaluated in human prostate cancer cell lines and compared with those of a control broccoli sprout extract. Selenium-enriched broccoli sprouts were superior to normal broccoli sprouts in inhibiting cell proliferation, decreasing prostate-specific antigen secretion, and inducing apoptosis of prostate cancer cells. Furthermore, selenium-enriched broccoli sprouts but, not normal broccoli sprouts, induced a downregulation of the survival Akt/mTOR pathway. Our results suggest that selenium-enriched broccoli sprouts could potentially be used as an alternative selenium source for prostate cancer prevention and therapy.
    BMC Cancer 11/2009; 9:414. · 3.33 Impact Factor
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    ABSTRACT: "Social nicotine dependence" is a newly-coined phrase for describing a psychological and psychosocial state associated with smoking. That new dependence is defined as a misperception of smoking caused by smokers' attempts, for example, to deny the ill effects of tobacco and/or to justify themselves by regarding smoking as acceptable cultural and social behavior. It can be quantified by a 10-item questionnaire, the Kano Test for Social Nicotine Dependence (KTSND). We examined the internal consistency as well as the criterion-related and construct validity and factor structure of KTSND. Self-administered questionnaires including the KTSND, smoking status, and stages in quitting smoking only for current smokers were collected from 666 industrial workers. The internal consistency of the KTSND assessed by Cronbach's alpha coefficient was 0.77. In addition, we found that an 8-item combination from among 10 items had a higher coefficient of 0.80. KTSND scores differed among three groups of smoking status as a criterion. Factor analysis clarified two potential factors: "an overestimation of smoking's effects to enhance physical and mental status" and "an insistence on smoking as acceptable cultural and social behavior." The KTSND proved to be valid in terms of the internal consistency and the inclusion of two key aspects of the misperception of smoking.
    Annals of epidemiology 06/2009; 19(11):815-22. · 2.95 Impact Factor
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    Hiroshi Koyama, Rizky Abdulah, Chiho Yamazaki
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    ABSTRACT: Selenium is an essential trace element and 25 selenoproteins, which contain the element in the form of selenocysteine, have been characterized in mammals. Selenium exerts its biological activity largely through these selenoproteins. However, some selenium compounds, such as selenite, Se-methylselenocysteine, methylseleninic acid, and selenomethionine, also have biological effects. Several studies indicate that these selenium compounds are among the most promising agents for cancer chemoprevention and anti-aging. A large chemoprevention study has been carried out using selenomethionine, because selenomethionine was thought to be an appropriate form of selenium supplementation for human nutritional. However, a randomized controlled trial shows that selenium-rich yeast (containing selenomethionine)may increase the risk for type-2 diabetes. The study of the chronic effects of selenium compounds including selenomethionine for usage in long-term supplementation is needed.
    Biomedical Research on Trace Elements. 04/2009; 20(1):19-29.
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    ABSTRACT: Selenium protection against cellular damage by oxygen radicals is accomplished through selenoproteins. Thus, selenium protection during the development of stroke, an oxidative stress-related disease, may not be appropriately reflected in the total serum selenium concentration. Therefore, we hypothesized that serum selenoproteins should also be measured to understand the relationship between selenium status and oxidative stress. To establish whether stroke is associated with changes in serum selenoprotein levels, a population-based, nested case-control study was performed. The subjects were recruited from 1632 residents older than 40 years who had completed health examinations in 1992. Blood samples collected from 30 controls and 30 initial stroke victims between 1992 and 1994 were analyzed for total serum selenium and selenium-containing protein distribution. Selenium-containing proteins were separated using 2 high-performance liquid chromatography columns in tandem and detected by inductively coupled plasma-mass spectrometry. The mean serum selenium concentration was lower in the patients who had a stroke than in the controls (105.2 vs 116.5 microg/L). Selenium contents in glutathione peroxidase and albumin did not show any significant difference; however, selenoprotein P was significantly lower in the stroke cases than in the controls (54.5 vs 63.0 microg/L, P = .006). Results from multivariate logistic regression analysis showed that reduced serum level of selenoprotein P was associated with a higher risk of stroke (odds ratio = 0.28; 95% confidence interval, 0.10-0.85).
    Nutrition research 03/2009; 29(2):94-9. · 2.59 Impact Factor
  • The Kitakanto Medical Journal 01/2009; 59(3):231-240.
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    ABSTRACT: Urinary incontinence (UI) is one of the most common and distressing conditions among nursing home residents. Although scheduled care is usually provided for them, incontinence care should be individualized regarding going to the toilet, changing diapers, and taking food and water. We have developed an individualized and comprehensive care strategy to address the problem. We conducted an intervention study that involved training chiefs of staffs, who in turn trained other staffs, and encouraging residents. A total of 153 elderly subjects selected from 1290 residents in 17 nursing homes were eligible to receive our individualized and comprehensive care. The goals of the care strategy were (i) to complete meal intake; (ii) to take fluids up to 1500 ml/day; (iii) to urinate in a toilet; (iv) to spend over 6h out of bed; and (v) to reduce time spent in wet diapers. We explained the aims of our strategy to the chiefs of staff of each nursing home and instructed them to encourage residents to take an active part in our individualized and comprehensive care strategy for 12 weeks. For 3 days before and after that period, we assessed the changes in fluid volume intake, time spent in wet diapers, size of diaper pads, and urination habits. The result was that fluid volume intake significantly increased (p<0.001) while time spent in wet diapers decreased (p<0.001). The number of residents wearing diapers decreased as did the size of pads during the day (p=0.0017). The proportion of residents using diapers at night was reduced and those using toilets at night increased (p=0.007). This study suggests that such an individualized and comprehensive care strategy can offer a measurable improvement in UI care.
    Archives of gerontology and geriatrics 01/2009; 49(2):278-83. · 1.36 Impact Factor
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    ABSTRACT: Cadmium (Cd) is known to cause various disorders in the testis, and metallothionein (MT) is known as a protein, which has a detoxification function for heavy metals. However, the changes of Fe, Cu, and Zn distribution in the testis induced by Cd exposure have not been well examined. Moreover, only a few studies have been reported on the localization of MT after Cd exposure. In this study, we have investigated the changes of Fe, Cu, and Zn distribution in Cd-exposed testis by a newly developed in air micro-Particle Induced X-ray Emission (PIXE) method. Also, we examined the distribution of MT expression in testis. In the testis of Cd-treated rats with significant increases of lipid peroxidation, the sertoli cell tight junction was damaged by Cd exposure, resulting from disintegration of the blood testis barrier (BTB). Evaluation by in air micro-PIXE method revealed that Cd and Fe distribution were increased in the interstitial tissues and seminiferous tubules. The histological findings indicated that the testicular tissue damage was advanced, which may have been caused by Fe flowing into seminiferous tubules followed by disintegration of the BTB. As a result, Fe was considered to enhance the tissue damage caused by Cd exposure. MT was detected in spermatogonia, spermatocytes, and Sertoli's cells in the testis of Cd-treated rats, but was not detected in interstitial tissues. These results suggested that MT was induced by Cd in spermatogonia, spermatocytes, and Sertoli's cells, and was involved in the resistance to tissue damage induced by Cd.
    BioMetals 03/2008; 21(1):71-81. · 3.28 Impact Factor

Publication Stats

244 Citations
48.53 Total Impact Points


  • 2013
    • Universitas Padjadjaran
      • Department of Pharmacology and Clinical Pharmacy
      Bandung, East Java, Indonesia
  • 2002–2011
    • Gunma University
      • • Department of Public Health
      • • Graduate School of Medicine
      Maebashi-shi, Gunma-ken, Japan
    • Hokuriku University
      Kanazawa, Ishikawa, Japan
    • National Institute for Environmental Studies
      • Center for Environmental Health Sciences
      Tsukuba, Ibaraki, Japan
  • 2008
    • Kyoto Prefectural University of Medicine
      • Department of Nursing
      Kioto, Kyōto, Japan
  • 2007
    • Tokyo University and Graduate School of Social Welfare
      Edo, Tōkyō, Japan
  • 2004
    • Jobu University