Y Obata

Aichi Medical University, Japan

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Publications (94)518.47 Total impact

  • Oncogene 08/2011; 30(33):3648. · 8.56 Impact Factor
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    ABSTRACT: The relationship between gastric cancer and serum vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2, which are soluble form receptor proteins of vascular endothelial growth factor (VEGF), has not been extensively studied. VEGF, sVEGFR-1 and sVEGFR-2 were measured in the sera obtained before surgical operation from 164 gastric cancer patients and from 164 healthy controls matched for age and gender. Compared with controls, the cases showed elevated VEGF (P < 0.01) and reduced sVEGFR-1 (P = 0.07) and sVEGFR-2 (P = 0.02). The difference in VEGF levels was small among men and when the outcome was early cancer. The difference in sVEGFR-1 levels was significant or borderline significant only in men and when the outcome was diffuse type cancer. The difference in sVEGFR-2 levels was significant only in men and when the outcome was advanced or diffuse type cancer. The sensitivities and specificities of VEGF, sVEGFR-1 and sVEGFR-2 were all approximately 60%. For diffuse type cancer, sVEGFR-2 showed a sensitivity of 62.4% and a specificity of 63.4%, which was similar to serum pepsinogen. In conclusion, elevated VEGF and reduced sVEGFR-1 and sVEGFR-2 in serum are characteristic of gastric cancer patients, and the value of serum sVEGFR-2 in the diagnosis of diffuse type gastric cancer should be further evaluated.
    Cancer Science 01/2011; 102(4):866-9. · 3.48 Impact Factor
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    ABSTRACT: We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription. The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation.
    Oncogene 11/2010; 29(47):6245-56. · 8.56 Impact Factor
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    ABSTRACT: Biliary tract cancer, encompassing gallbladder and bile duct cancers, has a poor prognosis, but little is known of the etiology. A nested case-control study was here conducted to evaluate the association between serum levels of IGF-I, IGF-II and IGFBP-3 and death from biliary tract cancer. In a large scale cohort study, 35 gallbladder and 42 bile duct cancers were observed during the follow-up. For each subject in the case group, 1-3 control subjects (228 in total) were selected randomly, matched for sex, age (as near as possible) and residential area. The subjects were divided into tertiles by circulating levels of IGF-I, IGF-II or IGFBP-3. Using conditional logistic regression, risks among the tertiles were compared adjusted for defecation, smoking and drinking habits. No remarkable differences in risks of gallbladder or bile duct cancer were observed among tertiles of IGF-I or IGF-II, and no remarkable trend was observed. Circulating IGFBP-3 showed an inverse U-shape association with gallbladder cancer and a U-shaped one with bile duct cancer. Associations between IGF-I or IGF-II and gallbladder or bile duct cancer thus were lacking or very weak. The observed U- and inverse U-shaped association of IGFBP-3 with the cancers is not suggestive of any meaningful relationships.
    Asian Pacific journal of cancer prevention: APJCP 12/2009; 10 Suppl:63-7. · 1.50 Impact Factor
  • Pancreas 01/2009; 38(5):593-594. · 2.95 Impact Factor
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    ABSTRACT: To analyze an abnormal gait pattern in mutant mice (Hugger), we conducted coarse-grained motion capture. Using a simple retroreflective marker-based approach, we could detect high-resolution mutant-specific gait patterns. The phenotypic gait patterns are caused by extreme vertical motion of limbs, revealing inefficient motor functions. To elucidate the inefficiency, we developed a musculoskeletal computer model of the mouse hindlimb based on X-ray CT data. By integrating motion data with the model, we determined mutant-specific musculotendon lengths, suggesting that three major muscles were involved in the abnormal gait. This approach worked well on laboratory mice, which were putatively too small to be motion capture subjects. Motion capture technology was originally developed for human study, and our approach may help fill neuroscience gaps between mouse and human behavioral phenotypes.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:5227-30.
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    ABSTRACT: Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort. At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models. During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women. Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.
    Pancreas 08/2008; 37(1):25-30. · 2.95 Impact Factor
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    ABSTRACT: Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.
    International Journal of Cancer 03/2008; 122(4):924-9. · 6.20 Impact Factor
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    ABSTRACT: It is unclear whether body mass index (BMI) and physical activity are associated with the risk of pancreatic cancer in Asian populations. We examined these associations in the Japanese Collaborative Cohort Study for Evaluation of Cancer Risk. Our cohort study included 110,792 Japanese men and women at enrollment (1988-1990). Data on height, body weight (at baseline and at age 20 years) and physical activity were obtained from a questionnaire. Cox proportional hazards models were used to estimate the relative risks of pancreatic cancer mortality. We observed a total of 402 pancreatic cancer deaths during the follow-up period. Men with a BMI of 30 or more at age 20 years had a 3.5-fold greater risk compared with men with a normal BMI. Women with a BMI of 27.5-29.9 at baseline had approximately 60% increased risk compared with women with a BMI of 20.0-22.4. In men, weight loss of 5 kg or more between 20 years of age and baseline age was associated with an increased risk of pancreatic cancer death. In contrast, women with weight loss of 5 kg or more over the same period had a decreased risk. Physical activity was not associated with pancreatic cancer risk in either men or women. Obesity in young adulthood may be associated with an increased risk of death from pancreatic cancer in Japanese men. The risk of pancreatic cancer in relation to BMI seems to differ according to sex and the period over which BMI was measured.
    International Journal of Cancer 07/2007; 120(12):2665-71. · 6.20 Impact Factor
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    ABSTRACT: Among the events that control cellular differentiation, the acetylation of histones plays a critical role in the regulation of transcription and the modification of chromatin. Jun dimerization protein 2 (JDP2), a member of the AP-1 family, is an inhibitor of such acetylation and contributes to the maintenance of chromatin structure. In an examination of Jdp2 'knock-out' (KO) mice, we observed elevated numbers of white adipocytes and significant accumulation of lipid in the adipose tissue in sections of scapulae. In addition, mouse embryo fibroblasts (MEFs) from Jdp2 KO mice were more susceptible to adipocyte differentiation in response to hormonal induction and members of the CCAAT/enhancer-binding proteins (C/EBP) gene family were expressed at levels higher than MEFs from wild-type mice. Furthermore, JDP2 inhibited both the acetylation of histone H3 in the promoter of the gene for C/EBPdelta and transcription from this promoter. Our data indicate that JDP2 plays a key role as a repressor of adipocyte differentiation by regulating the expression of the gene for C/EBPdelta via inhibition of histone acetylation.
    Cell Death and Differentiation 04/2007; 14(8):1398-405. · 8.37 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2007; 5(4):262-262.
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    ABSTRACT: To examine the relationship of baseline levels of serum TGF-beta1 to the subsequent risk of death from pancreatic cancer in a nested case-control study. The cases were 85 persons who had provided a blood sample at baseline and subsequently died of pancreatic cancer during the study period. For each case, three controls were randomly selected from among the cohort participants, and were matched for each case by sex, age (+/-1 year), and study area. Serum TGF-beta1 levels were measured with enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from conditional logistic models. The mean of serum TGF-beta1 levels was significantly higher among cases than among controls (p = 0.01). Individuals with serum TGF-beta1 levels in the highest quartile had a 2.5-fold increase in risk as compared with those in the lowest quartile (OR, 2.5; 95% CI, 0.9-6.9), after adjustment for month of blood draw, cigarette smoking, body mass index and history of diabetes. Excluding 12 pancreatic cancer deaths that occurred within three years of follow-up did not alter the positive association. Our prospective data indicate that high serum TGF-beta1 levels may be associated with an increased risk of death from pancreatic cancer.
    Cancer Causes and Control 11/2006; 17(8):1077-82. · 3.20 Impact Factor
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    ABSTRACT: The etiology of pancreatic cancer remains largely unknown. We examined the association of pancreatic cancer deaths with menstrual and reproductive factors in a cohort study involving Japanese women. A total of 63,273 women were followed up for mortality from 1988 to 1999. Information on menstrual and reproductive factors was obtained by a questionnaire survey at baseline. Cox proportional-hazards models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for death from pancreatic cancer in relation to menstrual and reproductive factors. During 631,401 person-years of follow-up, 154 women died from pancreatic cancer. Parity was not significantly associated with the risk of death from pancreatic cancer; the RR was 0.80 (95% CI, 0.31-2.11) for women with six or more births compared with women with zero or one birth. We found no significant overall association with other reproductive factors, including pregnancy, age at first birth, and menopause. The risk appeared to increase with increasing age at menarche; the RR was 1.49 (95% CI, 0.95-2.34) for women who had menarche after 16 years of age compared to those who had menarche before they were 15 years old. Our prospective data indicate that menstrual and reproductive factors are not associated with the risk of death from pancreatic cancer among Japanese women.
    Journal of Gastroenterology 10/2006; 41(9):878-83. · 3.79 Impact Factor
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    ABSTRACT: The significance of serum levels of transforming growth factor (TGF)-beta1 in the development of gastric cancer is unclear. The purpose of this study is to determine whether serum TGF-beta1 correlated with the clinicopathological findings of patients with gastric cancer. Transforming growth factor-beta1 levels in the serum of 275 gastric cancer patients and 275 gender- and age-matched healthy controls were measured with enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. The mean level of serum TGF-beta1 of gastric cancer patients (15.9 +/- 5.9 ng/mL) was significantly higher than that (13.9 +/- 7.4 ng/mL) of healthy controls (P < 0.01). The odds ratio for the subjects in the highest quartile (16.7 ng/mL or more) was 4.03 (95% confidence interval, 2.14-7.58), as compared with that for the subjects in the lowest quartile (0-9.5 ng/mL). Patients with venous invasion compared to those without venous invasion had significantly elevated serum TGF-beta1 (17.3 +/- 7.2 vs 15.0 +/- 5.1 ng/mL; P = 0.04). There were no statistically significant differences between the two groups categorized by histological type, lymph node metastasis and distant metastasis. Logistical regression analysis showed that venous invasion was significantly correlated with elevated serum TGF-beta1 levels (P = 0.02). The present study showed that an elevated serum TGF-beta1 level may be significantly correlated with venous invasion in gastric cancer patients.
    Journal of Gastroenterology and Hepatology 03/2006; 21(2):432-7. · 3.33 Impact Factor
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    ABSTRACT: The functional difference between the maternal and paternal genome, which is characterized by epigenetic modifications during gametogenesis, that is genomic imprinting, prevents mammalian embryos from parthenogenesis. Genomic imprinting leads to nonequivalent expression of imprinted genes from the maternal and paternal alleles. However, our research showed that alteration of maternal imprinting by oocyte reconstruction using nongrowing oocytes together with deletion of the H19 gene, provides appropriate expression of maternally imprinted genes. Here we discuss that further alteration of paternally imprinted gene expressions at chromosomes 7 and 12 allows the ng/fg parthenogenetic embryos to develop to term, suggesting that the paternal contribution is obligatory for the descendant.
    Ernst Schering Research Foundation workshop 02/2006;
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    ABSTRACT: Few epidemiological studies have examined associations between diet and pancreatic cancer in Japan. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we evaluated the relationship between dietary factors, including meat, vegetable, and fruit intake, and the risk of pancreatic cancer deaths. Among the original cohort established between 1988 and 1990, 46,465 men and 64,327 women aged 40-79 yr were followed-up through December 31,1999. During 1,042,608 person-years of follow-up, we documented 300 deaths from pancreatic cancer. A 33-item food-frequency questionnaire was used to assess dietary intake at the baseline survey. Cox proportional-hazards models were used to estimate the relative risks of pancreatic cancer death in relation to the intake frequency of food items. We did not observe an overall association between meat intake and pancreatic cancer risk. Except for a 50% decrease in risk associated with high fruit intake among men, we did not find other significant inverse relationships between vegetable and fruit intake and pancreatic cancer risk. Smoking did not modify the associations with dietary habits. Our study suggested that high consumption of pickles and wild edible plants, mainly bracken, might be related to increased pancreatic cancer risk; however, this finding should be confirmed in other epidemiological studies.
    Nutrition and Cancer 02/2006; 56(1):40-9. · 2.70 Impact Factor
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    ABSTRACT: Cryopreservation of male germ cells is a strategy for the conservation of species and strains valuable to biomedical researchers. However, to minimize damage that may occur during freezing and thawing, complex cryopreservation protocols that have been optimized for the stage and species of the male germ cell are usually employed. This study was undertaken to see whether mouse male germ cells could be safely cryopreserved for later use by freezing the whole epididymides and testes without cryoprotectant. Furthermore, we examined whether frozen male germ cells maintained their fertilization ability after international transportation on dry ice. Epididymides and testes were collected from sexually mature male ICR and C57BL/6Cr mice and placed in polypropylene cryotubes. The cryotubes were frozen at -80°C with or without a freezing container, or were plunged directly into liquid nitrogen (LN2). They were stored at -80°C or in LN2 from between one week and one year. Epididymides and testes were thawed by placing the cryotubes in a water bath at room temperature. B6D2F1 and C57BL/6Cr oocytes were microinseminated with either epididymal and testicular spermatozoa or round spermatids. After embryo transfer into pseudopregnant females, normal pups were obtained irrespective of the method of cryopreservation and cell type used. However, their birth rates (2-33%) were lower than those of our conventional microinsemination using fresh sperm or spermatids (20-60%). For transportation experiments, testes were collected from C57BL/6J mice and placed in a cryotube. The cryotubes were frozen at -80°C in a freezing container. On the day of transportation, the cryotubes were placed in a polystyrene foam case filled with dry ice and were transported from Harwell (UK) to Tsukuba (Japan) by air and land. After three days, the samples were delivered to the recipient facility and were stored at -80°C until use (about 1 month). After thawing and collection of spermatogenic cells, C57BL/6J oocytes were microinseminated with either testicular spermatozoa or elongated spermatids. After embryo transfer, 24 (34% per transfer) and 8 (16%) offspring, respectively, were obtained from the two groups. These results indicate that mouse male germ cells retain their nuclear integrity even after freezing epididymides or testes in freezers without cryoprotectant. Since this cryopreservation technique is very simple and allows storage at -80°C for at least several months, it may enable transportation of mouse male germ cells internationally on dry ice, even when the senders are not specialized in cryopreservation.
    Reproduction Fertility and Development 01/2006; 18(2). · 2.58 Impact Factor
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    ABSTRACT: We conducted a prospective cohort study to examine the association between alcohol intake and the risk of all-cause mortality among middle-aged and elderly Japanese men and women. At baseline (1988-1990), a total of 110,792 Japanese men and women aged 40 to 79 years were asked to complete a questionnaire that included information on alcohol intake, and were followed up for all-cause mortality through December 31, 1999. Relative risks (95% confidence interval) were calculated using Cox proportional-hazards models. The risk of all-cause mortality was lowest among current drinkers with an alcohol intake of 0.1 to 22.9 g/d (RR, 0.80; 95% CI, 0.72-0.88 for men; and RR, 0.88; 95% CI, 0.77-1.00 for women). Excessive mortality associated with heavy drinking (> or = 69 g/d) was observed for cancer, cardiovascular disease and injuries and other external causes in men, while significantly reduced mortality with light drinking was seen for cancer in men and CVD in women. For men, the benefit associated with light alcohol consumption (< 23 g/d) was more apparent among nonsmokers than among smokers. Our prospective data show a 12% to 20% decreased risk of all-cause mortality in both Japanese men and women who consumed less than 23 g/d of alcohol (approximately 2 drinks), although heavy drinking increased that risk.
    Annals of Epidemiology 10/2005; 15(8):590-7. · 2.48 Impact Factor
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    ABSTRACT: Helicobacter pylori infection and serum pepsinogen values are strongly related with stomach cancer. The aim of this study was to know what were these factors among general population. Subjects were randomly selected 633 control subjects in a nested case-control study for risk of stomach cancer. Most of them were from rural areas of Japan. Using frozen sera, pepsinogen I (PG I) and II (PG II) values and H. pylori antibody were measured. Those with PG I less than 50 ng/mL and the ratio of PG I to PG II (PG I/II) was less than 2.0 were defined as severe, those with PG I less than 70 ng/ml and PG I/II less than 3.0 were defined as mild and the other subjects were defined as no serological atrophy. About 70% of the subjects were H. pylori seropositive and the seroprevalence did not depend on age or sex. Percentages of those with severe serological atrophy increased with age from 10% in those aged 40-49 years to 38% in 70 and more, and percentages of those with mild serological atrophy were about 30% independent of age. The subjects, who were expected to represent populations of rural area of Japan, had high prevalence of both H. pylori infection and serological atrophy of gastric mucosa. These facts should be considered in discussing results of the nested case-control study.
    Journal of Epidemiology 07/2005; 15 Suppl 2:S126-33. · 2.11 Impact Factor
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    ABSTRACT: The role of serum manganese superoxide dismutase (MnSOD) in the development of gastric cancer has not been clearly defined. We conducted a case-control study to address the potential relationship between serum MnSOD levels and gastric cancer. Cases were 275 gastric cancer patients and controls were 275 sex and age-matched healthy persons. Serum MnSOD levels were determined by a commercially available enzyme-linked immunosorbent assay (ELISA). The mean(+/-standard deviation) of serum MnSOD levels was 177.4 +/- 87.3 ng/mL among cases and 169.4 +/- 56.7 ng/mL among controls. Gastric cancer patients had slightly higher serum MnSOD levels than the controls. After adjustment for pack-years of cigarette smoking and Helicobacter pylori infection, the odds ratio was 1.54(95% confidence interval; 0.79-3.01) for subjects in the highest quartile versus the lowest quartile. No significant differences were observed for serum MnSOD levels in gastric cancer patients according to clinicopathological factors such as disease stage, histological type, venous invasion, and lymph node metastasis. Our study suggested that serum MnSOD levels are not significantly associated with the increased risk of gastric cancer, although a weak association may exist.
    Journal of Epidemiology 06/2005; 15(3):90-5. · 2.11 Impact Factor

Publication Stats

2k Citations
518.47 Total Impact Points

Institutions

  • 2002–2009
    • Aichi Medical University
      • Department of Public Health
      Japan
  • 2007
    • RIKEN
      Вако, Saitama, Japan
  • 1998–2006
    • Tokyo University of Agriculture
      • • Department of Bioscience
      • • Department of Animal Science
      Edo, Tōkyō, Japan
  • 2001
    • Tsukuba Research Institute
      Edo, Tōkyō, Japan
    • City of Hope National Medical Center
      Duarte, California, United States
  • 2000–2001
    • Gunma University
      Maebashi, Gunma Prefecture, Japan
  • 1988–2001
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 1994
    • National Institute of Genetics
      Мисима, Shizuoka, Japan
  • 1991
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 1989
    • Mie University
      • Department of Clinical Oncology
      Tsu-shi, Mie-ken, Japan
  • 1979–1988
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, New York, United States