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Akira Sekikawa

Publications and source records attributed to Akira Sekikawa.

16 recordsLinked to original sources
PubMed2007

Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell survival via Akt pathway.

Activation of tyrosine kinases is an important factor during cancer development. Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma-carboxyglutamyl protein. Although many receptor tyrosine kinases and their ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is involved in gastric carcinogenesis has not been elucidated. The aim of this study was to investigate the expression of Gas6 and Axl in gastric cancer and also their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were highly expressed in a substantial proportion of human gastric cancer tissue and cell lines, and Gas6 expression was significantly associated with lymph node metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6-Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6-Axl signaling could be a novel therapeutic for gastric cancer.

Base Sequence↗
PubMed2006

Alcohol consumption and coronary artery calcium in middle-aged Japanese men.

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.

Adult↗
PubMed2006

Higher levels of adiponectin in American than in Japanese men despite obesity.

Levels of adiponectin are inversely associated with obesity levels. We examined the levels of adiponectin in American (n = 98) and Japanese (n = 92) men aged 40 to 49 years. Contrary to our expectations, the American men had higher levels of adiponectin than the Japanese men (13.3 +/- 5.8 vs 7.3 +/- 4.2 (microg/mL) despite higher levels of obesity. Smaller areas of visceral adipose tissue in American than in Japanese men may have resulted in the higher levels of adiponectin.

Adiponectin↗
PubMed2005

The determinants of plasma plasminogen activator inhibitor-1 levels differ for American and Japanese men aged 40-49.

BACKGROUND: Elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels were associated with higher incidence of type II diabetes. Elucidating the determinants of PAI-1 in various ethnicities may help to understand the susceptibility to developing diabetes. The aim of our study was to compare PAI-1 levels between Americans and the Japanese in the post-war generation and to elucidate the determinants of the PAI-1 levels. METHODS: We conducted a cross-sectional study on a total of 198 men aged 40-49 in the US (Body mass index (BMI): 27.0+/-3.3 kg/m(2)) and Japan (BMI: 23.3+/-3.1 kg/m(2)). Examination included physique measurement (BMI and waist girth), blood analysis (lipid profiles, glucose, insulin, C-reactive protein, and PAI-1), and life-style assessment by self-administered questionnaires. RESULTS: PAI-1 levels were significantly lower in American than in Japanese men, even after adjustment for age, waist girth, cigarette smoking, habitual alcohol drinking, and other factors. In the Americans, waist girth, insulin, and cigarette smoking were significantly associated with PAI-1 levels, while waist girth and triglycerides were significantly associated with PAI-1 levels in the Japanese. CONCLUSIONS: PAI-1 levels were significantly lower in American than in Japanese men and the determinants of PAI-1 levels differ for American and Japanese men aged 40-49.

Adult↗
PubMed2005

REG Ialpha protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer.

BACKGROUND & AIMS: Although a significant amount of regenerating gene (REG) Ialpha protein is present not only in normal gastric mucosa but also in gastric cancer tissues, its pathophysiologic role in gastric cancer development remains unclear. We investigated REG Ialpha protein expression in early gastric cancers, and examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on gastric cancer cells. METHODS: Early gastric cancer specimens were analyzed histologically using immunohistochemistry for REG Ialpha protein and proliferating cell nuclear antigen (PCNA). The effects of cytokines on REG Ialpha promoter activity and its messenger RNA (mRNA) expression in AGS (a kind of gastric cancer cell line) cells were examined by luciferase reporter assay and Northern blot analysis, respectively. Effects of REG Ialpha protein on cell growth and H2O2-induced apoptosis in AGS cells were examined by 3,-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase nick-end labeling (TUNEL) assays, respectively. RESULTS: REG Ialpha-positive early gastric cancers showed a significantly higher PCNA labeling index and more severe inflammatory cell infiltration in adjacent gastric mucosa than the negative cancers. REG Ialpha gene expression and its promoter activity were enhanced by interferon (IFN)-gamma and interleukin (IL)-6. REG Ialpha protein promoted cell growth and cell resistance to H2O2-induced apoptosis in AGS cells. These effects were abolished by concomitant treatment with anti-REG Ialpha antibody. REG Ialpha protein enhanced Akt phosphorylation and Bcl-xL expression in AGS cells. CONCLUSIONS: REG Ialpha gene is inducible by cytokine stimulation and its gene product may function as a mitogenic and/or an antiapoptotic factor in the development of early gastric cancer.

Apoptosis↗
PubMed2005

Cognitive impairment as a strong predictor of incident disability in specific ADL-IADL tasks among community-dwelling elders: the Azuchi Study.

PURPOSE: We examined differential effects of cognitive impairment on each of the activities of daily living (ADL) and instrumental activities of daily living (IADL) tasks. DESIGN AND METHODS: In a 3-year follow-up of community-dwelling elderly persons in Azuchi, Japan, we assessed cognition by using the Hasegawa Dementia Scale. We examined (a) the cross-sectional association between cognitive impairment and functional disability in each ADL-IADL item; (b) cognitive impairment as a risk factor for incident disability in each ADL-IADL item, through logistic regression models; and (c) probabilities of incident loss of ADL-IADL abilities or death in 3 years, using multinomial logistic regression models. We also calculated the population attributable risk (PAR%) of cognitive impairment on incident loss of task-specific ADL-IADL abilities. RESULTS: Cross-sectionally, the severity of cognitive impairment was associated with disability in each ADL-IADL task, with larger effects shown for ADL items. Longitudinally, minimally or mildly cognitively impaired individuals had a significantly higher risk of losing functional abilities compared with those with intact cognition. The PAR% indicated that cognitive impairment accounts for 11% to 36% of incident disability in ADL-IADL tasks, with the highest PAR% shown for the ability to feed oneself. IMPLICATIONS: Cognitively impaired subjects are heterogeneous; the severity of cognitive impairment has a different impact on incident loss of task-specific ADL-IADL abilities, and comorbidities could affect disabilities differently. Consideration of these heterogeneities will enrich future studies on the impact of cognitive impairment on ADL-IADL abilities.

Activities of Daily Living↗
PubMed2004

Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40-49 in Japan than in the US, despite a less favorable profile of major risk factors.

BACKGROUND: Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the US and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 in the US and Japan. METHODS: We conducted a cross-sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography. RESULTS: Systolic blood pressure, total cholesterol, low density lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese (122.6 +/- 14.1 versus 113.7 +/- 9.6 mmHg, P < 0.01; 5.72 +/- 0.90 versus 4.99 +/- 0.81 mmol/l (220.9 +/- 34.6 versus 192.8 +/- 31.3 mg/dl), P < 0.01; 3.52 +/- 1.01 versus 3.10 +/- 0.78 mmol/l (136.0 +/- 39.0 versus 119.7 +/- 30.0 mg/dl), P < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen were similar. High density lipoprotein (HDL)-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score >0 was strikingly lower among the Japanese than the Americans (13% versus 47%, P < 0.01). CONCLUSIONS: Much lower prevalence of coronary calcium despite a less favourable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance.

Adult↗
PubMed2004

STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells.

Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the role of STAT3 signaling in apoptosis and cellular proliferation in gastric cancer. Here we reported that STAT3 was constitutively activated in various human gastric cancer cells and its inhibition by ectopic dominant-negative STAT3 or Janus kinase inhibitor, tyrphostin AG490, induced apoptosis. Furthermore, STAT3 inhibition markedly decreased survivin expression, and forced expression of survivin rescued AGS cells from apoptosis induced by STAT3 inhibition. Although some reports demonstrated that the PI3K/Akt pathway regulates survivin expression, inhibition of the PI3K/Akt pathway did not affect survivin expression in AGS and MKN1 cells. Finally, activated form of STAT3, Tyr-705 phospho-stat3, was found in the nucleus of cancer cells in 11 of 40 (27.5%) human gastric cancer specimens. These findings suggest that constitutively activated STAT3 signaling supports gastric cancer cell survival in association with survivin expression.2004

Acute-Phase Proteins↗
PubMed2004

Expression of reg I alpha protein in human gastric cancers.

BACKGROUND/AIMS: Although regenerating gene(Reg) I alpha protein has a trophic effect on gastric epithelial cells, it is unclear whether Reg I alpha protein and its receptor are involved in gastric carcinogenesis. Therefore, we investigated the Reg I alpha protein expression in human gastric cancers and assessed its relationship to clinicopathological factors. METHODS: Sixty-one gastric cancer specimens were examined, using immunohistochemistry, for Reg I alpha protein, p53, and proliferating cell nuclear antigen. The expression of both Reg I alpha and Reg receptor mRNA was examined in seven human gastric cancer cell lines (MKN1, MKN28, MKN45, MKN74, KATOIII, GCIY, and AGS) by reverse transcription-polymerase chain reaction and Northern blot analysis. RESULTS: Twenty-three (37.7%) of the 61 gastric cancer tissues samples were positive for Reg I alpha protein. The Reg I alpha expression was significantly related to the presence of lymphatic invasion but not to tumor size, tumor stage, Lauren's classification, presence of venous invasion, lymph node metastases, or p53 overexpression. Gastric cancers positive for Reg I alpha protein showed a significantly higher proliferating cell nuclear antigen labeling index than negative ones. The expression of both Reg I alpha and Reg receptor mRNA was detected in all seven gastric cancer cell lines. CONCLUSION: Reg I alpha protein may play a role in the development of gastric cancers.

Cell Transformation, Neoplastic↗
PubMed2003

[Electron-beam computed tomography for identification of high-risk persons in primary prevention of coronary heart disease in the United States and its implication for Japan].

Coronary heart disease (CHD) is the leading cause of death in the United States (US). Approximately half of deaths from (CHD) occur out of hospital, most being sudden. The majority of sudden cardiac deaths occur in asymptomatic subjects. Recent lipid-lowering trials in asymptomatic subjects have demonstrated the potential for risk reduction for CHD events by primary prevention. It is, however, generally acknowledged that risk will be underestimated in asymptomatic subjects who fall into the category of intermediate risk by the traditional risk factors. Non-invasive measurements of subclinical atherosclerosis, which is the end result of risk-factor exposure, have the possibility of improving the risk stratification of asymptomatic subjects in intermediate-risk. Electron-beam computed tomography (EBCT) is a non-invasive and highly sensitive means to detect calcification within coronary arterial wall. Coronary artery calcification (CAC) is a recognized marker of atherosclerosis. Atherosclerotic burden of coronary arteries correlates strongly with the amount of CAC measured by EBCT. Studies examining the predictive value of CAC among asymptomatic subjects consistently reported that CAC is a risk for CHD. Two studies reported that unadjusted odds ratios of CAC for CHD were over 20. Incremental value of EBCT over the traditional risk assessment models, however, has not been established. Although CHD mortality in Japan remains uniquely low in industrialized countries, among men aged 30-49, risk factor profiles for CHD are similar between men in the US and Japan, except higher prevalence of cigarette smoking in Japan and higher prevalence of obesity in the US. It is reported that the declining trend in CHD mortality in Japan has recently slowed down in metropolitan areas, especially in men aged 30-49, and that the incidence has increased in middle-aged workers in a metropolitan area. A mortality validation study reported that the differences in CHD mortality between the US and Japan were not as large as suggested by vital statistics. It is, therefore, important to evaluate subclinical atherosclerosis measured by EBCT in men in recent birth cohorts in Japan and compare it to that in men in the US in order to predict future trend in CHD in Japan.

Adult↗