Nagano Matsushiro General Hospital

Nagano-shi, Japan

Nagano Matsushiro General Hospital

Nagano-shi, Japan
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Pandey J.P.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Namboodiri A.M.,Medical University of South Carolina | Iwasaki M.,Nagano Matsushiro General Hospital | And 3 more authors.
Clinical and Experimental Immunology | Year: 2014

Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life.We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148.0 ± 73.6 versus 126.1 ± 67.8 arbitrary units per ml; P < 0.0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies. © 2014 British Society for Immunology.


Pandey J.P.,Medical University of South Carolina | Namboodiri A.M.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Iwasaki M.,Research Center for Cancer Prevention and Screening | And 3 more authors.
Clinical and Experimental Immunology | Year: 2013

Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25-30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n=263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p=0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P=0·0067). In black subjects (n=42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P=0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer. © 2012 British Society for Immunology.


Itoh H.,Juntendo University | Iwasaki M.,Research Center for Cancer Prevention and Screening | Sawada N.,Research Center for Cancer Prevention and Screening | Takachi R.,Niigata University | And 8 more authors.
International Journal of Hygiene and Environmental Health | Year: 2014

Cadmium, an environmental pollutant, may act like an estrogen and be a potential risk factor for estrogen-dependent diseases such as breast cancer. We examined the hypothesis that higher dietary cadmium intake is associated with risk of overall and hormone receptor-defined breast cancer in Japanese women, a population with a relatively high cadmium intake. The study was conducted under a case-control design in 405 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Dietary cadmium intake was estimated using a food frequency questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor-defined subtypes were calculated by tertile of dietary cadmium intake. We found no significant association between dietary cadmium and risk of total breast cancer in either crude or multivariable-adjusted analysis. Adjusted ORs for tertiles of cadmium intake were 1.00, 1.19, and 1.23 (95% CI, 0.76-2.00; P for trend. = 0.39) for whole breast cancer. Further, no significant associations were seen across strata of menopausal status, smoking, and diabetes in multivariable-adjusted models except for adjusted OR for continuous cadmium intake in postmenopausal women. A statistically significant association was found for estrogen receptor-positive (ER+) tumors among postmenopausal women (adjusted OR. = 1.00, 1.16, and 1.94 [95% CI, 1.04-3.63; P for trend. = 0.032]). Although the present study found no overall association between dietary cadmium intake and breast cancer risk, higher cadmium intake was associated with increased risk of ER+ breast cancer in postmenopausal women, at least at regular intake levels in Japanese women in the general population. Further studies are needed to confirm this association. © 2013 Elsevier GmbH.


Pandey J.P.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Black L.,Medical University of South Carolina | Namboodiri A.M.,Medical University of South Carolina | And 4 more authors.
Immunobiology | Year: 2014

Immunoglobulin κ constant (IGKC) gene has recently been identified as a strong prognostic marker in several human solid tumors, including breast cancer. Although the mechanisms underlying the IGKC signature are not yet known, identification of tumor-infiltrating plasma cells as the source of IGKC expression strongly suggests a role for humoral immunity in breast cancer progression. The primary aim of the present investigation was to determine whether the genetic variants of IGKC, KM (κ marker) allotypes, are risk factors for breast cancer, and whether they influence the magnitude of humoral immunity to epidermal growth factor receptor 2 (HER2), which is overexpressed in 25-30% of breast cancer patients and is associated with poor prognosis. Using a matched case-control design, we genotyped a large (1719 subjects) study population from Japan and Brazil for KM alleles. Both cases and controls in this study population had been previously characterized for GM (γ marker) and Fcγ receptor (FcγR) alleles, and the cases had also been characterized for anti-HER2 antibodies. Conditional logistic regression analysis of the data showed that KM1 allele additively contributed to the risk of breast cancer in the Japanese subjects from Nagano: Compared to KM3 homozygotes, KM1 homozygotes were almost twice as likely to develop breast cancer (OR = 1.77, CI 1.06-2.95). Additionally, KM genotypes-individually and in particular epistatic combinations with FcγRIIa genotypes-contributed to the magnitude of anti-HER2 antibody responsiveness in the Japanese patients. This is the first report implicating KM alleles in the immunobiology of breast cancer. © 2013 Elsevier GmbH.


Kuchiba A.,National Cancer Center Research Institute | Kuchiba A.,National Cancer Center | Iwasaki M.,Research Center for Cancer Prevention and Screening | Ono H.,National Cancer Center Research Institute | And 7 more authors.
British Journal of Cancer | Year: 2014

Background:Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women.Methods:We conducted a hospital-based case-control study of 384 patients aged 20-74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model.Results:Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20-2.91) and 2.86 (95% CI=1.85-4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05).Interpretation:These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk. © 2014 Cancer Research Uk.


Iwasaki M.,Research Center for Cancer Prevention and Screening | Mizusawa J.,Center for Cancer Control and Information Services | Kasuga Y.,Nagano Matsushiro General Hospital | Yokoyama S.,Red Cross | And 4 more authors.
Nutrition and Cancer | Year: 2014

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, only a few epidemiological studies have examined this association, and findings have been inconsistent. We examined the association between green tea consumption and breast cancer risk in consideration of the hormone receptor status of tumors and investigated whether the association was modified by dietary and genetic factors based on a hospital-based case-control study in Nagano, Japan. A total of 369 pairs completed a validated food frequency questionnaire and provided blood samples. Four single nucleotide polymorphisms (SNPs) were genotyped: CYP19A1 (rs10046), COMT (rs4680), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131). We found no inverse association between green tea consumption and breast cancer risk. Compared with women who drank less than 120 ml of green tea per day, the adjusted odds ratio for women who drank more than 600 ml was 1.27 (95% confidence interval = 0.75-2.14; P for trend = 0.20). We also found no inverse association for either tumor subtype. No substantial effect modification was observed for menopausal status, 4 SNPs, or dietary intake of folate or isoflavone. This study provides additional evidence that green tea consumption is not associated with a decreased risk. © 2014 Copyright Taylor and Francis Group, LLC.


PubMed | Shinshu University, Komoro Kosei General Hospital, Shinonoi General Hospital, Saku Medical Center and 10 more.
Type: | Journal: International journal of cardiology | Year: 2017

Prior reports have revealed that complete revascularization (CR) by percutaneous coronary intervention (PCI) decreased ischemic events. However, little is known about the efficacy of CR using PCI in elderly patients with multi-vessel coronary artery disease (CAD). We evaluated the 1-year effectiveness of CR-PCI in elderly patients (75years old) with multi-vessel CAD.The SHINANO Registry, a prospective, observational, multi-center, all-comer cohort study, has enrolled 1923 patients. From this registry, we recruited 322 elderly patients with multi-vessel CAD. The primary endpoint was major adverse cardiovascular events ([MACE]: all-cause mortality, myocardial infarction, and stroke).Of the 322 elderly patients with multi-vessel CAD, 165 (51.2%) received CR and 157 (48.8%) received incomplete revascularization (ICR). MACE occurred in 44 (13.7%) patients. The incidence of MACE by survival analysis was significantly lower in the CR group than in the ICR group (7.4% vs. 21.1%, p<0.001). On multivariable Cox proportional hazards analysis of age, sex, and acute coronary syndrome (ACS), ACS and CR were independent predictors of MACE (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.29-4.80; p=0.007, HR, 0.40; 95% CI, 0.20-0.77; p=0.007, respectively). In propensity score matching of age, sex, previous heart failure, previous intracranial bleeding, ACS, and body mass index, the MACE rate was significantly lower in the CR group than in the ICR group (7.2% vs. 18.4%, p=0.015).Even in elderly patients over 75years old with multi-vessel CAD, CR-PCI appears to suppress mid-term ischemic events.


Matsunaga D.,Nagano Matsushiro General Hospital | Akizuki S.,Nagano Matsushiro General Hospital | Takizawa T.,Nagano Matsushiro General Hospital | Omae S.,Omae Sansuukokugo School | Kato H.,Shinshu University
Knee | Year: 2013

Background: Platelets are one of the most biocompatible and cost-effective sources of growth factors. Attention is being paid to autologous platelets and platelet-rich plasma. We developed a novel compact platelet-rich fibrin scaffold (CPFS) that was produced from blood and calcium gluconate only. The objective of this study was to investigate the potential of CPFS as a provisional scaffold in two rabbit models. Methods: In the first rabbit model, the central half of the patellar tendon was resected bilaterally. Allogenic CPFS was attached to the defect in the right knee, while the left knee was untreated. In the other model, the medial collateral ligament was removed bilaterally. The ligament of the right knee was reconstructed with allogenic CPFS, whereas the left knee was untreated. Results: After 12. weeks, the ultimate failure load and stiffness were higher for the right patellar tendon than for the left patellar tendon in the former model. It was found that CPFS promoted ligament repair tissue in contrast with that on the untreated side in the latter model. The ultimate failure load of the CPFS repair tissue at 20. weeks was 78% of that in healthy controls of the same age. Conclusions: CPFS enhanced the healing of tendons and ligaments. Clinical relevance: CPFS has the potential to accelerate healing of tendons and ligaments as a provisional bioscaffold or a material for graft augmentation. © 2013 Elsevier B.V.


Horiuchi H.,Nagano Matsushiro General Hospital | Akizuki S.,Nagano Matsushiro General Hospital | Tomita T.,Osaka University | Sugamoto K.,Osaka University | And 2 more authors.
Journal of Arthroplasty | Year: 2012

The purpose of the present study was to evaluate the in vivo kinematics of the posterior cruciate ligament-retaining total knee arthroplasty during weight-bearing and non-weight-bearing deep knee bending and compare these 2 different conditions. We evaluated the in vivo kinematics of the knee using fluoroscopy and femorotibial translation relative to the tibia tray by 2-dimensional/3-dimensional registration. In the weight-bearing state, the femoral component showed central pivot and bicondylar posterior rollback pattern. During non-weight-bearing, the movement anteriorly occurred on both the medial and lateral side during early flexion, whereas bicondylar femoral component rollback occurred after that. During non-weight-bearing, both the medial and lateral condyle significantly moved anteriorly compared with the weight-bearing state during early flexion. However, bicondylar femoral rollback occurred under both these conditions. © 2012 Elsevier Inc.


Momose T.,Nagano Matsushiro General Hospital | Morita T.,Nagano Matsushiro General Hospital | Misawa T.,Nagano Matsushiro General Hospital
Cardiovascular Intervention and Therapeutics | Year: 2013

Free-floating thrombi in the right atrium (RA) are extremely hazardous to patients with pulmonary thromboembolism, and optimal treatment methods remain unclear. We report a case of successful percutaneous intervention of a critical right atrial thrombus. The patient was a 50-year-old woman who had been under medication for acute myocarditis when she complained of sudden severe dyspnea. Echocardiography showed a mobile snake-like thrombus in the RA. The thrombus was pulled back to the distal inferior vena cava (IVC) using a catheter and an IVC filter was placed. Percutaneous treatment is useful for treating free-floating RA thrombi. © 2012 Japanese Association of Cardiovascular Intervention and Therapeutics.

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