PubMed | Red Cross, National Hospital Organization Hokkaido Cancer Center, Fukushima Medical University, Obihiro Kosei Hospital and 10 more.
Type: | Journal: Oncotarget | Year: 2017
The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-RII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-RII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-RII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-RII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.
PubMed | National Hospital Organization Hokkaido Cancer Center, Miyagi Cancer Center, Fukushima Medical University, Obihiro Kosei Hospital and 12 more.
Type: Journal Article | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016
Several American and Japanese guidelines recommend surgery for patients with c-stage I small-cell lung cancer (SCLC), whereas the European Society of Medical Oncology (ESMO) guidelines recommend surgery for patients with not only c-stage I but also c-stage II (T2N1) SCLC. In addition, previous studies identified various factors other than clinical stage that are related to survival in these patients. Thus, further validation and examination of the association of clinical stage and other clinical variables with survival are required for establishing practical management of early-stage SCLC.We reviewed the clinical courses of 156 SCLC patients who had undergone surgery at 17 institutions between January 2003 and January 2013.Clinical stages (tumor-node-metastasis [TNM] version 7) of the 156 patients were 98 cases in IA, 14 in IB, 16 in IIA, 7 in IIB, 18 in IIIA, and 3 in IIIB. Median overall survival (OS) was 33.3 months (95% confidence interval: 20.9-45.8). Multivariate analysis revealed that OS was longer in patients either at c-stage II and under, with a maximum tumor diameter of <20mm, with preoperative diagnosis, without a history or presence of other types of cancer, or who underwent prophylactic cranial irradiation (PCI).These results indicate that a history or presence of other types of cancer might be a major decisive factor for surgery. Patients with c-stages I and II (c-T2N1) can be considered for surgery, and PCI may be useful in patients undergoing surgery in a practical setting, partly supporting the ESMO guidelines.(1).
PubMed | Red Cross, Hokuyukai Neurological Hospital, Kushiro Rosai Hospital, Obihiro Kosei Hospital and 3 more.
Type: Journal Article | Journal: Cerebellum (London, England) | Year: 2016
To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinsons Disease-Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the UMSARS, SARA, BBS, MSA-QoL, and SCOPA-AUT. Score changes were evaluated using the standardized response mean (SRM). The correlation between disease duration and each score was examined. The first evaluation was conducted on 85 patients (60 patients with MSA cerebellar ataxia dominant subtype [MSA-C] and 25 patients with MSA Parkinsonism-dominant subtype [MSA-P]). Sixty-nine patients were examined after 6months and 63 patients after 12months. The UMSARS Part 4 had the largest SRM after 6months and the SARA after 12months. SRMs for MSA-P, the shorter duration group, and the early-onset group were larger than were those for MSA-C, the longer duration group, and the late-onset group. SRMs for items regarding skilled hand activities, walking, and standing were relatively large. Our study indicates that the UMSARS (parts 2 and 4), SARA, and BBS are sensitive scales for evaluating MSA progression over 12months. Items with large SRMs effectively evaluated short-term changes.
Furuhashi M.,Sapporo Medical University |
Fuseya T.,Sapporo Medical University |
Murata M.,Sapporo Medical University |
Hoshina K.,Sapporo Medical University |
And 18 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2016
Objective - Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes and macrophages, and elevated circulating FABP4 level is associated with obesity-mediated metabolic phenotype. We systematically investigated roles of FABP4 in the development of coronary artery atherosclerosis. Approach and Results - First, by immunohistochemical analyses, we found that FABP4 was expressed in macrophages within coronary atherosclerotic plaques and epicardial/perivascular fat in autopsy cases and macrophages within thrombi covering ruptured coronary plaques in thrombectomy samples from patients with acute myocardial infarction. Second, we confirmed that FABP4 was secreted from macrophages and adipocytes cultured in vitro. Third, we investigated the effect of exogenous FABP4 on macrophages and human coronary artery-derived smooth muscle cells and endothelial cells in vitro. Treatment of the cells with recombinant FABP4 significantly increased gene expression of inflammatory markers in a dose-dependent manner. Finally, we measured serum FABP4 level in the aortic root (Ao-FABP4) and coronary sinus (CS-FABP4) of 34 patients with suspected or known coronary artery disease. Coronary stenosis score assessed by the modified Gensini score was weakly correlated with CS-FABP4 but was not correlated with Ao-FABP4. A stronger correlation (r=0.59, P<0.01) was observed for the relationship between coronary stenosis score and coronary veno-arterial difference in FABP4 level, (CS-Ao)-FABP4, indicating local production of FABP4 during coronary circulation in the heart. Multivariate analysis indicated that (CS-Ao)-FABP4 was an independent predictor of the severity of coronary stenosis after adjustment of conventional risk factors. Conclusions - FABP4 locally produced by epicardial/perivascular fat and macrophages in vascular plaques contributes to the development of coronary atherosclerosis. © 2016 American Heart Association, Inc.
Furuhashi M.,Sapporo Medical University |
Ishimura S.,Sapporo Medical University |
Ota H.,Sapporo Medical University |
Hayashi M.,Obihiro Kosei Hospital |
And 6 more authors.
PLoS ONE | Year: 2011
Background: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality. Methods and Results: Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2±30.5 ng/ml) was significantly higher than that in males (315.8±30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05-25.31). Conclusion: These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD. © 2011 Furuhashi et al.
Cai H.,Hokkaido University |
Yabe I.,Hokkaido University |
Shirai S.,Hokkaido University |
Nishimura H.,Hokkaido University |
And 5 more authors.
Muscle and Nerve | Year: 2013
Introduction: Molecular studies have revealed that some patients with myopathies with rimmed vacuoles have pathogenic mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and Z-band alternatively spliced PDZ motif-containing protein (ZASP) genes. Methods: We investigated a patient with distal myopathy with rimmed vacuoles by muscle biopsy and sequenced 6 candidate genes. Results: The patient carried GNE compound heterozygous missense mutations (p.V421A and p.N635K) and a ZASP variant (p.D673N). This patient also presented with distal weakness sparing the quadriceps muscles and had atypical results for Z-band-associated protein immunostaining. This finding indicates that the GNE mutations are pathogenic, and the diagnosis is compatible with GNE myopathy. Conclusions: By combining pathological studies and candidate gene screening, we identified a patient with GNE myopathy due to novel GNE compound heterozygous mutations. © 2013 Wiley Periodicals, Inc.
Yamada T.,Hokkaido University |
Ishikawa S.,Hokkaido University |
Kataoka S.,Hakodate Central Hospital |
Uda T.,Obihiro Kosei Hospital |
And 5 more authors.
Hypertension in Pregnancy | Year: 2013
Objective: To examine the pathophysiology of reductions in antithrombin (AT) activity during pregnancy and to better characterize the laboratory features of pregnant women with severely depressed AT activity. Methods: Laboratory variables for blood samples obtained within 5d prior to delivery were compared among three women groups with severely depressed (<45%, n=6), modestly depressed (45-69%, n=10), and normal AT activity levels (>70%, n=134). Results: Pregnancy-induced hypertension was present in 16.7% (1/6), 30.0% (3/10), and 9.0% (12/134) of the women with the above-mentioned AT activities, respectively. The AT activities were significantly and negatively correlated with the D-dimer, urate, and creatinine levels. The D-dimer level was significantly and negatively correlated with the fibrinogen level. Women with AT activity <45% exhibited markedly elevated levels of hemoglobin and liver enzymes and a significantly lower level of fibrinogen than the other women groups, while the platelet count did not differ among the three groups. Conclusions: Enhanced thrombin generation was involved in the decrease in AT activity. AT activity can decrease in the absence of thrombocytopenia. The liver dysfunction that was seen in cases with severely depressed AT activity may have resulted from impairments in liver perfusion caused by microthromboses generated as a result of the relative lack of AT and/or the shortage of circulating plasma in women with reduced AT activities. © Informa Healthcare USA, Inc.