Seiichi Takenoshita

Fukushima Medical University, Hukusima, Fukushima, Japan

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Publications (277)589.89 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K(+) (KATP) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 μl aliquot of 340 μM KATP channel opener diazoxide or 100 μM KATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the KATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered KATP channel activity.
    Endocrine Journal 02/2015; 62(4). DOI:10.1507/endocrj.EJ14-0392 · 2.02 Impact Factor
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    ABSTRACT: Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. While many studies have investigated the ANXA1 expression in various tumor types, the role of ANXA1 is not fully understood. Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast cancer patients and compared the levels with clinicopathological factors. ANXA1 was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these positive cases were associated with triple-negative breast cancer (TNBC) (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1. Using this cell line, the functional role of ANXA1 in breast cancer was revealed and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction in cellular invasion. Further experiments indicated that ANXA1 was induced by hypoxia with hypoxia-inducible factor-1α induction. These results suggested that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia, were significantly associated with the worst patient outcome. This is particularly noted in TNBC, the group of breast cancer with the worst outcome for which new therapeutic implications are required.
    Oncology Reports 01/2015; 33(3). DOI:10.3892/or.2015.3720 · 2.19 Impact Factor
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    ABSTRACT: Even if grade 1 neuroendocrine tumors(NET)have low malignant potential, they may still be associated with lymph node metastasis. While the World Health Organization(WHO)classification requires determination of the grade of malignancy and presence of metastasis, it is also useful to evaluate tumor diameter, extent of invasion, and histological characteristics(cell variant, nuclear atypia, and ductal invasion). The authors present 2 cases of rectal NET excised by laparoscopic surgery. Considerations for surgical indications in rectal NET are made based on these case reports.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2014; 41(12):1820-2.
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    ABSTRACT: An inflammatory pseudotumor(IPT)of the liver is a rare benign disorder.As its characteristics based on computer tomography and magnetic resonance imaging findings are still unclear, it is difficult to distinguish IPT from malignant diseases of the liver.Herein, we report a case of IPT of the liver concurrent with advanced gallbladder cancer, which we could not diagnose preoperatively.First, we performed lateral segmentectomy of the liver.Second, a radical operation for gallbladder cancer was performed after confirming that the hepatic tumor was IPT via intraoperative pathological diagnosis.Therefore, modalities less invasive than surgical resection should be innovated, even though surgical resection is accurate.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2014; 41(12):2148-50.
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    ABSTRACT: The aim of this study was to compare the results between lateral lymph node dissection(LLND)alone, and preoperative radiotherapy(preRT)followed by LLND, for the treatment of locally advanced rectal cancer. This study assessed 44 consecutive patients with lower rectal cancer(clinical Stages II and III)without lateral lymph node metastasis by preoperative imaging at two hospitals. Twenty-five patients at one hospital received preoperative short-course radiation therapy(total 25 Gy)followed by a curative LLND operation(preRT group), and 19 patients at another hospital underwent a curative operation by LLND alone(non-preRT group). The 5-year locoregional relapse-free survival, disease-free survival, and overall survival rates were not different between the preRT and non-preRT groups. Although three patients in each group had lateral lymph node metastases, none developed pelvic sidewall recurrence. This study suggests that preRT followed by curative surgery with LLND for lower rectal cancers without lateral lymph node metastasis before surgery would not improve survival and local control rates.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2014; 41(12):1557-9.
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    ABSTRACT: Background/Aims: We examined whether conventional ultrasonography (US) and computed tomography (CT) were useful to evaluate liver hardness and hepatic fibrosis by comparing the results with those obtained by a tactile sensor using rats with liver fibrosis.Methodology: We used 44 Wistar rats in which liver fibrosis was induced by intraperitoneal administration of thioacetamide. The CT and US values of each liver were measured before laparotomy. After laparotomy, a tactile sensor was used to measure liver hardness. We prepared Azan stained sections of each excised liver specimen and calculated the degree of liver fibrosis (HFI: hepatic fibrosis index) by computed color image analysis.Results: The stiffness values and HFI showed a positive correlation (r=0.690, p<0.001), as did the tactile values and HFI (r=0.709, p<0.001).In addition, the stiffness and tactile values correlated positively with each other (r=0.814, p<0.001). There was no correlation between the CT values and HFI, as well as no correlation between the US values and HFI.Conclusion: We confirmed that it was difficult to evaluate liver hardness and HFI by CT or US examination, and considered that, at present, a tactile sensor is useful method for evaluating HFI.
    Fukushima journal of medical science 10/2014; 60(2). DOI:10.5387/fms.2013-7
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    ABSTRACT: Background: We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis based approach to study 12 cohorts consisting of 1069 TNM stage I lung adenocarcinoma patients from every suitable, publically available dataset. Materials and Methods: Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effects meta-analysis model was used to generate a pooled estimate for all cohorts. Results: The classifier was associated with prognosis in ten of the twelve cohorts (p<0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I (Hazard Ratio [HR], 2.66; 95% Confidence Interval [CI], 1.93-3.67; P<0.0001) patients and in stratified analyses of stage IA (HR, 2.69; 95%CI, 1.66-4.35; P<0.0001) and stage IB (HR, 2.69; 95%CI, 1.74-4.16; P<0.0001) patients. Conclusions: The -4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors Impact: Our results suggest that the 4-gene classifier may assist clinicians in decisions regarding postoperative management of early stage lung adenocarcinoma patients.
    Clinical Cancer Research 09/2014; 20(2_Supplement). DOI:10.1158/1055-9965.EPI-14-0182 · 8.19 Impact Factor
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    ABSTRACT: Purpose:To examine the clinical utility of intra-tumor micro (mi)RNAs as a biomarker for predicting responses to platinum-based doublet chemotherapy in patients with recurring lung adenocarcinoma (LADC). Experimental Design:The expression of miRNAs was examined in LADC tissues surgically resected from patients treated with platinum-based doublet chemotherapy at the time of LADC recurrence. Microarray-based screening of 904 miRNAs followed by quantitative reverse transcription-polymerase chain reaction-based verification in 40 test cohort samples, including 16 (40.0%) responders, was performed to identify miRNAs that are differentially expressed in chemotherapy responders and non-responders. Differential expression was confirmed in a validation cohort (n = 63 samples), including 18 (28.6%) responders. A miRNA signature that predicted responses to platinum-based doublet chemotherapy was identified and its accuracy was examined by principle component and support vector machine analyses. Genotype data for the TP53-Arg72Pro polymorphism, which is associated with responses to platinum-based doublet chemotherapy, were subsequently incorporated into the prediction analysis. Results:A signature comprising three miRNAs (miR-1290, miR-196b, and miR-135a*) enabled the prediction of a chemotherapeutic response (rather than progression-free and overall survival) with high accuracy in both the test and validation cohorts (82.5% and 77.8%). Examination of the latter was performed using miRNAs extracted from archived formalin-fixed paraffin-embedded tissues. Combining this miRNA signature with the TP53-Arg72Pro polymorphism genotype marginally improved the predictive power. Conclusions:The three-miRNA signature in surgically resected primary LADC tissues may by clinically useful for predicting responsiveness to platinum-based chemotherapy in patients with LADC recurrence.
    Clinical Cancer Research 09/2014; 20(18). DOI:10.1158/1078-0432.ccr-14-1096 · 8.19 Impact Factor
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    ABSTRACT: Abstract We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.
    International surgery 09/2014; 99(5):600-605. DOI:10.9738/INTSURG-D-13-00143.1 · 0.25 Impact Factor
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    ABSTRACT: Poor nutritional status is common in ovarian cancer. It is well known that the nutritional status of a patient with malignant disease is associated with survival, and that it can be assessed by serum levels of rapid turnover proteins (RTPs), such as retinol binding protein, prealbumin and transferrin. Systemic inflammation, usually observed in the form of elevated C-reactive protein (CRP) or neutrophil/lymphocyte ratio (NLR), occurs by various mechanisms involving numerous pro-inflammatory cytokines. These include interleukin (IL)-17 and other soluble protein mediators, such as soluble IL-2 receptor (sIL-2R) and vascular endothelial growth factor (VEGF). In this study, circulating levels of RTP were decreased in advanced stages of ovarian cancer, and significant inverse correlations were found between RTP levels and serum levels of CRP or NLR. CRP levels were also correlated with serum levels of VEGF and sIL-2R. Moreover, NLR, VEGF and sIL-2R levels, and IL-17 production, were all inversely correlated with RTP levels. These findings indicate that chronic inflammation may be associated with compromised immune function, such as an impaired T-cell response, via various inflammatory proteins, including sIL-2R, VEGF and IL-17. The key mechanisms leading to cancer cachexia, in which nutritional impairment is a major clinical issue, appear to be primarily immune reactions caused by chronic inflammation. Anti-inflammatory treatments may be effective in clinically improving various symptoms associated with these mechanisms.
    Oncology letters 02/2014; 7(2):373-377. DOI:10.3892/ol.2013.1735 · 0.99 Impact Factor
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    ABSTRACT: Recently there is a great advance in anti-colorectal cancer treatment. Several molecular targeting agents, mostly are antibody drugs, are playing an important role. It has recently been proven that new approaches using antibody to immunological checkpoints are effective against certain types of cancer. This is one of the reasons why cancer immunotherapy is now focused in the clinics. In this chapter, several effective immunotherapy against cancer are shown and discussed. Among several types of cancer immunotherapy, immunological cell therapy including lymphokine activated killer (LAK) cell, cytotoxic T lymphocytes (CTL), gamma delta T cell and dendritic cell therapies are reviewed. Major mechanisms that disturb cancer immunotherapy such as escape mechanisms are also discussed.
    Nippon rinsho. Japanese journal of clinical medicine 01/2014; 72(1):42-8.
  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2014; 75(2):457-461. DOI:10.3919/jjsa.75.457
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    ABSTRACT: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms in humans and myeloid-derived suppressor cells (MDSCs) contribute to the negative regulation of immune responses in the context of cancer and inflammation. In order to investigate the pathophysiology of thyroid cancer, peripheral blood mononuclear cells (PBMCs) were obtained from 49 patients with thyroid cancer, 18 patients with non-cancerous thyroid diseases and 22 healthy volunteers. The MDSC levels were found to be higher in patients with any type of thyroid cancer (P<0.05), patients with ATC (P<0.001) and patients with medullary thyroid carcinoma (P<0.05), when compared to patients with non-cancerous thyroid diseases. The MDSC levels were also higher in patients with stage III-IV thyroid cancer compared to those in patients with non-cancerous thyroid diseases (P<0.05). The stimulation index (SI) of phytohemagglutinin (PHA)-induced lymphocyte blastogenesis was significantly lower, the C-reactive protein (CRP) levels were significantly higher and the serum albumin levels were significantly lower in patients with ATC compared to those in patients with non-cancerous thyroid diseases. The SI was significantly lower in stage III and IV thyroid cancer compared to that in non-cancerous thyroid disease (P<0.05). Furthermore, the CRP levels were higher and the concentration of albumin was lower in stage IV thyroid cancer compared to those in non-cancerous thyroid disease (P<0.05). Patients with thyroid carcinoma were then classified into one of two groups according to a %PBMC of MDSC cut-off level of 1.578, which was the average %PBMC of MDSC of patients with any type of thyroid carcinoma. In patients with higher MDSC levels, the production of CRP and interleukin (IL)-10 was significantly higher (P<0.05) and the albumin levels were significantly lower (P<0.05) compared to those in patients with lower MDSC levels. These data indicate that MDSCs are increased in patients with ATC. Furthermore, these patients exhibited suppression of cell-mediated immune responses, chronic inflammation and nutritional impairment.
    Molecular and Clinical Oncology 11/2013; 1(6):959-964. DOI:10.3892/mco.2013.170
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    ABSTRACT: Pancellular dysplasia involving neuroendocrine cells has been shown to be comparatively rare but crucially implicated in the development of neuroendocrine tumors in ulcerative colitis (UC). We attempted to clarify the prevalence of chromogranin A expression as a marker of neuroendocrine differentiation in UC-associated neoplasia by immunohistochemical analyses of 26 lesions of low-grade dysplasia (LGD), 32 high-grade dysplasias (HGDs) and 27 invasive cancers (INVs), along with p53 expression. We additionally assessed the utility of these proteins for differential diagnosis between LGD and HGD. Chromogranin A was considered positive when immunoreactive cells were more than 5% of neoplastic lesions, and the positivity tended to be higher in HGDs (57.7%) or INVs (46.7%) than LGDs (32.0%). Focal or diffuse nuclear staining for p53 was defined as positive. The positive rate for p53 was also higher in HGDs (59.4%; P = 0.037) or INVs (59.3%) than LGDs (30.8%). A similar trend was found in co-positivity for both proteins (HGDs, 30.7%/INVs, 26.7% versus LGDs, 12.0%). No positivity for both proteins was identified in the non-neoplastic mucosa. The combination of the two proteins improved the sensitivity (66.7%), specificity (80.0%), positive predictive value (72.7%) and negative predictive value (75.0%) for HGD as compared to p53 alone (sensitivity, 57.7%; specificity 68.0%; positive predictive value, 65.2%; negative predictive value, 60.7%). In conclusion, we show here that neuroendocrine differentiation is relatively common and represents an early event in the UC-neoplasia pathway in which p53 and chromogranin A are coordinately up-regulated. Immunohistochemical assessment of their expression might provide a useful adjunct tool for grading dysplasia in UC.
    Human pathology 09/2013; DOI:10.1016/j.humpath.2013.06.008 · 2.81 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):438-438. DOI:10.1158/1538-7445.AM2013-438 · 9.28 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):20-20. DOI:10.1158/1538-7445.AM2013-20 · 9.28 Impact Factor
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    ABSTRACT: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with various types of gastrointestinal cancer compared to normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio (NLR) and significantly inversely correlated with cell-mediated immune response indicators [lymphocyte phytohemagglutinin (PHA)-blastogenesis and IL-12 induction] and patient nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism contributing to disease progression through enhancement of immune suppression or cachexia. Controlling the activation of Th17 cells may prove to be a valuable strategy for the treatment of gastrointestinal cancer patients.
    Molecular and Clinical Oncology 07/2013; 1(4):675-679. DOI:10.3892/mco.2013.134
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    ABSTRACT: A 64-year-old male patient was diagnosed with rectal gastrointestinal stromal tumor(GIST)by prostate biopsy, because of high PSA. We considered that a radical operation was impossible because the tumor occupied the pelvis, and we suspected prostate invasion. After neoadjuvant chemotherapy(imatinib mesylate 400 mg/day), the tumor size was reduced(90×85 mm→60×50mm), and we could thus perform radical resection. The patient is currently receiving adjuvant chemotherapy (imatinib mesylate 400 mg/day), without recurrence.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2013; 40(7):937-41.
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    ABSTRACT: Prognostic tests for early stage lung cancer patients may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival were evaluated using microarray data from 148 stage I lung adenocarcinoma patients. Seven genes associated with relapse-free survival were further examined by quantitative RT-PCR in 291 lung adenocarcinoma tissues from Japan, the United States and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publically available lung adenocarcinoma expression profiling datasets. The results suggests that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with microRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of stage I lung adenocarcinoma patients.
    Cancer Research 05/2013; 73(13). DOI:10.1158/0008-5472.CAN-13-0031 · 9.28 Impact Factor
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    ABSTRACT: A 59-year-old woman was diagnosed with triple-negative breast cancer(TNBC)(T2N0M0)and treated with primary systemic therapy. The patient was treated with 4 courses of epirubicin and cyclophosphamide(EC)therapy every 3 weeks, followed by weekly gemcitabine-paclitaxel combination therapy. As she was judged to have achieved a partial response(PR) by ultrasound and CT examination after eight courses, she underwent partial resection of the left breast. CR was revealed by the pathological examination of the resected specimen. Gemcitabine-paclitaxel combination therapy seems to be a one of the useful preoperative chemotherapies for TNBC.
    Gan to kagaku ryoho. Cancer & chemotherapy 05/2013; 40(5):623-5.

Publication Stats

3k Citations
589.89 Total Impact Points

Institutions

  • 1999–2015
    • Fukushima Medical University
      • • Department of Organ Regulatory Surgery
      • • Division of Surgery
      • • Division of Medicine
      Hukusima, Fukushima, Japan
  • 2010
    • Kawasaki Saiwai Hospital
      Kawasaki, Fukuoka, Japan
  • 2007
    • Saitama Medical University
      Saitama, Saitama, Japan
  • 2004
    • National Cancer Center, Japan
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
    • Akita University
      Akita, Akita, Japan
  • 1993–1999
    • Gunma University
      • • Department of Obstetrics and Gynecology
      • • School of Medicine
      Maebashi, Gunma Prefecture, Japan
  • 1997
    • National Cancer Institute (USA)
      • Laboratory of Human Carcinogenesis
      베서스다, Maryland, United States
  • 1996
    • National Institutes of Health
      • Laboratory of Human Carcinogenesis
      베서스다, Maryland, United States