Seiichi Takenoshita

Fukushima Medical University, Hukusima, Fukushima, Japan

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Publications (285)651.61 Total impact

  • Cancer Research 08/2015; 75(15 Supplement):1285-1285. DOI:10.1158/1538-7445.AM2015-1285 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):3415-3415. DOI:10.1158/1538-7445.AM2015-3415 · 9.33 Impact Factor
  • Putra Santoso · Yuko Maejima · Kensuke Kumamoto · Seiichi Takenoshita · Kenju Shimomura ·
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    ABSTRACT: ELABELA (ELA) is a novel hormone consisting of 32 amino acid peptides found in humans as well as other vertebrates and is considered to play an important role in the circulatory system through the apelin receptor (APJ). However, whether ELA also acts in the central nervous system remains unknown. Here, we show that ELA functions as an anorexigenic hormone in adult mouse brain. An intracerebroventricular injection of ELA reduces food intake and activates arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN), a hypothalamic region that regulates food intake. Cytosolic calcium ([Ca]i) measurement shows that ELA dose dependently increases [Ca]i in single AVP and CRH-immunoreactive neurons isolated from the PVN. Our data suggest that ELA functions as an anorexigenic hormone through activation of AVP and CRH neurons in the PVN.
    Neuroreport 07/2015; 26(14). DOI:10.1097/WNR.0000000000000431 · 1.52 Impact Factor
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    ABSTRACT: The objective of this study is to diminish postoperative complications after pylorus-preserving pancreaticoduodenectomy. Pylorus-preserving pancreaticoduodenectomy is still associated with major complications, especially leakage at pancreatojejunostomy and delayed gastric emptying. Traditional pylorus-preserving pancreaticoduodenectomy was performed in group A, while the novel procedure, an antecolic vertical duodenojejunostomy and internal pancreatic drainage with omental wrapping, was performed in group B (n = 40 each). We compared the following characteristics between the 2 groups: operation time, blood loss, time required before removal of nasogastric tube and resumption of food intake, length of hospital stay, and postoperative complications. The novel procedure required less time and was associated with less blood loss (both P < 0.0001). In the comparison of the 2 groups, group B showed less time for removal of nasogastric tubes and resumption of food intake, shorter hospital stays, and fewer postoperative complications (all P < 0.0001). The novel procedure appears to be a safe and effective alternative to traditional pancreaticoduodenectomy techniques.
    International surgery 05/2015; 100(5):882-890. DOI:10.9738/INTSURG-D-14-00246.1 · 0.47 Impact Factor
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    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 · 2.00 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 · 2.30 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 · 8.72 Impact Factor
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    ABSTRACT: Purpose: To examine the clinical utility of intratumor microRNAs (miRNA) 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-PCR-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 nonresponders. Differential expression was confirmed in a validation cohort (n = 63 samples), including 18 (28.6%) responders. An miRNA signature that predicted responses to platinum-based doublet chemotherapy was identified and its accuracy was examined by principal 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 (miR1290, miR196b, and miR135a*) 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. Conclusion: The three-miRNA signature in surgically resected primary LADC tissues may by clinically useful for predicting responsiveness to platinum-based doublet chemotherapy in patients with LADC recurrence.
    Clinical Cancer Research 09/2014; 20(18). DOI:10.1158/1078-0432.ccr-14-1096 · 8.72 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 · 0.47 Impact Factor
  • Masahiko Shibata · Kenji Gonda · Kensuke Kumamoto · Seiichi Takenoshita ·
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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 03/2014; 72(1):42-8.
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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 · 1.55 Impact Factor
  • Yohei Watanabe · Yasuhide Kofunato · Takashi Yazawa · Yoshimasa Ishii · Seiichi Takenoshita ·

    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; 44(11). DOI:10.1016/j.humpath.2013.06.008 · 2.77 Impact Factor

  • Cancer Research 08/2013; 73(8 Supplement):438-438. DOI:10.1158/1538-7445.AM2013-438 · 9.33 Impact Factor

  • Cancer Research 08/2013; 73(8 Supplement):20-20. DOI:10.1158/1538-7445.AM2013-20 · 9.33 Impact Factor

Publication Stats

4k Citations
651.61 Total Impact Points


  • 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
  • 2004
    • National Cancer Center, Japan
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
  • 2003
    • Tohoku University
      • Institute of Development, Aging and Cancer
      Sendai-shi, Miyagi-ken, Japan
  • 1993-2001
    • Gunma University
      • • Department of Surgery
      • • Department of Obstetrics and Gynecology
      • • School of Medicine
      Maebashi, Gunma, 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