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Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

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World Journal of Gastroenterology 2023年第23期29卷 3574-3594页

作者： takuya watanabe Department of Internal Medicine and Gastroenterology Watanabe Internal Medicine Aoyama ClinicNiigata-city 9502002Japan

Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.

关键词： Nodal and gastrointestinal follicular lymphoma Antibody-based therapy Bispecific antibody therapy Phosphatidylinositol-3 kinase inhibitor Epigenetic modulator Chimeric antigen receptor-T cell therapy

Treatment strategies for nodal and gastrointestinal follicular lymphoma:Current status and future development

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World Journal of Gastroenterology 2010年第44期16卷 5543-5554页

作者： takuya watanabe Department of Internal Medicine and Gastroenterology Medical HospitalThe Nippon Dental University School of Life Dentistry at Niigata

In recent years,therapies for follicular lymphoma (FL) have steadily improved.A series of phase Ⅲ trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival.Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy.For patients with relapsed or refractory FL,phase Ⅱ studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS),oblimersen sodium (a Bcl-2 antisense oligonucleotide),bendamustine,and rituximab,as well as veltuzumab,a new humanized anti-CD20 antibody,and epratuzumab.In addition,the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported.Furthermore,three phase Ⅲ studies on an idiotype vaccine are near completion.Unfortunately,these vaccines,which appeared highly effective in phase Ⅰ and Ⅱ trials,do not appear to result in prolonged PFS.This report will summarize the current knowledge on therapies for treatment of FL,and will conclude with a brief discussion of feasiblefuture options for effective treatments.Lastly,we added descriptions of the management of gastrointestinal FL,which is considered to be controversial because it is rare.

关键词： Anti-CD20 monoclonal antibody (rituximab) Follicular lymphoma Idiotype vaccines Immunoradiotherapy Treatment strategies

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

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World Journal of Gastroenterology 2009年第2期15卷 231-239页

作者： takuya watanabe Kenji Soga Haruka Hirono Katsuhiko Hasegawa Koichi Shibasaki Hirokazu Kawai Yutaka Aoyagi Department of Internal Medicine and Gastroenterology Medical Hospital The Nippon Dental University School of Life Dentistry at Niigata 1-8 Hamauracho Chu-o-ku Niigata 951-8580 Japan Department of Gastroen-terology Niigata University Graduate School of Medical and Dental Sciences 1-757 Asahimachi Chu-o-ku Niigata 951-8510 Japan

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)].Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

关键词：自体免疫肝炎自体免疫肝疾病肝细胞癌胆汁

Thermoelectric Properties of Misfit Layered Bismuth-Based Rhodium Oxides, (Bi,Pb)2Sr2Rh2Oy

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Journal of Materials Science and Chemical Engineering 2018年第7期6卷 97-103页

作者： takuya watanabe Hiroshi Irie Special Doctoral Program for Green Energy Conversion Science and Technology Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Yamanashi Japan Clean Energy Research Center University of Yamanashi Yamanashi Japan

Rhodium oxides, including a misfitlayered structure with alternate stacking of a rock salttype layer and a hexagonal RhO2 layer, are expected to have good thermoelectric properties. Among them, the thermoelectric properties (electrical conductivity (σ), Seebeck coefficient (S), Figure of merit (ZT) and calculated thermal conductivity (κ) by S, σ, ZT, and absolute temperature (T)) of bismuth-based rhodium oxides ((Bi1-x,Pbx) 2Sr2Rh2Oy, x = 0 and 0.02, hereafter BSR and BPSR, respectively) were investigated. In comparison with Bi2Sr2Co2Oy (BSC) at 700°C, S and κ enhanced (increased S, 110 (BSR) and 105 μV K-1 (BPSR) from 85 μV K-1 (BSC) and decreased κ, 0.32 (BSR) and 0.50 W m-1 K-1 (BPSR) from 1.75 W m-1 K-1 (BSC)), whereas σ decreased (15 (BSR) and 31 S cm-1 (BPSR) from 70 S cm-1 (BSC)). BPSR reached the highest ZT value of 0.067 at 700°C, compared to those of 0.056 (BSR) and 0.027 (BSC).

关键词： Electroceramics Layered Rhodium Oxide Misfit Layer Structure Thermoe-lectric Material Harman Method

Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic factor in rats with cerebral ischemia combined with amyloid-β42 peptide

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Journal of Traditional Chinese Medicine 2019年第1期39卷 50-58页

作者： Ai Nogami-Hara Kaori Kubota Kotaro Takasaki takuya watanabe Nobuaki Egahira Hikari Iba Risako Fujikawa Shutaro Katsurabayashi Funda Bolukbasi Hatip Izzettin Hatip-Al-Khatib Katsunori Iwasaki Department of Neuropharmacology Faculty of Pharmaceutical ScienceFukuoka UniversityFukuoka 814-0180Japan Institute for Aging and Brain Sciences Fukuoka UniversityFukuoka 814-0180Japan Department of Pharmacy Kyushu University HospitalFukuoka 812-8582Japan Department of Medical Pharmacology Faculty of MedicinePamukkale UniversityDenizli 20070Turkey

OBJECTIVE: To examine the effects of Yokukansan(YKS) extract on two endogenous modulators of anxiety, brain-derived neurotrophic factor(BDNF)and serotonin (5-HT)_(2A) receptors pharmacologically, in the ischemic rat model of dementia.METHODS: The cerebral ischemia(CI) was induced by bilateral occlusion of the vertebral and common carotid arteries(4-vessel occlusion ischemia). The CI was combined with the amyloid-β42 peptide(A42) injected intracerebroventricularly, and referreβdto as CI+Aβ. Anxiety-like behaviors were assessed by elevated plus maze(enclosed arm), light/dark transition test(dark chamber), and open-field test.Wet-dog shakes were induced by the 5-HT_(2A) receptor agonist 2, 5-dimethoxy-4-iodoamphetamine(DOI). The concentration of BDNF in serum was determined by enzyme-linked immuno sorbent assay.RESULTS: CI + Aβ increased anxiety, as demonstrated by the increase of time spent in the enclosed arms and dark chambers, and locomotion in the outer zone of the open field(thigmotaxis). CI + Adecreased the serum concentration of BDNF. YKS reβ-duced the anxiety-like behaviors, suppressed the DOI-induced wet-dog shakes and increased serum BDNF concentrations.CONCLUSION: Our findings suggest that YKS extract improves CI + Aβ-induced anxiety by antagonizing 5-HT_(2A) receptors and increasing BDNF.

关键词： Brain ischemia Amyloid beta-peptides Anxiety brain-derived neurotrophic factor Receptor serotonin 5-HT2A Yokukansan

Solitary pituitary metastasis resulting from pulmonary large cell neuroendocrine carcinoma

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World Journal of Respirology 2014年第1期4卷 8-10页

作者： takuya watanabe Kyoichi Kaira Masafumi Mizuide Noriaki Sunaga Nobuyuki Shibusawa Takeshi Hisada Tetsurou Satoh Masatomo Mori Masanobu Yamada Department of Medicine and Molecular Science Gunma University Graduate School of Medicine

Solitary pituitary metastasis is a rare phenomenon in human neoplasms. We report a case of lung cancer with the initial manifestation of endocrinopathy resulting from pituitary metastasis. The patient's initial diagnosis was a poorly differentiated carcinoma, however, morbid anatomy revealed a definite diagnosis of large cell neuroendocrine carcinoma(LCNEC). Clinical physicians should be aware of potential initial manifestations such as endocrine abnormalities including panhypopituitarism and diabetes insipidus due to solitary pituitary metastasis. This case demonstrates that an endocrine abnormality such as panhypopituitarism could be an initial manifestation of LCNEC.

关键词： Large cell neuroendocrine carcinoma Pituitary metastasis Solitary Endocrinopathy

A Study of Hie and LBP: The First Step to Improve Subjective Well-Being

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健康(英文) 2023年第10期15卷 1013-1023页

作者： Mayumi watanabe Chikako Tomiyama takuya Nikaido Masae Ryufuku Nozom Mandai Tokimasa Takeda Tsutomu Komine Faculty of Science and Engineering Chuo University Tokyo Japan Faculty of Health Sciences Kansai University of Health Sciences Osaka Japan Graduate School of Health Sciences Niigata University Niigata Japan Department of Orthopaedic Surgery School of Medicine Fukushima Medical University Fukushima Japan Translational Research Center Fukushima Medical University Fukushima Japan Faculty of Nursing Science Tsuruga Nursing University Tsuruga Japan Zinbunken Kyoto University Kyoto Japan

Backgrounds: Health does not only physical health, therefore, we need to study it from various viewpoints. Many Japanese female complain of a Hie or a low back pain (LBP), which they reduce their subjective well-being. We analyze. Those patients often have acupuncture therapy. In this study, we analyze the characteristics of Hie and LBP, the satisfaction level of alternative therapy and we pursue a tip to improve subjective well-being. Methods: Of 1000 women, Hie (+)/Hie (−) or LBP (+)/LBP (−), we compared their body temperature (BT) (axilla) and body mass index (BMI). Furthermore, the Chi test identified ten factors of “body” and seven “mind” information. Results: In the result of BT (axilla) while LBP indicated a significant difference. Both Hie and LBP showed difference in the opposite direction. Hie did now show such clear differences in “body” information. However, interestingly, all seven questions in the “mind” information showed statistical difference. Discussion and conclusion: One reason why those patients have acupuncture therapy may acupuncture therapy traditionally has not separate “mind” and “body” and it has the concept of “mind-body unity”. To improve subjective well-being, first we need to focus on “Mind” as well as “mind-body unity”. Mental-health support is important for patients with Hie or LBP to reduce physiological stress.

关键词： Hie Low Back Pain (LBP) Subjective Well-Being Body Temperature (BT)

Paraneoplastic syndromes associated with lung cancer

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World Journal of Clinical Oncology 2014年第3期5卷 197-223页

作者： Nobuhiro Kanaji Naoki watanabe Nobuyuki Kita Shuji Bandoh Akira Tadokoro Tomoya Ishii Hiroaki Dobashi takuya Matsunaga Department of Internal Medicine Division of Endocrinology and Metabolism Hematology Rheumatology and Respiratory MedicineFaculty of MedicineKagawa University

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy(Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cyto-kines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

关键词： Paraneoplastic syndrome Small cell lung cancer Non-small cell lung cancer Symptom Diagnosis Treatment Endocrine Neurologic Hematologic Trousseau’s syndrome

Progress in researches about focal adhesion kinase in gastrointestinal tract

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World Journal of Gastroenterology 2009年第47期15卷 5916-5923页

作者： Hui Fang Hao Yoshio Naomoto Xiao-Hong Bao Nobuyuki watanabe Kazufumi Sakurama Kazuhiro Noma Yasuko Tomono takuya Fukazawa Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Department of Gastroenterological Surgery Transplantation and Surgical Oncology Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama University Okayama 700-8558 Japan Shigei Medical Research Institute Okayama 700-8558 Japan

Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy.

关键词：粘着斑激酶胃肠道酪氨酸磷酸化蛋白酪氨酸激酶癌症治疗 FAK 受体蛋白生物过程