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Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma

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Acta Pharmaceutica Sinica B 2016年第2期6卷 101-105页

作者： Norihiro Sato Xiao-Bo Cheng shiro Kohi Atsuhiro Koga Keiji Hirata Department of Surgery 1 School of Medicine University of Occupational and Environmental Health

Progression of cancer is often associated with interactions between cancer cells and extracellular matrix(ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan(HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma(PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.

关键词： Pancreatic ductal adenocarcinoma Hyaluronan Tumor stroma Desmoplasia Tumor–stromal interaction Therapeutic target 4-Methylumbelliferone PEGPH20

Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light with controlled surface cooling

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Nano Research 2015年第12期8卷 3842-3852页

作者： Tessai Sugiura Daisuke Matsuki Junnosuke Okajima Atsuki Komiya shiro Mori Shigenao Maruyama Tetsuya Kodama Department of Mechanical Systems and Design Graduate School of Engineering Tohoku University Sendai 980-8579 Japan Laboratory of Biomedical Engineering for Cancer Department of Biomedical Engineering Graduate School of Biomedical Engineering Tohoku University Sendai 980-8575 Japan Institute of Fluid Science Tohoku University 2-1-I Katahira Aoba Ward Sendai 980-8577 Japan Department of Oral and Maxillofacial Surgery Tohoku University Hospital Sendai 980-8575 Japan

Photothermal therapy （PTT） using near-infrared （NIR） laser light and gold nanorods （GNRs） shows promise as a novel cancer treatment modality. However, the laser intensity required to destroy tumor cells located beneath the skin is greater than the threshold intensity that causes skin damage; thus, irradiation with laser light damages the skin as well as the tumor. Here, we show that a temperature control system allows metastatic lymph nodes （LNs） to be treated by PTT using NIR laser light and GNRs, without skin damage. A mouse model of LN metastasis was developed by injection of tumor cells, and the tumor-bearing proper axillary LN was treated with NIR laser light after injection of GNRs. The skin temperature was maintained at 45 ~C during irradiation by using a temperature control system. Bioluminescence imaging revealed that tumor progression was less in LNs exposed to NIR laser light and GNRs than in LNs exposed to NIR laser light alone or controls （no irradiation or GNRs）. Furthermore, the skin and LN capsule were macroscopically intact on day 9 after irradiation with NIR laser light, whereas tumor cells within the LN showed apoptosis. A numerical analysis demonstrated that the high-temperature zone and the LN region showing damage were localized to an area up to 3 mm in depth. The proposed novel PTT technique, using NIR laser light and GNRs with controlled surface cooling, could be applied clinically to treat metastatic LNs located within or outside the area accessible for surgical dissection.

关键词： lymph node metastasis photothermal therapy goId nanorods temperature control

Outcome of patients who have undergone total enteroscopy for obscure gastrointestinal bleeding

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World Journal of Gastroenterology 2012年第7期18卷 666-672页

作者： Takayoshi Shishido shiro Oka Shinji Tanaka Hiroki Imagawa Yoshito Takemura Shigeto Yoshida Kazuaki Chayama Department of Gastroenterology Hiroshima UniversityHiroshima 734-8551Japan Department of Endoscopy Hiroshima University HospitalHiroshima 734-8551Japan

AIM： To assess the diagnostic success and outcome among patients with obscure gastrointestinal bleeding who underwent total enteroscopy with double-balloon endoscopy.

关键词： Double-balloon endoscopy Small bowel Obscure gastrointestinal bleeding Total enteroscopy Outcome

Application of Automatic Chromatic Dispersion Compensation for Realization of All-Optical Network

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光学学报 2003年第S1期23卷 579-580页

作者： Mikio Yagi Hidenori Koyano shiro Ryu Shuichi Satomi Information and Communication Laboratories R&D P&S Supplier Unit Japan Telecom Co. Ltd. Shuwa Higashi Yaesu Bldg. 5F 2-9-1 Hatchobori Chuo-ku Tokyo 104-0032 JapanInformation and Communication Laboratories R&D P&S Supplier Unit Japan Telecom Co. Ltd. Shuwa Higashi Yaesu Bldg. 5F 2-9-1 Hatchobori Chuo-ku Tokyo 104-0032 JapanInformation and Communication Laboratories R&D P&S Supplier Unit Japan Telecom Co. Ltd. Shuwa Higashi Yaesu Bldg. 5F 2-9-1 Hatchobori Chuo-ku Tokyo 104-0032 JapanInformation and Communication Laboratories R&D P&S Supplier Unit Japan Telecom Co. Ltd. Shuwa Higashi Yaesu Bldg. 5F 2-9-1 Hatchobori Chuo-ku Tokyo 104-0032 Japan

We have studied the algorithm for the automatic chromatic dispersion compensation using bit error rate (BER) and Q-factor optimization for realization of dynamically reconfigurable all-optical .network. We have made s... 详细信息

关键词： for on it In have of Application of Automatic Chromatic Dispersion Compensation for Realization of All-Optical Network

Wittgenstein’s Picture Theory in the Quantum Mechanical Worldview

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Journal of Quantum Information Science 2020年第4期10卷 104-125页

作者： shiro Ishikawa Department of Mathematics Faculty of Science and Technology Keio University Yokohama Japan

Recently we proposed the linguistic Copenhagen interpretation (or, quantum language), which has a great power to describe both classical and quantum systems. Thus we think that quantum language can be viewed as the language of science. Therefore, it makes sense to study, from the quantum linguistic point of view, Wittgenstein’s picture theory, since he must have wanted to create a language of science. In this paper, we show that the proposition that Wittgenstein studied in his book “Tractatus Logico-Philosophicus” can be regarded as a binary projective measurement in classical quantum language. And thus, we conclude that Wittgenstein’s language (i.e., the language that he supposed in his book) is realized by classical quantum language. Hence, now we can fully understand Wittgenstein’s picture theory since the reason his book is incomprehensible is that he did not define his language.

关键词： Wittgenstein’s Picture Theory Quantum Language Linguistic Copenhagen Interpretation

Fuzzy Logic in the Quantum Mechanical Worldview;Related to Zadeh, Wittgenstein, Moore, Saussure, Quine, Lewis Carroll, etc.

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Journal of Applied Mathematics and Physics 2021年第7期9卷 1583-1610页

作者： shiro Ishikawa Department of Mathematics Faculty of Science and Technology Keio University Yokohama Japan

Recently we proposed the linguistic Copenhagen interpretation of quantum mechanics, which is called quantum language or measurement theory. This theory is valid for both quantum and classical systems. Thus we think that quantum language is one of the most powerful scientific theories, like statistics. In this paper we justify Zadeh’s fuzzy sets theory in quantum language, that is, fuzzy propositions are identified with binary measurements. This implies that the definition of “proposition” is, for the first time, acquired in the field of non-mathematics. Further, we assert that fuzzy logic is more natural than crisp logic in science. And furthermore, we discuss and solve Saussure’s linguistics, Moore’s paradox, Quine’s analytic-synthetic distinction and Lewis Carroll’s logical paradox. Therefore, from the philosophical point of view, our result gives a complete answer to Wittgenstein’s problem: “Why does logic work in our world?” and “What is a scientific proposition?” in his picture theory. That is, we simultaneously justify both Zadeh’s fuzzy sets and Wittgenstein’s picture theory in the quantum mechanical worldview.

关键词： Zadeh’s Fuzzy Sets Quantum Language Linguistic Copenhagen Interpretation

Packaging Effects on Fiber Bragg Grating Sensor Performance

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自动化学报 2006年第6期32卷 999-1007页

作者： HAO Jian-Zhong TAKAHASHI shiro CAI Zhao-Hui NG Jun Hong YANG Xiu-Feng CHEN Zhi-Hao LU Chao Institute for Infocomm Research 21 Heng Mui Keng Terrace Singapore 119613 Singapore Nanyang Technological University Nanyang Avenue Singapore 639798 Singapore

In this paper, the effects of packaging material and structure of fiber Bragg grating sensor performance are investigated. The effects of thermal expansion coefficient of different embedding materials on the temperature sensitivities of the FBG sensors are studied both theoretically and experimentally with good agreement, which provides a means for selection of FBG packaging material to achieve desired temperature sensitivity. We also demonstrate a 4-point bending structured FBG lateral force sensor that measures up to 242N force with well-preserved reflection spectrum, whereas for 3-point bending structure, multiple-peaks start to occur when applied force reaches 72N.

关键词： Fiber bragg grating sensor thermal expansion coefficient lateral force sensor

Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

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World Journal of Gastroenterology 2007年第28期13卷 3829-3835页

作者： Iwao Kaneko Shinji Tanaka shiro Oka Shigeto Yoshida Toru Hiyama Koji Arihiro Fumio Shimamoto Kazuaki Chayama Department of Medicine and Molecular Science Hiroshima University Graduate School of Biomedical ScienceHiroshimaJapan Department of Endoscopy Hiroshima University HospitalHiroshimaJapan Health Service Center Hiroshima UniversityHiroshimaJapan Department of Pathology Hiroshima University HospitalHiroshimaJapan Department of Health Science Prefectural University of HiroshimaFaculty of Human Culture and SocietyHiroshimaJapan

AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin- stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis. RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis. CONCLUSION: Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.

关键词： Submucosal colorectal cancer Microvessel density Lymphatic vessel density Mucin 1 Ki-67 Cathepsin D Matrix metalloproteinase-7 Lymph node metastasis Immunohistochemistry

Clinical significance of type V_I pit pattern subclassification in determining the depth of invasion of colorectal neoplasms

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World Journal of Gastroenterology 2008年第2期14卷 211-217页

作者： Hiroyuki Kanao Shinji Tanaka shiro Oka Iwao Kaneko Shigeto Yoshida Koji Arihiro Masaharu Yoshihara Kazuaki Chayama Department of Medicine and Molecular Science Hiroshima University Graduate School of Biomedical Science Hiroshima Japan Department of Endoscopy Hiroshima University Hospital Hiroshima Japan Department of Pathology Hiroshima University Hospital Hiroshima Japan Health Service Center Hiroshima University Hiroshima Japan

AIM: To clarify whether subclassification of the type VI pit pattern on the basis of magnifying colonoscopy findings is useful in determining the type and depth of invasion of colorectal ***: We retrospectively analyzed 272 colorectal neoplasms (117 dysplasias and 155 submucosal invasive carcinomas; 228 patients) with a type V pit pattern [type VI, n = 202; type VN, n = 70 (Kudo and Tsuruta classification system)]. We divided lesions with a type VI pit pattern into two subclasses, mildly irregular lesions and severely irregular lesions, according to the prominent and detailed magnifying colonoscopy findings. We examined the relation between these two subclasses and histology/invasion ***: One hundred and four lesions (51.5%) were judged to be mildly irregular, and 98 lesions (48.5%) were judged to be severely irregular. Ninety-seven (93.3%) mildly irregular lesions showed dysplasias or submucosal invasion of less than 1000 μm (SM < 1000 μm). Fifty-five (56.1%) severely irregular lesions showed submucosal invasion equal to or deeper than 1000 μm (SM ≥ 1000 μm). Mild irregularity was found significantly more often in dysplasias or lesions with SM < 1000 μm than in lesions with SM ≥ 1000 μm (P < 0.01).CONCLUSION: Subclassification of the type VI pit pattern is useful for identifying dysplasias or lesions with SM < 1000 μm.

关键词： Colorectal neoplasm Magnification Type VI pit pattern Depth of invasion