シスプラチン徐放ゼラチンハイドロゲルの簡便な作製法

京都大学新制・課程博士博士(医学)甲第24794号医博第4986号新制||医||1066(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 寺田 智祐, 教授 武藤 学, 教授 上杉 志成学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

ヒト前立腺におけるβ3-アドレナリン受容体の発現と機能

浜松医科大学学位論文　医博第730号（平成28年3月14日

Prognostic criteria in patients with gastrointestinal stromal tumors: a single center experience retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) are morphologically and clinically heterogeneous tumors, and their biological behavior is difficult to predict, ranging from clinically benign to malignant. The aim of our study was to reanalyze the value of the commonly used prognostic criteria and recently reported nomogram in predicting disease recurrence in patients with primary resectable GISTs.</p> <p>Methods</p> <p>The clinicopathological features of 60 patients with GISTs who underwent surgical resection between 1998 and 2010 at Hiroshima University Hospital were retrospectively reviewed. Tumors were classified according to the National Institutes of Health and Armed Forces Institute of Pathology criteria, and nomogram predictions were performed. The relationship between patient and tumor characteristics was tested by univariate analysis using the log-rank test. Furthermore, we assessed nomogram performance with the concordance index and calibration.</p> <p>Results</p> <p>The median patient follow-up was 4.1 years, with 6 of 60 patients experiencing recurrence. Recurrence was observed only in the high-risk group. The recurrence-free survival (RFS) was 93.0 and 89.9% after 2 and 5 years, respectively. The concordance indices of the nomogram prediction were 0.96 and 0.65 for all patients and the high-risk subgroup, respectively. Calibration of the nomogram-predicted RFS tended to overestimate the recurrence risk relative to the actual RFS.</p> <p>Conclusions</p> <p>Although the commonly used criteria provide an excellent estimation of tumor behavior, they are limited by prognostic heterogeneity. The predictive nomogram is a beneficial scoring system but not a direct RFS predictor. We need more consideration for small GISTs, particularly those less than 3 cm in diameter, and small GISTs should be analyzed as a subset with potentiality different biological behavior.</p

Alleviation of allergic conjunctivitis by (±)5(6)-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid in mice

Background: Allergic conjunctivitis (AC) is a common ophthalmologic disorder that causes symptoms that often reduces a patient’s quality of life (QOL). We investigated the effects of the eicosapentaenoic acid metabolite (±)5(6)-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid ((±)5(6)-DiHETE) on AC using a mouse model.Methods: BALB/c mice were sensitized with two injections of short ragweed pollen in alum, challenged fifth with pollen in eyedrops. The clinical signs and tear volume were evaluated at 15 min after the final challenge. Histamine-induced ocular inflammation model was prepared by instilling histamine onto the surface of the eye. Fifteen minutes after histamine application, tear volume was measured using the Schirmer tear test. Miles assay was performed to investigate vascular permeability. To cause scratching behavior 10 μg of serotonin was injected in the cheek.Results: Repeated topical application of pollen induced conjunctivitis, accompanied by eyelid edema and tearing in mice. Pollen application typically degranulates mast cells and recruits eosinophils to the conjunctiva. Intraperitoneal administration of 300 μg/kg of (±)5(6)-DiHETE significantly inhibited pollen-induced symptoms. The administration of (±)5(6)-DiHETE also attenuated mast cell degranulation and eosinophil infiltration into the conjunctiva. To assess the effects of (±)5(6)-DiHETE on the downstream pathway of mast cell activation in AC, we used a histamine-induced ocular inflammation model. Topical application of 4 μg/eye histamine caused eyelid edema and tearing and increased vascular permeability, as indicated by Evans blue dye extravasation. Intraperitoneal administration of 300 μg/kg or topical administration of 1 μg/eye (±)5(6)-DiHETE inhibited histamine-induced manifestations. Finally, we assessed the effects of (±)5(6)-DiHETE on itching. An intradermal injection of 10 μg serotonin in the cheek caused scratching behavior in mice. Intraperitoneal administration of 300 μg/kg (±)5(6)-DiHETE significantly inhibited serotonin-induced scratching.Conclusion: Thus, (±)5(6)-DiHETE treatment broadly suppressed AC pathology and could be a novel treatment option for AC

A Case of Malignant T-Cell Lymphoma of Gastric Origin Accompanied by Pyothorax

The patient was a 74-year-old man suffering from tuberculotic chronic pyothorax. He had hematemesis in January 2006. Hb was 6.1 g/dl. A type 2 tumor 3 cm in diameter was found in the vaulted region on the greater curvature side. It was diagnosed as a malignant lymphoma. WBC and differential count were normal, and the patient tested negative for HTVL-1 antibody. sIL2-R was elevated to 1,500 U/ml. The superficial lymph nodes were not palpable. CT examination was not remarkable for the liver and spleen. There was no generalized lymph node enlargement. Based on these findings, a diagnosis of malignant lymphoma of gastric origin was made. As the patient had respiratory disorders, too, wedge-shaped gastrectomy was performed to inhibit invasion. Pathological examination revealed CD3 positive large atypical lymphocytes diffusely, EBV positive, HP negative. As a result, a diagnosis of non-Hodgkin T-cell lymphoma was made. The tumor did not return for 1 year and 8 months after surgery, but the patient died of sudden aggravation of respiratory disorders in September 2007. Pathological anatomy was performed. The gastric remnant was left with lymphoma, and the bone marrow and systemic lymph nodes were negative for a malignant lymphoma. The possibility of stomach metastasis from the preoperative pyothorax-related malignant lymphoma was considered, but was ruled out because the lungs were devoid of a malignant lymphoma. We report a case of an extremely rare malignant T-cell lymphoma of gastric origin

Mechanobiological Signal Transduction in Differentiating Chondrocyte and New Configuration for Mechanical Stress Culture

Proceedings of the 2nd IEEE International Conference on Nano/Micro Engineered and Molecular Systems, January 16 - 19, 2007, Bangkok, Thailan

The tumor suppressor protein Tob functions as a transcriptional coregulator

[Curriculum Vitae & Summary] International Symposium on Tumor Biology in Kanazawa 2004 / Kanazawa, Japan February 12 and 13, 200

Octacalcium phosphate crystals including a higher density dislocation improve its materials osteogenecity

Herein, we show that the enhanced osteogenecity of octacalcium phosphate (OCP) biomaterial, recently identified as an important element in hybrid organic–inorganic nanocomposites involved in the initial hydroxyapatite crystal expansion in mammal bones, results from an enhanced chemical property, stemming from the presence of lattice strain and dislocations. Two types of OCPs were synthesized by wet-chemical processing in the presence (c-OCP) and absence (w-OCP) of gelatin, respectively, and subjected to structural, chemical, and biological analyses. High-resolution transmission electron microscopy (HRTEM) and fast Fourier transform (FFT) analyses revealed that c-OCP crystals contained approximately six times higher edge dislocations with Burgers vectors perpendicular to a-axis than that in the case of w-OCP. The dissolution of c-OCP crystal in tris-HCl buffer occurred toward the long axis of the crystal, most likely, toward the lattice strain along the c-axis direction, while w-OCP crystal dissolved toward the a-axis direction. The study suggested that the increment of internal energy by the higher dislocation density contributed promoting c-OCP dissolution and hydrolysis through decreasing the activation energy. c-OCP crystal displayed enhanced in vitro mesenchymal stem 2D cell and 3D spheroid differentiation, in vivo bone formation, and apatite crystallographic orientation in critical-sized rat calvarial defect model as compared to w-OCP crystal, at the same time, converting to apatite structure earlier than w-OCP. The present study demonstrates that dislocation-related dissolution along with enhanced conversion of OCP is a determinant in bone induction, which may be relevant to normal bone development utilizing OCP biomaterials.Hamai R., Sakai S., Shiwaku Y., et al. Octacalcium phosphate crystals including a higher density dislocation improve its materials osteogenecity. Applied Materials Today, 26, 101279. https://doi.org/10.1016/j.apmt.2021.101279