自己集合性分子糊による遺伝子操作を用いない細胞表面修飾法

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム京都大学新制・課程博士博士(医科学)甲第23116号医科博第127号新制||医科||8(附属図書館)京都大学大学院医学研究科医科学専攻(主査)教授 藤田 恭之, 教授 渡邊 直樹, 教授 岩田 想学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Reconsideration of Hormonal Therapy in the Era of Next‐ Generation Hormonal Therapy

Hormonal therapy is a major and effective tool in the treatment of prostate cancer patients. This is especially true for patients in the advanced stages of disease. Unfortunately, almost all prostate cancer cells will develop into castration‐resistant prostate cancer (CRPC) despite continued therapy and suppression of testosterone levels. Up until 5–6 years ago, there was little effective therapy for the treatment of CRPC patients. However, recently, a variety of methodologies and drugs such as cabazitaxel and sipuleucel‐T have been approved globally for the treatment of CRPC. Two novel drugs, abiraterone acetate and enzartamide, have also become available as potential treatment options. However, the anticancer effects of these two drugs are not always satisfactory in terms of prolonging survival. These drugs are also associated with adverse events and are expensive when compared with the costs of previously used anticancer drugs. In this section, we pay particular attention to hormonal therapies that do not include the use of abiraterone acetate or enzartamide. We believe that a detailed understanding of the range of currently available hormonal therapies, including their associated benefits and limitations, is important for supporting the prolongation of survival in patients with advanced prostate cancer. Therefore, this section offers a valuable discussion on the treatment strategies for prostate cancer including CRPC

Non-genetic cell-surface modification with a self-assembling molecular glue

A versatile non-genetic cell-surface modification method, in which a self-assembling small molecule is combined with Halo-tag proteins, permitted the sell functionalization

The Validity and Reliability of a Smartphone Application for Break-Point Angle Measurement during Nordic Hamstring Exercise

# Background A recently developed smartphone application (Nordic Angle) allows the automatic calculation of the break-point angle (BPA) during Nordic hamstring exercise (NHE) without transferring the collected data to a computer. The BPA is the point at which the hamstrings are unable to withstand force. However, the validity of the BPA values obtained by this method has not been examined. # Hypothesis/Purpose This study aimed to evaluate the validity and reliability of the Nordic Angle by comparing the BPA values of the Nordic Angle with those of two-dimensional motion analysis software that can calculate the angles and angular velocities of various joints. # Study Design Cohort assessing Validity and Reliability # Methods The validity of the Nordic Angle BPA data was verified by Spearman's correlation test for consistency with the movement analysis data, and the magnitude of the correlation was indicated by rs. The agreement between these measurements was examined using the Bland-Altman analysis. The reliability of the Nordic Angle and motion analysis was examined using the intraclass correlation coefficient (ICC) (1,k) based on data from repeated trials within a day. # Results Although the spearman correlation between the Nordic angle and the angle determined using motion analysis did not reach statistical significance (p = 0.052), a very large correlation was present (rs = 0.75). The difference between the mean values of the Nordic Angle and motion analysis was 0.4 ± 2.1°, and the limits of agreement ranged from -3.9° to 4.6°. In two BPA measurements, the Nordic Angle showed perfect reliability (ICC = 1.00, p \< 0.001), while motion analysis showed nearly perfect reliability (ICC = 0.97, p \< 0.001). # Conclusion The Nordic Angle, which has both validity and reliability, may be appropriate for field measurement because it allows immediate feedback of BPA and the measurement of many athletes. # Level of evidence 3b ©The Author(s

Composite pheochromocytoma of the adrenal gland: a case series

Background: Composite pheochromocytoma is a rare pathological condition characterized by elements of both pheochromocytoma and neurogenic tumors. However, detailed clinical outcomes of this tumor have not been fully shown. From 2007 to 2013, we experienced three cases of adrenal composite pheochromocytoma. In this report, we investigate the clinicopathological features of these three cases of composite pheochromocytoma and compare them with previously reported cases. Case presentations: Cases 1 and 2 were a 29-year-old Japanese woman and a 59-year-old Japanese man, respectively. They underwent laparoscopic left adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroma. Case 3 was a 53-year-old Japanese man who had been receiving hemodialysis for 17 years. He underwent laparoscopic right adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroblastoma. Although the Ki67-positive rates varied from 1.0 to 6.2% among the three cases, no clinical recurrences occurred. Despite the relatively high rate of Ki67 positivity, complete tumor resection resulted in favorable clinical outcomes. Conclusion: We experienced three cases of adrenal composite pheochromocytoma. Although the clinical findings and treatment outcomes of composite pheochromocytoma were similar to those of ordinary pheochromocytoma, further studies of the biological behavior and genetic profiles of composite pheochromocytoma are necessary to achieve a better understanding of this tumor

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review

Background: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortality Case presentation: A 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital. Conclusion: The present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC