Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer

Kazuhiro Takehara,Takashi Matsumoto,Junzo Hamanishi,Kosei Hasegawa,Motoki Matsuura,Kiyonori Miura,Shoji Nagao,Hidekatsu Nakai,Naotake Tanaka,Hideki Tokunaga,Kimio Ushijima,Hidemichi Watari,Yoshihito Y 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.2

Objective: The primary objective of this study was to evaluate the safety of niraparib 300 mg/dayin Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. Methods: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients withplatinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30days after initial niraparib administration) was justified by the incidences of a global pivotalphase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematologicaladverse event of niraparib. The overall safety analysis examined other treatment-emergentadverse events (TEAEs). Results: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1)kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib300 mg/day but this decreased in subsequent cycles (mean±standard deviation doseintensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. Noprogression-free or overall survival events occurred; only 1 of 4 response-evaluable patientshad a post-baseline tumor assessment (stable disease). Conclusion: The incidence of grade 3 or 4 thrombocytopenia-related events in Japaneseovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall,the safety profile was acceptable and consistent with the known safety profile and previousexperience with niraparib. Trial Registration: ClinicalTrials.gov Identifier: NCT03759587

Twin Rectal Tonsils Mimicking Carcinoid or Mucosa-Associated Lymphoid Tissue Lymphoma

Masanori Takehara,Naoki Muguruma,Shinji Kitamura,Tetsuo Kimura,Koichi Okamoto,Hiroshi Miyamoto,Yoshimi Bando,Tetsuji Takayama 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.5

The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosa-associated lymphoid tissue lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.

大阪財政と企業經營

竹原憲雄(Norio TAKEHARA) 啓明大學校産業經營硏究所 2002 啓明大學校ㆍ挑山學院大學國際學術세미나 Vol.2002 No.3

오사카 財政과 企業經營

타케하라 노리오(Norio TAKEHARA),김용기(번역자) 계명대학교 산학연구소 2000 經營經濟 Vol.33 No.1

Nutrigenomic Studies of Effects of Chlorella on Subjects with High-Risk Factors for Lifestyle-Related Disease

Toru Mizoguchi,Isao Takehara,Tohru Masuzawa,Toshiro Saito,Yo Naoki 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.3

In order to clarify the physiological effects of Chlorella intake on subjects with high-risk factors for lifestyle-related diseases, we conducted Chlorella ingestion tests on 17 subjects with high-risk factors for lifestyle-related diseases and 17 healthy subjects over a 16-week period, including a 4-week post-observation period. We conducted blood biochemical tests and analyzed gene expression profile in whole blood cells in the peripheral blood before and after Chlorella intake. We confirmed that in both groups, Chlorella intake resulted in noticeable reductions in body fat percentage, serum total cholesterol, and fasting blood glucose levels. Through gene expression analysis, we found that gene expression profiles varied with Chlorella intake and identified many genes that exhibited behavior such that after the completion of the intake period, expression levels returned to pre-intake expression ones. Among these were genes related to signal transduction molecules, metabolic enzymes, receptors, transporters, and cytokines. A difference in expression level was found between the two groups at the start of the tests, and we were able to identify genes with noticeable variance in expression level resulting from Chlorella intake in the high-risk factor group. These included genes involved in fat metabolism and insulin signaling pathways, which suggests that these pathways could be physiologically affected by Chlorella intake. There were clear variations in the expression profiles of genes directly related to uptake of glucose resulting from Chlorella intake, indicating that the activation of insulin signaling pathways could be the reason for the hypoglycemic effects of Chlorella.

GROWTH INHIBITION OF Acanthamoeba BY HYDROPEROXYNAPHTALIMIDES UPON PHOTOIRRADIATION

Matsugo, Seiichi,Takeuchi, Rie,Takehara, Yoshimi,Tsuruhara, Takashi Korean Society of Photoscience 1997 Journal of Photosciences Vol.4 No.3

Acanthamoeba strains were photoirradiated in the presence of light-sensitive organic peroxides (hydroperoxynaphthalimide derivatives) including a Photo-Fenton reagent at 366 nm. The survival rates of Acantharnoeba strains determined after 20 h culture showed a significant decrease only upon photoirradiated conditions. The most effective hydroperoxynaphthalimides among these compounds was the bromohydroperoxynaphthalimide (Br-HPO II). The minimum inhibitory concentration (MIC) of Br-HPO II is 100 times lower than that of hydrogen peroxide.

Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma

Tamaki Tanaka,Kazuhiro Takehara,Natsumi Yamashita,Mika Okazawa-Sakai,Kazuya Kuraoka,Norihiro Teramoto,Kenichi Taguchi,Katsushige Yamashiro,Hidenori Kato,Tomoya Mizunoe,Rie Suzuki,Dan Yamamoto,Arisa Ue 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5

Objective: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). Methods: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. Results: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30–90) and 46 (22–76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. Conclusion: The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Stabilization of a bicycle with two-wheel steering and two-wheel driving by driving forces at low speed

Chihiro Nakagawa,Yoshihiro Suda,Kimihiko Nakano,Shoichiro Takehara 대한기계학회 2009 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.23 No.4

Recently, the personal mobility vehicle (PMV), a vehicle suitable for personal use, has been developed. It moves at low speed and is sufficiently small that it can be ridden in pedestrian space. This vehicle is expected to be a new method of transportation that is practical and environmentally friendly. As one form of PMV, the authors propose a twowheel vehicle with two modes: a two-wheel steering and two-wheel driving bicycle mode and a parallel two-wheel mode. This vehicle has four electric motors, two for driving and two for steering, and one generator connected to the pedals. In the bicycle mode, the rider rotates the pedals to generate electric power, and the motors in the wheels produce torque using the generated energy. The front and rear wheels are steered by the electric motor according to the angle of the handle. Therefore, this bicycle is controlled by a steer-by-wire and a drive-by-wire system. In the parallel two-wheel mode, the vehicle is stabilized according to the theory of the inverted pendulum. In this paper, we focus on the bicycle mode and analyze its stability. Stabilizing the bicycle is not easy since the proposed vehicle has tires with small diameters and the traveling speed is assumed to be low. It is known that the stability of bicycles is tuned by adjusting the bicycle parameters and changing the rear steer angle. However, since we aim to use the vehicle in a narrow walking space at low speed, such conventional methods are not always suitable. The authors propose the stabilization of the bicycle using driving forces and design a controller using linear-quadratic control theory. The results of the numerical simulations show the proposed method is effective in stabilizing the bicycle.

Current status of hereditary breast and ovarian cancer practice among gynecologic oncologists in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO)

Yusuke Kobayashi,Kenta Masuda,Akira Hiraswa,Kazuhiro Takehara,Hitoshi Tsuda,Yoh Watanabe,Katsutoshi Oda,Satoru Nagase,Masaki Mandai,Aikou Okamoto,Nobuo Yaegashi,Mikio Mikami,Takayuki Enomoto,Daisuke A 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.5

Objective: The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management. Methods: A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC. Results: A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities. Conclusion: Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management.

The Relationship of Salivary Viscosity with Halitosis

Sachiko Komori,Takashi Zaitsu,Sachiko Takehara,Masayuki Ueno,Yoko Kawaguchi 대한예방치과학회 2016 International Journal of Clinical Preventive Denti Vol.12 No.1

Objective: The purpose of this research was to examine the relationship of salivary viscosity with halitosis. Methods: Subjects were 224 patients who visited a halitosis clinic. Instrumental measurements (Gas chromatography and Sulfide monitor) and the organoleptic assessment were used for the detection of halitosis. An oral health examination assessed the number of teeth present and decayed teeth, periodontal pocket depth and gingival bleeding, plaque index and tongue coating. Un-stimulated whole saliva was collected for 5 minutes. Salivary viscosity was measured using a cone-and-plate digital viscometer. The independent t-test and chi-square test were conducted to compare the means and distributional differences by malodor status. Logistic regression analysis was performed with malodor status as the dependent variable. Gender, age and oral health status were used as independent variables. Results: Chi-square tests demonstrated significant associations between salivary viscosity and H2S≥1.5, CH3SH≥0.5, (CH3)2S≥0.4, BreathtronⓇ≥251, and organoleptic score≥2.0 (p<0.05). Salivary viscosity (p<0.05) and the tongue coating (p<0.05) were significant variables in all malodor measurements (concentrations of H2S, CH3SH, (CH3)2S, total volatile sulfur compounds [VSCs], and the organoleptic score). Compared to subjects with low salivary viscosity, those with high salivary viscosity were significantly more likely to have malodor (odds ratio: ranging from 2.32 to 7.51). Conclusion: This study indicated that salivary viscosity as well as tongue coating were significant risk factors for halitosis measured by concentrations of H2S, CH3SH, (CH3)2S, total VSCs, and the organoleptic score.