Clinical activity of ASP 8273 in Asian patients with non‐small‐cell lung cancer with EGFR activating and T790M mutations

Murakami, Haruyasu,Nokihara, Hiroshi,Hayashi, Hidetoshi,Seto, Takashi,Park, Keunchil,Azuma, Koichi,Tsai, Chun‐,Ming,Yang, James Chih‐,Hsin,Nishio, Makoto,Kim, Sang‐,We,Kiura, Katsuyu John Wiley and Sons Inc. 2018 CANCER SCIENCE Vol.109 No.9

<P>Epidermal growth factor receptor (EGFR)‐activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non‐small‐cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose‐escalation/dose‐expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP8273 at RP2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP8273. In phase I, RP2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP8273 300 mg achieved a clinical response, ASP8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR‐activating and T790M mutations.</P>

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer

Naoya Murakami,Miho Watanabe,Takashi Uno,Shuhei Sekii,Kayoko Tsujino,Takahiro Kasamatsu,Yumiko Machitori,Tomomi Aoshika,Shingo Kato,Hisako Hirowatari,Yuko Kaneyasu,Tomio Nakagawa,Hitoshi Ikushima,Ken 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Tumor volume and lymphovascular space invasion as a prognostic factor in early invasive adenocarcinoma of the cervix

Isao Murakami,Takuma Fujii,Kaori Kameyama,Takashi Iwata,Miyuki Saito,Kaneyuki Kubushiro,Daisuke Aoki 대한부인종양학회 2012 Journal of Gynecologic Oncology Vol.23 No.3

Objective: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. Methods: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. Results: The median follow-up period was 64.3 months. The depth of stromal invasion was ≤3 mm in 33 cases and >3 mm, but ≤5 mm in 17 cases. The horizontal spread was ≤7 mm in 25 cases and >7 mm in 25 cases. One of the 33 cases that had tumor volumes of ≤500 mm^3, and three of the 17 cases with tumor volumes of >500 mm^3 were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p<0.0001). The frequency of pelvic lymph node metastases was significantly higher in the lymphovascular space invasion (LVSI)-positive group than in the LVSI-negative group (p=0.02). No adnexal metastasis or parametrial involvement was noted. Conclusion: Assessment of the depth of stromal invasion, tumor volume, and LVSI is critical for selecting an appropriate therapeutic modality. Non-radical methods of management are considered suitable for patients with LVSI-negative adenocarcinoma of the cervix exhibiting a stromal invasion depth of ≤5 mm and a tumor volume of ≤500 mm^3. Objective: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. Methods: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. Results: The median follow-up period was 64.3 months. The depth of stromal invasion was ≤3 mm in 33 cases and >3 mm, but ≤5 mm in 17 cases. The horizontal spread was ≤7 mm in 25 cases and >7 mm in 25 cases. One of the 33 cases that had tumor volumes of ≤500 mm^3, and three of the 17 cases with tumor volumes of >500 mm^3 were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p<0.0001). The frequency of pelvic lymph node metastases was significantly higher in the lymphovascular space invasion (LVSI)-positive group than in the LVSI-negative group (p=0.02). No adnexal metastasis or parametrial involvement was noted. Conclusion: Assessment of the depth of stromal invasion, tumor volume, and LVSI is critical for selecting an appropriate therapeutic modality. Non-radical methods of management are considered suitable for patients with LVSI-negative adenocarcinoma of the cervix exhibiting a stromal invasion depth of ≤5 mm and a tumor volume of ≤500 mm^3.

A Case Study of Human Resource Allocation for Effective Hotel Management

Kayoko Murakami,Seren Ozmehmet Tasan,Mitsuo Gen,Takashi Oyabu 대한산업공학회 2011 Industrial Engineeering & Management Systems Vol.10 No.1

The purpose of this study is to optimally allocate the human resources to tasks while minimizing the total daily human resource costs and smoothing the human resource usage. The human resource allocation problem (hRAP) under consideration contains two kinds of special constraints, i.e. operational precedence and skill constraints in addition to the ordinary constraints. To deal with the multiple objectives and the special constraints, first we designed this hRAP as a network problem and then proposed a Pareto multistage decision-based genetic algorithm (P-mdGA). During the evolutionary process of P-mdGA, a Pareto evaluation procedure called generalized Pareto-based scale-independent fitness function approach is used to evaluate the solutions. Additionally, in order to improve the performance of P-mdGA, we use fuzzy logic controller for fine-tuning of genetic parameters. Finally, in order to demonstrate the applicability and to evaluate the performance of the proposed approach, P-mdGA is applied to solve a case study in a hotel, where the managers usually need helpful automatic support for effectively allocating hotel staff to hotel tasks.

Edible Red Seaweed Hypnea asiatica Ameliorates High-Fat Diet-Induced Metabolic Diseases in Mice

Shigeru Murakami,Chihiro Hirazawa,Toshiki Mizutani,Takuma Ohya,Rina Yoshikawa,Ning Ma,Takahiko Ikemori,Takashi Ito,Chiaki Matsuzaki 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.11

Metabolic diseases, including obesity, diabetes, and fatty liver disease, are dramatically increasing around theworld. Seaweed is low in calories and rich in many active ingredients that are necessary for maintaining good health, and isexpected to be effective for preventing metabolic diseases. The purpose of this study was to examine the effects of a traditionalJapanese edible seaweed Hypnea asiatica (H. asiatica) on obesity, using a mouse model. H. asiatica was dried andpowdered, mixed with a high-fat diet, and fed to male C57BL/6J mice for 13 weeks. On the last day of the experiment, bloodsamples were collected under anesthesia and biochemical parameters such as lipids and adipokines were measured. Liver andadipose tissue were excised, weighed, and oxidant/antioxidant parameters were measured. Some mice were perfused with afixative solution containing formalin, and tissue specimens were prepared. A glucose tolerance test was used to assess insulinresistance. The inhibition of lipase activity was evaluated in vitro. Thirteen-week supplementation with H. asiatica suppressedbody weight gain, body fat accumulation, and blood glucose levels. H. asiatica also improved fatty liver and hypercholesterolemia,and reduced the oxidant and inflammatory parameters of serum and liver. H. asiatica increased fecal triglycerideexcretion and polyphenol-rich ethanol extract of H. asiatica inhibited lipase activity in vitro. These results suggest thatpolysaccharides and polyphenols in H. asiatica may ameliorate obesity and diabetes by inhibiting intestinal fat absorption andreducing oxidative stress and inflammation. H. asiatica may be useful in preventing metabolic diseases such as obesity,diabetes, and fatty liver.

Female Longitudinal Anal Muscles or Conjoint Longitudinal Coats Extend into the Subcutaneous Tissue along the Vaginal Vestibule: A Histological Study Using Human Fetuses

Yusuke Kinugasa,Takashi Arakawa,Hiroshi Abe,Jose Francisco Rodríguez-Vázquez,Gen Murakami,Kenichi Sugihara 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.3

Purpose: It is still unclear whether the longitudinal anal muscles or conjoint longitudinal coats (CLCs) are attached to the vagina, although such an attachment, if present, would appear to make an important contribution to the integrated supportive system of the female pelvic floor. Materials and Methods: Using immunohistochemistry for smooth muscle actin, we examined semiserial frontal sections of 1) eleven female late-stage fetuses at 28-37 weeks of gestation, 2) two female middle-stage fetus (2 specimens at 13 weeks), and, 3) six male fetuses at 12 and 37 weeks as a comparison of the morphology. Results: In late-stage female fetuses, the CLCs consistently (11/11) extended into the subcutaneous tissue along the vaginal vestibule on the anterior side of the external anal sphincter. Lateral to the CLCs, the external anal sphincter also extended anteriorly toward the vaginal side walls. The anterior part of the CLCs originated from the perimysium of the levator ani muscle without any contribution of the rectal longitudinal muscle layer. However, in 2 female middle-stage fetuses, smooth muscles along the vestibulum extended superiorly toward the levetor ani sling. In male fetuses, the CLCs were separated from another subcutaneous smooth muscle along the scrotal raphe (posterior parts of the dartos layer) by fatty tissue. Conclusion: In terms of topographical anatomy, the female anterior CLCs are likely to correspond to the lateral extension of the perineal body (a bulky subcutaneous smooth muscle mass present in adult women), supporting the vaginal vestibule by transmission of force from the levator ani.

Anococcygeal Raphe Revisited: A Histological Study Using Mid-Term Human Fetuses and Elderly Cadavers

Yusuke Kinugasa,Takashi Arakawa,Hiroshi Abe,Shinichi Abe,조백환,Gen Murakami,Kenichi Sugihara 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.4

Purpose: We recently demonstrated the morphology of the anococcygeal ligament. As the anococcygeal ligament and raphe are often confused, the concept of the anococcygeal raphe needs to be re-examined from the perspective of fetal development,as well as in terms of adult morphology. Materials and Methods: We examined the horizontal sections of 15 fetuses as well as adult histology. From cadavers,we obtained an almost cubic tissue mass containing the dorsal wall of the anorectum, the coccyx and the covering skin. Most sections were stained with hematoxylin and eosin or Masson-trichrome solution. Results: The adult ligament contained both smooth and striated muscle fibers. A similar band-like structure was seen in fetuses, containing: 1) smooth muscle fibers originating from the longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the external anal sphincter (EAS). However, in fetuses, the levator ani muscle did not attach to either the band or the coccyx. Along and around the anococcygeal ligament, we did not find any aponeurotic tissue with transversely oriented fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous tissue mass was located at a gap between bilateral levator ani slings; this site corresponded to the dorsal side of the ligament and the EAS in the immediately deep side of the natal skin cleft. Conclusion: We hypothesize that a classically described raphe corresponds to the specific subcutaneous tissue on the superficial or dorsal side of the anococcygeal ligament.

Distribution of elastic fibers in the head and neck: a histological study using late-stage human fetuses

Hideaki Kinoshita,Takashi Umezawa,Yuya Omine,Masaaki Kasahara,José,Francisco Rodrí,guez-Vá,zquez,Gen Murakami,Shinichi Abe 대한해부학회 2013 Anatomy & Cell Biology Vol.46 No.1

There is little or no information about the distribution of elastic fibers in the human fetal head. We examined this issue in 15 late-stage fetuses (crown-rump length, 220–320 mm) using aldehyde-fuchsin and elastica-Masson staining, and we used the arterial wall elastic laminae and external ear cartilages as positive staining controls. The posterior pharyngeal wall, as well as the ligaments connecting the laryngeal cartilages, contained abundant elastic fibers. In contrast with the sphenomandibular ligament and the temporomandibular joint disk, in which elastic fibers were partly present, the discomalleolar ligament and the fascial structures around the pterygoid muscles did not have any elastic fibers. In addition, the posterior marginal fascia of the prestyloid space did contain such fibers. Notably, in the middle ear, elastic fibers accumulated along the tendons of the tensor tympani and stapedius muscles and in the joint capsules of the ear ossicle articulations. Elastic fibers were not seen in any other muscle tendons or vertebral facet capsules in the head and neck. Despite being composed of smooth muscle, the orbitalis muscle did not contain any elastic fibers. The elastic fibers in the sphenomandibular ligament seemed to correspond to an intermediate step of development between Meckel’s cartilage and the final ligament. Overall, there seemed to be a mini-version of elastic fiber distribution compared to that in adults and a different specific developmental pattern of connective tissues. The latter morphology might be a result of an adaptation to hypoxic conditions during development.

Application of Model Predictive Control to Polishing Robot for Pushing Operation

Nobuaki Endo,Takashi Yoshimi,Koichiro Hayashi,Hiroki Murakami 제어로봇시스템학회 2022 제어로봇시스템학회 국제학술대회 논문집 Vol.2022 No.11

Much of the polishing work is done manually by skilled workers. It is not easy to teach robots to perform the detailed work of theirs and to configure and operate an appropriate control system to achieve this, and automation of this process has been delayed. Polishing is performed by pressing a rotating tool against the workpiece to be machined. To achieve this motion, PID control is used in the controllers of many robots. However, to determine the appropriate control gain, it is necessary to repeatedly adjust the control gain according to the processing target and processing conditions. The purpose of this research is to introduce Model Predictive Control (MPC) as a new control system for polishing robots. MPC is a control that predicts control output using a model of the control target. Therefore, we considered the target force value could be achieved without changing the MPC parameters when the force condition, a machining condition, is changed. In this paper, control block diagrams were created in MATLAB Simulink to apply MPC. The block diagram was then mounted on the actual machine to check whether it could be pressed with appropriate force, and the differences from PID were evaluated.

AKARI 탑재 적외선 카메라 IRC의 궤도상에서의 광학조절 및 성능

Woojung Kim,Takashi Onaka,Hidenori Kaneda,Hideo Matsuhara,Hiroshi Murakami,Takehiko Wada,Daisuke Ishihara,Naofumi Fujishiro,IRC Team 한국천문학회 2006 天文學會報 Vol.31 No.2