1.Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma
Moito IIJIMA ; Noriyuki OKONOGI ; Nakako Izumi NAKAJIMA ; Yukie MOROKOSHI ; Hiroaki KANDA ; Taiju YAMADA ; Yusuke KOBAYASHI ; Kouji BANNO ; Masaru WAKATSUKI ; Shigeru YAMADA ; Tadashi KAMADA ; Daisuke AOKI ; Sumitaka HASEGAWA
Journal of Gynecologic Oncology 2020;31(2):19-
OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274
;
Biopsy
;
Carcinoma, Squamous Cell
;
Disease-Free Survival
;
Flow Cytometry
;
Heavy Ion Radiotherapy
;
Humans
;
Radiotherapy
;
Treatment Outcome
;
Uterine Cervical Neoplasms
2.Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma
Moito IIJIMA ; Noriyuki OKONOGI ; Nakako Izumi NAKAJIMA ; Yukie MOROKOSHI ; Hiroaki KANDA ; Taiju YAMADA ; Yusuke KOBAYASHI ; Kouji BANNO ; Masaru WAKATSUKI ; Shigeru YAMADA ; Tadashi KAMADA ; Daisuke AOKI ; Sumitaka HASEGAWA
Journal of Gynecologic Oncology 2020;31(2):e19-
OBJECTIVE:
Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).
METHODS:
The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.
RESULTS:
The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.
CONCLUSION
CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
3.Relationship between screen time and nutrient intake in Japanese children and adolescents: a cross-sectional observational study.
Hiromasa TSUJIGUCHI ; Daisuke HORI ; Yasuhiro KAMBAYASHI ; Toshio HAMAGISHI ; Hiroki ASAKURA ; Junko MITOMA ; Masami KITAOKA ; Enoch Olando ANYENDA ; Thao Thi Thu NGUYEN ; Yohei YAMADA ; Koichiro HAYASHI ; Tadashi KONOSHITA ; Takiko SAGARA ; Aki SHIBATA ; Satoshi SASAKI ; Hiroyuki NAKAMURA
Environmental Health and Preventive Medicine 2018;23(1):34-34
BACKGROUND:
Sedentary behaviors have recently become an important public health issue. We aimed to investigate the relationship between screen time and nutrient intake in children and adolescents.
METHODS:
The present study was conducted in 2013. Data were collected from children and adolescents aged between 6 and 15 years old in Shika town. Questionnaires were distributed to 1459 subjects, 1414 of whom participated in the study (96.9%). Sedentary behaviors were assessed based on participants' screen behaviors (television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use). The main outcomes were the intake of nutrients from a validated food frequency questionnaire. Analysis of covariance (ANCOVA) was used to examine the significance of differences in nutrient intake estimates. Multivariate linear regression analyses, adjusting for age, BMI, and physical activity, were used to provide parameter estimates (β) and 95% CI for the relationship between screen time and nutrient intake.
RESULTS:
In boys, longer TV viewing times correlated or tended to correlate with a lower intake of protein, potassium, calcium, iron, vitamin K, vitamin B-2, and total dietary fiber. In girls, longer TV viewing times correlated with a lower intake of protein, sodium, calcium, vitamin D, and vitamin B-2. Longer TV viewing times correlated with a higher intake of n-6 fatty acids in girls. PC use was related or tended to be related to a lower intake of potassium, iron, vitamin K, and folic acid in boys, but not in girls. A relationship was observed between MP use and a lower intake of vitamin K in boys, and MP use and a higher intake of vitamin D in girls.
CONCLUSIONS
The present results revealed that longer TV viewing times are associated with less protein, minerals, vitamins, and total dietary fiber intake in children and adolescents. It was also revealed that boys with PC use have less minerals and vitamins. These results support the need to design intervention programs that focus on decreasing TV viewing time in both sexes and PC use in boys while encouraging adherence to dietary guidelines among children and adolescents.
Adolescent
;
Body Mass Index
;
Child
;
Cross-Sectional Studies
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Diet
;
Energy Intake
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Exercise
;
Female
;
Humans
;
Japan
;
Male
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Screen Time
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Sedentary Behavior
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Sex Factors
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Socioeconomic Factors
4.Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial.
Tadakazu HISAMATSU ; Reiko KUNISAKI ; Shiro NAKAMURA ; Tomoyuki TSUJIKAWA ; Fumihito HIRAI ; Hiroshi NAKASE ; Kenji WATANABE ; Kaoru YOKOYAMA ; Masakazu NAGAHORI ; Takanori KANAI ; Makoto NAGANUMA ; Hirofumi MICHIMAE ; Akira ANDOH ; Akihiro YAMADA ; Tadashi YOKOYAMA ; Noriko KAMATA ; Shinji TANAKA ; Yasuo SUZUKI ; Toshifumi HIBI ; Mamoru WATANABE
Intestinal Research 2018;16(3):494-498
No abstract available.
Crohn Disease*
;
Food, Formulated*
;
Humans
;
Infliximab*
5.The efficacy of acupuncture treatment on pain and ability with osteoarthritis of the knee-Examination of the curative effect by the depth of an acupuncture needle-
Tadashi MIYAMOTO ; Kazunori ITOH ; Hideki OCHI ; Mitsuhiko YAMADA ; Suzuyo OHASHI ; Megumi ITOI
Journal of the Japan Society of Acupuncture and Moxibustion 2009;59(4):384-394
[Objective]To evaluate the efficacy of the different depth of acupuncture on the motor function and the pain with osteoarthritis of the knee.
[Design]Single blind randomized controlled trial.
[Method]Subjects were randomly allocated to one of two groups. Acupuncture needles were inserted about 3mm in the superficial acupuncture group and 10 to 20 mm in the deep acupuncture group. Subjects in both groups received the treatments for ten minutes on ten tender points. Acupuncture sessions were performed once a week for 8 weeks and without treatment 4 weeks.
[Outcome Measures]Pain intensity (visual analogue scale :VAS) , Objective evaluation of the motor function (Timed Up &Go test, 20m walking time, Time of going up and down stairs) and QOL (Western Ontario and MacMaster Universities osteoarthritis index :WOMAC).
All measurements were recorded at baseline, 4th, 8th and 11thweek.
[Result]Motor function improved significantly only in the superficial acupuncture group(P<0.05). The degree of pain decreased significantly in both groups (P<0.05).
[Conclusion]Superficial acupuncture provided the improvements on pain and motor function and contributed to the QOL improvement. Therefore the superficial acupuncture would be suggested to be one of the most effective method for the acupuncture treatment of OA of the knee.
6.Effects of acupuncture stimulation at distal meridian point on ocular circulation -The comparison between LI4, GB20, BL18, GB37,and LI11-
Mayumi MIZUKAMI ; Tadashi YANO ; Jun YAMADA
Journal of the Japan Society of Acupuncture and Moxibustion 2008;58(4):616-625
[Objective]We researched the effect of five distal acupuncture points that is used for a treatment of eye disorders. [Method]This study was conducted on healthy non-smoking volunteers. We observed change at the time of the rest (Study 1, the control group n=65), and we observed effects of ocular circulation by acupuncture stimulation (Study 2, the stimulus group n=118). Stimulus groups were divided into five groups that are according to the acupoint stimulated as following:GB20 (Fuchi) group, LI4 (Gokoku) group, BL18 (Kanyu) group, GB37 (Komei) group and LI11 (Kyokuchi) group. Blood-flow velocity and pulsatility index (PI) in the central retinal artery (CRA) of the eye were measured using color Doppler imaging. An acupuncture needle was retained for 15min at the selected point. Dates were obtained at intervals of 7.5 min for a total of seven times during a 45-minute period while the subject was in the sitting position. [Results]In the control group showed no significant changeas for all cases of blood-flow velocity and PI. In groups with the stimulus showed that blood-flow velocity in the CRA was increased significantly and PI was decreased significantly. Blood pressure and heart rate scarcely changed in two groups.[Conclusion]These results suggest that acupuncture on the distal acupuncture points that is used for a treatment of eye disorders changes the circulation of CRA. The effect on the ocular circulation was greater in GB37 or in LI4, and was comparatively smaller in GB20.
7.Effects of Ocular Circulation by Acupuncture Stimulation on the crus outside-The comparison of GB36, GB37, GB38, and non-meridian point-
Mayumi MIZUKAMI ; Tadashi YANO ; Jun Yamada
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2006;69(3):201-212
We previously reported the possibility that acupuncture stimulation to the Guangming (GB37) increased retinal blood-flow volume. In this study, we examined whether this reaction was peculiar to GB37 by measuring the blood-flow velocity and pulsatility index (PI) of the central retinal artery (CRA) with Color Doppler imaging. The points to be stimulated were the Waiqiu (GB36), GB37, the Yangfu (GB38) or the non-meridian point on the outside of the crus. Acupuncture stimulus was applied to one point on the right side with a needle for 15min. Seven measurements were made at intervals of 7.5min during a 45-minute period while the subject (control group n=35, stimulus group n=89) was in the sitting position. Patterns of the change in blood-flow velocity and PI with time differed significantly between the five groups. An increase in retinal blood-flow volume occurred in the GB37 group only suggesting there was a peculiarity related to the meridian point. The reaction patterns of the right and left eyes were not significantly different. Blood pressure and heart rate exhibited no significant differences either. These results suggest the relevance of choosing GB37 for improving or maintaining the retinal blood-flow volume.
8.Effects of Ocular Circulation by Acupuncture Stimulation on Guangming (GB37)
Mayumi MIZUKAMI ; Tadashi YANO ; Jun YAMADA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2005;68(4):231-240
This study was conducted on 82 nonsmoking healthy young volunteers divided into two groups. The GB37 group consisted of 39 people who were subjected to stimulation of the Guangming (GB37), and the control group consisted of 43 people who were not so stimulated. Blood-flow velocity and pulsatility index (PI) in the central retinal artery (CRA) of the right eye were measured using Color Doppler imaging. Blood pressure and heart rate were also measured at the same time. The type of stimulus was acupuncture applied on the right GB37 with the needle retained for 15min. Seven measurements were made at intervals of 7.5min during a 45-minute period while the subject was in the sitting position. The GB37 group was first measured just before stimulation and observed for 30 min after the needle was removed. There were significant differences in blood-flow velocity and PI between the two groups. In the GB37 group, blood-flow velocity in the CRA increased remarkably and PI decreased remarkably. These values scarcely changed in the control group. There were no significant differences in blood pressure or heart rate between the two groups. These results suggest that acupuncture stimulus on GB37 changes the circulation of CRA by a mechanism other than blood pressure, resulting in an increase in retinal blood-flow volume.
9.Mechanism for Slowing Surface Electromyography During Fatiguing Contraction Revealed by Superimposed M-Wave Analysis.
HIROSHI YAMADA ; TOMOHIRO KIZUKA ; TADASHI MASUDA ; TAKASHI YOKOI ; FUMINARI KANEKO ; KIMIHIRO KANEKO ; MORIHOKO OKADA
Japanese Journal of Physical Fitness and Sports Medicine 2003;52(1):29-42
We studied the mechanism for slowing surface electromyography (EMG) during fatiguing contraction using superimposed M-wave analysis. Seven healthy male subjects exerted 60% maximum voluntary contraction of isometric abductions in the left first dorsal interosseous muscle (FDI) until exhaustion. Simultaneously with voluntary contractions, the ulnar nerve was electrically stimulated at supramaximal intensity, and volitional EMG and superimposed M-waves were obtained. We examined the behavior of muscle fiber conduction velocity (MFCV) and median frequency (MDF) for both EMG, with the following results:
1) MFCV calculated from volitional EMG of FDI was about 6 m/s during 60% MVC.
2) The waveform of voluntary EMG detected from FDI slowed in all subjects during fatiguing contraction at 60% MVC, indicating fatigue had developed in the muscle.
3) As fatigue progressed, the waveform of the superimposed M-wave tended to decrease in amplitude and increase in duration.
4) As fatigue progressed, MDF and MFCV in volitional EMG decreased significantly (p<0.04) . The rate of change was larger in MDF than in MFCV (p<0.01) .
5) As fatigue progressed, MDF and MFCV in the superimposed M-wave decreased significantly (p<0.01) . The rate of change was larger in NIDF than in MFCV (p<0.05) .
These results suggested that MFCV and other peripheral factors affected the slowing of volitional EMG. Elongation of the depolarization zone in muscle fiber is proposed as a peripheral factor.
10.Effects of Short-Term Immobilization on the Maximum Voluntary Contraction Force Analyzed by the Twitch Interpolation Method.
HIROSHI YAMADA ; TOMOHIRO KIZUKA ; TADASHI MASUDA ; KAZUHIKO SEKI ; TAKASHI YOKOI ; FUMINARI KANEKO ; MORIHOKO OKADA
Japanese Journal of Physical Fitness and Sports Medicine 2003;52(1):51-64
The purpose of this study was to examine the effects of short-term immobilization on the maximum voluntary contraction (MVC) force. The first dorsal interosseus (FDI) of 10 healthy male adults was immobilized for 1 week using casting tape. Atrophy of the muscle was estimated from a cross sectional view of magnetic resonance images (MRI) . To clarify the factors of a peripheral neuromuscular system contributing to the change in the MVC force, twitch force at rest was measured. The contribution of central factors was estimated from a voluntary activation (VA) index, which was obtained by the twitch interpolation method.
The MRI showed no significant changes in the cross sectional area. The MVC force declined after immobilization (p<0.01), and recovered after 1 week from the termination of immobilization (p<0.01) . Both the twitch force at rest and the VA at MVC declined after immobilization (p<0.01), and recovered after 1 week (p<0.05) .
The results indicate that the temporary decline of the MVC force was not accompanied by atrophy of the muscle. Furthermore the decline of the MVC was caused both by the deterioration of peripheral and central functions in the neuromuscular system. Possible factors in the peripheral and central neuromuscular systems affected by the immobilization were discussed.


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