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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.
ABSTRACT
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.
Subject(s)
Humans , B7-H1 Antigen , Biopsy , Carcinoma, Squamous Cell , Disease-Free Survival , Flow Cytometry , Heavy Ion Radiotherapy , Radiotherapy , Treatment Outcome , Uterine Cervical NeoplasmsABSTRACT
This review explores novel possibilities of skeletal muscle hypertrophy mechanism based on previous studies. Hypertrophy and/or regeneration of skeletal muscles are caused by activation of satellite cells, induced by mechanisms such as growth factors and cytokines. Many unsolved problems, however, yet remain concerning signaling pathways, activated by such substances, and regulation of transcriptional factors and cell cycles.In recent years, possible involvement of not only satellite cells but also tissue-specific stem cells in skeletal muscle hypertrophy has been reported from studies made on stem cell transplantation in muscle regeneration.It has been elucidated that differentiation plasticity of tissue-specific stem cells contributes to hypertrophy and/or regeneration of skeletal muscles. Moreover, satellite cells have come to be regarded as one kind of tissue-specific stem cells, since they have been known to exhibit diversity, by their differentiating into not only skeletal muscle cells but also other tissue cells, as well as self renewal capacity.This review also summarizes findings on signaling pathways based on ligand receptor characterization. Among the various signaling pathways, focus was especially placed on the possibilities of Wnt signaling pathway and Notch signaling pathway on skeletal muscle hypertrophy, indicating that Wnt expression in adult muscle stem cells leads to regulation of skeletal muscle hypertrophy.It has also become evident that Notch signaling pathway is associated with the activation of satellites cells, and that functional decline of such signaling pathway causes a decline in the activation of satellite cells. Such functional decline of Notch signaling pathway has also been revealed as the reason for the decline of regenerative capacity of skeletal muscles due to advancing age. Further discussion on the involvement of Notch signaling pathway in skeletal muscle hypertrophy is made based on these results. As indicated above, the roles of ligands and/or receptors of canonical growth factors, signaling pathways, and transcriptional factors contributing to skeletal muscle hypertrophy were reexamined in this review, after which the contribution of tissue-specific cells to skeletal muscle hypertrophy was discussed based on the results of muscle regeneration studies. Furthermore, focus was centered on Wnt and Notch signaling pathways, both of which are attracting renewed attention, and study was made on the possibility of the involvement of these pathways in skeletal muscle hypertrophy process.
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The effects of insulin administration on the normal growth of mouse skeletal muscle and its effect on induction of muscle hypertrophy by tenotomy were investigated in this experiment.<BR>1) The influence of insulin dosage on rat body weight was investigated.<BR>The results of examining the influence of insulin dosage on body weight showed significant increases in body weight in the 8.0U/Kg dosage group and 16.0 U/Kg dosage group compared to the control group.<BR>2) The influence of insulin dosage on rat blood glucose levels was investigated.<BR>The blood glucose values of the 1.0 U/kg dosage group were significantly lower than in the control group. They were significantly lower in the 1.0 U/kg dosage group than in the other dosage groups. The positive utilization of glucose in the peripheral organization was suggested.<BR>3) The effect of insulin dosage on skeletal muscle weight was tested.<BR>ANOVA shows a significant difference in soleus muscle weight as the insulin dosage rose. Soleus muscle weight at the 1.0 U/kg dosage was significantly higher than in the other groups. By contrast, no significant differences in muscle weight were observed in the control group as the dose insulin increased. The weight of fast muscle was unaffected by the size of the insulin dosage.<BR>4) The influence of insulin dosage on the compensatory muscle hypertrophy was examined.<BR>The influence of insulin dosage to the compensatory muscle hypertrophy was examined after one week. A 75% increase in soleus muscle after tenotomy was observed in the control group. Although the plantaris muscle showed an average 30% increase, the difference was not significant. A tendency for the weight of soleus muscle and plantaris muscle to increase after tenotomy was observed in the 2.0 U/kg dosage group, but the increments were not significantly different. Effect of tenotomy was observed weight of the soleus from an average of 7.3% in the 16.0 U/kg dosage group, but the increment was not significant. On the other hand, plantaris muscle weight increased about 65% and the increment was significant.
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The role of exercise in skeletal muscle hypertrophy was examined using op/op mice, which have a hereditary deficiency in the differentiation of macrophages. A tenotomy was performed to produce a compensation load for the soleus and plantaris muscles in op/op mice and a control group. After one week, the weight of the soleus and plantaris muscles had increased significantly. The cross-sectional area of the muscle fiber in the soleus of the control group increased as a result of the compensation load, indicating that the tenotomy had induced muscle fiber hypertrophy. However, the cross-sectional area of the muscle fiber in the soleus of the op/op mouse group did not change significantly. Instead, the tenotomy induced an increase in the number of thin fibers. The cross-sectional area of muscle fibers in the plantaris muscle, which is a fast muscle, decreased in the op/op mouse group. In conclusion, compensation loads in macrophage-deficient op/op mice do not result in muscle fiber hypertrophy.
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A study was conducted to investigate the mechanism of bone atrophy in various strains of inbred mice under the influence of tail-up suspension. Nine inbred strains of mice (NZB/N, NZW/N, AKR/N, Balb/C, C 57 BL, C 3 H/He, A/J, DBA, CBA/N) aged six weeks were used. Each strain was divided randomly into two groups, a suspension group (SG; n=5) and a control group (CG; n=5) . The suspension group were etherized and suspended with an elastic bandage. After one week, the tibiae were removed and their bone weights were measured using an electric balance (Metler; AE 240) . Their length was also measured with a vernier caliper. In all strains, body weight in the SG was significantly lower than that in the CG. From the bone weight and length in the CG, bone growth in the NZB/N, AKR/N, NZW/N and C3H/He strains was considered to be higher than in the other strains. On the other hand bone growth in the DBA, A/J, Balb/C, and CBA/N strains were lower than in the others. The absolute value of bone weight in the SG was significantly smaller than that in the CG in six strains (NZB/N, C 57 BL, A/J, NZW/N, C 3 H/He, Balb/C) . However in the DBA strain, the absolute value of bone weight in the SG was significantly higher than that in the CG.<BR>From the results of this investigation we suggest that the mechanism of normal bone growth is not the same as the mechanism of bone atrophy induced by tail-up suspension.
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Venous concentration of lysine and other 16 amino acids were determined in healthy 5 male 20-22 years of age subjects in the resting state, after 2 min from bigining of exercise, immediatetly after all-out exercise and 30 min after of the exercise with a bicycle ergometer at work intensities which will be fell into all-out in about 6 or 7 min.<BR>During 2 min exercise lysine only was increased, no change of glycine and puoline were observed and other amino acids were decreased. At the point of all out increase of threonine, lysine and histidine were observed, compared with resting state<BR>Alanine concentration at 30 min after of all out exercise was very high than that of resting state and same tendency but a little was observed on lysine. Other amino acids were decreased.<BR>A risk connected with exercise was discussed from the data of lysine obserbed high concentration during two min exercise concerning with the variation of other amino acids by the all-out exercise.
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The remarkable increase of branched amino acid and pretty decrease of lysine venous concentration were observed in healthy nine male and female adults by the brief fast.<BR>The increase of branched amino acid wasn't able to find by the various exercise generally. The increase of lysine venous concentration was found after the running more than 10km frequently.<BR>Only on the subjects of 44 and 55 years of age, the increase of branched chain amino acid and lysine were observed by the running. It looks like have to take precautions that aged people run under the conditions of empty stomach.
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The change in the venous concentration of amino acids in normal male and female adults was studied. After the brief fast (about 40 hours) except for a higher concentration of branched-chain amino acids in the plasma of female subjects, there was essentially no significant difference between the plasma composition of amino acids in female or male subjects. In only one male subject (Rohler's Index was 106), the transient fall of the branched-chain amino acid concentrations.<BR>Low caloric diet feedings resulted in a marked reductions of the plasma serine, glutamic acid, proline, glycine, arginine and threonine. On the other hand, high protein and high fat diet feedings resulted is a remarkable increasing of the branched-chain amino acid concentration and marked reduction of the plasma alanine concentration.
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Influence of the all out exercise by the bicycle ergometer, all out exercise by the treadmill and the 5000 meter track running on the venous and urine concentrations of amino acid with healthy male and female subjects (include junior high school boys) were tested. The subject who was observed remarkable rise in his venous concentrations of amino acids was not always rose in his urine concentration of that.<BR>Generally, increasing ratio of serum alanine concentration was small and both the serum concntrations of essential and non-essential amino acids were reduced. On the several subjects increase of essential amino acids especially branched chain amino acids were observed. It seemed to us the sign of proteolysis according with the exercise. Quite a few difference of the effect on the serum amino acid concentrations among the individuals are observed.
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962 male inhabitants aged from 30 to 60 in Kanto district were tested on their physique and physical fitness. The results were as follows.<BR>1) So their weight was havier than those of nations but on their height relatively that their Rohler's Index was biger than that of nations.<BR>2) Their motor ability was generally inferior than that of nations, especially it was remarkable on the subject on their thirties.<BR>3) The subjects who was superior on the ability of 5 minutes running had the biger Rohler's Index and larger skinfold than that of inferior one.<BR>4) Persons who had less skinfold were inferior on their other physical activities.<BR>5) The subject who had the skinfold ranged from 25mm to 39mm (i. e. had 14-21 percentage fat to their weight) showed highest ability with the running distance within 5 minutes, backward flexibility and vertical jump.<BR>6) It seems to me that the meaning of forward flexibility as the item of physical fitness should be discussed further more after a lot of investigations.