Treatment outcomes of gemcitabine plus nab-paclitaxel in pancreatic cancer patients with malignant ascites.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) therapy has been shown to improve the prognosis in patients with metastatic pancreatic cancer (PC); however, the efficacy and safety of GnP in PC patients with malignant ascites (MA) remains unknown. METHODS: We retrospectively investigated PC patients with peritoneal dissemination who had received GnP as first-line chemotherapy at our institution between March 2015 and August 2021. The following patient data were reviewed: patient characteristics, overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and relative dose intensity (RDI). The severity of MA was categorized based on the CT findings as grade 1 (small), grade 2 (moderate), or grade 3 (massive). RESULTS: A total of 189 patients were included; the study endpoints were compared between patients with each ascites grade and 41 patients without MA. The MA was classified as grade 1 in 85 patients, grade 2 in 41 patients, and grade 3 in 22 patients. In the patients with MA, the median OS, PFS and ORR were 11.2 months, 5.7 months and 24.3%, respectively. The OS and PFS decreased with increasing the severity of MA; in particular, patients with grade 2 and 3 showed a poorer prognosis. There were no differences in AEs, except for anorexia, or the RDI according to the severity of MA. CONCLUSION: GnP showed moderate efficacy with manageable safety profile in PC patients with MA. However, PC patients with moderate to massive ascites still have a dismal prognosis, and further development of effective treatments is needed.

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

Effects of lunges inserted in walking (eccentric walking) on lower limb muscle strength, physical and cognitive function of regular walkers.

INTRODUCTION: Walking is a popular exercise but does not increase lower limb muscle strength and balance. We hypothesized that muscle strength, physical and cognitive function would be improved by inserting lunges in conventional walking. METHODS: Eleven regular walkers (54-88 years) who had more than 5000 steps in exercise walking a day at least 5 days a week participated in this study. They walked as usual for the first 4 weeks and included lunges and descending stairs or slope walking (i.e., eccentric walking) for the next 8 weeks. The steps of eccentric walking were gradually increased from 100 to 1000 steps per week over 8 weeks. RESULTS: The average steps per day were 10,535 ± 3516 in the first 4 weeks, and 10,118 ± 3199 in the eccentric walking period without a significant difference. No significant changes in maximal voluntary isometric contraction torque of the knee extensors (MVC), 30-s chair stand (CS), 2-min step, balance assessed by center of pressure movement area with eyes close, sit and reach, a digit symbol substitution test (DSST) for cognitive function were observed in the first 4 weeks. However, significant (P < 0.05) improvements were evident in MVC (18.6 ± 15.7%), CS (24.2 ± 17.3%), balance ( - 45.3 ± 34.5%), and DSST (20.8 ± 16.7%) from weeks 4 to 12. Serum complement component 1q concentration decreased (P < 0.05) from weeks 4 to 12, although no changes in serum glucose, triglyceride, and cholesterol concentrations were observed. CONCLUSION: These results supported the hypothesis, and suggest that eccentric walking provides effects that are not achieved by conventional walking.

Assessing the validity of two-dimensional video analysis for measuring lower limb joint angles during fencing lunge.

Introduction: The fencing lunge (lunge), characterized by minimal body rotation, offers a movement well-suited for 2D video analysis. However, to the best of our knowledge, the validity of 2D video analysis for fencing has not been verified. This study aimed to validate 2D video analysis by comparing lower limb joints (hip, knee, and ankle joints) angles during lunge using both 2D video analysis and 3D motion analysis methods. Methods: Twenty-two male fencers performed lunge trials that were simultaneously recorded using eight motion capture cameras (Qualisys Miqus M1) and two digital video cameras (Sony AX-450 and AX450a). Results: The 2D video analysis results exhibited an extremely large correlation in knee joint angles of the front and rear legs in the sagittal with those from 3D motion analysis (r = 0.93-0.99). However, while a robust correlation was found between the ankle joint angles of the front and rear legs (r = 0.82-0.84), a large bias was also observed (-5.23° to -21.31°). Conversely, for the hip joints of the rear leg, a moderate correlation (r = 0.31) and a large bias (-10.89°) were identified. Conclusions: The results of this study will contribute to the development of coaching using 2D video analysis in competition settings because such analysis can be a useful alternative to 3D motion analysis when measuring the knee joint angle of the front leg and rear leg in the sagittal plane. However, for the ankle joint angle, further research on the optimal shooting position and height of the digital video camera is needed, whereas for the hip joint angle, 3D motion analysis is recommended at this time.

Relationships between Changes in Muscle Shear Modulus, Urinary Titin N- Terminal Fragment, and Maximum Voluntary Contraction Torque after Eccentric Exercise of the Elbow Flexors.

The study aimed to investigate the relationships between the shear modulus of the biceps brachii (BB) and brachialis muscle (BA) and the total of the two (BB+BA), and urinary titin N-terminal fragment (UTF), maximum voluntary isometric contraction (MVC), and other indirect markers. Fifteen healthy men performed five sets of 10 eccentric contractions using a dumbbell corresponding to 50% of MVC at 90° measured at baseline. The elbow joint of the left arm was extended from 90° to 180° (180° = full extension) in 5 s in the exercise, and was returned with support from the examiner to prevent concentric contraction. Shear modulus of BB and BA were measured by ultrasound shear wave elastography, and UTF, MVC, and range of motion of the elbow joint (ROM) were recorded before; immediately after; and 1, 24, 48, 72, 96, and 168 h after the exercise. After calculating the shear modulus of BB and BA, two values were added (BB+BA). The shear modulus peaked at 48 h, UTF peaked at 96 h, MVC and ROM changed largest at immediately, and muscle soreness peaked at 48 h post-exercise. Significant (p < 0.05) relationships were found between changes in BB shear modulus and BA shear modulus (r = 0.874), BB+BA shear modulus (r = 0.977), UTF (r = 0.681), and MVC (r = -0.538). Significant (p < 0.05) relationships were also observed between changes in BA shear modulus and BB+BA shear modulus (r = 0.957), UTF (r = 0.682), MVC (r = -0.522), and ROM (r = -0.600). Moreover, significant (p < 0.05) relationships were observed between changes in BB+BA shear modulus and UTF (r = 0.703), MVC (r = -0.549), and ROM (r = -0.547). These results indicate that shear modulus of each muscle (i.e., BB and BA) provide more precise information about muscle damage than UTF, MVC and ROM.

The Effect of Contrast Water Therapy on Dehydration during Endurance Training Camps in Moderate-Altitude Environments.

The effects of contrast water therapy (CWT) on dehydration at moderate altitudes during training camps remain unknown. We hypothesized that CWT reduces dehydration resulting from training at moderate altitudes and improves performance, akin to conditions at sea level. A 13-day endurance training camp was held at a moderate altitude of 1100 m and included 22 university athletes, who were divided into two groups (CWT group, n = 12; control (CON) group, n = 10). The sample size was calculated based on an α level of 0.05, power (1 ß) of 0.8, and effect size of 0.25 based on two-way ANOVA. Longitudinal changes over 13 days were compared using a two-group comparison model. Additionally, 16 athletes participated in an additional performance verification analysis. Subjective fatigue, body mass, and water content (total body water (TBW), extracellular water (ECW), and intracellular water) were measured using bioimpedance analysis every morning, and the titin N-terminal fragment in urine (UTF) was measured as an index of muscle damage. For performance verification, 10 consecutive jump performances (with the reactive strength index (RSI) as an indicator) were evaluated as neuromuscular function indices. The results indicated that the UTF did not significantly differ between the two groups. Moreover, the ECW/TBW values, indicative of dehydration, on days 4 and 5 in the CWT group were significantly lower than those in the CON group. However, there was no significant difference in RSI between the two groups. Therefore, although CWT reduces dehydration in the early stages of the training camp, it may not affect performance.

Polypharmacy-Related Shock Symptoms and Complications Associated with Phenothiazine: A Case Report.

This report describes a case of shock symptoms in a 72-year-old woman with epilepsy who had been in a state of polypharmacy, taking multiple antipsychotic drugs. After receiving a normal dose of periciazine, she exhibited impaired consciousness, hypothermia, and hypotension and was admitted to hospital. Despite poor response to vasopressors, conservative treatment led to gradual improvement. Subsequent pharmacokinetic analysis showed non-toxic blood concentrations of periciazine, suggesting that even small doses of phenothiazines could result in toxic symptoms. This case highlights the importance of monitoring for adverse reactions when prescribing multiple antipsychotic drugs, particularly in older polypharmacy patients.

Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study.

BACKGROUND: Patients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC. METHODS: We reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists. RESULTS: During the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7-14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p < 0.001) from 5.9 to 9.1 g/dL, and the median volume of red blood cell transfusion tended (p = 0.052) to decrease, from 1120 mL (range 280-3360 mL) to 280 mL (range 0-5560 mL) following the PRT. The median overall survival (OS) was 52 days (95% confidence interval [CI] 39-317). Of the 14 patients in whom hemostasis was achieved following PRT, chemotherapy could be started/resumed in seven patients (50%), and the median OS in these patients was 260 days (95% CI 76-not evaluable [NE]). Three patients experienced rebleeding (21.4%), on days 16, 22, and 25, after the start of PRT. CONCLUSION: This study showed that PRT is an effective and safe treatment modality for tumor bleeding in patients with unresectable PC.

Force-Velocity Profiling During the Braking Phase of Countermovement Jump: Relationship to Eccentric Strength and Validity of the 2-Point Method.

ABSTRACT: Nishiumi, D, Yamaguchi, S, Kurokawa, T, Wakamiya, K, and Hirose, N. Force-velocity profiling during the braking phase of countermovement jump: Relationship to eccentric strength and validity of the 2-point method. J Strength Cond Res 37(11): 2141-2148, 2023-The aims of this study were threefold: to investigate the force-velocity profile during the braking phase (bFVP) of the countermovement jump (CMJ) and its relationship with other performance indicators, and whether it could be measured using the two-point method. Sixteen trained men performed 6 different loaded CMJs (0%, 32 kg, 60, 80, 100, and 120% body mass), and eccentric strength measurements were determined. Scatter plots were created using the mean force and velocity during the braking phase of each loaded CMJ. The corrected Akaike's information criterion (AICc) was calculated by fitting linear, quadratic, and cubic regression equations to the bFVP and compared using the 1-way analysis of variance and Bonferroni's post hoc tests. A correlation analysis was performed between the bFVP and other performance indicators. A bias assessment was performed to validate the 2-point method of the bFVP. The significance level was set at p < 0.05. The AICc in the linear regression equation was significantly lower (p < 0.05) than those in the other regression equations. Significant correlations were found between the slope and theoretical maximum force of the bFVP obtained from the linear regression equation and eccentric 1 repetition maximum. The acceptable condition for bias was met by 0-120%. The bFVP is likely to have a linear relationship and can be associated with eccentric strength. Furthermore, the 2-point method in bFVP has validity.

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).

Translocation of nuclear chromatin distribution to the periphery reflects dephosphorylated threonine-821/826 of the retinoblastoma protein (pRb) in T24 cells treated with Bacillus Calmette-Guérin.

The standard treatment for non-muscle-invasive bladder cancer is intravesical Bacillus Calmette-Guérin (BCG) therapy, which is considered the only intravesical therapy that reduces the risk of progression to muscle-invasive cancer. BCG unresponsiveness, in which intravesical BCG therapy is ineffective, has become a problem. It is thus important to evaluate the effectiveness of BCG treatment for patients as soon as possible in order to identify the optimal therapy. Urine cytology is a noninvasive, easy, and cost-effective method that has been used during BCG treatment, but primarily only to determine benign or malignant status; findings concerning the efficacy of BCG treatment based on urine cytology have not been reported. We investigated the relationship between BCG exposure and nuclear an important criterion in urine cytology, i.e., nuclear chromatin patterns. We used three types of cultured cells to evaluate nuclear chromatin patterns and the cell cycle, and we used T24 cells to evaluate the phosphorylation of retinoblastoma protein (pRb) in six-times of BCG exposures. The results revealed that after the second BCG exposure, (i) nuclear chromatin is distributed predominantly at the nuclear periphery and (ii) the dephosphorylation of threonine-821/826 in pRb occurs. This is the first report of a dynamic change in the nuclear chromatin pattern induced by exposure to BCG. Molecular findings also suggested a relationship between this phenomenon and cell-cycle proteins. Although these results are preliminary, they contribute to our understanding of the cytomorphological changes that occur with BCG exposure.

Changes in Muscle Shear Modulus and Urinary Titin N-Terminal Fragment after Eccentric Exercise.

This study aimed to investigate the relationship between the muscle shear modulus of the biceps brachii, urinary titin N-terminal fragment (UTF), and other damage markers after eccentric exercise. Seventeen healthy males performed five sets of ten eccentric exercises with dumbbells weighing 50% of the maximum voluntary contraction (MVC) at the elbow joint. Muscle shear modulus with range of interest set to only biceps brachii muscle measured by ultrasound shear wave elastography, UTF, MVC, range of motion (ROM), and soreness (SOR) were recorded before, immediately after, and 1, 24, 48, 72, 96, and 168 h after eccentric exercise. Each marker changed in a time course pattern, as found in previous studies. The peak shear modulus showed a moderate negative correlation with peak MVC (r = -0.531, P < 0.05) and a strong positive correlation with peak UTF (r = 0.707, P < 0.01). Our study results revealed a significant relationship between muscle strength, shear modulus measured by ultrasound SWE, and titin measured by UTF, as a non-invasive damage marker after eccentric exercise to track changes in EIMD.

Diagnostic accuracy of ultra-low-dose CT colonography for the detection of colorectal polyps: a feasibility study.

PURPOSE: The aim of this feasibility study was to evaluate the diagnostic accuracy of ultra-low-dose CT colonography using iterative reconstruction algorithms with reference to standard colonoscopy. MATERIALS AND METHODS: Prior to this study, a phantom study was performed to investigate the optimal protocol for ultra-low-dose CT colonography. A total of 206 patients with average/high risk of colorectal cancer were recruited. After undergoing full bowel preparation, the patients were scanned in the prone and supine positions with the CT conditions set to 120 kV, standard deviation 45 to 50, and an adaptive iterative reconstruction algorithm applied. Two expert readers read the images independently. The main outcome measures were the per-patient and per-polyp accuracies for the detection of polyps ≥ 10 mm, with colonoscopy results as the reference standard. RESULTS: Two hundred patients (102 females, mean age 67.5 years) underwent both ultra-low-dose CT colonography and colonoscopy on the same day. The mean radiation exposure dose was 0.64 ± 0.34 mSv. On colonoscopy, 39 patients had 45 polyps ≥ 10 mm (non-polypoid morphology 7), including 4 cancers. Per-patient sensitivity, specificity, and accuracy of CT colonography for polyps ≥ 10 mm were 0.74, 0.96, and 0.92 for reader one, and 0.74, 0.99, and 0.94 for reader two, respectively. Per-polyp sensitivities for polyps ≥ 10 mm were 0.73 for reader one and 0.71 for reader two. On subgroup analysis by morphology, non-polypoid polyps ≥ 10 mm were not detected by both readers. CONCLUSION: Extreme ultra-low-dose CT colonography had an insufficient diagnostic performance for the detection of polyps ≥ 10 mm, because it was unable to detect non-polypoid polyps. This study showed that the problem with ultra-low-dose CT colonography was the lack of detectability of small-size polyps, especially non-polypoid polyps. To use ultra-low-dose CT colonography clinically, it is necessary to resolve the problems identified by this study.

Increase in foot arch asymmetry after full marathon completion.

Long-distance running results in lowering of the foot medial longitudinal arch, but it is unknown whether the left and right arches decrease equally. This study aimed to determine whether foot arch asymmetry increases upon completion of a full marathon and to identify factors capable of explaining the degree of asymmetry of navicular height and navicular height displacement. The three-dimensional foot posture data of 74 collegiate runners were obtained using an optical foot scanner system before (PRE) and immediately after (POST) a full marathon. The navicular height and arch height ratio (normalised navicular height by foot length) of both feet significantly decreased from PRE to POST full marathon completion (44.3 ± 6.3 mm versus 40.8 ± 6.5 mm, 17.8 ± 2.5 versus 16.6 ± 2.7, respectively; p < 0.001, both). The asymmetry of the arch height ratio was significantly greater POST than PRE marathon. Multiple linear regression analysis indicated that the POST-race Asymmetry Index (AI) of navicular height was significantly predicted by the PRE-race AI of navicular height; navicular height displacement was predicted by PRE-race navicular height and the marathon time. Full marathon running induced increasing asymmetry and lowering of the medial longitudinal arch in runners.

Changes in Urinary Titin N-terminal Fragment Concentration after Concentric and Eccentric Exercise.

We aimed to compare the urinary titin N-terminal fragment (UTF) concentration after concentric and eccentric exercise and to clarify the specific response of UTF to exercise-induced muscle damage (EIMD). Nine healthy young men performed 30 concentric elbow flexion exercises with maximum effort, rested for at least eight weeks, and performed eccentric exercises at the same workload using the same arm. Changes in the maximal voluntary isometric contraction (MVIC), muscle soreness (SOR), range of motion (ROM), serum creatine kinase (CK) activity, and UTF concentrations were recorded before and after for six consecutive days after exercise. There was no significant difference in workload during exercise between the two exercise types. However, serum CK activity increased after eccentric exercise (p < 0.05). Additionally, MVIC, SOR, ROM, and UTF concentration were significantly higher after eccentric exercise than after concentric exercise (p < 0.05). Although workload was the same, the UTF concentration greatly increased after eccentric exercise. Based on these results, we suggest that UTF can be a non-invasive and highly specific biomarker of EIMD.

Effects of rest interval array on training volume, perceived exertion, neuromuscular fatigue, and metabolic responses during agonist-antagonist muscle alternative training.

BACKGROUND: Agonist-antagonist muscle superset (SS) and paired-set (PS) strength training protocols enable the completion of training activities within a shorter period of time than traditional set. The purpose of this study was to investigate the effects of PS and SS through total volume (TV), set volume (SV), blood lactate concentration (LAC), rating of perceived exertion (RPE), and neuromuscular fatigue index (FInsm5). METHODS: Eleven males who train recreationally performed PS and SS consisting of bent-over row (BOR) and bench press (BP). In performing the PS, a single bout of BOR was followed by a rest interval of 60 seconds, the BP was then performed and followed by another rest interval of 60 seconds. When the SS was performed, a single bout of BOR and a single bout of BP were performed consecutively and followed by a single rest interval of 120 seconds. The exercise configurations were repeated until five sets were completed. The TV was calculated by multiplying the number of successful repetitions and the load. The LAC and RPE were measured at predetermined times. Electromyographic signals were recorded for use in the FInsm5 calculation. RESULTS: The RPE indicated that PS was significantly lower than SS (P<0.01). No significant differences between PS and SS were discovered in SV, TV, LAC, and FInsm5. CONCLUSIONS: This study demonstrates that PS has lower perceived exertion than SS when agonist-antagonist strength training protocols are selected as the training structure.

Changes in urinary titin N-terminal fragments as a biomarker of exercise-induced muscle damage in the repeated bout effect.

OBJECTIVES: Muscle damage symptoms induced by unaccustomed eccentric contraction exercise can be reduced by repeating the experience several times. This phenomenon is termed the repeated bout effect. Although traditional biochemical markers require invasive blood sampling, biochemical measurements have recently been developed that can be non-invasively performed using urinary titin N-terminal fragment (UTF). However, it is unclear whether UTF can reflect the repeated bout effect. Therefore, the aim of the present study was to clarify whether UTF decreased with the repeated bout effect. DESIGN: This study compared changes in muscle damage markers between bouts of exercise performed for the first and second time. METHODS: Eight young men performed 30 eccentric exercises of the elbow flexor on the first day of the first week (Bout 1). A second bout of eccentric exercises, same as the first, was performed 2 weeks later, (Bout 2). The dependent variables were muscle soreness (SOR), maximal voluntary isometric contraction (MVIC), range of motion (ROM), creatine kinase (CK), and UTF. All dependent variables were analyzed using two-way analysis of variance. RESULTS: No significant difference was observed in workload or peak torque between the first and second exercise bouts. SOR as well as CK and UTF were significantly lower and ROM and MVIC were significantly higher in Bout 2 in comparison to Bout 1. CONCLUSIONS: These results suggest that UTF sensitively reflects the repeated bout effect and exercise-induced muscle damage can be non-invasively measured.

Nuclear co-expression of p21 and p27 induced effective cell-cycle arrest in T24 cells treated with BCG.

A proposed mechanism underlying the effect of bacillus Calmette-Guérin (BCG) treatment for bladder cancer cells is as follows: BCG-induced crosslinking of cell-surface receptors results in the activation of signaling cascades, including cell-cycle regulators. However, the clinical significance of cell-cycle regulators such as p21 and p27 is controversial. Here we investigated the relationship between BCG exposure and p21 and p27. We used confocal laser microscopy to examine the expression levels of pKi67, p21 and p27 in T24 cells (derived from human urothelial carcinoma) exposed six times to BCG. We performed dual immunofluorescence staining methods for p21 and p27 and observed the localization of nuclear and cytoplasm expressions. We investigated the priority of p27 over p21 regarding nuclear expression by using p27 Stealth RNAi™ (p27-siRNA). With 2-h BCG exposure, the nuclear-expression level of p21 and p27 was highest, while pKi67 was lowest. The percentage of double nuclear-expression of p21 and p27 in BCG cells was significantly higher than that in control cells during the 1st to 6th exposure (P < 0.05), and the expression of pKi67 showed the opposite of this pattern. Approximately 10% of the nuclear p21 was independent of p27, whereas the cytoplasmic p21 was dependent on p27. Our results suggested that the nuclear co-expression of p21 and p27 caused effective cell-cycle arrest, and thus the evaluation of the nuclear co-expression of p21 and p27 might help determine the effectiveness of BCG treatment.