Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

A prospective study of the relationship between CRPC patient's quality of life after enzalutamide and serum testosterone levels measured via LC-MS/MS.

BACKGROUND: Enzalutamide (ENZ) is used in the treatment of patients with castration-resistant prostate cancer (CRPC). The quality of life (QoL) of CRPC patients during ENZ treatment is very important, but predictive markers of QoL have not been identified. We investigated the relationship between the serum testosterone (T) level before ENZ treatment and QoL changes in CRPC patients. PATIENTS AND METHODS: This prospective study was conducted between 2014 and 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients in whom QoL could be evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire at baseline, and after 4 and 12 weeks of ENZ treatment. Serum T levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The study population of 95 patients had a median age of 72 years and median prostate-specific antigen level of 21.6 ng/mL. The median overall survival from the commencement of ENZ treatment was 26.8 months. The median serum T level before ENZ treatment was 50.0 pg/mL. The mean total FACT-P scores at baseline, and after 4 and 12 weeks of ENZ treatment, were 95.8, 91.7, and 90.1, respectively. Differences in FACT-P scores between the high T level (High-T) group and low T level (Low-T) group (distinguished based on median split of the T level) were examined. The mean FACT-P scores were significantly higher in the High-T than Low-T group after both 4 and 12 weeks of ENZ treatment (98.5 vs. 84.6 and 96.4 vs. 82.2, respectively, both p < 0.05). The mean FACT-P score was significantly lower in the Low-T group after 12 weeks than before ENZ treatment (p < 0.05). CONCLUSION: The serum T level before treatment may be useful for predicting QoL changes after ENZ treatment in CRPC patients.

Avelumab plus axitinib therapy for renal cell carcinoma in a patient with pulmonary alveolar proteinosis: A case report.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the abnormal accumulation of surfactant-derived substances in the lungs. To the best of our knowledge, the successful treatment of metastatic renal cell carcinoma in patients with PAP has not been reported. Here, we describe such treatment of a patient via avelumab plus axitinib therapy. After four courses of treatment, computed tomography showed size reduction of the pulmonary metastatic nodule and improvement of PAP. This study highlights that avelumab plus axitinib therapy is a safe and effective treatment option for metastatic renal cell carcinoma, even in patients with PAP.

A Prospective Study of the Relationship Between Clinical Outcomes After Enzalutamide and Serum Androgen Levels Measured via Liquid Chromatography-tandem Mass Spectrometry in Patients with Castration-resistant Prostate Cancer.

BACKGROUND: Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. OBJECTIVE: To elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. DESIGN SETTING AND PARTICIPANTS: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: The median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs <12.5 g/dl), docetaxel treatment history (no vs yes), and DHT level (≥5.9 vs <5.9 pg/ml) were significant predictors of PSA-PFS (p < 0.05). Eastern Cooperative Oncology Group performance status (0 vs. 1-2), hemoglobin level (≥12.5 vs <12.5 g/dl), presence of visceral metastasis (no vs yes), amount of bone metastasis (extent of disease 0-2 vs 3-4), and docetaxel treatment history (no vs yes) were significant predictors of OS (p < 0.05). Binomial logistic analysis of the predictors of any grade of anorexia, malaise, and fatigue showed that the presence of visceral metastasis and a low DHT level (<5.9 pg/ml) were significant. CONCLUSIONS: Our results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events. PATIENT SUMMARY: We measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. We found that the levels of these hormones may be useful for predicting the efficacy of enzalutamide treatment, prognosis, and the occurrence of adverse side effects.

Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

BACKGROUND: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). METHODS: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales. RESULTS: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). CONCLUSION: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.

Oral administration of melatonin contained in drinking water increased bone strength in naturally aged mice.

Melatonin has recently been found to be a possible new regulator of bone metabolism. However, the influence of melatonin in natural age-related osteoporosis has not been fully elucidated yet, although there have been some reports regarding postmenopausal osteoporosis with melatonin treatments. The present study investigated the effects of long-term melatonin administration during the aging process on bone metabolism. Using quantitative computed tomography methods, we found that the total bone density of both the femur metaphysis and diaphysis decreased significantly in 20-month-old male mice. In the metaphysis, both trabecular bone mass and Polar-Strength Strain Index (SSI), which is an index of bone strength, decreased significantly. Judging from bone histomorphometry analysis, trabecular bone in 20-month-old male mice decreases significantly with age and is small and sparse, as compared to that of 4-month-old male mice. Loss of trabecular bone is one possible cause of loss of bone strength in the femoral bone. In the metaphysis, the melatonin administration group had significantly higher trabecular bone density than the non-administration group. The Polar-SSI, cortical area, and periosteal circumference in the diaphysis was also significantly higher with melatonin treatments. Since the melatonin receptor, MT2, was detected in both osteoblasts and osteoclasts of the femoral bone of male mice, we expect that melatonin acts on osteoblasts and osteoclasts to maintain the bone strength of the diaphysis and metaphysis. Thus, melatonin is a potential drug for natural age-related osteoporosis.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Melatonin is a potential drug for the prevention of bone loss during space flight.

Astronauts experience osteoporosis-like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O-methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast-inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.

An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression.

BACKGROUND: Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA velocity (PSAV) while monitoring oncologic outcomes and survival in Japanese patients. METHODS: We analyzed a total of 241 patients with mCRPC who were treated with ENZ. The patients' median age was 75 ± 7.9 years (range, 53-93 years). There were 171 (71%) predocetaxel cases, and 70 (29%) post docetaxel cases. PSA-progression-free survival (PFS) and overall survival (OS) were assessed according to Prostate Cancer Working Group 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1595). RESULTS: We observed 77 good response (GR; case in which PSA remained low after treatment) cases (31.9%), 125 acquired resistance (AR; decline in PSA after treatment followed by progression) cases (51.9%), and 39 primary resistance (PR; lack of decline in PSA) cases (16.2%). Predocetaxel, PSA-PFS, and OS were significantly higher compared with post docetaxel (PSA-PFS: 47.0 vs 13.4 weeks, P < .001; OS: not yet reached vs 80.7 weeks, P < .001). Multivariate analysis of prognostic factors, including PSA response at 4 weeks, was performed using Cox regression analysis. ECOG PS (0 vs 1-2), hemoglobin (Hb; ≥ 12.2 vs < 12.2 g/dL), time to CRPC ( ≥ 12 vs < 12 m), docetaxel treatment history (no vs yes), and a PSA reduction of 50% at 4 weeks were significant predictors of OS (all, P < .05). In cases of AR (n = 125), multivariate analysis showed that PSA kinetic factors, such as PSADT and PSAV (ng/mL/m), Hb, time to CRPC, PSADT ( ≥ 2 vs < 2 m), and PSAV ( < 20 vs ≥ 20 ng/mL/m), were all predictive of OS following PSA-progression (P < .05). CONCLUSIONS: Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostic factor for mCRPC patients.

Long working hours and skipping breakfast concomitant with late evening meals are associated with suboptimal glycemic control among young male Japanese patients with type 2 diabetes.

AIMS/INTRODUCTION: To assess the associations of working conditions, eating habits and glycemic control among young Japanese workers with type 2 diabetes. MATERIALS AND METHODS: This hospital- and clinic-based prospective study included 352 male and 126 female working patients with diabetes aged 20-40 years. Data were obtained from June to July 2012 and June to July 2013. Logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for suboptimal glycemic control (glycosylated hemoglobin level of ≥7%) obtained from June to July 2013. RESULTS: Multivariable logistic regression analysis showed that disease duration of ≥10 years (OR 2.43, 95% CI 1.02-5.80), glycosylated hemoglobin level of ≥7% in 2012 (OR 8.50, 95% CI 4.90-14.80), skipping breakfast and late evening meals (OR 2.50, 95% CI 1.25-5.00) and working ≥60 h/week (OR 2.92, 95% CI 1.16-7.40) were predictive of suboptimal glycemic control in male workers, whereas a glycosylated hemoglobin level of ≥7% in 2012 (OR 17.96, 95% CI 5.93-54.4), oral hyperglycemic agent therapy (OR 12.49, 95% CI 2.75-56.86) and insulin therapy (OR 11.60, 95% CI 2.35-57.63) were predictive of suboptimal glycemic control in female workers. CONCLUSIONS: Working ≥60 h/week and habitual skipping breakfast concomitant with late evening meals might affect the ability of young male workers with type 2 diabetes to achieve and maintain glycemic control.

[USEFULNESS OF VIVID (VISUALIZATION OF VARIOUS INTEGRATION WITH DIFFUSION) ON COGNITIVE FUSION PROSTATE BIOPSY].

(Purpose) We created an image reconstructing multiparametric MRI system called VIVID (Visualization of Various Integration with Diffusion) and examined the efficacy of VIVID in detecting prostate cancer. (Methods and materials) The subjects were 80 patients who underwent one target biopsy with reference to MRI images in addition to 8-20 biopsies. (Results) The significant cancer detection rate was 61%, the significant cancer detection rate of PI-RADS 4 or 5 was 55%, and the significant cancer detection rate of VIVID score 4 or 5 was 55%. Three cases with PI-RADS 4 at TZ lesion with positive T2WI only were evaluated as having VIVID scores 1 or 2. Cancer was not detected with target biopsy from the site. (Conclusion) Our finding suggest that VIVID correctly excludes TZ lesions with only T2WI positively in multiparametric MRI.

[CLINICAL OUTCOMES OF ABIRATERONE ACETATE FOR TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER: A RETROSPECTIVE ANALYSIS].

(Objective) We retrospectively evaluated the clinical efficacy and safety of abiraterone acetate (AA) in patients with castration-resistant prostate cancer (CRPC). (Methods) We analyzed the clinical records of 50 patients who had received AA in Gunma Cancer Center between October 2014 and June 2017. We assessed the response of prostate-specific antigen (PSA) to AA, and analyzed the association between overall survival and various parameters, including the types of primary hormonal therapy, PSA level, Gleason score, time to CRPC, prior treatment with enzalutamide (Enz) and docetaxel, and sites of metastases. (Results) The median patient age was 74.5 years and median PSA level at baseline was 15.9 ng/ml; 39 (78%) patients had Gleason score ≥8. Eleven (45.8%) of the 24 docetaxel-naïve patients achieved >50% reduction in PSA level from baseline as opposed to one (4.5%) of the 22 patients previously treated with docetaxel.Eleven (55%) of the 20 Enz-naïve patients achieved >50% reduction in PSA level from baseline compared to one (3.8%) of the 26 patients previously treated with Enz. The overall survival of the group with time to CRPC >12 months was significantly longer than that of the group with time to CRPC <12 months (p=0.035). In general, AA was tolerated; the most frequently reported adverse events included liver dysfunction (22%) and fatigue (6%). (Conclusion) Our results suggest that AA is tolerated and may be suitable for patients with time to CRPC >12 months.

Renal primitive neuroectodermal tumor with elevated plasma adrenocorticotropic hormone levels: A case report.

INTRODUCTION: Primitive neuroectodermal tumors are small round-cell tumors - Ewing sarcoma family, frequently occurring in the extremities, but rarely in the kidney. CASE PRESENTATION: A 58-year-old woman presented with whole-body edema and weakness of lower limb muscles. Computed tomography revealed a left renal tumor, and the plasma adrenocorticotropic hormone level was elevated. The tumor was surgically removed without complications, her plasma adrenocorticotropic hormone reverted to normal levels, and symptoms disappeared after surgery. Histopathological examination revealed a primitive neuroectodermal tumor arising in her kidney. The patient was alive without metastasis 3 years after the surgery. CONCLUSION: We report the first case of renal primitive neuroectodermal tumor accompanying elevated plasma adrenocorticotropic hormone levels which are thought to be produced and secreted in an ectopic fashion.

Psychological distress in men with prostate cancer and their partners before and after cancer diagnosis: a longitudinal study.

OBJECTIVE: To examine the relative risk of psychological distress of men with prostate cancer and their partners during the period before and after prostate cancer diagnosis compared with men without prostate cancer and their partners. METHODS: The participants reported questionnaires on psychological distress at four time points: before prostate cancer biopsy, and at 1, 3 and 6 months following prostate cancer diagnosis. We performed multiple logistic regression analyses to examine the relative risk of psychological distress. RESULTS: A total of 115 couples answered the questionnaires at all four time points. Men with prostate cancer showed a significantly higher risk of psychological distress compared to men without prostate cancer at 1 (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.9-13.1), 3 (OR = 3.2, 95% CI = 1.1-10.2) and 6 months following prostate cancer diagnosis (OR = 6.9, 95% CI = 2.3-25.7). Their partners showed a significantly higher risk of psychological distress compared to the partners of men without prostate cancer at 1 month following prostate cancer diagnosis (OR = 2.6, 95% CI = 1.1-6.6). CONCLUSIONS: Men with prostate cancer showed psychological distress during the 6 months following the cancer diagnosis. Their partners also showed psychological distress at 1 month following the cancer diagnosis. Inviting both men with prostate cancer and their partners to speak to their concerns, empathizing with them, finding the solutions together and monitoring of their psychological status regularly should be regarded as important following prostate cancer diagnosis.

Socioeconomic status and type 2 diabetes complications among young adult patients in Japan.

OBJECTIVE: To assess the relationship between socioeconomic status (SES) and complications of type 2 diabetes among young adults in Japan. DESIGN: A cross-sectional study. SETTING: Outpatient wards of 96 member hospitals and clinics of the Japan Federation of Democratic Medical Institutions. PARTICIPANTS: A total of 782 outpatients with type 2 diabetes (525 males, 257 females), aged 20-40 years as of March 31, 2012. After excluding 110 participants whose retinopathy diagnosis was in question, 672 participants were analyzed. MEASUREMENTS: We examined the relations between SES (educational level, income, type of public healthcare insurance, and employment status) and diabetes complications (retinopathy and nephropathy) using a multivariate logistic regression analysis. RESULTS: The prevalence of type 2 diabetic retinopathy was 23.2%, while that of nephropathy was 8.9%. The odds of having retinopathy were higher among junior high school graduates (OR 1.91, 95% CI 1.09-3.34), patients receiving public assistance (OR 2.19, 95% CI 1.20-3.95), and patients with irregular (OR 1.72, 95% CI 1.03-2.86) or no employment (OR 2.23, 95% CI 1.36-3.68), compared to those with a higher SES, even after covariate adjustment (e.g., age, gender, body mass index). Similarly, the odds of having nephropathy were higher among patients with middle (OR 3.61, 95% CI 1.69-8.27) or low income levels (OR 2.53, 95% CI 1.11-6.07), even after covariate adjustment. CONCLUSIONS: Low SES was associated with a greater likelihood of type 2 diabetes complications in young adults. These findings suggest the necessity of health policies that mitigate socioeconomic disparity and thereby reduce the prevalence of diabetic complications.

Acceleration of wound healing by ultrasound activation of TiO2 in Escherichia coli-infected wounds in mice.

Surgical site infections continue to be a common complication affecting surgical prognosis. Reactive oxygen species (ROS) are generated by ultrasound-irradiated titanium dioxide (TiO2 ) (UIT). Although excessive ROS production can cause cell damage, ROS at physiological levels mediate beneficial cellular responses, including angiogenesis. This study investigated whether UIT can promote healing of Escherichia coli-infected wounds. We used TiO2 and ultrasound irradiation using an ultrasonography machine at a frequency of 1.0 MHz and intensity of 0.4 W cm-2 . These levels are not bactericidal in vitro; therefore, we could study the effect of UIT on E. coli survival without interference of ultrasound effects. The number of cluster of differentiation 31-positive blood vessels, which are indicative of angiogenesis, was decreased by bacterial infection, and increased at the wound edges in the UIT-treated infected wounds, suggesting upregulation of neovascularization by UIT. Although UIT treatment did not decrease E. coli survival in vivo, it promoted healing of the infected wounds as evidenced by a significant decrease in the wound area in the UIT-treated mice. Our findings demonstrate that UIT promotes wound healing in surgical site infections and suggest beneficial use of the UIT-based approach as a novel therapeutic method to treat infected surgical wounds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2344-2351, 2017.

Sonocatalytic injury of cancer cells attached on the surface of a nickel-titanium dioxide alloy plate.

The present study demonstrates ultrasound-induced cell injury using a nickel-titanium dioxide (Ni-TiO2) alloy plate as a sonocatalyst and a cell culture surface. Ultrasound irradiation of cell-free Ni-TiO2 alloy plates with 1 MHz ultrasound at 0.5 W/cm(2) for 30s led to an increased generation of hydroxyl (OH) radicals compared to nickel-titanium (Ni-Ti) control alloy plates with and without ultrasound irradiation. When human breast cancer cells (MCF-7 cells) cultured on the Ni-TiO2 alloy plates were irradiated with 1 MHz ultrasound at 0.5 W/cm(2) for 30s and then incubated for 48 h, cell density on the alloy plate was reduced to approximately 50% of the controls on the Ni-Ti alloy plates with and without ultrasound irradiation. These results indicate the injury of MCF-7 cells following sonocatalytic OH radical generation by Ni-TiO2. Further experiments demonstrated cell shrinkage and chromatin condensation after ultrasound irradiation of MCF-7 cells attached on the Ni-TiO2 alloy plates, indicating induction of apoptosis.

Targeted and ultrasound-triggered cancer cell injury using perfluorocarbon emulsion-loaded liposomes endowed with cancer cell-targeting and fusogenic capabilities.

This study investigated the targeting and ultrasound-triggered injury of cancer cells using anticancer drug-free liposomes that contained an emulsion of perfluoropentane (ePFC5) and were co-modified with avidin as a targeting ligand for cancer cells and the hemagglutinating virus of Japan (HVJ) envelope to promote liposome fusion with the cells. These liposomes are designated as ePFC5-loaded avidin/HVJ liposomes. ePFC5-loaded liposomes were sensitized to ultrasound irradiation. Liposomes modified with avidin alone (avidin liposomes) showed binding to MCF-7 human breast cancer cells, and liposomes modified with HVJ envelope alone (HVJ liposomes) were found to fuse with MCF-7 cells. The irradiation of MCF-7 cells with 1 MHz ultrasound (30s, 1.2 W/cm(2), duty ratio 30%) combined with ePFC5-loaded avidin/HVJ liposomes resulted in a decrease in cell viability at 1h after irradiation to 43% of that of controls without ultrasound irradiation or liposomes. The cell viability was lower than that of cells treated with ultrasound irradiation with ePFC5-loaded avidin liposomes or ePFC5-loaded HVJ liposomes. This indicates that co-modification of liposome with avidin and HVJ envelope could enhance ultrasound-induced cell injury in the presence of ePFC5-loaded liposomes.

Carbon-ion Radiotherapy for Prostate Cancer: Analysis of Morbidities and Change in Health-related Quality of Life.

AIM: To prospectively evaluate the feasibility of carbon-ion radiotherapy (C-ion RT) for prostate cancer using a new compact-sized accelerator. PATIENTS AND METHODS: Seventy-six patients underwent C-ion RT at our center using a recommended dose fractionation of 57.6 GyE in 16 fractions established at the National Institute of Radiological Sciences. Health-related Quality of Life (HRQOL) assessment was also performed using the Medical Outcome Study 8-items Short Form Health Survey (SF-8) questionnaire. RESULTS: The median follow-up time was 51 months (range=8-58 months). Grade 2 gastrointestinal and genitourinary complications developed in 1 (1.3%) and 5 (6.6%) patients, respectively. Recurrences occurred in 4 patients, and the 4-year biochemical relapse-free rate was 94.6%. The HRQOL scores after C-ion RT were objectively well-maintained. CONCLUSION: Irrespective of the small number of patients of the study, C-ion RT for prostate cancer using the first commercial-based accelerator reproduced the toxicity outcomes at the NIRS.

Saccharification and ethanol fermentation from cholinium ionic liquid-pretreated bagasse with a different number of post-pretreatment washings.

Choline acetate (ChOAc), a cholinium ionic liquid (IL), was compared with 1-ethyl-3-methylimidazolium acetate (EmimOAc) with regard to biomass pretreatment, inhibition on cellulase and yeast, residuals in pretreated biomass, and saccharification and fermentation of pretreated biomass. Irrespective of ChOAc and EmimOAc, cellulose and hemicellulose saccharification of the IL-pretreated bagasse were over 90% and 60%, respectively. Median effective concentrations (EC50) based on cellulase activity were 32 wt% and 16 wt% for ChOAc and EmimOAc, respectively. The EC50 based on yeast growth were 3.1 wt% and 0.3 wt% for ChOAc and EmimOAc respectively. The residuals in IL-pretreated bagasse were 10% and 23% for ChOAc and EmimOAc, respectively, when washed 2 times after pretreatment. Ethanol yield on a bagasse basis were 60% and 24% for ChOAc and EmimOAc, respectively, in the saccharification and fermentation of IL-pretreated bagasse when washed 2 times. ChOAc-pretreated bagasse could be saccharified and fermented with fewer wash times than EmimOAc-pretreated bagasse.