Clinical response and pharmacokinetics of bendamustine as a component of salvage R-B(O)AD therapy for the treatment of primary central nervous system lymphoma (PCNSL)

Abstract Background A relatively high proportion of patients diagnosed with primary CNS lymphoma will experience recurrent disease, yet therapy options are limited in salvage therapy. This is the first study to evaluate a bendamustine-based combination regimen for the treatment of relapsed/refractory PCNSL and to characterize bendamustine pharmacokinetics in the human CSF. Methods Patients received bendamustine 75 mg/m2 for two days as part of R-B(O)AD administered intravenously every 4 weeks for up to 4 cycles. Response and adverse events of the regimen were assessed. A sparse sampling strategy and population based modeling approach was utilized for evaluation of plasma and CSF levels of bendamustine. Results Ten patients were enrolled into study of whom 70% were of refractory disease and with high IELSG prognostic risk scores. The ORR of R-BOAD was 50% (95% CI, 0.24 to 0.76) with one patient achieving CR and four PR. Primary toxicity of the regimen was reversible myelosuppression, mostly grade 3 or 4 neutropenia. The Cmax mean for plasma and CSF were 2669 ng/mL and 0.397 ng/mL, respectively, and patients with response at deep tumor sites displayed higher trends in peak exposure. Pharmacokinetic data was best described by a four-compartment model with first-order elimination of drug from central plasma and CSF compartments. Conclusions R-BOAD is an effective salvage option for PCNSL, but with significant hematologic toxicity. Bendamustine CSF levels are minimal; however correspond to plasma exposure and response. Trial registration ClinicalTrials.gov NCT03392714; retrospectively registered January 8, 2018

Effect of Rumen Protected Methionine and α-Tocopherol on Growth Performance, Carcass Characteristics, and Meat Composition of Late Fattening Hanwoo Steer in High-Temperature Seasons

This study was conducted to investigate the effects of rumen-protected methionine and α-tocopherol (RPMT) on growth performance, carcass characteristics, and meat composition of late fattening Hanwoo steers in high-temperature seasons. Fourteen steers were randomly assigned to one of two diets; control (commercial concentrate) and treatment (commercial concentrate + 20 g of RPMT). Average daily gain was 34% higher in the treatment group than in the control group; however, there was no significant difference due to the small number under investigation. Feed conversion ratio was lower in the treatment group than in the control group (p < 0.05). Supplementation of RPMT had little effect on the fatty acid composition of longissimus muscle. Metmyoglobin in the longissimus muscle was significantly lower in treatment group compared to the control group at the ninth day of storage (p < 0.05). The redness of the longissimus muscle was higher in the treatment group than in the control group on day 9 of storage (p < 0.01). Thus, the results suggest that RPMT have positive effects on growth performance, and Commission Internationale de l’Eclairage color stability in the longissimus muscle of late fattening Hanwoo steers in high-temperature seasons

Naïve CD8+ T cell derived tumor-specific cytotoxic effectors as a potential remedy for overcoming TGF-β immunosuppression in the tumor microenvironment

Despite of the potential implications for cancer immunotherapy, conventional approaches using in vitro expanded CD8(+) T cells have suboptimal outcomes, mostly due to loss of functionality from cellular exhaustion. We therefore investigated the phenotypic and functional differences among in vitro activated CD8(+) T cells of three different sources, namely naïve (NTeff), memory (MTeff) and tumor-infiltrating lymphocytes (TILeff) from human and mice, to better understand mechanisms behind potent effector functions and potential for overcoming current limitations. In line with the greater proliferation activity and longer telomere lengths of NTeff populations, cells of naïve origin exhibited significantly less amounts of T cell exhaustion markers than those of MTeff and TILeff, and moreover, acquired distinct expression patterns of memory-promoting transcription factors, T-bet and Eomes, induced in a rapid and sustainable manner. NTeff cells appeared to have lower expression of Foxp1 and were refractory to apoptosis upon TGF-β conditioning, implying better survival potential and resistance to tumor-induced immune suppression. Of CD8(+) T cell pools activated to tumor-specific CTLs, naïve cell generated effectors possessed the most potent cytotoxic activity, validating implications for use in rational design of adoptive immunotherapy

Wearable Shoe-Mounted Piezoelectric Energy Harvester for a Self-Powered Wireless Communication System

This study covers a self-powered wireless communication system that is powered using a piezoelectric energy harvester (PEH) in a shoe. The lead-zirconate-titanate (PZT) ceramic of the PEH was coated with UV resin, which (after curing under UV light) allowed it to withstand periodic pressure. The PEH was designed with a simple structure and placed under the sole of a shoe. The durability of the PEH was tested using a pushing tester and its applicability in shoes was examined. With periodic compression of 60 kg, the PEH produced 52 μW of energy at 280 kΩ. The energy generated by the PEH was used to power a wireless transmitter. A step-down converter with an under-voltage lockout function was used to gather enough energy to operate the wireless transmitter. The transmitter can be operated initially after walking 24 steps. After the transmitter has been activated, it can be operated again after 8 steps. Because a control center receives signals from the transmitter, it is possible to check the status of workers who work outside at night or mostly alone, to detect emergencies