CD8 TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory: deciphering immunogenicity of tumor antigens.

Background: CD8 tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA re-expressing CD8 T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood.

Development of a UPLC-MS/MS method for the therapeutic monitoring of L-asparaginase.

This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic acid-2,3,3-d were extracted from human plasma by protein precipitation with sulfosalicylic acid (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column with 25 mM ammonium formate and 0.

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).

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/m for two days as part of R-B(O)AD administered intravenously every 4 weeks for up to 4 cycles.

Clinical impact of induction treatment modalities and optimal timing of radiotherapy for the treatment of limited-stage NK/T cell lymphoma.

This study retrospectively investigated the optimal timing of radiotherapy (RT) in patients with limited-stage extranodal NK/T-cell lymphoma (ENTKL). Among 158 patients with newly diagnosed stage I/II ENKTL, 61 patients were treated with sequential chemotherapy followed by radiotherapy (SCRT), 55 with concurrent chemoradiotherapy followed by non-anthracycline-based chemotherapy (CCRT/CT), and 42 with chemotherapy (CT) only. The 5-year overall survival (OS) rate did not differ between SCRT (77.

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.

Construction of a database for published phase II/III drug intervention clinical trials for the period 2009-2014 comprising 2,326 records, 90 disease categories, and 939 drug entities.

Objectives: To construct a database of published clinical drug trials suitable for use 1) as a research tool in accessing clinical trial information and 2) in evidence-based decision-making by regulatory professionals, clinical research investigators, and medical practitioners.

Materials: Comprehensive information obtained from a search of design elements and results of clinical trials in peer reviewed journals using PubMed (http://www.ncbi.

Genetic polymorphisms of CASR and cancer risk: evidence from meta-analysis and HuGE review.

Background: CASR gene appears to be involved in cancer biology and physiology. However, a number of studies investigating CASR polymorphisms and cancer risks have presented inconclusive results. Thus, a systematic review and a meta-analysis of the effect of CASR polymorphisms on several cancer risks were performed to suggest a statistical evidence for the association of CASR polymorphisms with cancer risks.

Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1 polymorphisms in patients undergoing allogeneic hematopoietic stem cell transplantation.

Aim: A population pharmacokinetic (PPK) analysis was conducted to describe the influence of GSTA1 polymorphisms on intravenous busulfan in adults undergoing allogeneic hematopoietic stem cell transplantation.

Patients & Methods: A PPK model was developed from 36 patients by a one-compartment model with first-order elimination.

Results: The typical value of clearance and volume of distribution were 11.

Copy number variability analysis of pharmacogenes in patients with lymphoma, leukemia, hepatocellular, and lung carcinoma using The Cancer Genome Atlas data.

Objective: Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset.

Materials And Methods: One hundred and fifty-two pharmacogenes were selected from liver hepatocellular carcinoma, lung squamous cell carcinoma (LUSC), acute myeloid leukemia, and lymphoid neoplasm diffuse large B-cell lymphoma (DLBL).

Pharmacogenomic biomarker information in FDA-approved paediatric drug labels.

Gene maturation differs between paediatric and adult populations, and the extrapolation of adult pharmacogenomic information to paediatrics is not always appropriate. We sought to determine the extent of paediatric pharmacogenomic trial translation into US FDA-approved labels and to evaluate needs for biomarker studies. Using FDA's Table of Genomic Biomarkers and Drugs@FDA website, 38 pharmacogenomic biomarkers in 56 drug labels were identified with possible application in paediatrics.

Use of injectable drugs with oral-formulation alternatives for outpatients in South Korea.

This study analyzed the use of injectable drugs with oral-formulation alternatives in the outpatient setting in South Korea. We conducted a retrospective cross-sectional data analysis using 2008 National Health Insurance claims data. All active ingredients were categorized into dual-formulation ingredients (DFIs) and single formulation ingredients (SFIs), and were identified by the type of healthcare service provider (HSP) and anatomical therapeutic chemical (ATC) group.

Association between interleukin-10 promoter gene polymorphisms and acute graft-versus-host disease after hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Objectives: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk.