The pharmacokinetic profile and B-cell response to Reditux™ are comparable with those reported for MabThera™. Thus, MabThera™ can be substituted with Reditux™ for the treatment of B-cell lymphomas.
Imatinib is the standard first line treatment for chronic myeloid leukemia (CML). Owing to dose-related toxicities of Imatinib such as neutropenia, there is scope for treatment optimization through therapeutic drug monitoring (TDM). Trough concentration of 1 μg/mL is considered the therapeutic threshhold. Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation. Hence, Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration. Three approaches: conventional Raman spectroscopy (CRS), Drop coating deposition Raman (DCDR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) were employed to detect the required trough concentration of 1 μg/mL and above. Detection of therapeutically relevant concentrations (1 μg/mL) using SERS and suitable nanoparticle substrates has been demonstrated. Prospectively, rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.
Single-cell (scSeq) and single-nucleus sequencing (snSeq) are powerful tools to investigate cancer genomics at single cell resolution. Multiple studies have recently illuminated intratumoral heterogeneity in glioblastoma, however, the majority focused on molecular complexity of tumor cells, without considering unexplored host cell types that contribute to the microenvironment around tumor. To address the glioblastoma microenvironment composition and potential tumor-host interactions, we performed deep coverage sequencing of freshly resected primary GBM patient tissue without implementing any tumor enrichment strategies. The sequencing resulted in 902 cells and 1186 nuclei, respectively, passing quality control and with low mitochondrial gene percentage. We customized reference transcriptome by listing gene transcript loci as exons to take into account immature RNA, which greatly improved the alignment rate for singlenucleus data. We applied Cell Ranger pipelines (Version 3.0.2) and Seurat package (Version 2.3.1) and discovered 10 clusters in both scSeq and snSeq. Pathway analysis of each cluster signature in scSeq data along with known GBM microenvironment cell signatures revealed glioma tumor population along with surrounding microglia/macrophages, astrocytes, pericytes, oligodendrocytes, T cells and endothelial cells. The analysis of snSeq was able to capture the majority of cell types from patient tissues (tumor and microenvironment cells), but interestingly presented different cell type composition in microenvironment cell types such as microglia/macrophages. Integrating single-cell and single-nucleus transcriptomic data using canonical correlation analysis facilitated a comparison of snSeq and scSeq, contrasting depiction for certain cell types (e.g. NKX6-2 gene in Oligodendrocytes). Differential analysis of pathways between tumor and microenvironment cells unveiled potentially rewired pathways such as double strand break repair pathway. Our results demonstrate the cellular diversity of brain tumor microenvironment and lay a foundation to further investigate the individual tumor and host cell transcriptomes that are influenced not only by their cell identity but also by their interaction with surrounding microenvironment.
Method of administration markedly affects 13-cisRA pharmacokinetics in Indian neuroblastoma patients, supporting similar findings in UK patients. An appropriate oral liquid formulation of 13-cisRA that can be administered to all children with neuroblastoma is urgently needed on an international level.
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