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Organic anion-transporting polypeptide 1A2 (OATP1A2) is a drug uptake transporter known for broad substrate specificity, including many drugs in clinical use. Therefore, genetic variation in SLCO1A2 may have important implications to the disposition and tissue penetration of substrate drugs. In the present study, we demonstrate OATP1A2 protein expression in human brain capillary and renal distal nephron using immunohistochemistry. We also determined the extent of single nucleotide polymorphisms

Carrier-mediated processes, often referred to as transporters, play key roles in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney. The renal proximal tubule is the primary site of active transport for a wide variety of substrates, including organic anions/cations, peptides, and nucleosides. During the past decade, significant advances in molecular identification and characterization of transporter proteins have been made. Although it is generally noted tha

Organic anion transporting polypeptide 1B3 (OATP1B3, SLCO1B3) is normally expressed in hepatocytes. In this study, we showed frequent overexpression of OATP1B3 in colorectal adenocarcinomas. Quantitative reverse transcription-PCR analysis of 17 colon tumors indicated tumoral overexpression of OATP1B3 by approximately 100-fold, compared with 20 normal colon samples (P < 0.0001). Using immunohistochemistry on a tissue microarray containing 93 evaluable colon tumor specimens, we detected immunostai

Abstract Learning Objectives After completing this course, the reader will be able to: Explain how genetic factors contribute to variability in drug response. Apply this understanding to clinical outcomes in patients treated with specific chemotherapy agents. Describe approaches for improving clinical cancer therapy and cancer drug development. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Interindividual differences in tumor respons

OATP1B3 is a member of the OATP (organic anion transporting polypeptides) superfamily, responsible for mediating the transport of numerous endogenous and xenobiotic substances. Although initially reported to be exclusively expressed in the liver, several studies reported that OATP1B3 is frequently expressed in multiple types of cancers and may be associated with differing clinical outcomes. However, a detailed investigation on the expression and function of OATP1B3 protein in cancer has been lac

Carfilzomib is a novel class of peptidyl epoxyketone proteasome inhibitor and has demonstrated promising activity in multiple clinical trials to treat patients with multiple myeloma and other types of cancers. Here, we investigated molecular mechanisms underlying acquired resistance to carfilzomib and a potential strategy to restore cellular sensitivity to carfilzomib. H23 and DLD-1 cells (human lung and colon adenocarcinoma cell lines) with acquired resistance to carfilzomib displayed marked cr

genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modi

OBJECTIVE: To determine whether NMLR has more statistical strength than NLR in discriminating TB from non-TB infectious lung diseases. METHODS: Among patients who underwent 3 or more TB culture tests with molecular study between January 2016 and December 2017, 110 patients with TB, and 159 patients diagnosed with non-TB infectious lung diseases were enrolled. The original complete blood count (CBC) parameters and modified CBC indices, including NLR and NMLR, were analyzed. RESULTS: The NLR and N

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed

The discovery of NF-κB signaling pathways has greatly enhanced our understanding of inflammatory and immune responses. In the canonical NF-κB pathway, the proteasomal degradation of IκBα, an inhibitory protein of NF-κB, is widely accepted to be a key regulatory step. However, contradictory findings have been reported as to whether the immunoproteasome plays an obligatory role in the degradation of IκBα and activation of the canonical NF-κB pathway. Such results were obtained mainly using traditi