The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.

Interacción entre Valsartán y Repaglinida mediada por transportadores hepáticos OATPs (Organic Anion Transporting Polypeptides): a propósito de un caso / Interaction between Valsartan and Repaglinide mediated for hepatic transporters OATPs (Organic Anion Transporting Polypeptides): report of a case

Paciente de 69 años que acude a la farmacia a retirar su medicación. Recientemente ha sido diagnosticado de hipertensión y lleva 20 días en tratamiento con valsartán 160mg. Refiere que no quiere retirar uno de sus tratamientos para la diabetes porque sufre hipoglucemias al tomar el tratamiento con la comida, por lo que no toma la medicación al mediodía. El paciente tiene pautado: sitagliptina 100mg (0/1/0), Repaglinida 1mg (1/2/1), Tamsulosina 0.4mg (0/0/1) y Valsartán 160mg (1/0/0). El valsartán es sustrato del OATP1B1 a la vez que un inhibidor de éste y la repaglinida también. Esto causa una elevación plasmática de la repaglinida, ya que no puede ser metabolizada al tener bloqueado el transportador, lo que explicaría la hipoglucemia. Se le comunica al médico la sospecha de interacción y procede al cambio de medicación del paciente. Sustituye la repaglinida por metformina, lo que lleva al paciente a normalizar su glucemia y a seguir con la tensión controlada

A 69-year-old patient comes to the pharmacist to get his medication. He was recently diagnosed with hypertension and has been taken Valsartan 160mg during the last 20 days. He explains that he does not want to get one of his medicines for his diabetes because he suffers hypoglycemia when he takes the treatment while eating so he does not take it at noon. The patient is prescribed: sitagliptina 100mg (0/1/0), Repaglinida 1mg (1/2/1), Tamsulosina 0.4mg (0/0/1) and Valsartan 160mg (1/0/0). Valsartan is an OATP1B1 substrate and an inhibitor of it too, just as repaglinide. This causes a repaglinide plasma elevation because the transporter is blocked and the repaglinide can not be metabolized. Thus, there is a hypoglycemia. Repaglinide is replaced by Metformina. As a result, the glycaemia’s patient is stabilized and the blood pressure keeps controlled

SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers.

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) separate the brain and cerebrospinal fluid (CSF) from the systemic circulation and represent a barrier to the uptake of both endogenous compounds and xenobiotics into the brain. For compounds whose passive diffusion is limited due to their ionization or hydrophilicity, membrane transporters can facilitate their uptake across the BBB or BCSFB. Members of the solute carrier (SLC) and ATP-binding case (ABC) families are present on these barriers. Differences exist in the localization and expression of transport proteins between the BBB and BCSFB, resulting in functional differences in transport properties. This review focuses on the expression, membrane localization, and different isoforms present at each barrier. Diseases that affect the central nervous system including brain tumors, HIV, Alzheimer's disease, Parkinson's disease, and stroke affect the integrity and expression of transporters at the BBB and BCSFB and will be briefly reviewed.

Uric acid transporters hiding in the intestine.

CONTEXT: Hyperuricaemia is known as an abnormally increased uric acid level in the blood. Although it was observed many years ago, since uric acid excretion via the intestine pathway accounted for approximately one-third of total elimination of uric acid, the molecular mechanism of 'extra-renal excretion' was poorly understood until the finding of uric acid transporters. OBJECTIVE: The objective of this study was to gather all information related to uric acid transporters in the intestine and present this information as a comprehensive and systematic review article. METHODS: A literature search was performed from various databases (e.g., Medline, Science Direct, Springer Link, etc.). The key terms included uric acid, transporter and intestine. The period for the search is from the 1950s to the present. The bibliographies of papers relating to the review subject were also searched for further relevant references. RESULTS: The uric acid transporters identified in the intestine are discussed in this review. The solute carrier (SLC) transporters include GLUT9, MCT9, NPT4, NPT homolog (NPT5) and OAT10. The ATP binding cassette (ABC) transporters include ABCG2 (BCRP), MRP2 and MRP4. Bacterial transporter YgfU is a low-affinity and high-capacity transporter for uric acid. CONCLUSION: The present review may be helpful for further our understanding of hyperuricaemia and be of value in designing future studies on novel therapeutic pathways.