Organic Anion Transporting Polypeptides Expressed in Pancreatic Cancer May Serve As Potential Diagnostic Markers and Therapeutic Targets for Early Stage Adenocarcinomas
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Organic anion
Northern blot
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The liver plays an essential role in removing endogenous and exogenous compounds from the circulation. This function is mediated by specific transporters, including members of the family of organic anion transport proteins (OATPs) and the Na + ‐taurocholate transporting polypeptide (NTCP). In the present study, transporter protein expression was determined in liver samples from patients with cirrhosis or controls without liver disease. Five transporters (OATP1A2, OATP1B1, OATP1B3, OATP2B1, and NTCP) were studied. Transporter content in homogenates of human liver was quantified on western blots probed with transporter‐specific antibodies in which a calibrated green fluorescent protein‐tagged transporter standard was included. Liver samples from 21 patients with cirrhosis (hepatitis C in 17 and alcohol abuse in 4) and 17 controls without liver disease were analyzed. Expression of each of the transporters had a large spread, varying by an order of magnitude in cirrhotic and control livers. OATP1B1 was the most abundant transporter in controls ( P < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression ( P < 0.01). There was little difference in transporter expression with respect to age or sex. Despite the large variability in transporter expression within a group, analysis in individuals showed that those with high or low expression of one transporter had a similar magnitude in expression of the others. Conclusion: Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease.
Organic anion-transporting polypeptide
Liver disease
Efflux
Transport protein
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Organic anion
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Objectives: Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. Methods: In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. Results: In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions: Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer.
Pancreatic juice
Pancreatic Disease
Exocrine pancreas
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A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.
Efflux
Organic anion
Organic anion-transporting polypeptide
Solute carrier family
Xenobiotic
P-glycoprotein
Multidrug Resistance-Associated Proteins
Transport protein
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The SLC22 transporters belong to the solute carrier (SLC) transporter superfamily and have diverse functions and expression patterns that include the cellular uptake of organic cations, anions and zwitterions in the liver and kidneys. Important members from a pharmacokinetic perspective include the organic anion transporters 1–3 (OAT1–3) and the organic cation transporters 1 and 2 (OCT1 and OCT2). This chapter summarizes current knowledge about the function of OATs and OCTs, their preclinical characterization and the structural determinants of OAT- and OCT-mediated drug transport and drug–drug interactions.
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Organic anion-transporting polypeptide
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Three cases of chronic alcoholic pancreatitis associated with aberrant pancreas are reported. All three patients underwent laparotomy, and an aberrant pancreas was found in the jejunum of each of the three patients. Microscopic examination of the aberrant pancreas did not show any changes suggestive of chronic pancreatitis, despite severe chronic pancreatitis in the main pancreas.
Pancreatic Disease
Chronic alcoholic
Jejunum
Exocrine pancreas
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Organic anion
Anion exchanger
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