Expression of truncated Kir6.2 promotes insertion of functionally inverted ATP-sensitive K channels.

ATP-sensitive K (K) channels couple cellular metabolism to electrical activity in many cell types. Wild-type K channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane.

A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH.

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent.

Evaluations of Tumor Acidosis Within In Vivo Tumor Models Using Parametric Maps Generated with Acido CEST MRI.

Purpose: We aimed to develop pixelwise maps of tumor acidosis to aid in evaluating extracellular tumor pH (pHe) in cancer biology.

Procedures: MCF-7 and MDA-MB-231 mouse models were imaged during a longitudinal study. AcidoCEST MRI and a series of image processing methods were used to produce parametric maps of tumor pHe, and tumor pHe was also measured with a pH microsensor.

Evaluating pH in the Extracellular Tumor Microenvironment Using CEST MRI and Other Imaging Methods.

Tumor acidosis is a consequence of altered metabolism, which can lead to chemoresistance and can be a target of alkalinizing therapies. Noninvasive measurements of the extracellular pH (pHe) of the tumor microenvironment can improve diagnoses and treatment decisions. A variety of noninvasive imaging methods have been developed for measuring tumor pHe.

Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models.

The expression of carbonic anhydrase IX (CA IX) and its relationship to acidosis in lymphomas has not been widely studied. We investigated the protein expression of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos and Granta 519 lymphoma cell lines and tumor models, while also investigating the relationship with hypoxia. An imaging method, acidoCEST magnetic resonance imaging (MRI), was used to estimate lymphoma xenograft extracellular pH (pHe).

The reciprocal linear QUEST analysis method facilitates the measurements of chemical exchange rates with CEST MRI.

Magnetic resonance imaging (MRI) contrast media that are detected via chemical exchange saturation transfer (CEST) often require an accurate estimation of their chemical exchange rate, kex . A variety of analysis methods have been proposed to estimate kex , including the nonlinear QUEST analysis method that evaluates the CEST amplitude as a function of saturation time. We have derived a linear version of QUEST, termed the Reciprocal Linear QUEST (RL-QUEST) method.

Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.

Purpose: A practical, noninvasive method is needed to measure the extracellular pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have optimized a biomedical imaging method, termed acidoCEST MRI, to provide noninvasive assessments of tumor pHe in preclinical models of mammary carcinoma.

Methods: A CEST-FISP MRI method was optimized to detect the chemical exchange saturation transfer (CEST) of two amide protons of a clinically approved CT contrast agent, iopromide.

The Hanes-Woolf linear QUESP method improves the measurements of fast chemical exchange rates with CEST MRI.

Purpose: Contrast agents for chemical exchange saturation transfer MRI often require an accurate measurement of the chemical exchange rate. Many analysis methods have been reported that measure chemical exchange rates. Additional analysis methods were derived as part of this study.

Measuring in vivo tumor pHe with CEST-FISP MRI.

Paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents have been developed that can measure pH in solution studies, but these agents have not previously been detected in vivo. To use the PARACEST agent Yb-DO3A-oAA to measure the extracellular pH (pHe) in tumor tissue, a chemical exchange saturation transfer fast imaging with steady state precession MRI protocol was developed, the saturation period was optimized for sensitive chemical exchange saturation transfer (CEST) detection, and median filtering was used to remove artifacts in CEST spectra. These improvements were used to correlate pH with a ratio of two CEST effects of Yb-DO3A-oAA at a 7 T magnetic field strength (R(2) = 0.

Conformational States and kinetics of the calcium binding domain of NADPH oxidase 5.

Superoxide generated by human NADPH oxidase 5 (NOX5) is of growing importance for various physiological and pathological processes. The activity of NOX5 appears to be regulated by a self-contained Ca(2+) binding domain (CaBD). Recently Bánfi et al.