HDL in Endocrine Carcinomas: Biomarker, Drug Carrier, and Potential Therapeutic

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly upregulated in endocrine cancers, notably due to the high demand for cholesterol by cancer cells. Thus, the potential to exploit administration of cholesterol-free reconstituted or synthetic HDL (sHDL) to deplete cholesterol in endocrine cancer cell and stunt their growth of use chemotherapeutic drug loaded sHDL to target payload delivery to cancer cell has become increasingly attractive. This review focuses on the role of HDL and HDL-C in cancer and application of sHDLs as endocrine cancer therapeutics

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Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155986/1/art41237.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155986/2/art41237_am.pd

HDL in Endocrine Carcinomas: Biomarker, Drug Carrier, and Potential Therapeutic

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly upregulated in endocrine cancers, notably due to the high demand for cholesterol by cancer cells. Thus, the potential to exploit administration of cholesterol-free reconstituted or synthetic HDL (sHDL) to deplete cholesterol in endocrine cancer cell and stunt their growth of use chemotherapeutic drug loaded sHDL to target payload delivery to cancer cell has become increasingly attractive. This review focuses on the role of HDL and HDL-C in cancer and application of sHDLs as endocrine cancer therapeutics

Evolution of an elliptical bubble in an accelerating extensional flow

Mathematical models that describe the dynamical behavior of a thin gas bubble embedded in a glass fiber during a fiber drawing process have been discussed and analyzed. The starting point for the mathematical modeling was the equations presented in [1] for a glass fiber with a hole undergoing extensional flow. These equations were reconsidered here with the additional reduction that the hole, i.e. the gas bubble, was thin as compared to the radius of the fiber and of finite extent. The primary model considered was one in which the mass of the gas inside the bubble was fixed. This fixed-mass model involved equations for the axial velocity and fiber radius, and equations for the radius of the bubble and the gas pressure inside the bubble. The model equations assumed that the temperature of the furnace of the drawing tower was known. The governing equations of the bubble are hyperbolic and predict that the bubble cannot extend beyond the limiting characteristics specified by the ends of the initial bubble shape. An analysis of pinch-off was performed, and it was found that pinch-off can occur, depending on the parameters of the model, due to surface tension when the bubble radius is small. In order to determine the evolution of a bubble, a numerical method of solution was presented. The method was used to study the evolution of two different initial bubble shapes, one convex and the other non-convex. Both initial bubble shapes had fore-aft symmetry, and it was found that the bubbles stretched and elongated severely during the drawing process. For the convex shape, fore-aft symmetry was lost in the middle of the drawing process, but the symmetry was re-gained by the end of the drawing tower. A small amount of pinch-off was observed at each end for this case, so that the final bubble length was slightly shorter than its theoretical maximum length. For the non-convex initial shape, pinch-off occurred in the middle of the bubble resulting in two bubbles by the end of the fiber draw. The two bubbles had different final pressures and did not have fore-aft symmetry. An extension of the fixed-mass model was considered in which the gas in the bubble was allowed to diffuse into the surrounding glass. The governing equations for this leaky-mass model were developed and manipulated into a form suitable for a numerical treatment

High‐Density Lipoprotein in Lupus: Disease Biomarkers and Potential Therapeutic Strategy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152788/1/art41059_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152788/2/art41059.pd

Battle of GLP-1 delivery technologies

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and fierce competition among the manufacturers of these products. As rapid elimination is a major challenge for clinical application of GLP-1 RAs, various half-life extension strategies have been successfully employed including sequential modification, attachment of fatty-acid to peptide, fusion with human serum albu- min, fusion with the fragment crystallizable (Fc) region of a monoclonal antibody, sustained drug delivery sys- tems, and PEGylation. In this review, we discuss the scientific rationale of the various half-life extension strategies used for GLP-1 RA development. By analyzing and comparing different approved GLP-1 RAs and those in development, we focus on assessing how half-life extending strategies impact the pharmacokinetics, pharmacodynamics, safety, patient usability and ultimately, the commercial success of GLP-1 RA products. We also anticipate future GLP-1 RA development trends. Since similar drug delivery strategies are also applied for de- veloping other therapeutic peptides, we expect this case study of GLP-1 RAs will provide generalizable concepts for the rational design of therapeutic peptides products with extended duration of action

An Optically Discovered Outburst from XTE J1859+226

Using the Zwicky Transient Facility, in 2021 February we identified the first known outburst of the black hole X-ray transient XTE J1859+226 since its discovery in 1999. The outburst was visible at X-ray, UV, and optical wavelengths for less than 20 days, substantially shorter than its full outburst of 320 days in 1999, and the observed peak luminosity was 2 orders of magnitude lower. Its peak bolometric luminosity was only 2 × 1035 erg s−1, implying an Eddington fraction of about 3 × 10−4. The source remained in the hard spectral state throughout the outburst. From optical spectroscopy measurements we estimate an outer disk radius of 1011 cm. The low observed X-ray luminosity is not sufficient to irradiate the entire disk, but we observe a surprising exponential decline in the X-ray light curve. These observations highlight the potential of optical and infrared synoptic surveys to discover low-luminosity activity from X-ray transients

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.Fil: Garcia Fabiani, Maria Belen. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Haase, Santiago. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Comba, Andrea. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carney, Stephen. University of Michigan; Estados UnidosFil: McClellan, Brandon. University of Michigan; Estados UnidosFil: Banerjee, Kaushik. University of Michigan; Estados UnidosFil: Alghamri, Mahmoud S.. University of Michigan; Estados UnidosFil: Syed, Faisal. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University of Michigan; Estados UnidosFil: Nuñez, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: González, Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aikins, Marisa E.. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Moon, James J.. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido

The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties

goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid (PL) composition affects its cholesterol efflux and anti-inflammatory properties. An ApoA-I mimetic peptide, 5A, was combined with either SM or POPC. Both lipid formulations exhibited similar in vitro cholesterol efflux by ABCA1, but 5A-SM exhibited higher ABCG1- and SR-BI-mediated efflux relative to 5A-POPC (P < 0.05). Injection of both rHDLs in rats resulted in mobilization of plasma cholesterol, although the relative potency was 3-fold higher for the same doses of 5A-SM than for 5A-POPC. Formation of pre HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing a higher extent of pre formation relative to 5A-POPC. Both rHDLs exhibited anti-inflammatory properties, but 5A-SM showed higher inhibition of TNF-, IL-6, and IL-1 release than did 5A-POPC (P < 0.05). Both 5A-SM and 5A-POPC showed reduction in total plaque area in ApoE(-/-) mice, but only 5A-SM showed a statistically significant reduction over placebo control and baseline (P < 0.01). The type of PL used to reconstitute peptide has significant influence on rHDL's anti-inflammatory and anti-atherosclerosis properties