Search results for "statin"

2019

Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. Further, we examined the possible relationship between the microbial surface molecule flagellin and CRC. CRC cells (C26) were inoculated into mice. Activin receptor (ACVR) ligands were blocked, either before tumor formation or before and after, to increase muscle mass and prevent muscle loss. The effects of flagellin on C26-cells were studied in vitro. The occurrence of similar phenomena were studied in murine and human tumors. Cancer modulated the gut microbiota witho…

An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling

2017

Signaling receptors dynamically exit cilia upon activation of signaling pathways such as Hedgehog. Here, we find that when activated G protein-coupled receptors (GPCRs) fail to undergo BBSome-mediated retrieval from cilia back into the cell, these GPCRs concentrate into membranous buds at the tips of cilia before release into extracellular vesicles named ectosomes. Unexpectedly, actin and the actin regulators drebrin and myosin 6 mediate ectosome release from the tip of cilia. Mirroring signal-dependent retrieval, signal-dependent ectocytosis is a selective and effective process that removes activated signaling molecules from cilia. Congruently, ectocytosis compensates for BBSome defects as…

The HDAC6 Inhibitor tubacin induces release of CD133+ extracellular vesicles from cancer cells

2017

Tumor-derived extracellular vesicles (EVs) are emerging as an important mode of intercellular communication, capable of transferring biologically active molecules that facilitate the malignant growth and metastatic process. CD133 (Prominin-1), a stem cell marker implicated in tumor initiation, differentiation and resistance to anti-cancer therapy, is reportedly associated with EVs in various types of cancer. However, little is known about the factors that regulate the release of these CD133+ EVs. Here, we report that the HDAC6 inhibitor tubacin promoted the extracellular release of CD133+ EVs from human FEMX-I metastatic melanoma and Caco-2 colorectal carcinoma cells, with a concomitant dow…

Abstract C097: Pyrrolo[2′,3′:3,4]cyclohepta[1,2-d][1,2]oxazoles: A new class of antimitotic agents

2019

Abstract Tubulin-binding molecules constitute an important class of antineoplastic agents, with broad activity in both solid and hematologic malignancies. Oxazoles represent the core structure of many drug candidates with multiple targets, providing an attractive scaffold in medicinal chemistry. Diaryl[1,2]oxazoles have emerged as potent analogues of the antitubulin compound combretastatin A-4 (CA-4). Naphtylcombretastin and its derivatives incorporating the isoxazole moiety displayed potent cytotoxic effects and inhibition of tubulin polymerization. In particular, 5-(naphthalen-2-yl)-4-(TMP)-1,2-oxazole and 4-(naphthalen-2-yl)-5-(TMP)-1,2-oxazole showed the same inhibitory potency as napht…

The activation of NMDA receptors alters the structural dynamics of the spines of hippocampal interneurons

2017

N-Methyl-d-Aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play a key role in the structural plasticity of excitatory neurons, but to date little is known about their influence on the remodeling of interneurons. Among hippocampal interneurons, the somatostatin expressing cells in the CA1 stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change their density in response to different stimuli. In order to understand the role of NMDAR activation on the structural dynamics of the spines of somatostatin expressing interneurons in …

Are the Myokines the Mediators of Physical Activity-Induced Health Benefits?

2016

BACKGROUND: The concept of the muscle as a secretory organ, developed during the last decades, partially answers to the issue of how the crosstalk between skeletal muscle and distant tissues happens. The beneficial effects of exercise transcend the simple improved skeletal muscle functionality: systemic responses to exercise have been observed in distal organs like heart, kidney, brain and liver. Increasing data have accumulated regarding the synthesis, the kinetics of release and the biological roles of muscular cytokines, now called myokines. The most recent techniques have meaningfully improved the identification of the muscle cell secretome, but several issues regarding the extent of se…

Ancient goat genomes reveal mosaic domestication in the Fertile Crescent

2018

How humans got their goatsLittle is known regarding the location and mode of the early domestication of animals such as goats for husbandry. To investigate the history of the goat, Dalyet al.sequenced mitochondrial and nuclear sequences from ancient specimens ranging from hundreds to thousands of years in age. Multiple wild populations contributed to the origin of modern goats during the Neolithic. Over time, one mitochondrial type spread and became dominant worldwide. However, at the whole-genome level, modern goat populations are a mix of goats from different sources and provide evidence for a multilocus process of domestication in the Near East. Furthermore, the patterns described suppor…

Muscle and serum metabolomes are dysregulated in colon-26 tumor-bearing mice despite amelioration of cachexia with activin receptor type 2B ligand bl…

2019

Cancer-associated cachexia reduces survival, which has been attenuated by blocking the activin receptor type 2B (ACVR2B) ligands in mice. The purpose of this study was to unravel the underlying physiology and novel cachexia biomarkers by use of the colon-26 (C26) carcinoma model of cancer cachexia. Male BALB/c mice were subcutaneously inoculated with C26 cancer cells or vehicle control. Tumor-bearing mice were treated with vehicle (C26+PBS) or soluble ACVR2B either before (C26+sACVR/b) or before and after (C26+sACVR/c) tumor formation. Skeletal muscle and serum metabolomics analysis was conducted by gas chromatography-mass spectrometry. Cancer altered various biologically functional groups …

Reported muscle symptoms during statin treatment amongst Italian dyslipidaemic patients in the real‐life setting: the PROSISA Study

2021

Aim: Statin-associated muscle symptoms (SAMS) are a major determinant of poor treatment adherence and/or discontinuation, but a definitive diagnosis of SAMS is challenging. The PROSISA study was an observational retrospective study aimed to assess the prevalence of reported SAMS in a cohort of dyslipidaemic patients. Methods: Demographic/anamnestic data, biochemical values and occurrence of SAMS were collected by 23 Italian Lipid Clinics. Adjusted logistic regression was performed to estimate odds ratio (OR) and 95% confidence intervals for association between probability of reporting SAMS and several factors. Results: Analyses were carried out on 16 717 statin-treated patients (mean ± SD, …

On the role of cystatin C in cancer progression

2018

Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter. The specific mechanisms underlying these opposing effects at present remain murky and are the subject of many current investigations. On the other hand, a complete knowle…