Gaur S.,University of Houston |
Gaur S.,Cedars Sinai Medical Center |
Wen Y.,University of Houston |
Song J.H.,University of Houston |
And 12 more authors.
Oncotarget | Year: 2015
While several new therapies are FDA-approved for bone-metastatic prostate cancer (PCa), patient survival has only improved marginally. Here, we report that chitosan nanoparticle-mediated delivery of miR-34a, a tumor suppressive microRNA that downregulates multiple gene products involved in PCa progression and metastasis, inhibited prostate tumor growth and preserved bone integrity in a xenograft model representative of established PCa bone metastasis. Expression of miR-34a induced apoptosis in PCa cells, and, in accord with downregulation of targets associated with PCa growth, including MET and Axl and c-Myc, also induced a form of non-canonical autophagy that is independent of Beclin-1, ATG4, ATG5 and ATG7. MiR-34a-induced autophagy is anti-proliferative in prostate cancer cells, as blocking apoptosis still resulted in growth inhibition of tumor cells. Thus, combined effects of autophagy and apoptosis are responsible for miR-34a-mediated prostate tumor growth inhibition, and have translational impact, as this non-canonical form of autophagy is tumor inhibitory. Together, these results provide a new understanding of the biological effects of miR-34a and highlight the clinical potential for miR-34a delivery as a treatment for bone metastatic prostate cancer.
Nathan K.,University of Houston |
Nathan K.,The Houston Methodist Research Institute |
Contreras-Vidal J.L.,University of Houston |
Contreras-Vidal J.L.,The Houston Methodist Research Institute
Frontiers in Human Neuroscience | Year: 2016
Recent mobile brain/body imaging (MoBI) techniques based on active electrode scalp electroencephalogram (EEG) allow the acquisition and real-time analysis of brain dynamics during active unrestrained motor behavior involving whole body movements such as treadmill walking, over-ground walking and other locomotive and non-locomotive tasks. Unfortunately, MoBI protocols are prone to physiological and non-physiological artifacts, including motion artifacts that may contaminate the EEG recordings. A few attempts have been made to quantify these artifacts during locomotion tasks but with inconclusive results due in part to methodological pitfalls. In this paper, we investigate the potential contributions of motion artifacts in scalp EEG during treadmill walking at three different speeds (1.5, 3.0, and 4.5 km/h) using a wireless 64 channel active EEG system and a wireless inertial sensor attached to the subject’s head. The experimental setup was designed according to good measurement practices using state-of-the-art commercially available instruments, and the measurements were analyzed using Fourier analysis and wavelet coherence approaches. Contrary to prior claims, the subjects’ motion did not significantly affect their EEG during treadmill walking although precaution should be taken when gait speeds approach 4.5 km/h. Overall, these findings suggest how MoBI methods may be safely deployed in neural, cognitive, and rehabilitation engineering applications. © 2016 Nathan and Contreras-Vidal.
Miller E.W.,University of Nevada, Reno |
Cao T.N.,The Houston Methodist Research Institute |
Pflughoeft K.J.,University of Nevada, Reno |
Sumby P.,University of Nevada, Reno |
Sumby P.,The Houston Methodist Research Institute
Molecular Microbiology | Year: 2014
RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined. © 2014 John Wiley & Sons Ltd.
Santagiuliana R.,University of Padua |
Ferrari M.,The Houston Methodist Research Institute |
Ferrari M.,Cornell College |
Schrefler B.A.,University of Padua |
Schrefler B.A.,The Houston Methodist Research Institute
Computer Methods in Applied Mechanics and Engineering | Year: 2016
The avascular multiphase model for tumor growth, developed by the authors in previous works, is enhanced to include angiogenesis. The original model comprises the extracellular matrix (ECM) as porous solid phase and three fluid phases: living and necrotic tumor cells (TCs), host cells (HCs), and the interstitial fluid. In this paper we add transport of tumor angiogenic factor (TAF) and of endothelial cells. The density of the endothelial cells represents the newly created vessels in a smeared manner. Co-opted blood vessels can be added as line element with flow or can be taken into account as boundary condition. The model is hence of the continuum-discrete type. Two examples show the potential of the newly enhanced model. The first deals with growth of a 2D tumor spheroid in a square tissue domain. From a blood vessel, posed on one side of the domain, angiogenesis takes place through the migration of endothelial cells from the vessel to the tumor. The second one is the simulation of cutaneous melanoma growth with the diffusion of TAF from the living tumor cells and the consequent development of a new vessel network, represented by the endothelial cells density. The introduction of angiogenesis will allow for simulating the delivery of chemotherapeutic and nanoparticle-mediated agents to the vascular tumor, and for evaluation of the therapeutic effect. © 2016 Elsevier B.V..
Jacquet K.,Laval University |
Fradet-Turcotte A.,Laval University |
Fradet-Turcotte A.,The Lunenfeld Tanenbaum Research Institute |
Avvakumov N.,Laval University |
And 13 more authors.
Molecular Cell | Year: 2016
The NuA4/TIP60 acetyltransferase complex is a key regulator of genome expression and stability. Here we identified MBTD1 as a stable subunit of the complex, and we reveal that, via a histone reader domain for H4K20me1/2, MBTD1 allows TIP60 to associate with specific gene promoters and to promote the repair of DNA double-strand breaks by homologous recombination. It was previously suggested that TIP60-dependent acetylation of H4 regulates binding of the non-homologous end joining factor 53BP1, which engages chromatin through simultaneous binding of H4K20me2 and H2AK15ub. We find that the TIP60 complex regulates association of 53BP1 partly by competing for H4K20me2 and by regulating H2AK15ub. Ubiquitylation of H2AK15 by RNF168 inhibits chromatin acetylation by TIP60, while this residue can be acetylated by TIP60 in vivo, blocking its ubiquitylation. Altogether, these results uncover an intricate mechanism orchestrated by the TIP60 complex to regulate 53BP1-dependent repair through competitive bivalent binding and modification of chromatin. © 2016 Elsevier Inc..