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https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#1
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27910059/gene-therapy-for-post-infarction-ventricular-tachycardia
#2
J Kevin Donahue
Cardiac arrhythmias are a leading cause of morbidity and mortality in the developed world. In particular, cardiac arrest or sudden cardiac death is the leading cause of death in these countries. Death generally results from a ventricular tachyarrhythmia, and pathology data have shown that cardiac arrest victims very frequently have evidence of coronary atherosclerosis with either acute ischemia or healed myocardial infarction. In this work, we describe an animal model that reproducibly has inducible ventricular tachyarrhythmias after healing of a myocardial infarction scar and a gene delivery method that allows gene transfer to the scar and surrounding myocardial tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27908937/the-centrosome-a-multitalented-renaissance-organelle
#3
REVIEW
Anastassiia Vertii, Heidi Hehnly, Stephen Doxsey
The centrosome acts as a microtubule-organizing center (MTOC) from the G1 to G2 phases of the cell cycle; it can mature into a spindle pole during mitosis and/or transition into a cilium by elongating microtubules (MTs) from the basal body on cell differentiation or cell cycle arrest. New studies hint that the centrosome functions in more than MT organization. For instance, it has recently been shown that a specific substructure of the centrosome-the mother centriole appendages-are required for the recycling of endosomes back to the plasma membrane...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27908756/a-novel-curcumin-derivative-which-inhibits-p-glycoprotein-arrests-cell-cycle-and-induces-apoptosis-in-multidrug-resistance-cells
#4
Vanessa Lopes-Rodrigues, Ana Oliveira, Marta Correia-da-Silva, Madalena Pinto, Raquel T Lima, Emília Sousa, M Helena Vasconcelos
Cancer multidrug resistance (MDR) is a major limitation to the success of cancer treatment and is highly associated with the overexpression of drug efflux pumps such as P-glycoprotein (P-gp). In order to achieve more effective chemotherapeutic treatments, it is important to develop P-gp inhibitors to block/decrease its activity. Curcumin (1) is a secondary metabolite isolated from the turmeric of Curcuma longa L.. Diverse biological activities have been identified for this compound, particularly, MDR modulation in various cancer cell models...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908159/a-preclinical-microbeam-facility-with-a-conventional-x-ray-tube
#5
Stefan Bartzsch, Craig Cummings, Stephan Eismann, Uwe Oelfke
PURPOSE: Microbeam radiation therapy is an innovative treatment approach in radiation therapy that uses arrays of a few tens of micrometer wide and a few hundreds of micrometer spaced planar x-ray beams as treatment fields. In preclinical studies these fields efficiently eradicated tumors while normal tissue could effectively be spared. However, development and clinical application of microbeam radiation therapy is impeded by a lack of suitable small scale sources. Until now, only large synchrotrons provide appropriate beam properties for the production of microbeams...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27907969/neuroprotection-in-critical-care-neurology
#6
Menno R Germans, Hieronymus D Boogaarts, R Loch Macdonald
Ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury-all have in common early brain injury due to brain tissue destruction, reduced cerebral blood flow and oxygen delivery, and overall substantial morbidity and mortality. The pathophysiology of brain tissue damage likely includes common cellular mechanisms. Neuroprotection has seldom, if ever, been shown to reduce early brain injury. Secondary brain injury develops after these conditions due to macroscopic events such as increased intracranial pressure and reduced cerebral blood flow, as well as cellular processes including vascular damage, inflammation, and apoptotic/necrotic cell death...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27907064/nad-is-a-food-component-that-promotes-exit-from-dauer-diapause-in-caenorhabditis-elegans
#7
Mykola Mylenko, Sebastian Boland, Sider Penkov, Julio L Sampaio, Benoit Lombardot, Daniela Vorkel, Jean-Marc Verbavatz, Teymuras V Kurzchalia
The free-living soil nematode Caenorhabditis elegans adapts its development to the availability of food. When food is scarce and population density is high, worms enter a developmentally arrested non-feeding diapause stage specialized for long-term survival called the dauer larva. When food becomes available, they exit from the dauer stage, resume growth and reproduction. It has been postulated that compound(s) present in food, referred to as the "food signal", promote exit from the dauer stage. In this study, we have identified NAD+ as a component of bacterial extract that promotes dauer exit...
2016: PloS One
https://www.readbyqxmd.com/read/27906635/a-specific-inhibitor-of-lactate-dehydrogenase-overcame-the-resistance-toward-gemcitabine-in-hypoxic-mesothelioma-cells-and-modulated-the-expression-of-the-human-equilibrative-transporter-1
#8
Elisa Giovannetti, Leticia G Leon, Valentina E Gómez, Paolo A Zucali, Filippo Minutolo, Godefridus J Peters
Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906177/-normalizing-the-malignant-phenotype-of-luminal-breast-cancer-cells-via-alpha-v-beta-3-integrin
#9
Hanan Abu-Tayeh, Keren Weidenfeld, Alisa Zhilin-Roth, Sagi Schif-Zuck, Sonja Thaler, Cristina Cotarelo, Tuan Z Tan, Jean P Thiery, Jeffrey E Green, Geula Klorin, Edmond Sabo, Jonathan P Sleeman, Maty Tzukerman, Dalit Barkan
Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27904673/microrna-206-acts-as-a-tumor-suppressor-in-bladder-cancer-via-targeting-yrdc
#10
Bisheng Huang, Wei Zhai, Guanghui Hu, Chi Huang, Tiancheng Xie, Jingwei Zhang, Yunfei Xu
Accumulating evidence suggested that microRNA (miRNA) plays important regulatory roles in the initiation and development of various cancers. Previous study showed that microRNA-206 (miR-206) is dysregulated in human bladder cancer tissues, however, the biological function and underlying mechanisms of miR-206 in human bladder cancer remain unknown. In the present study, we aimed to investigate the clinical significance of miR-206 and its target gene YRDC in human bladder cancer, and to determine its effects on oncogenic phenotypes of this disease...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903392/-resuscitation-efficacy-of-extracorporeal-membrane-oxygenation-in-non-postcardiotomy-adult-patients-with-cardiac-arrest
#11
L Huang, Y W Liu, T Li, X M Hu, D W Duan, P Wu
Objective: To evaluate the resuscitation efficacy of extracorporeal membrane oxygenation (ECMO) for non-postcardiotomy cardiac arrest adult patients post failed conventional cardiopulmonary resuscitation (CCPR). Methods: We retrospectively analyzed the clinical data of a total of 25 consecutive adults who suffered from non-postcardiotomy cardiac arrest and were treated with ECMO post failed CCPR in our hospital between January 2010 and January 2015. Inclusion criteria included: 18 to 75 years old; the duration from cardiac arrest to CCPR initiation<5 minutes; no recovery of spontaneous circulation within 10 min after implementation of standard CCPR, and the length of CCPR <90 minutes...
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27903220/santavac-%C3%A2-a-novel-universal-antigen-composition-for-developing-cancer-vaccines
#12
Petr Genrievich Lokhov, Elena Evgenevna Balashova
BACKGROUND: Development of a universal cancer vaccine for the prevention of all cancers has been under development for many years. Antiangiogenic cancer vaccines elicit immune responses with the potential of destroying tumor vasculature endothelial cells without affecting vasculature integrity in normal tissues. The methods used in the development of antigen compositions comprising these vaccines have been recently improved and described in this report in the context of SANTAVAC ™ development - the first cancer vaccine based on endothelial cell heterogeneity...
November 30, 2016: Recent Patents on Biotechnology
https://www.readbyqxmd.com/read/27902925/targeted-inhibition-of-wrn-helicase-replication-stress-and-cancer
#13
REVIEW
Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27902467/autocrine-il-6-mediates-pituitary-tumor-senescence
#14
Melanie Sapochnik, Mariana R Haedo, Mariana Fuertes, Pablo Ajler, Guillermo Carrizo, Andrés Cervio, Gustavo Sevlever, Günter K Stalla, Eduardo Arzt
Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901520/depot-antipsychotics-where-do-we-stand
#15
Ahsan Y Khan, Salman Salaria, Muhammad Ovais, George D Ide
BACKGROUND: Nonadherence to medication is a major problem for patients with schizophrenia. To counter this problem, pharmaceutical companies began developing depot antipsychotics. Although there are currently 5 first-generation and 6 second-generation depot antipsychotics available worldwide, many physicians are still reluctant to use this category of drug initially. This review provides the latest information about the use of depot antipsychotics in schizophrenia treatment as well as several studies in support of depot antipsychotic use as first-line treatment for patients with schizophrenia...
November 2016: Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists
https://www.readbyqxmd.com/read/27901512/mitochondrial-dysfunction-in-alveolar-and-white-matter-developmental-failure-in-premature-infants
#16
Vadim S Ten
At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants...
November 30, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#17
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900008/discovery-of-genes-from-feces-correlated-with-colorectal-cancer-progression
#18
Chia-Long Lee, Chi-Jung Huang, Shung-Haur Yang, Chun-Chao Chang, Chi-Cheng Huang, Chih-Cheng Chien, Ruey-Neng Yang
Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. Markers of CRC may serve to provide the basis for decision-making, and may assist in cancer prevention, detection and prognostic prediction. DNA and messenger (m)RNA molecules that are present in human feces faithfully represent CRC manifestations. In the present study, exogenous mouse cells verified the feasibility of total fecal RNA as a marker of CRC. Furthermore, five significant genes encoding solute carrier family 15, member 4 (SLC15A4), cluster of differentiation (CD)44, 3-oxoacid CoA-transferase 1 (OXCT1), placenta-specific 8 (PLAC8) and growth arrest-specific 2 (GAS2), which are differentially expressed in the feces of CRC patients, were verified in different CRC cell lines using quantitative polymerase chain reaction...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899257/juglanin-induces-apoptosis-and-autophagy-in-human-breast-cancer-progression-via-ros-jnk-promotion
#19
Zhu-Lei Sun, Jin-Long Dong, Jiang Wu
Breast cancer is one of the most common primary malignant tumors of among women, the long-term survival of which has stagnated in the past decades. Juglanin as a natural production mainly extracted from green walnut husks of Juglans mandshurica has been defined as the functional composition among a series of compounds. It showed powerful protective effect in various diseases by inhibiting inflammation and tumor cells growth. However, the effect of juglanin on human breast cancer and the underlying mechanisms remains to be elucidated...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27898051/preparation-of-6-8-11-amino-chloro-oxoisoaporphine-and-group-10-metal-complexes-and-evaluation-of-their-in-vitro-and-in-vivo-antitumor-activity
#20
Qi-Pin Qin, Jiao-Lan Qin, Ting Meng, Gui-Ai Yang, Zu-Zhuang Wei, Yan-Cheng Liu, Hong Liang, Zhen-Feng Chen
A series of group-10 metal complexes 1-14 of oxoisoaporphine derivatives were designed and synthesized. 1-14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1-6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1-6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand L(a) exhibited less side effects than 6 with 8-amino substituted ligand L(b) and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model...
November 29, 2016: Scientific Reports
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