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https://www.readbyqxmd.com/read/28918046/microrna-as-therapeutic-targets-for-chronic-wound-healing
#1
REVIEW
Eoghan J Mulholland, Nicholas Dunne, Helen O McCarthy
Wound healing is a highly complex biological process composed of three overlapping phases: inflammation, proliferation, and remodeling. Impairments at any one or more of these stages can lead to compromised healing. MicroRNAs (miRs) are non-coding RNAs that act as post-transcriptional regulators of multiple proteins and associated pathways. Thus, identification of the appropriate miR involved in the different phases of wound healing could reveal an effective third-generation genetic therapy in chronic wound care...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918039/crispr-cas9-mediated-knockin-application-in-cell-therapy-a-non-viral-procedure-for-bystander-treatment-of-glioma-in-mice
#2
Oscar Meca-Cortés, Marta Guerra-Rebollo, Cristina Garrido, Salvador Borrós, Nuria Rubio, Jeronimo Blanco
The use of non-viral procedures, together with CRISPR/Cas9 genome-editing technology, allows the insertion of single-copy therapeutic genes at pre-determined genomic sites, overcoming safety limitations resulting from random gene insertions of viral vectors with potential for genome damage. In this study, we demonstrate that combination of non-viral gene delivery and CRISPR/Cas9-mediated knockin via homology-directed repair can replace the use of viral vectors for the generation of genetically modified therapeutic cells...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917833/values-based-shared-decision-making-in-the-antenatal-period
#3
REVIEW
Stephanie K Kukora, Renee D Boss
Despite advances in life-saving technology for critically ill neonates, challenges continue to arise for infants delivered with extreme prematurity, congenital anomalies, and genetic conditions that exceed the limits of currently available interventions. In these situations, parents are forced to make cognitively and emotionally difficult decisions, in discussion with a neonatologist, regarding how aggressively to provide supportive measures at the time of delivery and at what point burdens of therapy outweigh benefits...
September 13, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28917518/genome-stability-of-programmed-stem-cell-products
#4
REVIEW
Ulrich Martin
Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives...
September 13, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28917271/cognitive-impairment-and-chemotherapy-a-brief-overview
#5
REVIEW
Milena Vitali, Carla Ida Ripamonti, Fausto Roila, Claudia Proto, Diego Signorelli, Martina Imbimbo, Giulia Corrao, Angela Brissa, Gallucci Rosaria, Filippo de Braud, Marina Chiara Garassino, Giuseppe Lo Russo
Patients with cancer are experiencing long-term survival following chemotherapy, but the treatment may also be associated with short and long-term toxicity, including the possibility of cognitive dysfunction. A literature overview indicated a significant association between chemotherapy and cognitive impairment but prospective longitudinal research is warranted to examine the degree and persisting nature of this decline. Although chemotherapeutic agents are unlikely to cross the blood-brain barrier, it has been alleged that the occurrence of neurotoxicity is linked to the pro-inflammatory cytokine pathways...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28917219/reuma-pt-contribution-to-the-knowledge-of-immune-mediated-systemic-rheumatic-diseases
#6
Maria José Santos, Helena Canhão, Ana Filipa Mourão, Filipa Oliveira Ramos, Cristina Ponte, Cátia Duarte, Anabela Barcelos, Fernando Martins, José António Melo Gomes
Patient registries are key instruments aimed at a better understanding of the natural history of diseases, at assessing the effectiveness of therapeutic interventions, as well as identifying rare events or outcomes that are not captured in clinical trials. However, the potential of registries goes far beyond these aspects. For example, registries promote the standardization of clinical practice, can also provide information on domains that are not routinely collected in clinical practice and can support decision-making...
September 14, 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28917058/lineage-tracing-of-genome-edited-alleles-reveals-high-fidelity-axolotl-limb-regeneration
#7
Grant Parker Flowers, Lucas D Sanor, Craig M Crews
Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs...
September 16, 2017: ELife
https://www.readbyqxmd.com/read/28916833/inhibition-of-wnt-%C3%AE-catenin-pathway-and-histone-acetyltransferase-activity-by-rimonabant-a-therapeutic-target-for-colon-cancer
#8
Maria Chiara Proto, Donatella Fiore, Chiara Piscopo, Silvia Franceschelli, Valentina Bizzarro, Chiara Laezza, Gianluigi Lauro, Alessandra Feoli, Alessandra Tosco, Giuseppe Bifulco, Gianluca Sbardella, Maurizio Bifulco, Patrizia Gazzerro
In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis. Increasing evidence showed that the endocannabinoids control tumor growth and progression, both in vitro and in vivo. We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916750/comprehensive-multiregional-analysis-of-molecular-heterogeneity-in-bladder-cancer
#9
Mathilde Borg Houlberg Thomsen, Iver Nordentoft, Philippe Lamy, Søren Vang, Line Reinert, Christophe Kamungu Mapendano, Søren Høyer, Torben F Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#10
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916596/cutaneous-angiosarcoma-a-current-update
#11
REVIEW
Elina Shustef, Viktoryia Kazlouskaya, Victor G Prieto, Doina Ivan, Phyu P Aung
Cutaneous angiosarcoma (cAS) is a rare malignant neoplasm with variable clinical presentation. Although a distinct vascular tumour, cAS shares many overlapping histopathological features with other vasoformative and epithelioid tumours or 'mimickers'. cAS shows aggressive behaviour and carries a grave prognosis, thus early diagnosis is of paramount importance to achieve the best possible outcomes. Recently, several genetic studies were conducted leading to the identification of novel molecular targets in the treatment of cAS...
September 15, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28916311/lenalidomide-maintenance-after-first-line-therapy-for-high-risk-chronic-lymphocytic-leukaemia-cllm1-final-results-from-a-randomised-double-blind-phase-3-study
#12
Anna Maria Fink, Jasmin Bahlo, Sandra Robrecht, Othman Al-Sawaf, Ali Aldaoud, Holger Hebart, Kathleen Jentsch-Ullrich, Steffen Dörfel, Kirsten Fischer, Clemens-Martin Wendtner, Thomas Nösslinger, Paolo Ghia, Francesc Bosch, Arnon P Kater, Hartmut Döhner, Michael Kneba, Karl-Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
BACKGROUND: The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. METHODS: In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations...
September 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#13
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915357/a-i-yigp-i-mutant-strain-is-a-small-colony-variant-of-i-e-coli-i-and-shows-pleiotropic-antibiotic-resistance
#14
Hui Xia, Qiongwei Tang, Jie Song, Jiang Ye, Haizhen Wu, Huizhan Zhang
Small colony variants (SCVs) are a commonly observed subpopulation of bacteria that have a small colony size and distinctive biochemical characteristics. SCVs are more resistant to some antibiotics than the wild-type, and usually cause persistent infections in the clinic. SCV studies have been very active during the past two decades, especially of <i>Staphylococcus aureus</i>. However, fewer studies on <i>Escherichia coli </i>SCVs exist, so we studied an <i>E. coli </i>SCV during an experiment involving the deletion of the<i> yigP</i> locus...
September 15, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28915335/ecm-related-myopathies-and-muscular-dystrophies-pros-and-cons-of-protein-therapies
#15
Pam M Van Ry, Tatiana M Fontelonga, Pamela Barraza-Flores, Apurva Sarathy, Andreia M Nunes, Dean J Burkin
Extracellular matrix (ECM) myopathies and muscular dystrophies are a group of genetic diseases caused by mutations in genes encoding proteins that provide critical links between muscle cells and the extracellular matrix. These include structural proteins of the ECM, muscle cell receptors, enzymes, and intracellular proteins. Loss of adhesion within the myomatrix results in progressive muscle weakness. For many ECM muscular dystrophies, symptoms can occur any time after birth and often result in reduced life expectancy...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28915150/tics-and-tourette-a-clinical-pathophysiological-and-etiological-review
#16
Russell C Dale
PURPOSE OF REVIEW: Describe developments in the etiological understanding of Tourette syndrome. RECENT FINDINGS: Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors...
September 14, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28914994/hessian-based-quantitative-image-analysis-of-host-pathogen-confrontation-assays
#17
Zoltan Cseresnyes, Kaswara Kraibooj, Marc Thilo Figge
Host-fungus interactions have gained a lot of interest in the past few decades, mainly due to an increasing number of fungal infections that are often associated with a high mortality rate in the absence of effective therapies. These interactions can be studied at the genetic level or at the functional level via imaging. Here, we introduce a new image processing method that quantifies the interaction between host cells and fungal invaders, for example, alveolar macrophages and the conidia of Aspergillus fumigatus...
September 15, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28914844/-molecular-genetic-predictors-of-resistance-to-anti-helicobacter-pylori-therapy
#18
I V Maev, D N Andreev
In current clinical practice, there is no optimal empirical therapy for Helicobacter pylori (H. pylori) infection and there is a progressive decrease in the efficiency of classical eradication therapy (ET) regimens. The variability in the efficiency of ET in a specific patient is largely due to the heterogeneous molecular genetic mechanisms underlying the resistance of the microorganism to the components of the treatment regimens. The basis of the mechanisms for antibiotic resistance in H. pylori is mainly the point mutations in some genes, which determine alterations in the mechanisms of action of drugs, such as clarithromycin (domain V of 23S rRNA), metronidazole (rdxA, frxA), amoxicillin (pbp1A), tetracycline (16S rRNA), and levofloxacin (gyrA)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28914782/the-future-challenge-of-reactive-oxygen-species-ros-in-hypertension-from-bench-to-bed-side
#19
REVIEW
Gabriele Togliatto, Giusy Lombardo, Maria Felice Brizzi
Reactive oxygen species (ROS) act as signaling molecules that control physiological processes, including cell adaptation to stress. Redox signaling via ROS has quite recently become the focus of much attention in numerous pathological contexts, including neurodegenerative diseases, kidney and cardiovascular disease. Imbalance in ROS formation and degradation has also been implicated in essential hypertension. Essential hypertension is characterized by multiple genetic and environmental factors which do not completely explain its associated risk factors...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28914717/the-relationship-between-mismatch-repair-deficiency-and-pd-l1-expression-in-breast-carcinoma
#20
Anne M Mills, Erik A Dill, Christopher A Moskaluk, Jaroslaw Dziegielewski, Tim N Bullock, Patrick M Dillon
Mismatch repair (MMR) deficiency in solid tumors has recently been linked to susceptibility to immunotherapies targeting the programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) axis. Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common. We assessed the relationship between PD-L1 and MMR protein expression by immunohistochemistry in 245 primary and 40 metastatic breast carcinomas...
September 13, 2017: American Journal of Surgical Pathology
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