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https://www.readbyqxmd.com/read/27907930/microrna-profiling-in-clear-cell-renal-cell-carcinoma-tissues-potentially-links-tumorigenesis-and-recurrence-with-obesity
#1
X Shu, M A Hildebrandt, J Gu, N M Tannir, S F Matin, J A Karam, C G Wood, X Wu
BACKGROUND: Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence. METHODS: Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs. RESULTS: A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples...
December 1, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27892764/stat3-mediated-smad3-activation-underlies-oncostatin-m-induced-senescence
#2
Benjamin L Bryson, Damian J Junk, Rocky Cipriano, Mark W Jackson
Cytokines in the developing tumor microenvironment (TME) can drive transformation and subsequent progression towards metastasis. Elevated levels of the Interleukin-6 (IL-6) family cytokine Oncostatin M (OSM) in the breast TME correlate with aggressive, metastatic cancers, increased tumor recurrence, and poor patient prognosis. Paradoxically, OSM engages a tumor-suppressive, Signal Transducer and Activator of Transcription 3 (STAT3)-dependent senescence response in normal and non-transformed human mammary epithelial cells (HMEC)...
November 28, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27889062/monoallelic-mutations-in-the-translation-initiation-codon-of-klhl24-cause-skin-fragility
#3
Yinghong He, Kristin Maier, Juna Leppert, Ingrid Hausser, Agnes Schwieger-Briel, Lisa Weibel, Martin Theiler, Dimitra Kiritsi, Hauke Busch, Melanie Boerries, Katariina Hannula-Jouppi, Hannele Heikkilä, Kaisa Tasanen, Daniele Castiglia, Giovanna Zambruno, Cristina Has
The genetic basis of epidermolysis bullosa, a group of genetic disorders characterized by the mechanically induced formation of skin blisters, is largely known, but a number of cases still remain genetically unsolved. Here, we used whole-exome and targeted sequencing to identify monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding kelch-like protein 24 (KLHL24) in 14 individuals with a distinct skin-fragility phenotype and skin cleavage within basal keratinocytes...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27880722/deletion-of-8p-is-an-independent-prognostic-parameter-in-prostate-cancer
#4
Martina Kluth, Nina Nadine Amschler, Rami Galal, Christina Möller-Koop, Phillipp Barrow, Maria Christina Tsourlakis, Frank Jacobsen, Andrea Hinsch, Corinna Wittmer, Stefan Steurer, Till Krech, Franziska Büscheck, Till Sebastian Clauditz, Burkhard Beyer, Waldemar Wilczak, Markus Graefen, Hartwig Huland, Sarah Minner, Thorsten Schlomm, Guido Sauter, Ronald Simon
Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27864305/oncogenic-mechanisms-of-histone-h3-mutations
#5
Daniel N Weinberg, C David Allis, Chao Lu
Recurrent missense mutations in histone H3 were recently reported in pediatric gliomas and soft tissue tumors. Strikingly, these mutations only affected a minority of the total cellular H3 proteins and occurred at or near lysine residues at positions 27 and 36 on the amino-terminal tail of H3 that are subject to well-characterized posttranslational modifications. Here we review recent progress in elucidating the mechanisms by which these mutations perturb the chromatin landscape in cells through their effects on chromatin-modifying machinery, particularly through inhibition of specific histone lysine methyltransferases...
November 18, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27855171/cholera-in-cameroon-2000-2012-spatial-and-temporal-analysis-at-the-operational-health-district-and-sub-climate-levels
#6
Moise C Ngwa, Song Liang, Ian T Kracalik, Lillian Morris, Jason K Blackburn, Leonard M Mbam, Simon Franky Baonga Ba Pouth, Andrew Teboh, Yang Yang, Mouhaman Arabi, Jonathan D Sugimoto, John Glenn Morris
INTRODUCTION: Recurrent cholera outbreaks have been reported in Cameroon since 1971. However, case fatality ratios remain high, and we do not have an optimal understanding of the epidemiology of the disease, due in part to the diversity of Cameroon's climate subzones and a lack of comprehensive data at the health district level. METHODS/FINDINGS: A unique health district level dataset of reported cholera case numbers and related deaths from 2000-2012, obtained from the Ministry of Public Health of Cameroon and World Health Organization (WHO) country office, served as the basis for the analysis...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27810699/improved-survival-in-metastatic-breast-cancer-1985-2016
#7
Marie Sundquist, Lars Brudin, Göran Tejler
PURPOSE: In the last 25 years new treatment options in breast cancer have evolved. We wanted to determine whether the survival of; patients with metastatic breast cancer have improved during this period. METHODS: Patients consecutively diagnosed with disseminated breast cancer 1985-2014 in the County of Kalmar, Sweden, were identified and followed to 2016. Survival was calculated for each successive 5 year interval. Separate analyses were performed for pts with ER and/or PR and HER2 positive tumours resp...
October 28, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27807831/quantitative-clinical-imaging-methods-for-monitoring-intratumoral-evolution
#8
Joo Yeun Kim, Robert A Gatenby
Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27803193/imprints-and-dppa3-are-bypassed-during-pluripotency-and-differentiation-coupled-methylation-reprogramming-in-testicular-germ-cell-tumors
#9
J Keith Killian, Lambert C J Dorssers, Britton Trabert, Ad J M Gillis, Michael B Cook, Yonghong Wang, Joshua J Waterfall, Holly Stevenson, William I Smith, Natalia Noyes, Parvathy Retnakumar, J Hans Stoop, J Wolter Oosterhuis, Paul S Meltzer, Katherine A McGlynn, Leendert H J Looijenga
Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and differentiated somatic references...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27803053/polymorphisms-in-microrna-binding-sites-of-mucin-genes-as-predictors-of-clinical-outcome-in-colorectal-cancer-patients
#10
Veronika Vymetalkova, Barbara Pardini, Fabio Rosa, Katerina Jiraskova, Cornelia Di Gaetano, Petra Bendova, Miloslav Levy, Veronika Veskrnova, Tomas Buchler, Ludmila Vodickova, Alessio Naccarati, Pavel Vodicka
Polymorphisms in microRNA (miRNA) binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and susceptibility to common diseases. Mucins have been identified as markers of adverse prognosis. We hypothesized that genetic variations in miRNA binding sites located in mucin genes may modulate signaling response and the maintenance of genomic stability ultimately affecting cancer susceptibility, efficacy of chemotherapy and survival.In the present study, we analyzed the association of single nucleotide polymorphisms in predicted miRNA target sites (miRSNPs) of mucin genes with colorectal cancer (CRC) risk and clinical outcome...
November 1, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27798559/targeting-the-atp-dependent-formation-of-herpesvirus-ribonucleoprotein-particle-assembly-as-an-antiviral-approach
#11
Sophie Schumann, Brian R Jackson, Ian Yule, Steven K Whitehead, Charlotte Revill, Richard Foster, Adrian Whitehouse
Human herpesviruses are responsible for a range of debilitating acute and recurrent diseases, including a number of malignancies. Current treatments are limited to targeting the herpesvirus DNA polymerases, but with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. Here, we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs)...
October 31, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27768764/combination-of-cancer-stem-cell-markers-cd44-and-cd24-is-superior-to-aldh1-as-a-prognostic-indicator-in-breast-cancer-patients-with-distant-metastases
#12
Yoshiya Horimoto, Atsushi Arakawa, Noriko Sasahara, Masahiko Tanabe, Sei Sai, Takanori Himuro, Mitsue Saito
The combination of CD44 and CD24, or aldehyde dehydrogenase 1 (ALDH1) alone, is a widely used cancer stem cell marker in breast cancer. However, no conclusion has yet been reached as to which marker is the best for characterizing cancer stemness. Immunohistochemical evaluation using cancer stem cell markers is clearly less common clinically than in basic experiments and how the expressions of these markers relate to patient outcomes remains controversial. To investigate whether combining these markers might improve the prediction of patient outcomes, we immunohistochemically examined clinical samples...
2016: PloS One
https://www.readbyqxmd.com/read/27738187/chitayat-syndrome-hyperphalangism-characteristic-facies-hallux-valgus-and-bronchomalacia-results-from-a-recurrent-c-266a-g-p-tyr89cys-variant-in-the-erf-gene
#13
M Balasubramanian, H Lord, S Levesque, H Guturu, F Thuriot, G Sillon, A M Wenger, D L Sureka, T Lester, D S Johnson, J Bowen, A R Calhoun, D H Viskochil, G Bejerano, J A Bernstein, D Chitayat
BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype...
October 13, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27724956/long-term-effects-on-luminal-and-mucosal-microbiota-and-commonly-acquired-taxa-in-faecal-microbiota-transplantation-for-recurrent-clostridium-difficile-infection
#14
Jonna Jalanka, Eero Mattila, Hanne Jouhten, Jorn Hartman, Willem M de Vos, Perttu Arkkila, Reetta Satokari
BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). It restores the disrupted intestinal microbiota and subsequently suppresses C. difficile. The long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. Further, the specific bacteria behind the treatment efficacy are also investigated. METHODS: We performed a high-throughput microbiota profiling using a phylogenetic microarray analysis of 131 faecal and mucosal samples from 14 rCDI patients pre- and post-FMT during a 1-year follow-up and 23 samples from the three universal donors over the same period...
October 11, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27693233/recurrent-de-novo-dominant-mutations-in-slc25a4-cause-severe-early-onset-mitochondrial-disease-and-loss-of-mitochondrial-dna-copy-number
#15
Kyle Thompson, Homa Majd, Christina Dallabona, Karit Reinson, Martin S King, Charlotte L Alston, Langping He, Tiziana Lodi, Simon A Jones, Aviva Fattal-Valevski, Nitay D Fraenkel, Ann Saada, Alon Haham, Pirjo Isohanni, Roshni Vara, Inês A Barbosa, Michael A Simpson, Charu Deshpande, Sanna Puusepp, Penelope E Bonnen, Richard J Rodenburg, Anu Suomalainen, Katrin Õunap, Orly Elpeleg, Ileana Ferrero, Robert McFarland, Edmund R S Kunji, Robert W Taylor
Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations...
October 6, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27676790/distribution-of-the-branches-of-common-and-superficial-fibular-nerves-to-peronei-longus-et-brevis-muscles-use-in-the-treatment-of-spasticity-of-fibular-muscles
#16
Christian Fontaine, Jean-Christophe Porchet, Aurélien Aumar, Michel-Yves Grauwin, Nadine Nachef, Étienne Allart
OBJECTIVE: Beside the posterior leg compartment, spasticity of the hemiplegic patient can involve other muscle groups in the leg. Spasticity of the lateral compartment is responsible of a vertical clonus that may be confused with the clonus of the triceps surae (long fibular) or a transverse clonus (short fibular), and by the liveliness of the tendon reflex when striking their tendon. Beside recurrent botulinum toxin injections, this spasticity may be treated by a hyponeurotisation by partial section of the branches of the superficial fibular nerve to the muscle(s) concerned...
September 2016: Annals of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/27636225/an-expert-review-of-pharmacogenomics-of-sickle-cell-disease-therapeutics-not-yet-ready-for-global-precision-medicine
#17
Khuthala Mnika, Gift D Pule, Collet Dandara, Ambroise Wonkam
Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids...
October 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27630826/treatment-of-elderly-patients-with-squamous-cell-carcinoma-of-the-head-and-neck
#18
REVIEW
Petr Szturz, Jan B Vermorken
The demographics of squamous cell carcinoma of the head and neck (SCCHN) is marked by a growing number of patients aged 65 and over, which is in line with global projections for other cancer types. In developed countries, more than half of new SCCHN cases are diagnosed in older people, and in 15 years from now, the proportion is expected to rise by more than 10%. Still, a high-level evidence-based consensus to guide the clinical decision process is strikingly lacking. The available data from retrospective studies and subset analyses of prospective trials suffer from a considerable underrepresentation of senior participants...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27589370/knock-in-of-the-recurrent-r368x-mutation-of-prkar1a-that-represses-camp-dependent-protein-kinase-a-activation-a-model-of-type-1-acrodysostosis
#19
Catherine Le Stunff, Francoise Tilotta, Jérémy Sadoine, Dominique Le Denmat, Claire Briet, Emmanuelle Motte, Eric Clauser, Pierre Bougnères, Catherine Chaussain, Caroline Silve
In humans, activating mutations in the PRKAR1A gene cause acrodysostosis 1 (ACRDYS1). These mutations result in a reduction in PKA activation caused by an impaired ability of cAMP to dissociate mutant PRKAR1A from catalytic PKA subunits. Two striking features of this rare developmental disease are renal resistance to PTH and chondrodysplasia resulting from the constitutive inhibition of PTHR1/Gsa/AC/cAMP/PKA signaling. We developed a knock-in of the recurrent ACRDYS1 R368X PRKAR1A mutation in the mouse. No litters were obtained from [R368X]/[+] females (thus no homozygous [R368X]/[R368X] mice)...
September 2, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27577194/pericardial-tamponade-due-to-haemorrhagic-pericardial-effusion-as-a-complication-of-prasugrel-a-case-report
#20
Fathima Aaysha Cader, M Maksumul Haq, Sahela Nasrin, Md Rezaul Karim
BACKGROUND: Striking an adequate balance between bleeding risks and prevention of stent thrombosis can be challenging in the setting of percutaneous coronary intervention (PCI) with drug eluting stents (DES) in acute myocardial infarction (MI). This is more pronounced in patients treated with both low molecular weight heparin (LMWH) and dual antiplatelet therapy (DAPT). Prasugrel, a second generation thienopyridine with more potent platelet inhibition capability, is associated with significant bleeding risks...
August 30, 2016: BMC Cardiovascular Disorders
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