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https://www.readbyqxmd.com/read/29778982/efficient-co-delivery-of-neo-epitopes-using-dispersion-stable-layered-double-hydroxide-nanoparticles-for-enhanced-melanoma-immunotherapy
#1
Ling-Xiao Zhang, Xi-Xiu Xie, Dong-Qun Liu, Zhi Ping Xu, Rui-Tian Liu
Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth...
May 10, 2018: Biomaterials
https://www.readbyqxmd.com/read/29777446/the-degree-of-hiv-1-amino-acid-variability-is-strictly-related-to-different-disease-progression-rates
#2
Rossana Scutari, Monica Faieta, Roberta D'Arrigo, Lavinia Fabeni, Cristina Mussini, Andrea Cossarizza, Claudio Casoli, Carlo Federico Perno, Valentina Svicher, Claudia Alteri, Stefano Aquaro
The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2)...
May 17, 2018: Virus Genes
https://www.readbyqxmd.com/read/29776931/shuffling-the-neutral-drift-of-unspecific-peroxygenase-in-saccharomyces-cerevisiae
#3
Javier Martin-Diaz, Carmen Paret, Eva García-Ruiz, Patricia Molina-Espeja, Miguel Alcalde
Unspecific peroxygenase (UPO) is a highly promiscuous biocatalyst and its selective mono(per)oxygenase activity makes it useful for many synthetic chemistry applications. Among the broad repertory of library creation methods for directed enzyme evolution, genetic drift allows neutral mutations to be accumulated gradually within a polymorphic network of variants. In this study, we conducted a campaign of genetic drift with UPO in Saccharomyces cerevisiae so that neutral mutations were simply added and recombined in vivo With low mutational loading and an activity threshold of 45% of the parent's native function, mutant libraries enriched in folded and active UPO variants were generated...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#4
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29771783/hiv-1-drug-resistance-among-ugandan-adults-attending-an-urban-out-patient-clinic
#5
Amrei von Braun, Christine Sekaggya-Wiltshire, Nadine Bachmann, Deogratius Ssemwanga, Alexandra U Scherrer, Maria Nanyonjo, Anne Kapaata, Pontiano Kaleebu, Huldrych F Günthard, Barbara Castelnuovo, Jan Fehr, Andrew Kambugu
BACKGROUND: Little is known about prevalence of drug resistance among HIV-infected Ugandans, a setting with over 15 years of public-sector access to antiretroviral therapy (ART) and where virological monitoring was only recently introduced. SETTING: This study was conducted in the adults' out-patient clinic of the Infectious Diseases Institute, Kampala, Uganda. METHODS: HIV genotyping was performed in ART naïve patients and in treatment experienced patients on ART for ≥ six months with virological failure (≥1000 copies/mL)...
April 27, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29769311/tumor-associated-calreticulin-variants-functionally-compromise-the-peptide-loading-complex-and-impair-its-recruitment-of-mhc-i
#6
Najla Arshad, Peter Cresswell
Major histocompatibility complex-I-β2 m dimers (MHC-I) bind peptides derived from intracellular proteins, enabling the immune system to distinguish between normal cells and those expressing pathogen-derived or mutant proteins. The peptides bind to MHC-I in the endoplasmic reticulum (ER), and this binding is facilitated by the peptide-loading complex (PLC), which contains calreticulin (CRT). CRT associates with MHC-I via a conserved glycan present on MHC-I and recruits it to the PLC for peptide binding. Somatic frameshift mutations in CRT (CRT-FS) drive the proliferation of a subset of myeloproliferative neoplasms (MPNs), which are chronic blood tumors...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29762171/hiv-transmission-in-discordant-couples-in-africa-in-the-context-of-art-availability
#7
Evonne Woodson, Alec Goldberg, Clive Michelo, Debby Basu, Sijia Tao, Raymond Schinazi, Yong Jiang, William Kilembe, Etienne Karita, Susan Allen, Eric Hunter
OBJECTIVE: This study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1 discordant couples in the context of ART. DESIGN: We identified 9 Zambian and 7 Rwandan acutely-infected, epidemiologically-linked couples from government CVCT clinics where transmitting partners reported being on ART near the time of transmission. METHODS: We quantified viral load (VL) and plasma antiretroviral (ARV) drug concentrations near the time of transmission and used these as surrogate measures for adherence...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29760186/hypertrophic-cardiomyopathy-mutations-increase-myofilament-ca-2-buffering-alter-intracellular-ca-2-handling-and-stimulate-ca-2-dependent-signalling
#8
Paul Robinson, Xing Liu, Alexander Sparrow, Suketu Patel, Yin Hua Zhang, Barbara Casadei, Hugh Watkins, Charles S Redwood
Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca2+ -sensitivity. Mouse models exhibit increased Ca2+ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca2+ - buffering and altered Ca2+ -handling contribute to HCM pathogenesis via activation of Ca2+ -dependent signalling. Here, we determined the primary effects of HCM mutations on intracellular Ca2+ -handling and Ca2+ -dependent signalling in a model system possessing Ca2+ -handling mechanisms and contractile protein isoforms close to human in the absence of potentially confounding remodeling...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29759595/her2-positive-lobular-versus-ductal-carcinoma-of-the-breast-pattern-of-first-recurrence-and-molecular-insights
#9
Lucia Da Ros, Anna Moretti, Patrizia Querzoli, Massimo Pedriali, Laura Lupini, Cristian Bassi, Paolo Carcoforo, Massimo Negrini, Antonio Frassoldati
BACKGROUND: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC). PATIENTS AND METHODS: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies...
April 18, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29759113/distinct-roles-of-atm-and-atr-in-the-regulation-of-arp8-phosphorylation-to-prevent-chromosome-translocations
#10
Jiying Sun, Lin Shi, Aiko Kinomura, Atsuhiko Fukuto, Yasunori Horikoshi, Yukako Oma, Masahiko Harata, Masae Ikura, Tsuyoshi Ikura, Roland Kanaar, Satoshi Tashiro
Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment...
May 8, 2018: ELife
https://www.readbyqxmd.com/read/29754816/the-cohesin-ring-uses-its-hinge-to-organize-dna-using-non-topological-as-well-as-topological-mechanisms
#11
Madhusudhan Srinivasan, Johanna C Scheinost, Naomi J Petela, Thomas G Gligoris, Maria Wissler, Sugako Ogushi, James E Collier, Menelaos Voulgaris, Alexander Kurze, Kok-Lung Chan, Bin Hu, Vincenzo Costanzo, Kim A Nasmyth
As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners...
April 30, 2018: Cell
https://www.readbyqxmd.com/read/29753376/effectiveness-of-sofosbuvir-ribavirin-and-peg-ifn%C3%AE-2a-in-the-treatment-of-na%C3%A3-ve-egyptian-patients-with-chronic-hepatitis-c-virus-genotype-4
#12
Fatma Abdallah, Gehad Mohamed, Mohsen Ibrahim, Mokhtar El Tarabily
BACKGROUND: Egypt is one of the largest epidemic areas of hepatitis C virus (HCV) in the world. Its prevalent genotype is 4 with a majority of subtype 4a. In 2013, the Food and Drug Administration approved a new direct-acting antiviral drug (sofosbuvir) to treat patients with chronic HCV infection. In Egypt, the patients are already being treated with sofosbuvir in conjunction with ribavirin and pegylated interferon alfa-2a (PEG-IFNα-2a) for 12 weeks since 2015. The present study was planned to explain the efficacy of this treatment regimen against the HCV genotype 4a in Egyptian patients and its pretreatment predictive factors of virological response...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29752295/-arid1a-deficiency-may-predict-response-to-immune-checkpoint-blockade
#13
(no author information available yet)
ARID1A deficiency impairs mismatch repair to increase tumor mutation load and promote tumor progression.
May 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29749584/droplet-digital-pcr-detects-high-rate-of-tp53-r249s-mutants-in-cell-free-dna-of-middle-african-patients-with-hepatocellular-carcinoma
#14
Agnès Marchio, Marie Amougou Atsama, Aubin Béré, Narcisse-Patrice Komas, Dominique Noah Noah, Paul Jean Adrien Atangana, Serge-Magloire Camengo-Police, Richard Njouom, Claudine Bekondi, Pascal Pineau
Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique...
May 10, 2018: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29748615/specific-targeting-of-point-mutations-in-egfr-l858r-positive-lung-cancer-by-crispr-cas9
#15
Alvin Ho-Kwan Cheung, Chit Chow, Jinglin Zhang, Yuhang Zhou, Tingting Huang, Kayla Ching-Kei Ng, Terry Cho-Tsun Or, Yoyo Yao Yao, Yujuan Dong, Jackie Mei-Wah Fung, Lei Xiong, Aden Ka-Yin Chan, Wai-Ming Raymond Lung, Wei Kang, Ka-Fai To
Cancer cells are defined genetically by the mutations they harbor, commonly single nucleotide substitutions. Therapeutic approaches which specifically target cancer cells by recognizing these defining genetic aberrations are expected to exhibit minimal side-effects. However, current protein-based targeted therapy is greatly limited by the range of genes that can be targeted, as well as by acquired resistance. We hypothesized that a therapeutic oligonucleotide-based strategy may address this need of specific cancer targeting...
May 10, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29748148/clinical-and-biochemical-features-of-different-molecular-etiologies-of-familial-chylomicronemia
#16
Robert A Hegele, Amanda J Berberich, Matthew R Ban, Jian Wang, Andres Digenio, Veronica J Alexander, Laura D'Erasmo, Marcello Arca, Alan Jones, Eric Bruckert, Erik S Stroes, Jean Bergeron, Fernando Civeira, Joseph L Witztum, Daniel Gaudet
BACKGROUND: Familial chylomicronemia syndrome (FCS) is an ultra-rare phenotype that is usually caused by biallelic mutations in the LPL gene encoding lipoprotein lipase, or less often in APOC2, APOA5, LMF1, or GPIHBP1 genes encoding cofactors or interacting proteins. OBJECTIVES: We evaluated baseline phenotypes among FCS participants in a phase 3 randomized placebo-controlled trial of volanesorsen (NCT02211209). METHODS: Baseline clinical, fasting, and postfat load metabolic markers were assessed...
April 4, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29747387/design-and-performance-of-property-gradient-ternary-nitride-coating-based-on-process-control
#17
Pei Yan, Kaijie Chen, Yubin Wang, Han Zhou, Zeyu Peng, Li Jiao, Xibin Wang
Surface coating is an effective approach to improve cutting tool performance, and multiple or gradient coating structures have become a common development strategy. However, composition mutations at the interfaces decrease the performance of multi-layered coatings. The key mitigation technique has been to reduce the interface effect at the boundaries. This study proposes a structure design method for property-component gradient coatings based on process control. The method produces coatings with high internal cohesion and high external hardness, which could reduce the composition and performance mutations at the interface...
May 9, 2018: Materials
https://www.readbyqxmd.com/read/29742518/immune-checkpoint-inhibitors-in-the-treatment-of-patients-with-neuroendocrine-neoplasia
#18
Matthias M Weber, Christian Fottner
BACKGROUND: Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. METHOD: Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29741737/genetic-and-epigenetic-features-of-rapidly-progressing-idh-mutant-astrocytomas
#19
Timothy E Richardson, Adwait Amod Sathe, Mohammed Kanchwala, Gaoxiang Jia, Amyn A Habib, Guanghua Xiao, Matija Snuderl, Chao Xing, Kimmo J Hatanpaa
IDH-mutant astrocytomas are significantly less aggressive than their IDH-wildtype counterparts. We analyzed The Cancer Genome Atlas dataset (TCGA) and identified a small group of IDH-mutant, WHO grade II-III astrocytomas (n = 14) with an unexpectedly poor prognosis characterized by a rapid progression to glioblastoma and death within 3 years of the initial diagnosis. Compared with IDH-mutant tumors with the typical, extended progression-free survival in a control group of age-similar patients, the tumors in the rapidly progressing group were characterized by a markedly increased level of overall copy number alterations ([CNA]; p = 0...
May 7, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29740579/the-role-of-genetics-in-advancing-precision-medicine-for-alzheimer-s-disease-a-narrative-review
#20
REVIEW
Yun Freudenberg-Hua, Wentian Li, Peter Davies
Alzheimer's disease (AD) is the most common type of dementia, which has a substantial genetic component. AD affects predominantly older people. Accordingly, the prevalence of dementia has been rising as the population ages. To date, there are no effective interventions that can cure or halt the progression of AD. The only available treatments are the management of certain symptoms and consequences of dementia. The current state-of-the-art medical care for AD comprises three simple principles: prevent the preventable, achieve early diagnosis, and manage the manageable symptoms...
2018: Frontiers in Medicine
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