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https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#1
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#2
Kevin D Quinn, Michaela Schedel, Yasmeen Nkrumah-Elie, Anthony Joetham, Michael Armstrong, Charmion Cruickshank-Quinn, Richard Reisdorph, Erwin W Gelfand, Nichole Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213834/molecular-simulation-of-receptor-occupancy-and-tumor-penetration-of-an-antibody-and-smaller-scaffolds-application-to-molecular-imaging
#3
Kelly D Orcutt, Gregory P Adams, Anna M Wu, Matthew D Silva, Catey Harwell, Jack Hoppin, Manabu Matsumura, Masakatsu Kotsuma, Jonathan Greenberg, Andrew M Scott, Robert A Beckman
PURPOSE: Competitive radiolabeled antibody imaging can determine the unlabeled intact antibody dose that fully blocks target binding but may be confounded by heterogeneous tumor penetration. We evaluated the hypothesis that smaller radiolabeled constructs can be used to more accurately evaluate tumor expressed receptors. PROCEDURES: The Krogh cylinder distributed model, including bivalent binding and variable intervessel distances, simulated distribution of smaller constructs in the presence of increasing doses of labeled antibody forms...
February 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28213717/the-minor-collagens-in-articular-cartilage
#4
REVIEW
Yunyun Luo, Dovile Sinkeviciute, Yi He, Morten Karsdal, Yves Henrotin, Ali Mobasheri, Patrik Önnerfjord, Anne Bay-Jensen
Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions...
February 17, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28213655/molecular-characterization-of-the-unique-mesostephanus-appendiculatus-trematoda-cyathocotylidae-by-small-ribosomal-rna-from-egypt
#5
Nasr M El-Bahy, Eman K Bazh, Shimaa S Sorour, Nagwa M Elhawary
M esostephanus appendiculatus (Family: Cyathocotylidae) is one of the unique trematodes that complete their cycles in human and animal intestines in many countries of the world. The main source of its transmission is eating raw or undercooked infected fish muscle. Earliest analyses of genes to different parasites supported the analysis of helminthes either biological or morphological. This paper detected M. appendiculatus sequence with GenBank accession number gb (KY026782). Comparison of M. appendiculatus with other helminthes using BioEdit 7 and MEGA7 program shows some similarity in different points along its sequence...
February 18, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28213654/molecular-epidemiology-of-leptospira-serogroup-pomona-infections-among-wild-and-domestic-animals-in-spain
#6
Z J Arent, C Gilmore, J M San-Miguel Ayanz, L Quevedo Neyra, F J García-Peña
Strains of Leptospira serogroup Pomona are known to cause widespread animal infections in many parts of the world. Forty-three isolates retrieved from domestic animals and wild small mammals suggest that serogroup Pomona is epidemiologically relevant in Spain. This is supported by the high prevalence of serovar Pomona antibodies in livestock and wild animals. In this study, the strains were serologically and genetically characterized in an attempt to elucidate their epidemiology. Serological typing was based on the microscopic agglutination test but molecular typing involved species-specific polymerase chain reaction, restriction endonuclease analysis, and multiple-locus variable-number tandem repeat analysis...
February 17, 2017: EcoHealth
https://www.readbyqxmd.com/read/28213571/mir-146a-b-a-family-with-shared-seeds-and-different-roots
#7
Mark Paterson, Alison J Kriegel
MicroRNAs are small, non-coding, RNAs known for their powerful modulation of molecular processes, making them a major focus for studying pathological mechanisms. The human miR-146 family of microRNAs consists of two member genes - MIR146A and MIR146B These two miRNAs are located on different chromosomes and exhibit differential regulation in many cases. However, they are nearly identical in sequence and share a seed sequence, thus they are predicted to target the same set of genes. A large proportion of the miR-146 literature focuses on its role in regulating the innate immune response in the context of various pathologies by modulating two widely studied target genes in the toll-like receptor signaling cascade...
February 17, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28213570/blunted-transcriptional-response-to-skeletal-muscle-ischemia-in-rats-with-chronic-kidney-disease-potential-role-for-impaired-ischemia-induced-angiogenesis
#8
Rafael U Heiss, Fabian Fahlbusch, Johannes Jacobi, Christoph Daniel, Arif B Ekici, Nada Cordasic, Kerstin Amann, Andrea Hartner, Karl F Hilgers
Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without CKD to identify potential molecular mechanisms underlying impaired angiogenesis in CKD. CKD was induced in male rats by 5/6 nephrectomy (SNX); control rats were sham operated (sham). Eight weeks later, ischemia of the right limb was induced by ligation and resection of the femoral artery...
February 17, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28213528/leptospira-interrogans-serogroup-pomona-infections-in-the-uk-is-there-a-real-threat-for-farm-animals
#9
Z Arent, C Gilmore, A M Barlow, L Smith, W A Ellis
Current typing of Leptospira strains requires a combination of both serological and molecular methods. Study of the epidemiology of strains within the Pomona serogroup has proved problematic due to the limitations of serological typing methods. This is particularly true of the two main complexes within this group, namely the Pomona, Monjakov, Kennewicki cluster in Leptospira interrogans species and the Mozdok, Tsaratsovo, Kunming, Altodouro cluster in Leptospira kirschneri Strains from the south of England have been shown previously to belong to L kirschneri serovar Mozdok, strains of which are maintained by small rodents in western Europe...
February 17, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28213139/antimycobacterial-antimicrobial-activity-experimental-ft-ir-ft-raman-nmr-uv-vis-dsc-and-dft-transition-state-chemical-reactivity-nbo-nlo
#10
Poonam Rawat, R N Singh, Alok Ranjan, Sartaj Ahmad, Rajat Saxena
As part of a study of pyrrole hydrazone, we have investigated quantum chemical calculations, molecular geometry, relative energy, vibrational properties and antimycobacterial/antimicrobial activity of pyrrole-2-carboxaldehyde isonicotinyl hydrazone (PCINH), by applying the density functional theory (DFT) and Hartree Fock (HF). Good reproduction of experimental values is obtained and with small percentage error in majority of the cases in comparison to theoretical result (DFT). The experimental FT-IR and Raman wavenumbers were compared with the respective theoretical values obtained from DFT calculations and found to agree well...
February 11, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28212848/major-vectors-and-vector-borne-diseases-in-small-ruminants-in-ethiopia-a-systematic-review
#11
REVIEW
Kassahun Asmare, Takele Abayneh, Berhanu Sibhat, Dessie Shiferaw, Barbara Szonyi, Randi I Krontveit, Eystein Skjerve, Barbara Wieland
Vector-borne diseases are among major health constraints of small ruminant in Ethiopia. While various studies on single vector-borne diseases or presence of vectors have been conducted, no summarized evidence is available on the occurrence of these diseases and the related vectors. This systematic literature review provides a comprehensive summary on major vectors and vector-borne diseases in small ruminants in Ethiopia. Search for published and unpublished literature was conducted between 8th of January and 25th of June 2015...
February 14, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28212799/rho-mancing-to-sensitize-calcium-signaling-for-contraction-in-the-vasculature-role-of-rho-kinase
#12
T Szasz, R C Webb
Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212751/stable-heritable-germline-silencing-directs-somatic-silencing-at-an-endogenous-locus
#13
Olga Minkina, Craig P Hunter
The importance of transgenerationally inherited epigenetic states to organismal fitness remains unknown as well-documented examples are often not amenable to mechanistic analysis or rely on artificial reporter loci. Here we describe an induced silenced state at an endogenous locus that persists, at 100% transmission without selection, for up to 13 generations. This unusually persistent silencing enables a detailed molecular genetic analysis of an inherited epigenetic state. We find that silencing is dependent on germline nuclear RNAi factors and post-transcriptional mechanisms...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28212545/snora74b-gene-silencing-inhibits-gallbladder-cancer-cells-by-inducing-phlpp-and-suppressing-akt-mtor-signaling
#14
Yiyu Qin, Li Meng, Yang Fu, Zhiwei Quan, Mingzhe Ma, Mingzhe Weng, Zhengdong Zhang, Cuixiang Gao, Xinghua Shi, Koulan Han
Small nucleolar RNAs (snoRNAs) have been implicated in the development of many cancers. We therefore examined the differential expression of snoRNAs between gallbladder cancer (GBC) tissues and matched adjacent non-tumor tissues using expression microarray analysis with confirmation by quantitative real-time PCR (qRT-PCR). Western blot analysis showed that SNORA74B levels were higher in GBC than non-tumor tissues. SNORA74B expression was positively associated with local invasion, advanced TNM stage, CA19-9 level, and Ki67 expression in patients with GBC, while it was negatively associated with expression of PHLPP, an endogenous Akt inhibitor...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212270/antitumor-effects-of-laminaria-extract-fucoxanthin-on-lung-cancer
#15
ChengHan Mei, ShunChang Zhou, Lin Zhu, JiaXiong Ming, FanDian Zeng, Rong Xu
Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC) is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX), a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time...
February 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28212155/molecular-markers-in-lung-cancer-role-of-ebus
#16
Semra Bilaçeroğlu
PURPOSE OF REVIEW: As demonstrated by the recent therapeutic advances in nonsmall cell lung cancer (NSCLC), a personalized approach can considerably reduce its mortality. RECENT FINDINGS: Molecular tests identifying genetic mutations in NSCLC have led to a shift towards more effective and personalized therapies targeted to these alterations. Adequate tissue is required for diagnosing, subcharacterizing, and genotyping NSCLC by morphological, immunohistochemical, and molecular techniques...
February 16, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#17
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#18
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#19
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28210726/exploring-the-interaction-of-phenothiazinium-dyes-methylene-blue-new-methylene-blue-azure-a-and-azure-b-with-trna-phe-spectroscopic-thermodynamic-voltammetric-and-molecular-modeling-approach
#20
Puja Paul, Soumya Sundar Mati, Subhash Chandra Bhattacharya, Gopinatha Suresh Kumar
This study focuses on the understanding of the interaction of phenothiazinium dyes methylene blue (MB), new methylene blue (NMB), azure A (AZA) and azure B (AZB) with tRNA(Phe) with particular emphasis on deciphering the mode and energetics of the binding. Strong intercalative binding to tRNA(Phe) was observed for MB, NMB and AZB, bound by a partial intercalative mode. AZA has shown groove binding characteristics. From spectroscopic studies binding affinity values of the order of 10(5) M(-1) were deduced for these dyes; the trend varied as MB > NMB > AZB > AZA...
February 17, 2017: Physical Chemistry Chemical Physics: PCCP
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