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Clinical and Translational Medicine

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https://www.readbyqxmd.com/read/28597408/single-cell-rna-sequencing-of-the-brain
#1
REVIEW
Raquel Cuevas-Diaz Duran, Haichao Wei, Jia Qian Wu
Single-cell RNA-sequencing (scRNA-seq) is revolutionizing our understanding of the genomic, transcriptomic and epigenomic landscapes of cells within organs. The mammalian brain is composed of a complex network of millions to billions of diverse cells with either highly specialized functions or support functions. With scRNA-seq it is possible to comprehensively dissect the cellular heterogeneity of brain cells, and elucidate their specific functions and state. In this review, we describe the current experimental methods used for scRNA-seq...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28577109/phosgene-induced-acute-lung-injury-ali-differences-from-chlorine-induced-ali-and-attempts-to-translate-toxicology-to-clinical-medicine
#2
REVIEW
Wenli Li, Juergen Pauluhn
BACKGROUND: Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and inhaled-dose-dependent etiopathologies and associated preventive or therapeutic treatment strategies. METHODS: Cardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28510121/can-glypican-3-be-a-disease-specific-biomarker
#3
REVIEW
Chaolei Chen, Xiaomin Huang, Zhaojian Ying, Dengmin Wu, Yani Yu, Xiangdong Wang, Chengshui Chen
BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28493232/anthracycline-induced-cardiotoxicity-biomarkers-and-omics-technology-in-the-era-of-patient-specific-care
#4
REVIEW
Shayan Moazeni, Martin Cadeiras, Eric H Yang, Mario C Deng, Kim-Lien Nguyen
Anthracyclines are highly effective against a variety of malignancies. However, their dose-dependent cardiotoxic effects can potentially limit their use. In the past decade, serum biomarkers have been used to diagnose, monitor, predict, and prognosticate disease. Biomarkers such as cardiac troponin and natriuretic peptides have some predictive value, but still lack reliability in this patient population. Novel biomarkers such as galectin-3, soluble ST-2 proteins, myeloperoxidase, and fibrocytes are being explored as potential biomarkers to reliably predict the onset of cardiotoxicity...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28474232/ets-targeted-therapy-can-it-substitute-for-mek-inhibitors
#5
REVIEW
Osamu Tetsu, Frank McCormick
BACKGROUND: The RAS/MAPK pathway has been intensively studied in cancer. Constitutive activation of ERK1 and ERK2 is frequently found in cancer cells from a variety of tissues. In clinical practice and clinical trials, small molecules targeting receptor tyrosine kinases or components in the MAPK cascade are used for treatment. MEK1 and MEK2 are ideal targets because these enzymes are physiologically important and have narrow substrate specificities and distinctive structural characteristics...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28405930/single-cell-sequencing-and-tumorigenesis-improved-understanding-of-tumor-evolution-and-metastasis
#6
REVIEW
Darrell L Ellsworth, Heather L Blackburn, Craig D Shriver, Shahrooz Rabizadeh, Patrick Soon-Shiong, Rachel E Ellsworth
Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#7
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28332147/lessons-from-the-swamp-developing-small-molecules-that-confer-salamander-muscle-cellularization-in-mammals
#8
LETTER
JungIn Um, Da-Woon Jung, Darren Reece Williams
The ability of salamanders, such as newts, to regenerate damaged tissues has been studied for centuries. A prominent example of this regenerative power is the ability to re-grow entire amputated limbs. One important step in this regeneration process is skeletal muscle cellularization, in which the muscle fibers break down into dedifferentiated, mononuclear cells that proliferate and form new muscle in the replacement limb. In contrast, mammalian skeletal muscle does not undergo cellularization after injury...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28251572/translational-research-in-pediatric-pulmonary-disease-2017
#9
Bruce K Rubin
As readers of this journal know, translational research is the application of basic science findings to improve clinical care; a process that was once called "bench-to-bedside" research. In my field of pediatric pulmonary disease, the rapid advancement of basic science understanding into improved clinical care has been, to use an appropriate term, breathtaking. In this perspective article, I will describe a few of these advances, as they relate to specific pulmonary diseases.
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28251571/survivin-a-radiogenetic-promoter-for-glioblastoma-viral-gene-therapy-independently-from-carg-motifs
#10
George E Naoum, Zeng B Zhu, Donald J Buchsbaum, David T Curiel, Waleed O Arafat
BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28220395/single-cell-sequencing-a-distinct-new-field
#11
REVIEW
Jian Wang, Yuanlin Song
Single cell sequencing (SCS) has become a new approach to study biological heterogeneity. The advancement in technologies for single cell isolation, amplification of genome/transcriptome and next-generation sequencing enables SCS to reveal the inherent properties of a single cell from the large scale of the genome, transcriptome or epigenome at high resolution. Recently, SCS has been widely applied in various clinical and research fields, such as cancer biology and oncology, immunology, microbiology, neurobiology and prenatal diagnosis...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28197968/integrating-phosphoproteomics-into-the-clinical-management-of-prostate-cancer
#12
LETTER
Larry C Cheng, Victor M Tan, Shridar Ganesan, Justin M Drake
Phosphoproteomic analysis of tumor samples has the potential to uncover significant insights into kinase signaling networks present in late stage prostate cancer that are complementary to genomic and transcriptomic approaches. Phosphoproteomics could potentially aid drug development in clinical trial design as well as provide utility for oncologists in the personalized therapeutic management of individual cancers through identifying novel biomarkers and druggable targets. Rapid advancement of targeted mass spectrometry platforms is underway to integrate phosphoproteomic technology with genomic assays to soon translate this information into the cancer clinic...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28176278/re-choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer%C3%A2
#13
LETTER
Michael McKay
No abstract text is available yet for this article.
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28108884/precision-medicine-in-immune-checkpoint-blockade-therapy-for-non-small-cell-lung-cancer
#14
LETTER
Xiaoming Liu, William C Cho
Immune checkpoint blockade therapy by targeting the programmed death protein 1/programmed death ligand 1 (PD-L1) axis using antibodies has yielded promising clinical responses in patients with non-small cell lung cancer (NSCLC). However, owing to the dynamic expression of PD-L1, degree of mutational/neoantigen load, intratumoral heterogeneity, infiltrated immune cells of tumor microenvironment of NSCLC, the response rates to these agents are limited, despite several companion diagnostic assays by detecting PD-L1 in tumor cells have been introduced into clinical practice...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101783/tissue-is-the-issue-and-tissue-competition-re-biopsy-for-mutation-t790-where-and-why
#15
LETTER
Paul Zarogoulidis, Mina Gaga, Haidong Huang, Kaid Darwiche, Aggeliki Rapti, Wolfgang Hohenforst-Schmidt
Lung cancer is still the leading cause of death among all cancers. During the last 15 years, pharmacogenomics of lung cancer have established targeted therapy with tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) positive patients in adenocarcinoma or mixed adenosquamus lung cancer patients. However; while novel drugs are released in the market, at the same time novel mutations are observed after tyrosine kinase inhibitor administration. Recently the novel mutation T790 was observed and is highly prevalent in patients already treated with a TKI...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#16
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28054277/contact-allergy-to-aluminium-induced-by-commonly-used-pediatric-vaccines
#17
LETTER
E Bergfors, B Trollfors, A Inerot, A Gente Lidholm
No abstract text is available yet for this article.
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28050779/a-current-perspective-on-cancer-immune-therapy-step-by-step-approach-to-constructing-the-magic-bullet
#18
REVIEW
Gabriele D'Errico, Heather L Machado, Bruno Sainz
Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28050778/a-systematic-approach-to-cancer-evolution-beyond-selection
#19
William B Miller, John S Torday
Cancer is typically scrutinized as a pathological process characterized by chromosomal aberrations and clonal expansion subject to stochastic Darwinian selection within adaptive cellular ecosystems. Cognition based evolution is suggested as an alternative approach to cancer development and progression in which neoplastic cells of differing karyotypes and cellular lineages are assessed as self-referential agencies with purposive participation within tissue microenvironments. As distinct self-aware entities, neoplastic cells occupy unique participant/observer status within tissue ecologies...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28044245/mri-detection-of-endothelial-cell-inflammation-using-targeted-superparamagnetic-particles-of-iron-oxide-spio
#20
Joyce M S Chan, Maggie S H Cheung, Richard G J Gibbs, Kishore K Bhakoo
BACKGROUND: There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells. METHODS: The in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO...
December 2017: Clinical and Translational Medicine
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