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Clinical and Translational Medicine

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https://www.readbyqxmd.com/read/28101783/tissue-is-the-issue-and-tissue-competition-re-biopsy-for-mutation-t790-where-and-why
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27995592/clinical-protein-science-developments-for-patient-monitoring-in-hospital-central-laboratories
#7
LETTER
Johan Malm, György Marko-Varga
Patient care relies heavily on standardized tests performed in hospital laboratories, typically including clinical chemistry, pathology and microbiology. With the introduction of personalized medicine tremendous efforts have been made to identify new biomarkers of disease with various omics technologies, often including mass spectrometry. In order to validate new biomarkers and perform clinical studies high quality biobank samples are of key importance. In this editorial different aspects of mass spectrometry in future personalized medicine are discussed...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27921284/safety-concerns-and-hidden-agenda-behind-hpv-vaccines-another-generation-of-drug-dependent-society
#8
LETTER
Mahin Khatami
Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research ('medical/scientific ponzi schemes') is potent recipe for failed therapeutics that kills patients but generates huge corporate profit. American health status ranks last among other developed nations despite the highest amount that USA invests in healthcare...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27921283/choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer
#9
REVIEW
Sonali Bhattacharjee, Saikat Nandi
BACKGROUND: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27905089/novel-paradigm-for-immunotherapy-of-ovarian-cancer-by-engaging-prophylactic-immunity-against-hepatitis-b-virus
#10
Marek Malecki, Emily Putzer, Caroline Quach, Chaitanya Dodivenaka, Xenia Tombokan
BACKGROUND: Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27766605/evaluation-of-patients-with-multiple-sclerosis-using-reverse-nutech-functional-score-and-expanded-disability-status-scale-after-human-embryonic-stem-cell-therapy
#11
Geeta Shroff
BACKGROUND: The expanded disability status scale (EDSS) is a validated and reliable tool to assess the extent of disabilities in patients with multiple sclerosis (MS). However, the use of this tool has been found to be limited in assessing various symptoms of MS that are important. Our study aimed at evaluating the efficacy of a new scoring system, reverse nutech functional score (RNFS) as compared to EDSS in assessing patients with MS treated with human embryonic stem cell (hESC) therapy...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27766604/a-braided-cancer-river-connects-tumor-heterogeneity-and-precision-medicine
#12
James J Hsieh, Emily H Cheng
With the ever-increasing complexity of tumor heterogeneity (TH) discovered through cancer genome sequencing, it is apparent that TH has become the biggest hurdle for precision cancer therapeutics. Through studying the genomics of exceptional responders to targeted therapeutic agents in kidney cancer, we demonstrated parallel convergent gene/pathway/capability/function evolution of kidney cancer in the context of TH, which prompted us to propose a new cancer evolution model "the braided cancer river model". Based on this model, we might be able to outsmart a given cancer type within an individual patient through simultaneously inhibiting preferred parallel pathways or sequential nodes...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27766603/role-of-physiotherapy-in-the-mobilization-of-patients-with-spinal-cord-injury-undergoing-human-embryonic-stem-cells-transplantation
#13
Geeta Shroff, Dipin Thakur, Varun Dhingra, Deepak Singh Baroli, Deepanshu Khatri, Rahul Dev Gautam
BACKGROUND: The major complication faced by patients with chronic static spinal cord injury (SCI) is the loss of mobilization. With the aim to rehabilitate SCI patients, physiotherapy is performed worldwide. However, it only helps the patients to live with their disabilities. An interdisciplinary management involving human embryonic stem cell (hESC) therapy along with physiotherapy as a supportive therapy offers regenerative treatment of the patients with SCI. MAIN BODY: The present study focuses on the role of physiotherapy in the mobilization of patients with SCI (paraplegic 136; tetraplegics 90) undergoing hESC therapy...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27766602/clinical-study-of-gene-eden-vir-novirin-in-genital-herpes-suppressive-treatment-safely-decreases-the-duration-of-outbreaks-in-both-severe-and-mild-cases
#14
Hanan Polansky, Edan Itzkovitz, Adrian Javaherian
BACKGROUND: We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27709523/serum-levels-of-s100a6-are-unaltered-in-patients-with-resectable-cholangiocarcinoma
#15
Sven H Loosen, Fabian Benz, Jennifer Niedeggen, Maximilian Schmeding, Florian Schüller, Alexander Koch, Mihael Vucur, Frank Tacke, Christian Trautwein, Christoph Roderburg, Ulf P Neumann, Tom Luedde
BACKGROUND: Elevated expression levels of S100A6, a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies. Moreover, increased serum levels of S100A6 were suggested as a novel biomarker for various inflammatory and malignant diseases including lung and gastric cancer. However, up to now, serum concentrations of S100A6 have not been analyzed in patients with cholangiocarcinoma (CCA). METHODS: S100A6 mRNA expression levels were analyzed in human and murine CCA tumor samples, using semi-quantitative reverse transcriptase PCR...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27709522/adult-pulmonary-tuberculosis-as-a-pathological-manifestation-of-hyperactive-antimycobacterial-immune-response
#16
Pawan Kumar
The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27596232/pharmacokinetics-of-oseltamivir-in-infants-under-the-age-of-1-year
#17
Rashmi Dixit, Slade Matthews, Gulam Khandaker, Karen Walker, Marino Festa, Robert Booy
BACKGROUND: Oseltamivir is the only antiviral treatment recommended for influenza in young children over the age of 1 year. There is scant data on oseltamivir pharmacokinetics (PK) in infants <1 year. We set out to perform PK measurements in infants who received oseltamivir. METHODS: This study was a prospective, uncontrolled, open label evaluation of the pharmacokinetics of oseltamivir metabolism, safety of oseltamivir, viral clearance in infants <12 months diagnosed with influenza by nasopharyngeal influenza nucleic acid antigen test (NAAT)...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27590145/jnk-inhibition-reduces-lung-remodeling-and-pulmonary-fibrotic-systemic-markers
#18
Jos L J van der Velden, Ying Ye, James D Nolin, Sidra M Hoffman, David G Chapman, Karolyn G Lahue, Sarah Abdalla, Peng Chen, Yong Liu, Brydon Bennett, Nasreen Khalil, Donna Sutherland, William Smith, Gerald Horan, Mahmoud Assaf, Zebulun Horowitz, Rajesh Chopra, Randall M Stevens, Maria Palmisano, Yvonne M W Janssen-Heininger, Peter H Schafer
BACKGROUND: Lung remodeling and pulmonary fibrosis are serious, life-threatening conditions resulting from diseases such as chronic severe asthma and idiopathic pulmonary fibrosis (IPF). Preclinical evidence suggests that JNK enzyme function is required for key steps in the pulmonary fibrotic process. However, a selective JNK inhibitor has not been investigated in translational models of lung fibrosis with clinically relevant biomarkers, or in IPF patients. METHODS: The JNK inhibitor CC-930 was evaluated in the house dust mite-induced fibrotic airway mouse model, in a phase I healthy volunteer pharmacodynamic study, and subsequently in a phase II multicenter study of mild/moderate IPF (n = 28), with a 4-week, placebo-controlled, double-blind, sequential ascending-dose period (50 mg QD, 100 mg QD, 100 mg BID) and a 52-week open-label treatment-extension period...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27558401/is-cancer-a-severe-delayed-hypersensitivity-reaction-and-histamine-a-blueprint
#19
Mahin Khatami
Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27539581/therapeutic-use-of-stem-cells-for-cardiovascular-disease
#20
REVIEW
Whitney Faiella, Rony Atoui
Stem cell treatments are a desirable therapeutic option to regenerate myocardium and improve cardiac function after myocardial infarction. Several different types of cells have been explored, each with their own benefits and limitations. Induced pluripotent stem cells possess an embryonic-like state and therefore have a high proliferative capacity, but they also pose a risk of teratoma formation. Mesenchymal stem cells have been investigated from both bone marrow and adipose tissue. Their immunomodulatory characteristics may permit the use of allogeneic cells as universal donor cells in the future...
December 2016: Clinical and Translational Medicine
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