336,094 results match your criteria Gene Therapy & Molecular Biology [Journal]


Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology.

J Mol Diagn 2019 Feb 19. Epub 2019 Feb 19.

Department of Medicine, Division of Clinical Pharmacology.

The Clinical Laboratory Improvement Amendments (CLIA) of 1988 requires that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SOD2, TLR4, and TPMT were validated in a CLIA-accredited laboratory. As no known reference materials were available, DNA samples that were from Coriell Cell Repositories (Camden, NJ) were used for the analytical validation studies. Read More

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http://dx.doi.org/10.1016/j.jmoldx.2019.01.009DOI Listing
February 2019

Autologous Transplantation for Male Germ Cell Tumors: Improved Outcomes over 3 decades.

Biol Blood Marrow Transplant 2019 Feb 19. Epub 2019 Feb 19.

Medical College of Wisconsin, Milwaukee, WI.

Purpose: The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCT) is well established. Optimal timing and number (single, ST vs. tandem, TT vs. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.02.015DOI Listing
February 2019

Reactive cholangiocytes differentiate into proliferative hepatocytes with efficient DNA repair in mice with chronic liver injury.

J Hepatol 2019 Feb 19. Epub 2019 Feb 19.

Laboratory of Hepato-gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium. Electronic address:

Background And Aim: Chronic liver diseases are characterized by expansion of the small immature cholangiocytes - a mechanism named ductular reaction (DR) - which have the capacity to differentiate in hepatocytes. We investigated the kinetics of DR differentiation into hepatocytes as well as several important features as functional maturity, clonal expansion and resistant to stress of the newly formed hepatocytes in mice with long-term liver damage.

Methods: We tracked cholangiocytes using osteopontin-iCreER and hepatocytes with AAV8-TBG-Cre. Read More

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http://dx.doi.org/10.1016/j.jhep.2019.02.003DOI Listing
February 2019

Lipid gene nanocarriers for the treatment of skin diseases: current state-of-the-art.

Eur J Pharm Biopharm 2019 Feb 19. Epub 2019 Feb 19.

Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liege, Belgium.

Nucleic acids carried by non-viral nanovectors have demonstrated high potential as a therapeutic strategy for gene-related diseases. The dermal or transdermal gene delivery allow to target local skin diseases or to reach the blood stream. However, the skin is the first defense barrier of the body and must be overcome to distribute nucleic acids. Read More

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http://dx.doi.org/10.1016/j.ejpb.2019.02.012DOI Listing
February 2019

β-Catenin and yes-associated protein 1 cooperate in hepatoblastoma pathogenesis.

Am J Pathol 2019 Feb 19. Epub 2019 Feb 19.

Department of Gynecology, Shiyan Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China. Electronic address:

Hepatoblastoma (HB), the most common pediatric primary liver neoplasm, show nuclear localization of β-catenin and yes-associated protein1 (YAP1) in almost 80% of the cases. Co-expression of constitutively active S127A-YAP1 and ΔN90 deletion-mutant-β-catenin (YAP1-ΔN90-β-catenin) causes HB in mice. Since heterogeneity in downstream signaling is being identified owing to mutational differences even in β-catenin gene alone, we investigated if co-expression of point-mutants of β-catenin (S33Y or S45Y) with S127A-YAP1 led to similar tumors as YAP1-ΔN90-β-catenin. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.02.002DOI Listing
February 2019

Innovation in Chemistry, Manufacturing, and Controls - A Regulatory Perspective From Industry.

J Pharm Sci 2019 Feb 19. Epub 2019 Feb 19.

Regulatory Affairs CMC, Amgen Inc., Thousand Oaks, CA, USA.

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. Additionally, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. Read More

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http://dx.doi.org/10.1016/j.xphs.2019.02.007DOI Listing
February 2019

IL12 p35 and p40 subunit genes administered as pPAL plasmid constructs do not improve protection of pPAL-LACK vaccine against canine leishmaniasis.

PLoS One 2019 22;14(2):e0212136. Epub 2019 Feb 22.

Laboratory of Molecular Parasitology, Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.

Leishmania infantum causes zoonotic visceral leishmaniasis (ZVL) in the Mediterranean basin and South America. The parasite has been shown to co-infect HIV patients and an outbreak in central Spain was reported in the last decade. Therfore, ZVL is a public health problem, dogs being the parasite's reservoir. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212136PLOS
February 2019

Association of Missense Polymorphism in HSD3B1 With Outcomes Among Men With Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone.

JAMA Netw Open 2019 Feb 1;2(2):e190115. Epub 2019 Feb 1.

Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Importance: Recently, genetic polymorphism in HSD3B1 encoding 3β-hydroxysteroid dehydrogenase-1 has been shown to be associated with oncological outcome when treated with androgen-deprivation therapy (ADT) for prostate cancer. Upfront abiraterone combined with ADT has proved survival benefit. However, its effect on oncological outcome among different ethnicities and in abiraterone treatment remain unclear. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2019.0115DOI Listing
February 2019

What Factors Are Associated With Early Mortality in Patients Undergoing Femur Surgery for Metastatic Lung Cancer?

Clin Orthop Relat Res 2018 Sep;476(9):1815-1822

J. H. Kim, Orthopaedic Oncology Clinic, National Cancer Center, Goyang-Si, Korea S. W. Seo, C. H. Chung, Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Pathologic fractures of the femur resulting from metastasis severely increase mortality in patients with nonsmall cell lung cancer (NSCLC). However, factors associated with early mortality after surgery have not been elucidated.

Questions/purposes: The purpose of this study was to identify clinical and laboratory factors available to surgeons before surgery for a metastatic femur in patients with metastatic lung cancer that might be associated with mortality at 1 and 3 months. Read More

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http://dx.doi.org/10.1007/s11999.0000000000000101DOI Listing
September 2018

Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration.

J Neurotrauma 2019 Feb 22. Epub 2019 Feb 22.

Universidade Federal do Rio Grande do Sul, 28124, Departamento de Bioquímica, ICBS, Porto Alegre, RS, Brazil ;

Traumatic brain injury (TBI) increases Ca2+ influx into neurons and desynchronizes mitochondrial function leading to energy depletion and apoptosis. This process may be influenced by brain testosterone (TS) levels, which are known to decrease after TBI. We hypothesized that a TS based therapy could preserve mitochondrial neuroenergetics after TBI, thereby reducing neurodegeneration. Read More

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http://dx.doi.org/10.1089/neu.2018.6266DOI Listing
February 2019

Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naïve and Experienced Individuals from Western India.

AIDS Res Hum Retroviruses 2019 Feb 22. Epub 2019 Feb 22.

Armed Forces Medical College, 29590, Internal Medicine, Pune, Maharashtra, India ;

Background: The Indian national AIDS control program heavily relies on low cost nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI). With global increase in resistance to these, alternative antiretroviral combinations need to be explored. Owing to higher potency, better efficacy and tolerability, recently WHO recommended integrase strand transfer inhibitor (INSTI) based first-line antiretroviral therapy (ART). Read More

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http://dx.doi.org/10.1089/AID.2018.0272DOI Listing
February 2019

Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor T-cell therapy.

Expert Rev Hematol 2019 Feb 22. Epub 2019 Feb 22.

a Division of Medical Oncology, Department of Internal Medicine , University of Washington School of Medicine , Seattle , WA , USA.

Introduction: Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated remarkable anti-tumor activity in B-cell malignancies and is under investigation in other hematologic malignancies and solid tumors. While highly efficacious, post-infusion T cell activity often results in massive cytokine release precipitating cytokine release syndrome (CRS), the signature toxicity of CAR T cells. This toxicity is characterized by systemic immune activation resulting in fever, hypotension, respiratory insufficiency and capillary leak. Read More

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http://dx.doi.org/10.1080/17474086.2019.1585238DOI Listing
February 2019

Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet.

Diabetes Metab J 2019 Feb;43(1):3-30

Division of Endocrinology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Read More

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http://dx.doi.org/10.4093/dmj.2018.0259DOI Listing
February 2019

The neuroplastic effect of olfactory training to the recovery of olfactory system in mouse model.

Int Forum Allergy Rhinol 2019 Feb 21. Epub 2019 Feb 21.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next-generation sequencing to evaluate the effects of OT on mRNA sequencing in the olfactory area.

Methods: Mice in each group were administered 300 mg of 3-methylindole per kilogram of mouse weight. Read More

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http://dx.doi.org/10.1002/alr.22320DOI Listing
February 2019

Is there a place for dornase alfa therapy in lung transplantation?

Transpl Int 2019 Feb 21. Epub 2019 Feb 21.

Transplantation Centre, University Medical Center Ljubljana, Zaloška 7, 1000, Ljubljana, Slovenia.

Dornase alfa is a DNase, produced by recombinant gene technology, that digests extracellular deoxyribonucleic acid (DNA). Nebulized dornase alfa exerts a mucolytic effect. It is indicated for use in cystic fibrosis (CF) which is characterised by the presence of viscous purulent airways secretions rich in highly polymerized DNA. Read More

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http://dx.doi.org/10.1111/tri.13414DOI Listing
February 2019

Skewed B cell receptor repertoire and reduced antibody avidity in patients with DOCK8 deficiency.

Scand J Immunol 2019 Feb 21:e12759. Epub 2019 Feb 21.

Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy, and early onset malignancy. Immunological abnormalities include lymphopenia, CD8 T cell cytoskeleton dysfunction, defective B cell memory, and variable serum immunoglobulin levels. Here, we analyze the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titer, and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. Read More

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http://dx.doi.org/10.1111/sji.12759DOI Listing
February 2019

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy.

J Inherit Metab Dis 2019 Feb 21. Epub 2019 Feb 21.

Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Introduction: Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C -bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. Read More

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http://doi.wiley.com/10.1002/jimd.12042
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http://dx.doi.org/10.1002/jimd.12042DOI Listing
February 2019
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Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.

J Cell Physiol 2019 Feb 21. Epub 2019 Feb 21.

Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.

Cyclin-dependent kinase 8 (CDK8) is a mediator complex-associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8-and its paralog CDK19-have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. Read More

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http://dx.doi.org/10.1002/jcp.28321DOI Listing
February 2019

MUL1 Gene Polymorphisms And Parkinson's Disease Risk.

Acta Neurol Scand 2019 Feb 22. Epub 2019 Feb 22.

Neurology Department of the People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, PR China.

Objectives: Parkinson's disease (PD) is afflicting millions of patients worldwide, and gene therapy may be a hope for cure. Recent researches have shown that MUL1 may play a key role in PD pathogenesis, but no specific genetic variants has been identified. This study was aimed to verify the hypothesis that variants in MUL1 gene were associated with PD risk in a Chinese cohort. Read More

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http://dx.doi.org/10.1111/ane.13081DOI Listing
February 2019

Free Polyethylenimine Enhances Substrate-Mediated Gene Delivery on Titanium Substrates Modified With RGD-Functionalized Poly(acrylic acid) Brushes.

Front Chem 2019 7;7:51. Epub 2019 Feb 7.

Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE, United States.

Substrate mediated gene delivery (SMD) is a method of immobilizing DNA complexes to a substrate via covalent attachment or nonspecific adsorption, which allows for increased transgene expression with less DNA compared to traditional bolus delivery. It may also increase cells receptivity to transfection via cell-material interactions. Substrate modifications with poly(acrylic) acid (PAA) brushes may improve SMD by enhancing substrate interactions with DNA complexes via tailored surface chemistry and increasing cellular adhesion via moieties covalently bound to the brushes. Read More

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http://dx.doi.org/10.3389/fchem.2019.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374293PMC
February 2019

Bevacizumab Combined With Oxaliplatin/Capecitabine in Patient With Refractory and Recurrent Mucinous Adenocarcinoma of the Appendix: A Case Report.

Front Oncol 2019 7;9:55. Epub 2019 Feb 7.

The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.

Primary appendiceal adenocarcinoma with peritoneal pseudomyxoma (PPM) has a high recurrence rate and refractory to medical interventions such as repetitive debulking surgery and systemic chemotherapy. Genome-based targeted therapy for such cases has not been well-documented. Here we present a 63-years-old women, who was diagnosed with recurrent mucinous adenocarcinoma of the appendix with local invasions and peritoneal carcinomatosis, was refractory to systemic chemotherapy after surgery. Read More

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http://dx.doi.org/10.3389/fonc.2019.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374296PMC
February 2019

Implementing TMB measurement in clinical practice: considerations on assay requirements.

ESMO Open 2019 24;4(1):e000442. Epub 2019 Jan 24.

Department of Biopathology, Centre Jean Perrin, Clermont-Ferrand, France.

Clinical evidence demonstrates that treatment with immune checkpoint inhibitor immunotherapy agents can have considerable benefit across multiple tumours. However, there is a need for the development of predictive biomarkers that identify patients who are most likely to respond to immunotherapy. Comprehensive characterisation of tumours using genomic, transcriptomic, and proteomic approaches continues to lead the way in advancing precision medicine. Read More

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http://dx.doi.org/10.1136/esmoopen-2018-000442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350758PMC
January 2019

Perspectives on immunotherapy via oncolytic viruses.

Infect Agent Cancer 2019 11;14. Epub 2019 Feb 11.

Department of Molecular Medicine, University of Padua, Via A. Gabelli, 63, 35121 Padua, Italy.

Background: With few exceptions, current chemotherapy and radiotherapy protocols only obtain a slightly prolonged survival with severe adverse effects in patients with advanced solid tumors. In particular, most solid malignancies not amenable to radical surgery still carry a dismal prognosis, which unfortunately is also the case for relapsing disease after surgery. Even though targeted therapies obtained good results, clinical experience showed that tumors eventually develop resistance. Read More

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http://dx.doi.org/10.1186/s13027-018-0218-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371415PMC
February 2019

Introns as Gene Regulators: A Brick on the Accelerator.

Authors:
Alan B Rose

Front Genet 2018 7;9:672. Epub 2019 Feb 7.

Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, United States.

A picture is beginning to emerge from a variety of organisms that for a subset of genes, the most important sequences that regulate expression are situated not in the promoter but rather are located within introns in the first kilobase of transcribed sequences. The actual sequences involved are difficult to identify either by sequence comparisons or by deletion analysis because they are dispersed, additive, and poorly conserved. However, expression-controlling introns can be identified computationally in species with relatively small introns, based on genome-wide differences in oligomer composition between promoter-proximal and distal introns. Read More

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http://dx.doi.org/10.3389/fgene.2018.00672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374622PMC
February 2019

Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy.

Sci Rep 2019 Feb 21;9(1):2482. Epub 2019 Feb 21.

University of Miami, Miller School of Medicine, Department of Microbiology and Immunology, Miami, Florida, USA.

Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. Read More

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http://dx.doi.org/10.1038/s41598-019-38906-yDOI Listing
February 2019

K-Ras G-domain binding with signaling lipid Phosphatidyl inositol (4,5) phosphate (PIP2): Membrane association, protein orientation and function.

J Biol Chem 2019 Feb 21. Epub 2019 Feb 21.

Physiology and Biophysics, Case Western Reserve Univ. Medical School, United States.

Ras genes potently drive human cancers, with mutated proto-oncogene GTPase KRAS4B (K-Ras4B) being the most abundant isoform. Targeted inhibition of oncogenic gene products is considered the "holy grail" of present-day cancer therapy, and recent discoveries of small-molecule KRas4B inhibitors were made thanks to a deeper understanding of the structure and dynamics of this GTPase. Since interactions with biological membranes are key for Ras function, Ras-lipid interactions have become a major focus, especially since such interactions evidently involve both the Ras C terminus for lipid anchoring and its G-protein domain. Read More

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http://dx.doi.org/10.1074/jbc.RA118.004021DOI Listing
February 2019

RUNX1 inhibits proliferation and induces apoptosis of t(8;21) leukemia cells via KLF4 mediated transactivation of P57.

Haematologica 2019 Feb 21. Epub 2019 Feb 21.

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and PUMC

RUNX1 is a key transcription factor in hematopoiesis and its disruption is one of the most common aberrations in acute myeloid leukemia. RUNX1 alterations affect its DNA binding capacity and transcriptional activities, leading to the deregulation of transcriptional targets and abnormality in proliferation and differentiation of myeloid cells. Identification of RUNX1 target genes and elucidation of their biological functions are of great importance to find new therapeutic strategies for RUNX1-altered leukemia. Read More

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http://dx.doi.org/10.3324/haematol.2018.192773DOI Listing
February 2019

Recent trends in treatment of thalassemia.

Blood Cells Mol Dis 2019 Feb 4. Epub 2019 Feb 4.

Pediatric Hematology & BMT Unit, Pediatrics Department, Cairo University, Cairo, Egypt. Electronic address:

Thalassemia is a common inherited monogenic disease. It is characterized by chronic hemolysis, ineffective erythropoiesis (IE) and iron overload. Despite advances in transfusion practices and chelation therapy, still many limitations in delivering these standard therapies exist. Read More

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http://dx.doi.org/10.1016/j.bcmd.2019.01.006DOI Listing
February 2019

miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.

Biochem Biophys Res Commun 2019 Feb 18. Epub 2019 Feb 18.

Department of Oncology-Pathology, Visionsgatan 4, Karolinska Institutet, S-17164, Stockholm, Sweden; Theme Cancer, Karolinska University Hospital, S-17176, Stockholm, Sweden. Electronic address:

Lung cancer causes the highest number of cancer-related deaths worldwide. Resistance to therapy is a major clinical issue contributing to the poor prognosis of lung cancer. In recent years, targeted therapy has become a concept where subgroups of non-small cell lung cancer (NSCLC) with genetically altered receptor tyrosine kinases are targeted by tyrosine kinase inhibitors (TKIs). Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.02.016DOI Listing
February 2019

Crizotinib with or without an EGFR-TKI in treating EGFR-mutant NSCLC patients with acquired MET amplification after failure of EGFR-TKI therapy: a multicenter retrospective study.

J Transl Med 2019 Feb 21;17(1):52. Epub 2019 Feb 21.

Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Background: MET amplification is associated with acquired resistance to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in treating non-small-cell lung cancer (NSCLC); however, the therapeutic strategy in these patients is undefined. Herein we report the clinical outcomes of patients with c-MET amplification resistance to EGFR-TKIs treated with crizotinib.

Methods: We retrospectively analyzed advanced NSCLC patients from five sites who were diagnosed with EGFR-mutant NSCLC and received EGFR-TKI treatment. Read More

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http://dx.doi.org/10.1186/s12967-019-1803-9DOI Listing
February 2019

Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention.

Expert Rev Gastroenterol Hepatol 2019 Feb 27;13(2):157-171. Epub 2018 Nov 27.

c Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy.

Introduction: Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. Read More

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http://dx.doi.org/10.1080/17474124.2019.1549988DOI Listing
February 2019

Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation.

Int J Mol Sci 2019 Feb 20;20(4). Epub 2019 Feb 20.

Department of Biochemistry and Molecular Biology, University of Debrecen, Faculty of Medicine, 4032 Debrecen, Hungary.

Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. Read More

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http://dx.doi.org/10.3390/ijms20040926DOI Listing
February 2019

Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells.

Pharmaceutics 2019 Feb 20;11(2). Epub 2019 Feb 20.

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Petaling Jaya, Malaysia.

Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Read More

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http://dx.doi.org/10.3390/pharmaceutics11020089DOI Listing
February 2019

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Cancers (Basel) 2019 Feb 19;11(2). Epub 2019 Feb 19.

Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India.

The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, microRNAs, Pin 1, Hes-5, BMI1, Ebp2. Read More

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http://dx.doi.org/10.3390/cancers11020246DOI Listing
February 2019

Non-viral vectors based on cationic niosomes and minicircle DNA technology enhance gene delivery efficiency for biomedical applications in retinal disorders.

Nanomedicine 2019 Feb 18. Epub 2019 Feb 18.

NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address:

Low transfection efficiency is a major challenge to overcome in non-viral approaches to reach clinical practice. Our aim was to explore new strategies to achieve more efficient non-viral gene therapies for clinical applications and in particular, for retinal diseases. Cationic niosomes and three GFP-encoding genetic materials consisting on minicircle (2. Read More

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http://dx.doi.org/10.1016/j.nano.2018.12.018DOI Listing
February 2019

Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies.

Neuron 2019 Feb;101(4):560-583

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address:

Autosomal-recessive cerebellar ataxias (ARCAs) comprise a heterogeneous group of rare degenerative and metabolic genetic diseases that share the hallmark of progressive damage of the cerebellum and its associated tracts. This Review focuses on recent translational research in ARCAs and illustrates the steps from genetic characterization to preclinical and clinical trials. The emerging common pathways underlying ARCAs include three main clusters: mitochondrial dysfunction, impaired DNA repair, and complex lipid homeostasis. Read More

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http://dx.doi.org/10.1016/j.neuron.2019.01.049DOI Listing
February 2019

miR-486-5p Inhibits Inflammatory Response, Matrix Degradation and Apoptosis of Nucleus Pulposus Cells through Directly Targeting FOXO1 in Intervertebral Disc Degeneration.

Cell Physiol Biochem 2019 18;52(1):109-118. Epub 2019 Feb 18.

Department of Traumatology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.

Background/aims: microRNA-486-5p (miR-486-5p) and forkhead box protein O1 (FOXO1) play an important role in the development of intervertebral disc degeneration (IDD). However, their molecular mechanisms in IDD remain unknown.

Methods: qRT-PCR assay was used to identify miR-486-5p expression in nucleus pulposus (NP) cells. Read More

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http://dx.doi.org/10.33594/000000008DOI Listing
February 2019

A near-haploid clone harboring a BCR/ABL1 gene fusion in an adult patient with newly diagnosed B-lymphoblastic leukemia.

Genes Chromosomes Cancer 2019 Feb 20. Epub 2019 Feb 20.

Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

The detection of recurrent genetic abnormalities in B-lymphoblastic leukemia (B-ALL) is critical for risk stratification and therapy-related decisions. Near-haploidy (24-30 chromosomes), a subgroup of hypodiploidy (<46 chromosomes), and BCR/ABL1 gene fusions are both recurrent genetic abnormalities in B-ALL and are considered adverse prognostic findings, although outcomes in BCR/ABL1-positive patients have improved with tyrosine kinase inhibitor therapy. While near-haploid clones are primarily observed in children and rarely harbor structural abnormalities, BCR/ABL1-positive B-ALL is primarily observed in adults. Read More

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http://dx.doi.org/10.1002/gcc.22744DOI Listing
February 2019

ALK Expression in Small Cell Lung Cancer.

Histopathology 2019 Feb 20. Epub 2019 Feb 20.

Dept of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.

Introduction: ALK immunohistochemistry has shifted from a screening tool to a sole determinant for ALK-targeted therapy. Recent articles have referred to SCLC transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment-naïve SCLC in a comprehensive manner.

Methods: We examined ALK expression in a consecutive series of SCLC tumors, and the expression mechanism was analyzed regarding gene rearrangement, copy number changes, and point mutations. Read More

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http://dx.doi.org/10.1111/his.13842DOI Listing
February 2019

Generation of insulin-producing hepatocyte-like cells from human Wharton's jelly mesenchymal stem cells as an alternative source of islet cells.

J Cell Physiol 2019 Feb 20. Epub 2019 Feb 20.

Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Islet cell transplantation, as a treatment of type 1 diabetes, has a lot of complexity such as allograft rejections and an insufficient number of donors. The liver can be used as a replacement for endogenous insulin production. Hepatocytes can inherently respond to glucose levels and secrete proteins. Read More

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http://dx.doi.org/10.1002/jcp.28352DOI Listing
February 2019

Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report.

Invest New Drugs 2019 Feb 21. Epub 2019 Feb 21.

Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.

An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT. Read More

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http://dx.doi.org/10.1007/s10637-019-00742-2DOI Listing
February 2019

Effect of pressure profile of shock waves on lipid membrane deformation.

PLoS One 2019 21;14(2):e0212566. Epub 2019 Feb 21.

Department of Mechanical, Industrial & Systems Engineering, University of Rhode Island, Kingston, RI, United States of America.

Use of shock waves to temporarily increase the permeability of the cell membrane is a promising approach in drug delivery and gene therapy to allow the translocation of macromolecules and small polar molecules into the cytoplasm. Our understanding of how the characteristics of the pressure profile of shock waves, such as peak pressure and pulse duration, influences membrane properties is limited. Here we study the response of lipid bilayer membranes to shock pulses with different pressure profiles using atomistic molecular dynamics simulations. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212566PLOS
February 2019

The sustained release of basic fibroblast growth factor accelerates angiogenesis and the engraftment of the inactivated dermis by high hydrostatic pressure.

PLoS One 2019 21;14(2):e0208658. Epub 2019 Feb 21.

Department of Plastic and Reconstructive Surgery, Kansai Medical University, Hirakata, Osaka, Japan.

We developed a novel skin regeneration therapy combining nevus tissue inactivated by high hydrostatic pressure (HHP) in the reconstruction of the dermis with a cultured epidermal autograft (CEA). The issue with this treatment is the unstable survival of CEA on the inactivated dermis. In this study, we applied collagen/gelatin sponge (CGS), which can sustain the release of basic fibroblast growth factor (bFGF), to the inactivated skin in order to accelerate angiogenesis. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208658PLOS
February 2019

Adaptive downregulation of Cl-/HCO3- exchange activity in rat hepatocytes under experimental obstructive cholestasis.

PLoS One 2019 21;14(2):e0212215. Epub 2019 Feb 21.

Instituto de Fisiología Experimental (IFISE)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas-Universidad Nacional de Rosario, Rosario, Argentina.

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212215PLOS
February 2019

New Frontier in Lipids: PCSK9 Inhibitors and Implications for the Life Insurance Industry.

Authors:
Alacia J Tarpley

J Insur Med 2019 Feb 21. Epub 2019 Feb 21.

Since the Framingham Heart Study solidified cholesterol as a causative agent in the development of coronary heart disease there has been an explosion of research in the field of lipidology. Many therapeutic options have come and gone as we have been refining the goals of therapy to match the mortality outcome data of large clinical trials. A new frontier has emerged with the introduction of the PCSK9 inhibitors that are able with monthly injections to lower LDL cholesterol >60% with favorable side effect profiles and recently published favorable mortality data. Read More

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http://dx.doi.org/10.17849/insm-47-4-1-6.1DOI Listing
February 2019

Hyperammonemia From Ureaplasma Infection in an Immunocompromised Child.

J Pediatr Hematol Oncol 2019 Feb 15. Epub 2019 Feb 15.

Miller Children's and Women's Hospital Long Beach.

Idiopathic hyperammonemia is a rare, poorly understood, and often lethal condition that has been described in immunocompromised patients. This report describes an immunocompromised patient with acute myelogenous leukemia who developed persistent hyperammonemia up to 705 µmol/L (normal, 0 to 47 µmol/L) refractory to multiple different therapies. However, after beginning azithromycin and then doxycycline therapy for Ureaplasma species infection, the patient showed immediate and sustained clinical improvement and resolution of ammonia levels. Read More

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http://dx.doi.org/10.1097/MPH.0000000000001414DOI Listing
February 2019

MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle.

Elife 2019 Feb 21;8. Epub 2019 Feb 21.

Department of Physiology and Functional Genomics, University of Florida, Gainesville, United States.

In the present study we show that the master myogenic regulatory factor, MYOD1, is a positive modulator of molecular clock amplitude and functions with the core clock factors for expression of clock-controlled genes in skeletal muscle. We demonstrate that MYOD1 directly regulates the expression and circadian amplitude of the positive core clock factor . We identify a non-canonical E-box element in and demonstrate that is required for full MYOD1-responsiveness. Read More

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http://dx.doi.org/10.7554/eLife.43017DOI Listing
February 2019

D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway.

Integr Cancer Ther 2019 Jan-Dec;18:1534735419828832

2 Chung Shan Medical University, Taichung, Taiwan.

Cisplatin induces anorexia, weight loss, loss of adipose tissue, skeletal muscle atrophy, and serious adverse effects that can cause premature termination of chemotherapy. The aim of this study was to use an animal model to assess cisplatin therapy (3 cycles) with and without d-methionine to investigate its protective effects on cisplatin-induced anorexia and skeletal muscle wasting. Wistar rats were divided into 3 groups and treated as follows: saline as control (group 1), intraperitoneal cisplatin once a week for 3 weeks (group 2), and intraperitoneal cisplatin once a week for 3 weeks plus oral administration of d-methionine (group 3). Read More

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http://dx.doi.org/10.1177/1534735419828832DOI Listing
February 2019

Tyrosine kinase inhibitor acquired resistance mechanism alternates between EGFR and ALK in a lung adenocarcinoma patient.

Thorac Cancer 2019 Feb 20. Epub 2019 Feb 20.

Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Drive gene mutation positive non-small cell lung cancer achieves reliable clinical responses to subsequent target therapy. However, most patients will inevitably develop disease progression with multiple treatment failure. Next generation sequencing can identify clear resistance mechanisms. Read More

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http://dx.doi.org/10.1111/1759-7714.13015DOI Listing
February 2019

Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter.

Nucleic Acids Res 2019 Feb 21. Epub 2019 Feb 21.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

Long noncoding RNAs (lncRNAs) may either repress or activate HIV-1 replication and latency; however, specific mechanisms for their action are not always clear. In HIV-1 infected CD4+ T cells, we performed RNA-Sequencing (RNA-Seq) analysis and discovered an up-regulation of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), an lncRNA previously described in cancer cells that associate with cancer pathogenesis. Moreover, we found that MALAT1 promoted HIV-1 transcription and infection, as its knockdown by CRISPR/Cas9 markedly reduced the HIV-1 long terminal repeat (LTR)-driven gene transcription and viral replication. Read More

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http://dx.doi.org/10.1093/nar/gkz117DOI Listing
February 2019