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cell and gene therapy

Sa Liu, Yulong Chen, Shiping Xie, Qianlei Xu, Jianshe Chen, Changhai Wang, Zhao Wang, Suna Ma, Xingwei Wu, Ning Zhang
OBJECTIVES: Traditional Chinese Medicine (TCM) applied in the clinic as a complementary and alternative therapy has helped improve immunity and reduce side effects and symptomatic treatment in patients with HIV/AIDS. However, the mechanisms of TCM syndromes are not clear. Transcriptomics enables the study of such TCM syndromes. DESIGN: This study compared the messenger RNA (mRNA) expressions of healthy persons and patients with HIV/AIDS who had two common TCM syndromes, qi-yin deficiency and dampness-heat retention, to find the difference in HIV/AIDS with TCM syndromes...
October 19, 2016: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
Zhen-Yao Chen, Xin Chen, Zhao-Xia Wang
MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jeganathan Manivannan, Manjunath Prashanth, Venkatesan Saravana Kumar, Manickaraj Shairam, Jayachandran Subburaj
Since there is no precise therapy for treating vascular calcification by directly targeting the vascular wall, we aim to unveil novel drug targets through mining the molecular effect of a high phosphate environment on vascular cells through computational methods. Here, we hypothesize that manipulation of the vascular pathogenic network by small molecule therapeutics predicted from prior knowledge might offer great promise. With this, we intend to understand the publicly available transcriptomic data of vascular smooth muscle cells and endothelial cells exposed to the high phosphate induced vascular calcification milieu and to re-examine the above published experiments for reasons different from those examined in the previous studies through multilevel systems biological understanding...
October 18, 2016: Molecular BioSystems
Matthew L Paff, Scott L Nuismer, Andrew D Ellington, Ian J Molineux, Ryan H May, James J Bull
BACKGROUND: We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus. RESULTS: Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved...
2016: Journal of Biological Engineering
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 14, 2016: Cellular Signalling
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
Alicia M Waters, Laura L Stafman, Evan F Garner, Smitha Mruthyunjayappa, Jerry E Stewart, Gregory K Friedman, Jennifer M Coleman, James M Markert, G Yancey Gillespie, Elizabeth A Beierle
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134...
October 2016: Translational Oncology
Pavitra Ramachandran, Vivian Lee, Zhangyong Wei, Ji Yun Song, Giulia Casal, Therese Cronin, Keirnan Willett, Rachel Huckfeldt, Jessica I W Morgan, Tomas S Aleman, Albert M Maguire, Jean Bennett
Within the next decade, we will see many gene therapy clinical trials for eye diseases progress, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in pre-clinical mouse studies. Because there are numerous anatomic, and physiologic differences between the eyes of mice and 'men' and because surgical delivery approaches and immunologic responses also differ between these species, we evaluated the transduction characteristics of two promising new serotypes AAV7m8 and AAV8BP2, in retinas of animals that are most similar to those of humans: non-human primates (NHPs)...
October 18, 2016: Human Gene Therapy
Shanshan Xu, Lanlan Dong, Yingying Shi, Liujun Chen, Peipei Yuan, Shuang Wang, Zhi Li, Yan Sun, Song Han, Jun Yin, Biwen Peng, Xiaohua He, Wanhong Liu
Human foamy virus (HFV) is a complex and unique retrovirus with the longest genomes among retroviruses used as vectors for gene therapy. Long non-coding RNAs (lncRNAs) are regarded as key regulators that involved in diverse biological processes during viral infection. However, the role of lncRNAs in HFV infection remains unknown. In this study, we utilized next-generation sequencing to first characterize lncRNAs in 293T cells after HFV infection, evaluating length distribution, exon number distribution, volcano picture and lncRNA class distribution...
October 18, 2016: AIDS Research and Human Retroviruses
Pravin Kesarwani, Paramita Chakraborty, Radhika Gudi, Shilpak Chatterjee, Gina Scurti, Kyle Toth, Patt Simms, Mahvash Husain, Kent Armeson, Shahid Husain, Elizabeth Garrett-Mayer, Chethamarakshan Vasu, Michael I Nishimura, Shikhar Mehrotra
Advancements in adoptive cell transfer therapy (ACT) has led to the use of T cells engineered with tumor specific T cell receptors, which after rapid expansion can be obtained in sufficient numbers for treating patients. However, due to massive proliferation these cells are close to replicative senescence, exhibit exhausted phenotype, and also display increased susceptibility to activation induced cell death. We have previously shown that tumor reactive T cells undergo caspase-independent cell death upon TCR restimulation with cognate antigen, which involves reactive oxygen species and c-jun N-terminal kinase...
October 14, 2016: Oncotarget
Marina Cavazzana, Jean-Antoine Ribeil, Chantal Lagresle-Peyrou, Isabelle André-Schmutz
When considering inherited diseases that can be treated by gene transfer into Hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and ALD. In all other settings (X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency, Wiskott-Aldrich syndrome and β-hemoglobinopathies), the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics...
October 17, 2016: Stem Cells and Development
Yin-Ku Liang, Liu-Jiao Bian
Kringle 5, the fifth fragment of plasminogen, is known to be important for inhibiting the proliferation and migration of vascular endothelial cell (VEC), while not having any effects on normal endothelial cells. Therefore, it may be a potential tumor therapy candidate. However, the ligand of the Kringle 5 in VEC has not yet been identified. In this study, the possible ligand of Kringle 5 in vitro was screened and validated using Ph.D.-7 phage display peptide library with molecular docking, along with surface plasma resonance (SPR)...
2016: PloS One
Liang Li, Jian-Wei Zhang, Gregory Jenkins, Fang Xie, Erin E Carlson, Brooke L Fridley, William R Bamlet, Gloria M Petersen, Robert R McWilliams, Liewei Wang
BACKGROUND: Pancreatic cancer is a rapidly fatal disease with gemcitabine remaining the first-line therapy. We performed a genotype-phenotype association study to identify biomarkers for predicting gemcitabine treatment outcome. MATERIALS AND METHODS: We selected the top 200 single nucleotide polymorphisms (SNPs) identified from our previous genome-wide association study to associate with overall survival using 400 patients treated with/or without gemcitabine, followed by imputation analysis for regions around the identified SNPs and a replication study using an additional 537 patients by the TaqMan genotyping assay...
October 4, 2016: Pharmacogenetics and Genomics
Siobhan O Burns, Alex Zarafov, Adrian J Thrasher
PURPOSE OF REVIEW: Primary immunodeficiencies (PIDs) are inherited conditions where components of the immune system are missing or dysfunctional. Over 300 genes have been causally linked to monogenic forms of PID, including a number that regulate the actin cytoskeleton. The majority of cytoskeletal defects disrupt assembly and disassembly of filamentous actin in multiple immune cell lineages impacting functions such as cell migration and adhesion, pathogen uptake, intercellular communication, intracellular signalling, and cell division...
October 5, 2016: Current Opinion in Hematology
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
(no author information available yet)
No abstract text is available yet for this article.
October 17, 2016: Human Gene Therapy
(no author information available yet)
No abstract text is available yet for this article.
October 17, 2016: Human Gene Therapy
Edward Tuddenham
The declarative title is a fair summary of research described in this paper (Targeting Factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice)(10) , is a fair summary of research described in this paper, which is itself the 14th in a series from the group of researchers led by Montgomery who, since 2003 have progressively advanced the idea of storing factor VIII in platelets to treat hemophilia A. Why, one might ask, would one do such a thing when evolution has selected endothelial cells as both the site for synthesis and release of factor VIII complexed with Von Willebrand factor to provide the cofactor when and where needed?(1,2) The answer lies in the unfortunate fact that a high proportion of patients with hemophilia develop resistance to factor VIII due to alloimmunity to the protein, which is foreign to their immune system, leading to production of inhibitory antibodies to the cofactor...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
Wei Zhang, Jianzhou Liu, Jianxin Qiu, Xiaoliang Fu, Qisheng Tang, Fan Yang, Zhiguang Zhao, He Wang
MicroRNAs (miRNAs) have emerged as important regulators in cancer that are implicated in regulation of various cellular processes. miR-382 has been proposed as a tumor suppressor by several recent studies. However, the function of miR-382 in prostate cancer remains unknown. In this study, we aimed to investigate the potential function of miR-382 in prostate cancer. We found that miR-382 was significantly decreased in prostate cancer specimens and cancer cell lines. The overexpression of miR-382 in prostate cancer cells markedly inhibited cell proliferation, migration, and invasion...
October 3, 2016: Oncology Reports
Masato Chiba, Yosuke Togashi, Shuta Tomida, Hiroshi Mizuuchi, Yu Nakamura, Eri Banno, Hidetoshi Hayashi, Masato Terashima, Marco A De Velasco, Kazuko Sakai, Yoshihiko Fujita, Tetsuya Mitsudomi, Kazuto Nishio
Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found...
October 17, 2016: International Journal of Oncology
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