Read by QxMD icon Read

Gene therapy

Deepthi Alapati, Edward E Morrisey
While our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis and alpha 1 antitrypsin deficiency is extensive, treatment options are lacking. Since the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intra-tracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene editing technology is a promising approach to repair or inactivate disease causing mutations...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Cheng-Feng Chiang, Mike Flint, Jin-Mann S Lin, Christina F Spiropoulou
Andes virus (ANDV) is the major cause of hantavirus pulmonary syndrome (HPS) in South America. Despite a high fatality rate (up to 40%), no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection...
2016: PloS One
Jakarwan Yostawonkul, Suvimol Surassmo, Tawin Iempridee, Wittaya Pimtong, Kunat Suktham, Warayuth Sajomsang, Pattarapond Gonil, Uracha Rungsardthong Ruktanonchai
A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200-400nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE>90%)...
September 29, 2016: Colloids and Surfaces. B, Biointerfaces
Jay N Lozier, Mark T Kloos, Elizabeth P Merricks, Nathaly Lemoine, Margaret H Whitford, Robin A Raymer, Dwight A Bellinger, Timothy C Nichols
Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons...
2016: Comparative Medicine
Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
Hiroko Kitahara, Mariko Hirai, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition...
October 21, 2016: Oncology Reports
Eva Vidomanova, Peter Racay, Ivana Pilchova, Erika Halasova, Jozef Hatok
Glioblastoma (GB) is the most frequent and biologically the most aggressive primary brain tumor in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy and chemotherapy. Resistance to therapy is a major obstacle, even with optimal treatment with a survival median of only 12-15 months. The heterogeneity and treatment response of GB makes this tumor type a challenging area of research. The aim of our study was to study the response of normal human astrocyte (HA) and human GB (T98G) cell lines to apoptosis inhibitors in vitro...
October 21, 2016: Oncology Reports
Han-Shi Zeng, Wei-Xia Lin, Shu-Tao Zhao, Zhan-Hui Zhang, Heng-Wen Yang, Feng-Ping Chen, Yuan-Zong Song, Zhi-Nan Yin
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder resulting from biallelic mutations of the SLC25A13 gene. Due to the lack of well‑recognized clinical or biochemical diagnostic criteria, the definitive diagnosis of this disease relies on the genetic analysis of SLC25A13 at present. As novel large deletion/insertion mutations of the SLC25A13 gene are difficult to detect using routine DNA analytic approaches, the timely diagnosis of patients with these types of mutations remains a challenge...
October 21, 2016: Molecular Medicine Reports
Edgar Teddy Quispe-Soto, Gloria M Calaf
Global cancer burden increased to 14.1 million new cases in 2012; and breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Curcumin is the major bioactive ingredient extracted from the rhizome of the plant Curcuma longa (turmeric). Paclitaxel is a microtubule-stabilizing agent originally isolated from the bark of Taxus brevifolia. Curcumin and paclitaxel were evaluated with two human breast cancer cell lines as the luminal MCF-7 and the basal-like MDA-MB-231 that are either positive or negative for hormonal receptors estrogen receptor, progesterone receptor and HER2, respectively...
October 19, 2016: International Journal of Oncology
Yusaku Osako, Naohiko Seki, Yoshiaki Kita, Keiichi Yonemori, Keiichi Koshizuka, Akira Kurozumi, Itaru Omoto, Ken Sasaki, Yasuto Uchikado, Hiroshi Kurahara, Kosei Maemura, Shoji Natsugoe
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC...
October 21, 2016: International Journal of Oncology
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumor effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms which depends both on the type of virus and the route of delivery. Here, we show that intra-tumoral (i.t.) oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumor response. In contrast, systemically delivered VSV expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumor CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumor activity...
October 25, 2016: Gene Therapy
Arnaldo N S Silva, Jordy Coffa, Varsha Menon, Lindsay C Hewitt, Kakoli Das, Yohei Miyagi, Dan Bottomley, Hayley Slaney, Toru Aoyama, Wolfram Mueller, Tomio Arai, Iain B Tan, Niantao Deng, Xiu B Chan, Patrick Tan, Akira Tsuburaya, Kentaro Sakamaki, Jeremy D Hayden, Takaki Yoshikawa, Ilse Zondervan, Suvi Savola, Heike I Grabsch
OBJECTIVE: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). BACKGROUND: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. METHODS: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status...
October 24, 2016: Annals of Surgery
Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch
RATIONALE: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology but different causal mechanisms may reflect a need for patient-tailored therapies. OBJECTIVES: Endothelial cells differentiated from induced pluripotent stem cells were compared to pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns, that differed from those in unused donor cells...
October 25, 2016: American Journal of Respiratory and Critical Care Medicine
Hong Tao, Yiran Cai, Liang Shi, Junfang Tang, Zhidong Liu, Zitong Wang, Lianqi Bai, Zhe Liu
BACKGROUND: Recent research into lung cancer-related driver genes has identified a distinctive molecular subtype of non-small cell lung cancer (NSCLC) - anaplastic lymphoma kinase (ALK)-positive NSCLC. We evaluated the clinical features and survival rates of ALK-positive lung adenocarcinoma patients who had undergone surgery but had not received ALK inhibitor therapy, along with the characteristics of patients with distant metastases. METHODS: Clinical data of 40 patients with ALK-positive, postsurgical lung adenocarcinoma were retrospectively analyzed...
October 24, 2016: Thoracic Cancer
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
S Pontikakis, C Papadaki, M Tzardi, M Trypaki, M Sfakianaki, F Koinis, E Lagoudaki, L Giannikaki, A Kalykaki, E Kontopodis, Z Saridaki, N Malamos, V Georgoulias, J Souglakos
To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR...
October 25, 2016: Pharmacogenomics Journal
Paula Castro, Shahid Zaman, Anthony Holland
People with Down's syndrome (DS) are at high risk for developing Alzheimer's disease (AD) at a relatively young age. This increased risk is not observed in people with intellectual disabilities for reasons other than DS and for this reason it is unlikely to be due to non-specific effects of having a neurodevelopmental disorder but, instead, a direct consequence of the genetics of DS (trisomy 21). Given the location of the amyloid precursor protein (APP) gene on chromosome 21, the amyloid cascade hypothesis is the dominant theory accounting for this risk, with other genetic and environmental factors modifying the age of onset and the course of the disease...
October 24, 2016: Journal of Neurology
Vellingiri Balachandar, Venkatesan Dhivya, Mohan Gomathi, Subramaniam Mohanadevi, Balasubramanian Venkatesh, Bharathi Geetha
Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs...
2016: Stem Cell Investigation
Genevieve M Weir, Olga Hrytsenko, Tara Quinton, Neil L Berinstein, Marianne M Stanford, Marc Mansour
BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously...
2016: Journal for Immunotherapy of Cancer
Le Li, Creed M Stary
Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs) are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response...
2016: Oxidative Medicine and Cellular Longevity
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"