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https://www.readbyqxmd.com/read/29471014/epigenomic-drugs-and-the-germline-collateral-damage-in-the-home-of-heritability
#1
REVIEW
Patrick S Western
The testis and ovary provide specialised environments that nurture germ cells and facilitate their maturation, culminating in the production of mature gametes that can found the following generation. The sperm and egg not only transmit genetic information, but also epigenetic modifications that affect the development and physiology of offspring. Importantly, the epigenetic information contained in mature sperm and oocytes can be influenced by a range of environmental factors, such as diet, chemicals and drugs...
February 19, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29470824/turning-up-the-heat-an-evaluation-of-the-evidence-for-heating-to-promote-exercise-recovery-muscle-rehabilitation-and-adaptation
#2
REVIEW
Hamish McGorm, Llion A Roberts, Jeff S Coombes, Jonathan M Peake
Historically, heat has been used in various clinical and sports rehabilitation settings to treat soft tissue injuries. More recently, interest has emerged in using heat to pre-condition muscle against injury. The aim of this narrative review was to collate information on different types of heat therapy, explain the physiological rationale for heat therapy, and to summarise and evaluate the effects of heat therapy before, during and after muscle injury, immobilisation and strength training. Studies on skeletal muscle cells demonstrate that heat attenuates cellular damage and protein degradation (following in vitro challenges/insults to the cells)...
February 22, 2018: Sports Medicine
https://www.readbyqxmd.com/read/29470815/identification-of-mir-9-as-a-negative-factor-of-insulin-secretion-from-beta-cells
#3
Dongzhi Hu, Yi Wang, Haiyang Zhang, Dalu Kong
MicroRNA is a novel class of small noncoding RNA that has been implicated in a variety of physiological and pathological processes, including glucose homeostasis and diabetes mellitus. So far, a few studies have reported that miRNAs may be an important regulator in glucose-stimulated insulin secretion (GSIS) pathway. However, the role of miRNAs in this process remains unclear. The levels of miRNAs in mouse islets and MIN6 cells were determined by quantitative RT-PCR. Concentration of insulin was determined by ELISA, and the expression of the target protein was determined with western blot assay...
February 22, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29470523/a-late-but-fitter-revertant-cell-explains-the-high-frequency-of-revertant-mosaicism-in-epidermolysis-bullosa
#4
Peter C van den Akker, Anna M G Pasmooij, Hans Joenje, Robert M W Hofstra, Gerard J Te Meerman, Marcel F Jonkman
Revertant mosaicism, or "natural gene therapy", is the phenomenon in which germline mutations are corrected by somatic events. In recent years, revertant mosaicism has been identified in all major types of epidermolysis bullosa, the group of heritable blistering disorders caused by mutations in the genes encoding epidermal adhesion proteins. Moreover, revertant mosaicism appears to be present in all patients with a specific subtype of recessive epidermolysis bullosa. We therefore hypothesized that revertant mosaicism should be expected at least in all patients with recessive forms of epidermolysis bullosa...
2018: PloS One
https://www.readbyqxmd.com/read/29469136/acute-lymphoblastic-leukemia-in-a-child-with-leri-weill-syndrome-and-complete-shox-gene-deletion-a-case-report
#5
Jana Volejnikova, Jirina Zapletalova, Marie Jarosova, Helena Urbankova, Vojta Petr, Eva Klaskova, Marshall S Horwitz, Marian Hajduch, Vladimir Mihal
BACKGROUND: Leri-Weill syndrome (LWS) ranks among conditions with short stature homeobox gene (SHOX) haploinsufficiency. Data on possible association of SHOX aberrations with malignant diseases are scarce. METHODS AND RESULTS: We report a unique case of an 8-year-old girl who was successfully treated for acute lymphoblastic leukemia (pre-B ALL, intermediate risk) and was subsequently diagnosed with LWS due to characteristic clinical appearance (short disproportionate stature, Madelung deformity of the wrist) and molecular genetic examination (complete deletion of SHOX)...
February 21, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29468433/merging-perspectives-genotype-directed-molecular-therapy-for-hereditary-diffuse-gastric-cancer-hdgc-and-e-cadherin-egfr-crosstalk
#6
Dandan Li, Winifred Lo, Udo Rudloff
Hereditary diffuse gastric cancer is a cancer predisposition syndrome associated with germline mutations of the E-cadherin gene (CDH1; NM_004360). Male CDH1 germline mutation carriers have by the age of 80 years an estimated 70% cumulative incidence of gastric cancer, females of 56% for gastric and of 42% for lobular breast cancer. Metastatic HDGC has a poor prognosis which is worse than for sporadic gastric cancer. To date, there have been no treatment options described tailored to this molecular subtype of gastric cancer...
February 22, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29468364/antitumor-in-situ-vaccination-effect-of-tnf%C3%AE-and-il-12-plasmid-dna-electrotransfer-in-a-murine-melanoma-model
#7
Urska Kamensek, Maja Cemazar, Ursa Lampreht Tratar, Katja Ursic, Gregor Sersa
Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy approaches for the localized transfer of multiple genes into tumors in vivo; therefore, it is especially promising for delivering different cytokines that are toxic if administered systemically. In this study, we used concomitant intratumoral GET of two cytokines: tumor necrosis factor alpha (TNFα), a potent cytotoxic cytokine to induce in situ vaccination, and interleukin 12 (IL-12), an immunostimulatory cytokine to boost the primed local immune response into a systemic one...
February 21, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29468275/-the-innate-immune-system-in-oropharyngeal-squamous-cell-carcinoma-immune-modulation-by-hpv
#8
REVIEW
S Wagner, H Böckmann, S Gattenlöhner, J P Klussmann, C Wittekindt
Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer...
February 15, 2018: HNO
https://www.readbyqxmd.com/read/29468011/ligase-iv-inhibitor-scr7-enhances-gene-editing-directed-by-crispr-cas9-and-ssodn-in-human-cancer-cells
#9
Zheng Hu, Zhaoying Shi, Xiaogang Guo, Baishan Jiang, Guo Wang, Dixian Luo, Yonglong Chen, Yuan-Shan Zhu
Background: Precise genome editing is essential for both basic and translational research. The recently developed CRISPR/Cas9 system can specifically cleave a designated site of target gene to create a DNA double-strand break, which triggers cellular DNA repair mechanism of either inaccurate non-homologous end joining, or site-specific homologous recombination. Unfortunately, homology-directed repair (HDR) is challenging due to its very low efficiency. Herein, we focused on improving the efficiency of HDR using a combination of CRISPR/Cas9, eGFP, DNA ligase IV inhibitor SCR7, and single-stranded oligodeoxynucleotides (ssODN) in human cancer cells...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29467944/distinct-expression-of-cdca3-cdca5-and-cdca8-leads-to-shorter-relapse-free-survival-in-breast-cancer-patient
#10
Nam Nhut Phan, Chih-Yang Wang, Kuan-Lun Li, Chien-Fu Chen, Chung-Chieh Chiao, Han-Gang Yu, Pung-Ling Huang, Yen-Chang Lin
Breast cancer is a dangerous disease that results in high mortality rates for cancer patients. Many methods have been developed for the treatment and prevention of this disease. Determining the expression patterns of certain target genes in specific subtypes of breast cancer is important for developing new therapies for breast cancer. In the present study, we performed a holistic approach to screening the mRNA expression of six members of the cell division cycle-associated gene family (CDCA) with a focus on breast cancer using the Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467932/characterization-of-aptamer-mediated-gene-delivery-system-for-liver-cancer-therapy
#11
Zhongbing Liu, Xiaoduan Sun, Shuangli Xiao, Yan Lin, Chunhong Li, Na Hao, Meiling Zhou, Ruolan Deng, Siyun Ke, Zhirong Zhong
Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we aimed to design a kind of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5-PTEN...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467904/human-sodium-iodide-transporter-gene-mediated-imaging-and-therapy-of-mouse-glioma-comparison-between-188-re-and-131-i
#12
Rui Guo, Yun Xi, Min Zhang, Ying Miao, Miao Zhang, Biao Li
Novel treatment options are urgently required for patients with glioma who are not effectively treated through standard therapy. Human sodium iodide symporter (hNIS) is a molecular target of certain tumors types. Compared with131 I,188 Re possesses a higher energy and shorter half-life; therefore, the effects of188 Re and131 I were compared in hNIS-mediated gene imaging and therapy in the present study. Recombinant human brain glioma cell line U87 was transfected with a recombinant lentiviral vector containing hNIS (U87-hNIS)...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467889/serum-immunoglobulin-e-response-as-a-marker-for-unfavorable-prognosis-following-cholesteryl-pullulan-mage-a4-vaccination
#13
Takehiro Abiko, Takahiro Tsuchikawa, Kengo Miyauchi, Masataka Wada, Noriaki Kyogoku, Toshiaki Shichinohe, Yoshihiro Miyahara, Shinichi Kageyama, Hiroaki Ikeda, Hiroshi Shiku, Satoshi Hirano
Since 2009, a cancer vaccine clinical trial was conducted with melanoma antigen gene-A4 as an immunogenic agent. The levels of IgG1, IgG2 and IgG3, which are known to be Type 1 T helper cell-associated antibodies, and the levels of IgG4 and IgE, which are known to be Type 2 T helper cell-associated antibodies, were measured and used as biomarkers for predicting therapeutic effect. The results of the present study indicated a strong positive correlation between IgG2 and IgG4, with a correlation coefficient of R=0...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467875/potential-prognostic-biomarkers-identified-by-dna-methylation-profiling-analysis-for-patients-with-lung-adenocarcinoma
#14
Liankui Han, Gang Xu, Chuan Xu, Bo Liu, Di Liu
Lung adenocarcinoma is frequently occurring type of lung cancer with high metastatic risk. We performed a DNA methylation profiling analysis to identify possible prognostic markers involved in lung adenocarcinoma. DNA methylation profiling data (GSE66386) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially methylated genes were identified using a limma package. GO enrichment analysis was performed to identify vital functions related to differential gene methylation, and pathway analysis was performed to assess the associations between different proteins with regard to regulation of cell function and metabolism...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29467575/nanoscale-polysaccharide-derivative-as-an-aeg-1-sirna-carrier-for-effective-osteosarcoma-therapy
#15
Fen Wang, Jia-Dong Pang, Lei-Lei Huang, Ran Wang, Dan Li, Kang Sun, Lian-Tang Wang, Li-Ming Zhang
Background: Nanomedicine, which is the application of nanotechnology in medicine to make medical diagnosis and treatment more accurate, has great potential for precision medicine. Despite some improvements in nanomedicine, the lack of efficient and low-toxic vectors remains a major obstacle. Objective: The aim of this study was to prepare an efficient and low-toxic vector which could deliver astrocyte elevated gene-1 ( AEG-1 ) small interfering RNA (siRNA; siAEG-1) into osteosarcoma cells effectively and silence the targeted gene both in vitro and in vivo...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29467486/eric-recommendations-for-tp53-mutation-analysis-in-chronic-lymphocytic-leukemia-update-on-methodological-approaches-and-results-interpretation
#16
REVIEW
J Malcikova, E Tausch, D Rossi, L A Sutton, T Soussi, T Zenz, A P Kater, C U Niemann, D Gonzalez, F Davi, M Gonzalez Diaz, C Moreno, G Gaidano, K Stamatopoulos, R Rosenquist, S Stilgenbauer, P Ghia, S Pospisilova
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29467441/linc01016-promotes-the-malignant-phenotype-of-endometrial-cancer-cells-by-regulating-the-mir-302a-3p-mir-3130-3p-nfya-satb1-axis
#17
Xin Pan, Da Li, Jianing Huo, Fanfei Kong, Hui Yang, Xiaoxin Ma
Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis and cancer progression and are tightly associated with the phenotypes of numerous cancers. However, the functional roles underlying these effects are unknown. The expression levels of LINC01016, miR-302a-3p, miR-3130-3p, NFYA, and SATB1 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in 33 endometrial cancer tissues and 20 normal tissues. Bioinformatics analyses, luciferase reporter analyses, chromatin immunoprecipitation (ChIP) assays, and qRT-PCR assays were performed to verify potential binding sites...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29467336/frameshift-events-predict-anti-pd-1-l1-response-in-head-and-neck-cancer
#18
Glenn J Hanna, Patrick Lizotte, Megan Cavanaugh, Frank C Kuo, Priyanka Shivdasani, Alexander Frieden, Nicole G Chau, Jonathan D Schoenfeld, Jochen H Lorch, Ravindra Uppaluri, Laura E MacConaill, Robert I Haddad
Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating squamous cell carcinoma of the head and neck (SCCHN), but objective response rates are low. PD-1 ligand (PD-L1) expression alone is not considered a robust predictor of response and additional biomarkers are needed. This 3-year observational cohort followed 126 SCCHN patients treated with anti-PD-1/L1 therapy. Prior to treatment, 81 (64%) had targeted massively parallel tumor sequencing. Of these, 42 (52%) underwent fluorescence-activated cell sorting and PD-L1 immunohistochemistry for tumor immunoprofiling...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29467274/jak2-inhibitor-sar302503-abrogates-pd-l1-expression-and-targets-therapy-resistant-non-small-cell-lung-cancers
#19
Sean Pitroda, Melinda Stack, Gene-Fu Liu, Sui-Sui Song, Lucy Chen, Hua Liang, Akash D Parekh, Xiaona Huang, Paul B Roach, Mitchell C Posner, Ralph R Weichselbaum, Nikolai N Khodarev
Lung cancer is the leading cause of cancer deaths worldwide. Approximately 85% of all lung cancers are non-small-cell histology (NSCLC). Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than fifteen percent of patients survive beyond five years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide...
February 21, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29467147/alectinib-for-advanced-alk-positive-non-small-cell-lung-cancer
#20
REVIEW
Ashley C Ly, Jacqueline L Olin, Morgan B Smith
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: In patients with NSCLC driven by mutations of ALK , the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC...
February 21, 2018: American Journal of Health-system Pharmacy: AJHP
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