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https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#1
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29785138/a-review-of-soft-tissue-sarcomas-translation-of-biological-advances-into-treatment-measures
#2
REVIEW
Ngoc T Hoang, Luis A Acevedo, Michael J Mann, Bhairavi Tolani
Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29785036/a-novel-microrna-signature-predicts-survival-in-liver-hepatocellular-carcinoma-after-hepatectomy
#3
Qiang Fu, Fan Yang, Tengxiao Xiang, Guoli Huai, Xingxing Yang, Liang Wei, Hongji Yang, Shaoping Deng
Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer. In the current study, genome-wide miRNA-Seq and mRNA profiles in 318 LIHC patients derived from The Cancer Genome Atlas (TCGA) were analysed to identify miRNA-based signatures for LIHC prognosis with survival analysis and a semi-supervised principal components (SPC) method. A seven-miRNA signature was confirmed for overall survival (OS) prediction by comparing miRNA profiles in paired primary tumour and solid tumour normal tissues...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#4
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29785010/genome-wide-analyses-identify-68-new-loci-associated-with-intraocular-pressure-and-improve-risk-prediction-for-primary-open-angle-glaucoma
#5
Anthony P Khawaja, Jessica N Cooke Bailey, Nicholas J Wareham, Robert A Scott, Mark Simcoe, Robert P Igo, Yeunjoo E Song, Robert Wojciechowski, Ching-Yu Cheng, Peng T Khaw, Louis R Pasquale, Jonathan L Haines, Paul J Foster, Janey L Wiggs, Chris J Hammond, Pirro G Hysi
Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4 . Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP...
May 21, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29784926/clinical-utility-of-circulating-non-coding-rnas-an-update
#6
REVIEW
Simone Anfossi, Anna Babayan, Klaus Pantel, George A Calin
Over the past decade, the amount of research and the number of publications on associations between circulating small and long non-coding RNAs (ncRNAs) and cancer have grown exponentially. Particular focus has been placed on the development of diagnostic and prognostic biomarkers to enable efficient patient management - from early detection of cancer to monitoring for disease recurrence or progression after treatment. Owing to their high abundance and stability, circulating ncRNAs have potential utility as non-invasive, blood-based biomarkers that can provide information on tumour biology and the effects of treatments, such as targeted therapies and immunotherapies...
May 21, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29784744/the-changing-treatment-landscape-for-metastatic-urothelial-carcinoma
#7
Thomas W Flaig
Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#8
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784537/artificial-intelligence-a-joint-narrative-on-potential-use-in-pediatric-stem-and-immune-cell-therapies-and-regenerative-medicine
#9
REVIEW
Irena Sniecinski, Jerard Seghatchian
Artificial Intelligence (AI) reflects the intelligence exhibited by machines and software. It is a highly desirable academic field of many current fields of studies. Leading AI researchers describe the field as "the study and design of intelligent agents". McCarthy invented this term in 1955 and defined it as "the science and engineering of making intelligent machines". The central goals of AI research are reasoning, knowledge, planning, learning, natural language processing (communication), perception and the ability to move and manipulate objects...
May 9, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29783934/the-impact-of-pharmacokinetic-gene-profiles-across-human-cancers
#10
Michael T Zimmermann, Terry M Therneau, Jean-Pierre A Kocher
BACKGROUND: The right drug to the right patient at the right time is one of the ideals of Individualized Medicine (IM) and remains one of the most compelling promises of the post-genomic age. The addition of genomic information is expected to increase the precision of an individual patient's treatment, resulting in improved outcomes. While pilot studies have been encouraging, key aspects of interpreting tumor genomics information, such as somatic activation of drug transport or metabolism, have not been systematically evaluated...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#11
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29782246/precision-medicine-and-radiogenomics-in-breast-cancer-new-approaches-toward-diagnosis-and-treatment
#12
Katja Pinker, Joanne Chin, Amy N Melsaether, Elizabeth A Morris, Linda Moy
Precision medicine is medicine optimized to the genotypic and phenotypic characteristics of an individual and, when present, his or her disease. It has a host of targets, including genes and their transcripts, proteins, and metabolites. Studying precision medicine involves a systems biology approach that integrates mathematical modeling and biology genomics, transcriptomics, proteomics, and metabolomics. Moreover, precision medicine must consider not only the relatively static genetic codes of individuals, but also the dynamic and heterogeneous genetic codes of cancers...
June 2018: Radiology
https://www.readbyqxmd.com/read/29781781/gene-expression-microarray-analysis-reveals-prognostic-markers-of-survival-in-high-grade-astrocytomas
#13
Jun Yang, Ziming Hou, Changjiang Wang, Hao Wang, Hongbing Zhang
OBJECTIVE: High grade astrocytoma (HGA) as an aggressive brain tumor, is always correlated with poor prognosis. In this paper, we aimed to explore the genetic prognostic biomarkers for HGA. METHODS: The genome-wide expression profile of 26 brain tumor samples obtained from 26 patients with HGA was downloaded from Gene Expression Omnibus. The risk genes for prognosis of HGA were identified and verified by the data in TCGA database. Protein-protein interaction (PPI) network of risk factor genes was constructed and significant module was screened...
May 21, 2018: Neurological Research
https://www.readbyqxmd.com/read/29781548/multi-omics-in-high-grade-serous-ovarian-cancer-biomarkers-from-genome-to-the-immunome
#14
Cole Clifford, Natasha Vitkin, Sarah Nersesian, Gillian Reid-Schachter, Julie-Ann Francis, Madhuri Koti
Epithelial ovarian cancer (EOC) is a lethal gynaecological disease that imposes significant burden on health care and patient quality of life. High-grade serous carcinoma of the ovary (HGSC) is the most prevalent histological type of EOC. A vast majority of HGSC cases are diagnosed at late stages of the disease, limiting the opportunity for clinical intervention and resulting in a 10-year survival rate of <20%. Recent innovations in high-throughput molecular analysis of patient-derived specimens may address these clinical challenges by providing an enhanced understanding of the molecular aetiology of ovarian cancer, in addition to offering several opportunities for rational biomarker and targeted therapy discovery...
May 21, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29780635/liquid-biopsy-for-lung-cancer-early-detection
#15
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Alessandro D'Aveni, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Chiara Lazzari, Giuseppe Altavilla, Rafael Rosell
Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780592/preleukemic-and-second-hit-mutational-events-in-an-acute-myeloid-leukemia-patient-with-a-novel-germline-runx1-mutation
#16
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29780391/concepts-collide-genomic-immune-and-microbial-influences-on-the-tumor-microenvironment-and-response-to-cancer-therapy
#17
REVIEW
Miles C Andrews, Alexandre Reuben, Vancheswaran Gopalakrishnan, Jennifer A Wargo
Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780361/challenges-and-promises-for-planning-future-clinical-research-into-bacteriophage-therapy-against-pseudomonas-aeruginosa-in-cystic-fibrosis-an-argumentative-review
#18
REVIEW
Martina Rossitto, Ersilia V Fiscarelli, Paola Rosati
Although early aggressive and prolonged treatment with specific antibiotics can extend survival in patients with cystic fibrosis (CF) colonized by opportunistic Pseudomonas aeruginosa (PA), antibiotics fail to eradicate the infecting multidrug-resistant (MDR) PA strains in CF. Century-long research has suggested treating patients with bacteriophages (phages, prokaryotic viruses) naturally hosted by bacteria. Although the only phage types used in therapy, lytic phages, lyse PA aggregated in biofilm matrix by depolymerase degrading enzymes, how they can effectively, safely, and persistently do so in patients with CF is unclear...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29779986/photodynamic-therapy-corrects-abnormal-cancer-associated-gene-expression-observed-in-actinic-keratosis-lesions-and-induces-a-remodeling-effect-in-photodamaged-skin
#19
Florence Joly, Sophie Deret, Bastien Gamboa, Corinne Menigot, Paul Fogel, Carine Mounier, Pascale Reiniche, Farzaneh Sidou, Jérome Aubert, John Lear, Anthony A Fryer, Francesca Zolezzi, Johannes J Voegel
BACKGROUND: Actinic keratoses (AK) are proliferations of neoplastic keratinocytes in the epidermis resulting from cumulative exposure to ultraviolet radiation (UVR), which are liable to transform into squamous cell carcinoma (SCC). Organ Transplant Recipients (OTR) have an increased risk of developing SCC as a consequence of long-term immunosuppressive therapy. The aim of this study was to determine the molecular signature of AKs from OTR prior to treatment with methyl aminolevulinate-photodynamic therapy (MAL-PDT), and to assess what impact the treatment has on promoting remodeling of the photo-damaged skin...
May 17, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29779585/translational-studies-provide-insights-for-the-etiology-and-treatment-of-cortical-bone-osteoporosis
#20
REVIEW
Robert Brommage, Claes Ohlsson
Increasing attention is being focused on the important contributions of cortical bone to bone strength, fractures and osteoporosis therapies. Recent progress in human genome wide association studies in combination with high-throughput mouse gene knockout phenotyping efforts of multiple genes and advanced conditional gene inactivation in mouse models have successfully identified genes with crucial roles in cortical bone homeostasis. Particular attention in this review is given to genes, such as WNT16, POSTN and SFRP4, that differentially affect cortical and trabecular bone architecture...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
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