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https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#1
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#2
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28820183/technique-of-retinal-gene-therapy-delivery-of-viral-vector-into-the-subretinal-space
#3
K Xue, M Groppe, A P Salvetti, R E MacLaren
PurposeSafe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges.MethodsOur subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy...
August 18, 2017: Eye
https://www.readbyqxmd.com/read/28819565/genomic-and-immune-heterogeneity-are-associated-with-differential-responses-to-therapy-in-melanoma
#4
Alexandre Reuben, Christine N Spencer, Peter A Prieto, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, John P Miller, Xizeng Mao, Mariana Petaccia De Macedo, Jiong Chen, Xingzhi Song, Hong Jiang, Pei-Ling Chen, Hannah C Beird, Haven R Garber, Whijae Roh, Khalida Wani, Eveline Chen, Cara Haymaker, Marie-Andrée Forget, Latasha D Little, Curtis Gumbs, Rebecca L Thornton, Courtney W Hudgens, Wei-Shen Chen, Jacob Austin-Breneman, Robert Szczepaniak Sloane, Luigi Nezi, Alexandria P Cogdill, Chantale Bernatchez, Jason Roszik, Patrick Hwu, Scott E Woodman, Lynda Chin, Hussein Tawbi, Michael A Davies, Jeffrey E Gershenwald, Rodabe N Amaria, Isabella C Glitza, Adi Diab, Sapna P Patel, Jianhua Hu, Jeffrey E Lee, Elizabeth A Grimm, Michael T Tetzlaff, Alexander J Lazar, Ignacio I Wistuba, Karen Clise-Dwyer, Brett W Carter, Jianhua Zhang, P Andrew Futreal, Padmanee Sharma, James P Allison, Zachary A Cooper, Jennifer A Wargo
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28819460/a-tumor-ph-responsive-supramolecular-photosensitizer-for-activatable-photodynamic-therapy-with-minimal-in-vivo-skin-phototoxicity
#5
Xingshu Li, Bi-Yuan Zheng, Mei-Rong Ke, Yongfan Zhang, Jian-Dong Huang, Juyoung Yoon
A major challenge in photodynamic therapy (PDT) is the development of new tumor-targeting photosensitizers. The tumor-specific activation is considered to be an effective strategy for designing these photosensitizers. Herein, we describe a novel tumor-pH-responsive supramolecular photosensitizer, LDH-ZnPcS8, which is not photoactive under neutral conditions but is precisely and efficiently activated in a slightly acidic environment (pH 6.5). LDH-ZnPcS8 is prepared by using a simple coprecipitation method based on the electrostatic interaction between negatively charged octasulfonate-modified zinc(II) phthalocyanine (ZnPcS8) and cationic hydroxide layers of layered double hydroxide (LDH)...
2017: Theranostics
https://www.readbyqxmd.com/read/28818953/new-horizons-for-precision-medicine-in-biliary-tract-cancers
#6
REVIEW
Juan W Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X Zhu
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e...
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#7
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28818298/enhancing-the-pediatric-drug-development-framework-to-deliver-better-pediatric-therapies-tomorrow
#8
Christina Bucci-Rechtweg
Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development...
August 14, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28818232/review-of-the-endothelial-pathogenic-mechanism-of-tie2-related-venous-malformation
#9
REVIEW
Zhong Du, JiaWei Zheng, ZhiYuan Zhang, YanAn Wang
BACKGROUND: Venous malformation (VM) is a type of disease involving vascular morphogenesis in humans. Clinically, VM can be sporadic or inherited. TIE2, also known as TEK or HYK, is a member of the receptor tyrosine kinase subfamily and is highly conserved among species. In 1996, an arginine-to-tryptophan substitution at position 849 (R849W) in TIE2 was found to induce hereditary VM. Additional alterations in TIE2 involved in the pathogenesis of inherited or sporadic VM have since been reported...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28817233/evaluation-and-quantitative-analysis-of-11-compounds-in-morinda-officinalis-using-ultra-high-performance-liquid-chromatography-and-photodiode-array-detection-coupled-with-chemometrics
#10
Xiangsheng Zhao, Weijun Kong, Yakui Zhou, Jianhe Wei, Meihua Yang
Morinda officinalis (Rubiaceae) is a traditional Chinese medicine widely used for the treatment of impotence and osteoporosis in clinical therapy. In the present study, a rapid and simple ultra high performance liquid chromatography with photodiode array detection method was developed and validated for the simultaneous determination of 11 bioactive compounds in M. officinalis. This assay method was validated with respect to linearity (R(2)( ) > 0.9991), precision, repeatability, limit of detection, limit of quantification, and accuracy (with observed recovery rates between 94...
August 17, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28816315/a-highly-selective-and-sensitive-fluorescent-nanosensor-for-dopamine-based-on-formate-bridged-tb-iii-complex-and-silver-nanoparticles
#11
Huihui Li, Jin Shen, Rongwei Cui, Chongmei Sun, Yanyan Zhao, Xia Wu, Na Li, Bo Tang
Highly selective determination of dopamine (DA) over other catecholamines is an urgent need for the precise diagnosis and therapy of DA related diseases. Herein, a new formate-bridged Tb(iii)-complex and silver nanoparticles (AgNPs) enhanced fluorescent nanosensor was constructed. HCOO(-) acted as a co-ligand of Tb(iii) and also as a linker between the Tb(iii) complex and AgNPs and more readily combined with the primary amine of DA than with epinephrine (EP). The formate-bridged action strengthened AgNPs-based surface enhanced fluorescence of the Tb(3+)-DA complex and improved the selectivity towards DA...
August 17, 2017: Analyst
https://www.readbyqxmd.com/read/28815101/characterizing-the-strength-of-evidence-in-fda-labels-for-pharmacogenomic-biomarker-guided-medication-use
#12
Lauren Chin, Beth Devine, Sarah Baradaran, Katelyn Keyloun, William Canestaro, Jonathan Pham
There is great heterogeneity in drug treatment response that is thought to be due to individual-level allelic variation in pharmacogenomic biomarkers. FDA Drug Labels provide information to guide pharmacogenomic biomarker use. Yet, the strength of evidence for clinical validity and clinical utility is lacking. We characterized the strength of evidence and treatment recommendations contained in FDA Drug Labels as of December 2015. Pharmacogenomic biomarker information was provided for 137 drugs, involving 49 pharmacogenomic biomarkers, constituting 166 drug-biomarker pairs...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28814499/therapeutic-stimulation-for-restoration-of-function-after-spinal-cord-injury
#13
REVIEW
Aiva Ievins, Chet T Moritz
Paralysis due to spinal cord injury can severely limit motor function and independence. This review summarizes different approaches to electrical stimulation of the spinal cord designed to restore motor function, with a brief discussion of their origins and the current understanding of their mechanisms of action. Spinal stimulation leads to impressive improvements in motor function along with some benefits to autonomic functions such as bladder control. Nonetheless, the precise mechanisms underlying these improvements and the optimal spinal stimulation approaches for restoration of motor function are largely unknown...
September 2017: Physiology
https://www.readbyqxmd.com/read/28812273/a-precision-medicine-approach-to-oxytocin%C3%A2-trials
#14
Elissar Andari, Rene Hurlemann, Larry J Young
In this chapter, we introduce a new area of social pharmacology that encompasses the study of the role of neuromodulators in modulating a wide range of social behaviors and brain function, with the interplay of genetic and epigenetic factors. There are increasing evidences for the role of the neuropeptide oxytocin in modulating a wide range of social behaviors, in reducing anxiety, and in impacting the social brain network. Oxytocin also promotes social functions in patients with neuropsychiatric disorders, such as autism and reduces anxiety and fear in anxiety disorders...
August 16, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28812050/caveats-in-the-established-understanding-of-cmt1a
#15
Jun Li
Charcot-Marie-Tooth disease type-1A (CMT1A) is one of the most common types of inherited peripheral nerve diseases. It is caused by the trisomy of chromosome 17p12 (c17p12), a large DNA segment of 1.4 Mb containing PMP22 plus eight other genes. The size of c17p12 is formidable for any cloning technique to manipulate, and thus precludes production of models in vitro and in vivo that can precisely recapitulate the genetic alterations in humans with CMT1A. This limitation and other factors have led to several assumptions, which have yet been carefully scrutinized, serving as key principles in our understanding of the disease...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#16
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28811267/app-a%C3%AE-structural-diversity-and-alzheimer-s-disease-pathogenesis
#17
REVIEW
Alex E Roher, Tyler A Kokjohn, Steven G Clarke, Michael R Sierks, Chera L Maarouf, Geidy E Serrano, Marwan S Sabbagh, Thomas G Beach
The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1-40 and 1-42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that amplified production of some APP/Aβ species, perhaps exacerbated by differential gene expression and reduced peptide degradation, creates a diverse spectrum of modified species which disrupt brain homeostasis and accelerate AD neurodegeneration...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28809861/high-frequency-measurement-of-depressive-severity-in-a-patient-treated-for-severe-treatment-resistant-depression-with-deep-brain-stimulation
#18
S Sani, J Busnello, R Kochanski, Y Cohen, R D Gibbons
Although there have been previous studies of deep-brain stimulation (DBS), we present, to our knowledge, the first example of high-frequency depressive severity measurement-based DBS treatment in particular and psychiatric treatment in general. Daily post-surgical e-mail prompts for a period of 6 months resulted in 93 administrations of a computerized adaptive test (CAT) of depression severity (CAT-Depression Inventory or CAT-DI) via the internet. There was an average of 3.37 weekly measurements with an average separation of 2...
August 15, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28809467/multidimensional-control-of-cas9-by-evolved-rna-polymerase-based-biosensors
#19
Jinyue Pu, Kaitlin Kentala, Bryan C Dickinson
Systems to control Cas9 with spatial and temporal precision offer opportunities to decrease side effects, protect sensitive tissues, and create gene therapies that are only activated at defined times and places. Here, we present the design of new Cas9 controllers based on RNA polymerase (RNAP)-based biosensors that produce gRNAs, thereby regulating target knockout. After development and validation of a new abscisic acid-inducible biosensor to control Cas9, we lowered the background of the system using continuous evolution...
August 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#20
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
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