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https://www.readbyqxmd.com/read/29141225/a-comprehensive-patient-derived-xenograft-collection-representing-the-heterogeneity-of-melanoma
#1
Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C Gangadhar, David E Elder, Lauren E Haydu, Jennifer A Wargo, Michael A Davies, Yiling Lu, Gordon B Mills, Dennie T Frederick, Michal Barzily-Rokni, Keith T Flaherty, Dave S Hoon, Michael Guarino, Joseph J Bennett, Randall W Ryan, Nicholas J Petrelli, Carol L Shields, Mizue Terai, Takami Sato, Andrew E Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn
Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141147/a-water-soluble-galactose-decorated-cationic-photodynamic-therapy-agent-based-on-bodipy-to-selectively-eliminate-biofilm
#2
Xiaomei Dai, Xuelei Chen, Yu Zhao, Yunjian Yu, Xiaosong Wei, Xinge Zhang, Chaoxing Li
A multitude of serious chronic infections involved in bacterial biofilms that are difficult to eradicate. Here, a water-soluble galactose functionalized cationic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photodynamic therapy agent was synthesized for selectively eliminating the bacterial biofilm. These conjugates can capture bacteria to form aggregations through electrostatic interaction and then generate a large number of reactive oxygen species (ROS) under visible light irradiation to kill the bacteria without the emergence of bacterial resistance...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29141062/management-of-severe-acne-vulgaris-with-topical-therapy
#3
Linda Stein Gold, Hilary E Baldwin, Tina Lin
<p>Acne vulgaris (acne) is the most common skin disease we see in dermatology practice. Although rare in childhood, severe acne can affect up to 12% of the adolescent population. A chronic disease, it requires both aggressive management and effective maintenance strategies. Oral antibiotics, in combination with topical agents are recommended for treatment, with topical agents being continued as maintenance therapy to minimize resistance and recurrence. However, concerns with systemic side effects have recently resulted in a greater focus on the potential of fixed combination topical therapies to treat severe acne...
November 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29141010/multiple-effects-of-toxins-isolated-from-crotalus-durissus-terrificus-on-the-hepatitis-c-virus-life-cycle
#4
Jacqueline Farinha Shimizu, Carina Machado Pereira, Cintia Bittar, Mariana Nogueira Batista, Guilherme Rodrigues Fernandes Campos, Suely da Silva, Adélia Cristina Oliveira Cintra, Carsten Zothner, Mark Harris, Suely Vilela Sampaio, Victor Hugo Aquino, Paula Rahal, Ana Carolina Gomes Jardim
Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle...
2017: PloS One
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#5
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29140706/a-galactosylated-pro-drug-of-ursodeoxycholic-acid-design-synthesis-characterization-and-pharmacological-effects-in-a-rat-model-of-estrogen-induced-cholestasis
#6
Francesca Di Guida, Claudio Pirozzi, Salvatore Magliocca, Anna Santoro, Adriano Lama, Roberto Russo, Maria Nieddu, Lucia Burrai, Gianpiero Boatto, Maria Pina Mollica, Federica Sodano, Loretta Lazzarato, Konstantin Chegaev, Rosaria Meli, Giuseppina Mattace Raso, Maria Grazia Rimoli
Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#7
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29140112/a-2017-review-of-pharmacotherapy-for-treating-focal-epilepsy-where-are-we-now-and-how-will-treatment-develop
#8
Andreas Schulze-Bonhage
Focal epilepsy is the most common type of epilepsy with approximately 30 million patients affected worldwide. There is a major challenge to develop new antiepileptic treatments as currently approximately one third of patients remain uncontrolled under our best standards of care. Areas covered: An overview is given on first- and second generation antiepileptic drugs and their mechanisms of action, and on recent new strategies for antiepileptic targets, including drugs aiming at disease modification. Expert opinion: Newer antiepileptic drugs have enabled a better tolerated and individualized treatment for many patients...
November 15, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29140079/progress-and-trends-in-aie-based-bioprobes-a-brief-overview
#9
Ju Mei, Youhong Huang, He Tian
Luminescent bioprobes are powerful analytical means for biosensing and optical imaging. Luminogens featured with aggregation-induced emission (AIE) attributes have emerged as ideal building blocks for high-performance bioprobes. Bioprobes constructed with AIE luminogens have been identified to be a novel class of FL light-up probing tools. In contrast to conventional bioprobes based on the luminophores with aggregation-caused quenching (ACQ) effect, the AIE-based bioprobes enjoy diverse superiorities, such as lower background, higher signal-to-noise ratio and sensitivity, better accuracy, and more outstanding resistance to photobleaching...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29139555/tauroursodeoxycholic-acid-inhibits-intestinal-inflammation-and-barrier-disruption-in-nafld-mice
#10
Weijun Wang, Jinfang Zhao, Wenfang Gui, Dan Sun, Haijiang Dai, Li Xiao, Huikuan Chu, Fan Du, Qingjing Zhu, Bernd Schnabl, Kai Huang, Ling Yang, Xiaohua Hou
BACKGROUND AND PURPOSE: The gut-liver axis is associated with the progression of non-alcoholic fatty liver disease (NAFLD). Targeting the gut-liver axis and bile acid-based pharmaceuticals are potential therapies for NAFLD. The effect of tauroursodeoxycholic acid (TUDCA), a candidate medicine for NAFLD, on intestinal barrier function, intestinal inflammation, gut lipid transport and microbiota composition in a murine NAFLD model were analysed. EXPERIMENTAL APPROACHES: An NAFLD mouse model was established by feeding mice with a high-fat diet (HFD) for 16 weeks...
November 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29139080/a-review-of-insulin-resistance-in-type-1-diabetes-is-there-a-place-for-adjunctive-metformin
#11
REVIEW
Gagan Priya, Sanjay Kalra
There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with insulin resistance, increased insulin dose requirements and poor glycemic control. Insulin resistance is also seen during puberty and is strongly related to increased risk of cardiovascular disease. The role of metformin as an adjunct to ongoing intensive insulin therapy in type 1 diabetics has been evaluated in several randomized trials, including the recently concluded T1D Exchange Network trial in adolescents and the REMOVAL trial in adults...
November 14, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29139042/obesity-and-altered-aspirin-pharmacology
#12
REVIEW
Nicholas B Norgard
Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis, and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction...
November 14, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29138992/use-of-ketamine-in-elderly-patients-with-treatment-resistant-depression
#13
REVIEW
Carolina Medeiros da Frota Ribeiro, Patricio Riva-Posse
PURPOSE OF REVIEW: The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports...
November 15, 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29138921/world-trends-for-h-pylori-eradication-therapy-and-gastric-cancer-prevention-strategy-by-h-pylori-test-and-treat
#14
REVIEW
Hidekazu Suzuki, Hideki Mori
Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies.
November 14, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29138583/efficacy-of-intravenous-tigecycline-in-patients-with-acinetobacter-complex-infections-results-from-14-phase-iii-and-phase-iv-clinical-trials
#15
Hal Tucker, Michele Wible, Ashesh Gandhi, Alvaro Quintana
Background: Acinetobacter infections, especially multidrug-resistant (MDR) Acinetobacter infections, are a global health problem. This study aimed to describe clinical outcomes in patients with confirmed Acinetobacter spp. isolates who were treated with tigecycline in randomized clinical trials. Materials and methods: Data from 14 multinational, randomized (open-label or double-blind), and active-controlled (except one) Phase III and IV studies were analyzed using descriptive statistics...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29138561/a-simple-reduction-sensitive-micelles-co-delivery-of-paclitaxel-and-dasatinib-to-overcome-tumor-multidrug-resistance
#16
Jun Li, Ruitong Xu, Xiao Lu, Jing He, Shidai Jin
Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C18 as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29138515/targeting-a-non-oncogene-addiction-to-the-atr-chk1-axis-for-the-treatment-of-small-cell-lung-cancer
#17
Fabian Doerr, Julie George, Anna Schmitt, Filippo Beleggia, Tim Rehkämper, Sarah Hermann, Vonn Walter, Jean-Philip Weber, Roman K Thomas, Maike Wittersheim, Reinhard Büttner, Thorsten Persigehl, H Christian Reinhardt
Small cell lung cancer (SCLC) is a difficult to treat subtype of lung cancer. One of the hallmarks of SCLC is its almost uniform chemotherapy sensitivity. However, chemotherapy response is typically transient and patients frequently succumb to SCLC within a year following diagnosis. We performed a transcriptome analysis of the major human lung cancer entities. We show a significant overexpression of genes involved in the DNA damage response, specifically in SCLC. Particularly CHEK1, which encodes for the cell cycle checkpoint kinase CHK1, is significantly overexpressed in SCLC, compared to lung adenocarcinoma...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138500/circulating-androgen-receptor-combined-with-18f-fluorocholine-pet-ct-metabolic-activity-and-outcome-to-androgen-receptor-signalling-directed-therapies-in-castration-resistant-prostate-cancer
#18
V Conteduca, E Scarpi, P Caroli, S Salvi, C Lolli, S L Burgio, C Menna, G Schepisi, S Testoni, G Gurioli, G Paganelli, V Casadio, F Matteucci, U De Giorgi
The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-inneuroendocrine-prostate-cancer
#19
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon M Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul K Azad, Xuhong Cao, Jeri Kim, Paul Corn, Christopher Logothetis, Ana M Aparicio, Arul M Chinnayan, Nora M Navone, Patricia Troncoso, Timothy C Thompson
PURPOSE: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphological criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for NEPC. RESULTS: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public datasets and a panel of 28 PDX models we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#20
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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