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https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#1
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27933487/evaluation-of-standardized-triple-intrathecal-therapy-toxicity-in-oncohematological-pediatric-patients
#2
Raquel Olmos-Jiménez, María Sacramento Díaz-Carrasco, Ana Galera-Miñarro, Juan Francisco Pascual-Gazquez, Alberto Espuny-Miró
Background The administration of triple intrathecal therapy with methotrexate, cytarabine and a corticosteroid for the prophylaxis and treatment of neoplastic cell infiltration in the central nervous system in hematological malignancies is a widespread practice. There is limited information available about its toxicity profile. Several factors related to intrathecal preparation can affect toxicity. Thus, it was decided to standardize intrathecal chemotherapy, trying to obtain the best toxicity profile. Objective To assess the toxicity of a standardized triple intrathecal chemotherapy in oncohematological pediatric patients and to establish risk factors of toxicity...
December 8, 2016: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/27932180/liver-transplant-recipient-with-tumefactive-demyelinating-lesions-a-case-report-and-literature-review
#3
D-L Wan, K-W Ren, L-L Zhang, B Wang, Z L Zhai, X-Y Zhang, Y-C Yang, S-S Zheng
Tumefactive demyelinating lesions (TDLs) that may resemble brain neoplasms or abscesses are uncommon but noteworthy. A solid knowledge of how to distinguish TDLs from malignancy or infection is a key step to avoid unnecessary medical or surgical interventions. Almost all the intracranial demyelination diseases after liver transplantation (LT) refer to central pontine myelinolysis or extrapontine myelinolysis; TDLs after LT have never been reported. In 2005, a 45-year-old Chinese male underwent orthotopic LT due to "acute on chronic liver failure" in our hospital...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932160/successful-short-term-intravenous-treatment-of-disseminated-nocardia-farcinica-infection-with-severe-hyponatremia-after-kidney-transplantation-a-case-report
#4
A L Herzog, C Wanner, K Lopau
BACKGROUND: Nocardia is a genus of gram-positive Actinomycetes that are ubiquitous in decaying organic material, soil, and water. Some Nocardia species can infect humans, mainly by airborne transmission. Several reports describe disseminated infections, which are rare and mostly affect strongly immunocompromised patients because intact T-cell-mediated immunity is the major protective mechanism. CASE REPORT: We report a case of disseminated pulmonary, cerebral, and cutaneous infection with Nocardia farcinica in a 66-year-old kidney transplant recipient treated with low-dose triple immunosuppression...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932093/midterm-results-of-renal-transplantation-from-controlled-cardiac-death-donors-are-similar-to-those-from-brain-death-donors
#5
O Lafuente, B Sánchez-Sobrino, M Pérez, P López-Sánchez, D Janeiro, E Rubio, A Huerta, M Marques, M R Llópez-Carratala, J J Rubio, J Portolés
BACKGROUND: The systematic use of grafts from controlled donors after cardiac death (cDCD) started in our country in 2012 and expanded with the strategic support of National Transplant Organization. We present our experience in kidney transplantation with organs from cDCD donors with a mean follow-up of 3 years. METHODS: Observational prospective study of all transplants performed in our center in 2012-2013 followed to 2016. The immunosuppression protocols were triple therapy for low-risk recipients from a standard brain death donor (DBD), adding basiliximab or thymoglobulin induction for extended-criteria donor or high-risk recipient, respectively, and thymoglobulin induction plus triple therapy for all cDCD recipients...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931291/effects-of-the-addition-of-tiotropium-on-airway-dimensions-in-symptomatic-asthma
#6
Makoto Hoshino, Junichi Ohtawa, Kenta Akitsu
BACKGROUND: Tiotropium, a once-daily, long-acting anticholinergic bronchodilator, has shown efficacy and safety as an add-on to maintenance therapy in patients with symptomatic asthma. OBJECTIVE: The aim of the present study was to assess the effect of tiotropium on airway geometry and airway inflammation in patients with asthma who were symptomatic despite treatment with inhaled corticosteroid (ICS) plus a long-acting beta 2agonist (LABA). METHODS: In total, 53 patients with symptomatic asthma who received ICS plus LABA and who had a prebronchodilator forced expiratory volume in 1 second of 6090% of the predicted value were randomized to the addition of tiotropium 5 g once daily (n = 25) or no add-on (n = 28) to maintenance therapy for 48 weeks...
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27928647/triple-drug-combination-of-zidovudine-efavirenz-and-lamivudine-loaded-lactoferrin-nanoparticles-an-effective-nano-first-line-regimen-for-hiv-therapy
#7
Prashant Kumar, Yeruva Samrajya Lakshmi, Anand K Kondapi
PURPOSE: To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile. METHODS: Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics...
December 7, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27927046/advances-in-chemical-pharmacotherapy-to-manage-advanced-breast-cancer
#8
Andrea Gombos, Ahmad Awada
Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life. Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents...
December 7, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27923595/vitamin-d-compounds-inhibit-cancer-stem-like-cells-and-induce-differentiation-in-triple-negative-breast-cancer
#9
REVIEW
Naing Lin Shan, Joseph Wahler, Hong Jin Lee, Min Ji Bak, Soumyasri Das Gupta, Hubert Maehr, Nanjoo Suh
Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures...
December 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27923592/developments-in-targeted-therapy-in-melanoma
#10
REVIEW
V C Amann, E Ramelyte, S Thurneysen, R Pitocco, N Bentele-Jaberg, S M Goldinger, R Dummer, J Mangana
Melanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations). The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF- and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma...
November 5, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27922751/new-therapies-for-asthma-and-copd
#11
Nicholas J Gross, Peter J Barnes
Asthma and COPD (chronic obstructive pulmonary disease) are two common diseases for which current treatments are less than optimal and for which new drugs are greatly needed. Better understanding of the cellular and molecular mechanisms of these diseases has identified new targets for therapy and several new drugs are in development. Although most new treatments on the market are improvements in existing classes of drug or new combination of treatments, the clinicaltrials.gov website indicates 50 and 100 new medications for both asthma and COPD and many of these are entirely new...
December 6, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27920512/the-burden-of-chronic-obstructive-pulmonary-disease-associated-with-maintenance-monotherapy-in-the-uk
#12
Susan C Edwards, Sian E Fairbrother, Anna Scowcroft, Gavin Chiu, Andrew Ternouth, Brian J Lipworth
BACKGROUND: This study characterized a cohort of chronic obstructive pulmonary disease (COPD) patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization. METHODS: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013) or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#13
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919946/in-vivo-selection-of-intermediately-and-highly-malignant-variants-of-triple-negative-breast-cancer-in-orthotopic-nude-mouse-models
#14
Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M Hoffman
AIM: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MATERIALS AND METHODS: MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×10(7) cells/site) were initially injected subcutaneously in the flank of nude mice...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918572/risk-of-hiv-escape-using-sub-optimal-antiretroviral-dual-or-monotherapy
#15
Carmen de Mendoza
Budget constrictions have pushed some researchers to explore whether antiretroviral therapy with one or two drugs instead of the well-established triple-drug regimens may be able to maintain undetectable viremia in HIV-infected individuals, at least used as simplification in patients already with viral suppression under standard triple therapy. With the advent of co-formulations and the improved safety of the newest antiretroviral agents, there is no other reason than cost to justify moving from triple to dual or monotherapy...
October 2016: AIDS Reviews
https://www.readbyqxmd.com/read/27917405/efficacy-and-safety-of-3-week-response-guided-triple-direct-acting-antiviral-therapy-for-chronic-hepatitis-c-infection-a-phase-2-open-label-proof-of-concept-study
#16
George Lau, Yves Benhamou, Guofeng Chen, Jin Li, Qing Shao, Dong Ji, Fan Li, Bing Li, Jialiang Liu, Jinlin Hou, Jian Sun, Cheng Wang, Jing Chen, Vanessa Wu, April Wong, Chris L P Wong, Stella T Y Tsang, Yudong Wang, Leda Bassit, Sijia Tao, Yong Jiang, Hui-Mien Hsiao, Ruian Ke, Alan S Perelson, Raymond F Schinazi
BACKGROUND: To shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor-NS5B nucleotide analogue. METHODS: In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNA <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27917369/management-of-multiple-myeloma-and-usage-of-bortezomib-perspective-from-india-and-ukraine
#17
Amit Garg, Mykhaylo Morgunskyy, Yogesh Belagali, Namita Gupta, Shyam Prasad Akku
Novel treatment strategies have remarkably improved the multiple myeloma (MM) patients' survival, with associated increased costs. A joint panel meet of international experts from India and Ukraine was held in New Delhi on May 19, 2016 focusing on MM management, bortezomib role, unmet medical needs, and current challenges. The health-care system for oncology in India is majorly private vs. government-based in Ukraine. In India, electrophoresis, serum-free light chain assays, bone marrow tests, and X-rays are available modes of diagnosis...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916721/triple-stent-therapy-for-the-treatment-of-vertebral-dissecting-aneurysms-efficacy-and-safety
#18
Yeongu Chung, Sung Ho Lee, Seok Keun Choi, Bum Joon Kim, Kyung Mi Lee, Eui Jong Kim
No abstract text is available yet for this article.
December 1, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#19
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27915983/recognition-mechanisms-and-applications-of-peptide-nucleic-acids-targeting-double-stranded-dna
#20
Wenjia Li, Huanhuan Shi, Bo Dong, Kaixuan Nie, Zhengchun Liu, Nongyue He
Targeting double-stranded DNA (dsDNA) with high affinity and specificity has become a hot topic in biochemistry and molecular biology research. Gene diagnosis and therapy, DNA manipulation, and gene expression regulation could be achieved based on certain recognition principles through specific interactions between dsDNA and natural nucleotides or synthesized ligands. Some ligands (e.g., peptide nucleic acids (PNAs), triple helix-forming oligonucleotides (TFOs), oligopolyamides, and zinc-finger peptides) show sufficient affinity and specificity for targeting dsDNA sequences...
October 28, 2016: Current Medicinal Chemistry
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