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Combined Elements Therapy

Pei Y Liu, Nicholas Sokolowski, Su T Guo, Faraz Siddiqi, Bernard Atmadibrata, Thomas J Telfer, Yuting Sun, Lihong Zhang, Denise Yu, Joshua Mccarroll, Bing Liu, Rui H Yang, Xiang Y Guo, Andrew E Tee, Ken Itoh, Jenny Wang, Maria Kavallaris, Michelle Haber, Murray D Norris, Belamy B Cheung, Jennifer A Byrne, David S Ziegler, Glenn M Marshall, Marcel E Dinger, Rachel Codd, Xu D Zhang, Tao Liu
BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy. After screening a library of 2697 small molecule compounds, we found that two classes of compounds, the quinone-containing compounds such as nanaomycin and anti-microtubule drugs such as vincristine, exerted the best synergistic anticancer effects with the BET bromodomain inhibitor JQ1 in neuroblastoma cells. Mechanistically, the quinone-containing compound nanaomycin induced neuroblastoma cell death but also activated the Nrf2-antioxidant signaling pathway, and the BET bromodomain proteins BRD3 and BRD4 formed a protein complex with Nrf2...
October 13, 2016: Oncotarget
Marius N Stan, Mario Salvi
Rituximab (RTX) use in open label series has been associated with very encouraging responses in patients with active and moderate-to-severe Graves' Orbitopathy (GO). Recently randomized controlled trials of RTX have been performed in such patients in order to answer the question of clinical efficacy and the safety profile of this agent. That data, reported separately, focused on Clinical Activity Score (CAS) and indicated in one trial a strong benefit of RTX in comparison with IV glucocorticoids while the other trial noted the absence of a benefit by comparison with placebo...
October 19, 2016: European Journal of Endocrinology
M E Cazzaniga, L Cortesi, A Ferzi, L Scaltriti, F Cicchiello, M Ciccarese, S Della Torre, F Villa, M Giordano, C Verusio, M Nicolini, A R Gambaro, L Zanlorenzi, E Biraghi, L Legramandi, E Rulli
PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS)...
October 17, 2016: Breast Cancer Research and Treatment
Julie C Fitzgerald, Scott L Weiss, Niranjan Kissoon
OBJECTIVE: To review important articles in the field of pediatric shock and pediatric septic shock published subsequent to the Fifth Edition of the Rogers' Textbook of Pediatric Intensive Care. DATA SOURCES: The U.S. National Library of Medicine PubMed ( was searched for combination of the term "pediatric" and the following terms: "sepsis, septic shock, shock, antibiotics, extracorporeal membrane oxygenation, and steroid." The abstract lists generated by these searches were screened for potential inclusion...
September 30, 2016: Pediatric Critical Care Medicine
Teresa Graziano, Angela Amoruso, Stefania Nicola, Francesca Deidda, Serena Allesina, Marco Pane, Pietro Piffanelli, Francesco Strozzi, Luca Mogna, Mario Del Piano
GOALS: The aim of the study was to unequivocally demonstrate the nontransmissibility of the genes mediating the resistance of the strain Bifidobacterium longum W11 (LMG P-21586) to rifaximin. BACKGROUND: Most antibiotic treatments can induce unfavorable side effects such as antibiotic-associated diarrhea, which is largely attributable to the disruption of the intestinal microbiota. The parallel intake of probiotic bacteria might reduce these events, even if with generally very poor results...
November 2016: Journal of Clinical Gastroenterology
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
Wonmo Sung, Seongmoon Jung, Sung-Joon Ye
The aim of this study is to investigate the dosimetric characteristics of nanoparticle-enhanced Auger therapy. Monte Carlo (MC) simulations were performed to assess electron energy spectra and dose enhancement distributions around a nanoparticle. In the simulations, two types of nanoparticle structures were considered: nanoshell and nanosphere, both of which were assumed to be made of one of five elements (Fe, Ag, Gd, Au, and Pt) in various sizes (2-100 nm). Auger-electron emitting radionuclides (I-125, In-111, and Tc-99m) were simulated within a nanoshell or on the surface of a nanosphere...
October 7, 2016: Physics in Medicine and Biology
Anders Rosendal Korshoej, Guilherme Bicalho Saturnino, Line Kirkegaard Rasmussen, Gorm von Oettingen, Jens Christian Hedemann Sørensen, Axel Thielscher
OBJECTIVE: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. METHODS: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma...
2016: PloS One
Karol Jaroch, Maciej Karolak, Przemysław Górski, Alina Jaroch, Adrian Krajewski, Aleksandra Ilnicka, Anna Sloderbach, Tomasz Stefański, Stanisław Sobiak
For the first time combretastatins were isolated from African willow tree Combretum Caffrum. Subsequent studies have shown the impact of combretastatin A4 phosphate, a water-soluble prodrug, on endothelial cells in tumor vascular system. The same effect was not observed in the vascular system. This selectivity is associated with combretastatins mechanism of action: binding to colchicine domain of microtubules, which affects the cytoskeleton functionality of immature endothelial cells. At the same time, combretastatins directly induce cell death via apoptosis and/or mitotic catastrophe pathways...
August 24, 2016: Pharmacological Reports: PR
Hoyong Lim, Kyung-Chang Kim, Junseock Son, Younghyun Shin, Cheol-Hee Yoon, Chun Kang, Byeong-Sun Choi
HIV-1 reservoirs remain a major barrier to HIV-1 eradication. Although combination antiretroviral therapy (cART) can successfully reduce viral replication, it cannot reactivate HIV-1 provirus in this reservoir. Therefore, HIV-1 provirus reactivation strategies by cell activation or epigenetic modification are proposed for the eradication of HIV-1 reservoirs. Although treatment with the protein kinase A (PKA) activator cyclic AMP (cAMP) or epigenetic modifying agents such as histone deacetylase inhibitors (HDACi) alone can induce HIV-1 reactivation in latently infected cells, the synergism of these agents has not been fully evaluated...
September 24, 2016: Virus Research
Jean-Marie Beis, Morgane Renard
OBJECTIVE: Anti-NMDA (N-Methyl-D-Aspartate) receptor encephalitis (NMDA-E) is the second cause of autoimmune encephalitis in adults. The objectives of this presentation are to describe the main clinical elements and rehabilitation specificities. OBSERVATIONS: Three female inpatients (mean age: 25) present with moderate to severe behavioural and/or psychiatric disorders, seizures and presence of associated tumor in one patient. Presence of anti-NMDA antibodies in the cerebrospinal liquid confirmed diagnosis...
September 2016: Annals of Physical and Rehabilitation Medicine
Simona Scarano, Samuele Lisi, Corinne Ravelet, Eric Peyrin, Maria Minunni
The failure of therapeutic treatment of Alzheimer's disease (AD) patients can be related to the late onset of symptoms and, consequently, to a delayed pharmacological aid to counteract neurodegenerative progression. This is coupled to the fact that the diagnosis based on clinical criteria alone introduces high misdiagnosis rate. The availability of assessed biomarkers is therefore of crucial importance not only to counteract late diagnosis, but also to manage patients at high risk of AD development eligible for novel therapies...
October 12, 2016: Analytica Chimica Acta
Safiyeh Aghazadeh, Razieh Yazdanparast
Trastuzumab has been successfully used as a first-line therapy specific for HER2-overexressing breast cancer patients. However, despite the effectiveness of trastuzumab, the occurrence of inherent and acquired resistance remains as the main challenge of the therapy. Thus, this has motivated efforts toward finding new therapeutic strategies including combining trastuzumab with other drugs to enhance its therapeutic efficacy. In that line, we investigated the capability of mycophenolic acid (MPA), an inhibitor of de novo guanine nucleotide synthesis with potential anti-cancer activity, on improving the response to trastuzumab among SKBR3 cells as well as trastuzumab resistant SKBR3-TR cells...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
Marta Biedka, Tamara Kuźba-Kryszak, Tomasz Nowikiewicz, Agnieszka Żyromska
Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect...
2016: Contemporary Oncology Współczesna Onkologia
Orly Sarid, Julie Cwikel, Johanna Czamanski-Cohen, Ephrat Huss
This paper presents an overview of a combined, evaluated protocol, cognitive behavioural and art therapy treatment (CB-ART), for the treatment of women with perinatal mood and anxiety disorders (PMADs). The protocol integrates cognitive behavioural interventions and art therapy. CB-ART focuses on changing distressing image, symptom or memory (ISM) that interferes with functioning. The method directs clients to identify compositional elements that characterize their stressful ISM and to alter the element in their imagination, in bodily sensations and on the page...
September 19, 2016: Archives of Women's Mental Health
Róbert Gábor Kiss
Antithrombotic drug therapy is a main cornerstone - sometimes a fairly uneven cornerstone - of today's clinical practice. Patients treated with antithrombotic drugs appear sometimes unawaited at those of our colleagues, who are not necessarily experts of this narrow field. Furthermore, new and newer molecules of antiplatelet and anticoagulant medicines have come into practice, frequently in combination. This dramatic development has been important to patients; pharmacological - and recently nonpharmacological - antithrombotic treatment has paved the way to improve current modalities in cardiology...
September 2016: Orvosi Hetilap
Bor Kos, Juan Luis Vásquez, Damijan Miklavčič, Gregers G G Hermann, Julie Gehl
OBJECTIVE: Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. MATERIAL AND METHODS: Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min...
2016: PeerJ
Kai-Oliver Henrich, Sebastian Bender, Maral Saadati, Daniel Dreidax, Moritz Gartlgruber, Chunxuan Shao, Carl Herrmann, Manuel Wiesenfarth, Martha Parzonka, Lea Wehrmann, Matthias Fischer, David J Duffy, Emma Bell, Alica Torkov, Peter Schmezer, Christoph Plass, Thomas Höfer, Axel Benner, Stefan M Pfister, Frank Westermann
The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor- and cell line-derived global histone modification analyses and epigenetic drug treatment in vitro We found that DNA methylation patterns identify divergent patient subgroups with respect to survival and clinicobiologic variables, including amplified MYCN Transcriptome integration and histone modification-based definition of enhancer elements revealed intragenic enhancer methylation as a mechanism for high-risk-associated transcriptional deregulation...
September 15, 2016: Cancer Research
Ernest Moles, Kirsten Moll, Jun-Hong Ch'ng, Paolo Parini, Mats Wahlgren, Xavier Fernàndez-Busquets
Parasite proteins exported to the surface of Plasmodium falciparum-parasitized red blood cells (pRBCs) have a major role in severe malaria clinical manifestation, where pRBC cytoadhesion and rosetting processes have been strongly linked with microvascular sequestration while avoiding both spleen filtration and immune surveillance. The parasite-derived and pRBC surface-exposed PfEMP1 protein has been identified as one of the responsible elements for rosetting and, therefore, considered as a promising vaccine candidate for the generation of rosette-disrupting antibodies against severe malaria...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ziyad Ben Taleb, Kenneth D Ward, Taghrid Asfar, Rana Jaber, Raed Bahelah, Wasim Maziak
BACKGROUND: In high-income countries, quitting cigarette smoking is associated with weight gain, which can reduce motivation to abstain. Whether smoking cessation is associated with weight gain in a low-income country context has never been investigated. We aimed to determine the post-cessation changes in body mass index (BMI) and its predictors among smokers who received a smoking cessation intervention in a low-income country setting. METHODS: We performed post hoc analyses of data from 269 smokers who participated in a two-group, parallel-arm, double-blind, placebo-controlled randomized trial of combined nicotine replacement therapy (NRT) and behavioral counseling in primary care clinics in Aleppo, Syria...
September 9, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
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