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https://www.readbyqxmd.com/read/29352735/s-nitrosated-poly-propylene-sulfide-nanoparticles-for-enhanced-nitric-oxide-delivery-to-lymphatic-tissues
#1
Alex Schudel, Lauren F Sestito, Susan N Thomas
Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases affecting lymphatic tissues, which range from infectious and cardiovascular diseases to cancer. Existing technologies available for NO therapy, however, provide poor bioactivity within lymphatic tissues. In this work, we address this technology gap with a NO encapsulation and delivery strategy leveraging the formation of S-nitrosothiols on lymphatic-targeting Pluronic-stabilized, poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the lymphatic versus systemic delivery of NO resulting from intradermal administration of SNO-NP benchmarked against a commonly used, commercially available small molecule S-nitrosothiol NO donor, examined signs of toxicity systemically as well as localized to the site of injection, and investigated SNO effects on lymphatic transport and NP uptake by LN-resident cells...
January 20, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29352572/phase-i-combination-study-of-the-parp-inhibitor-veliparib-plus-carboplatin-and-gemcitabine-in-patients-with-advanced-ovarian-cancer-and-other-solid-malignancies
#2
Heidi J Gray, Katherine Bell-McGuinn, Gini F Fleming, Mihaela Cristea, Hao Xiong, Danielle Sullivan, Yan Luo, Mark D McKee, Wijith Munasinghe, Lainie P Martin
OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In this phase I study, patients with metastatic or unresectable solid tumors and ≤2 prior chemotherapy regimens received veliparib combined with carboplatin area under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21-day cycle for maximum 10cycles, followed by optional veliparib maintenance therapy...
January 15, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#3
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352450/carrier-mediated-uptake-of-clonidine-in-cultured-human-lung-cells
#4
Marc Le Vée, Elodie Jouan, Olivier Fardel
The lung is a preferential organ site for accumulation of lipophilic basic amine drugs, so-called pneumophilic drugs and belonging to various pharmacological classes, which can result in lung toxicity. In order to investigate the mechanism involved in such pulmonary accumulation of drugs, uptake of clonidine, used here as a prototypical basic amine drug, was characterized in cultured human lung cells. Clonidine accumulation in lung alveolar A549 cells was found to be temperature- and pH-dependent; it was saturable, with a Michaelis-Menten affinity constant (Km) value of 569...
January 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#5
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#6
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351883/titanium-dioxide-nanoparticle-exposure-reduces-algal-biomass-and-alters-algal-assemblage-composition-in-wastewater-effluent-dominated-stream-mesocosms
#7
Moncie V Wright, Cole W Matson, Leanne S Baker, Benjamin T Castellon, Preston S Watkins, Ryan S King
A 5-week mesocosm experiment was conducted to investigate the toxicity of titanium dioxide nanoparticles (TiO2NPs) to periphytic algae in an environmentally-realistic scenario. We used outdoor experimental streams to simulate the characteristics of central Texas streams receiving large discharges of wastewater treatment plant effluent during prolonged periods of drought. The streams were continually dosed and maintained at two concentrations. The first represents an environmentally relevant concentration of 0...
January 16, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29351667/what-to-expect-and-when-benznidazole-toxicity-in-chronic-chagas-disease-treatment
#8
E Aldasoro, E Posada, A Requena-Méndez, A Calvo-Cano, N Serret, A Casellas, S Sanz, D Soy, M J Pinazo, J Gascon
Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials...
January 16, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29351570/joint-adolescent-adult-early-phase-clinical-trials-to-improve-access-to-new-drugs-for-adolescents-with-cancer-proposals-from-the-multi-stakeholder-platform-accelerate
#9
N Gaspar, L V Marshall, D Binner, R Herold, R Rousseau, P Blanc, R Capdeville, J Carleer, C Copland, Y Kerloeguen, K Norga, L Pacaud, M-A Sevaux, C Spadoni, J Sterba, F Ligas, T Taube, M Uttenreuther-Fischer, S Chioato, M A O'Connell, B Geoerger, J-Y Blay, J C Soria, S Kaye, B Wulff, L Brugières, G Vassal, A D J Pearson
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351198/superoxide-dismutase-mimetic-gc4419-enhances-the-oxidation-of-pharmacological-ascorbate-and-its-anticancer-effects-in-an-h%C3%A2-o%C3%A2-dependent-manner
#10
Collin D Heer, Andrew B Davis, David B Riffe, Brett A Wagner, Kelly C Falls, Bryan G Allen, Garry R Buettner, Robert A Beardsley, Dennis P Riley, Douglas R Spitz
Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several cancer types...
January 19, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29350913/environmentally-triggerable-retinoic-acid-inducible-gene-i-agonists-using-synthetic-polymer-overhangs
#11
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna M Pyle, John T Wilson
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities...
January 19, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29350469/in-vitro-to-in-vivo-benchmark-dose-comparisons-to-inform-risk-assessment-of-quantum-dot-nanomaterials
#12
REVIEW
Brittany A Weldon, William C Griffith, Tomomi Workman, David K Scoville, Terrance J Kavanagh, Elaine M Faustman
Engineered nanomaterials are currently under review for their potential toxicity; however, their use in consumer/commercial products has continued to outpace risk assessments. In vitro methods may be utilized as tools to improve the efficiency of risk assessment approaches. We propose a framework to compare relationships between previously published in vitro and in vivo toxicity assessments of cadmium-selenium containing quantum dots (QDs) using benchmark dose (BMD) and dosimetric assessment methods. Although data were limited this approach was useful for identifying sensitive assays and strains...
January 19, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29350463/brim-p-a-phase-i-open-label-multicenter-dose-escalation-study-of-vemurafenib-in-pediatric-patients-with-surgically-incurable-braf-mutation-positive-melanoma
#13
Julia C Chisholm, Jozef Suvada, Ira J Dunkel, Michela Casanova, Weijiang Zhang, Natasha Ritchie, YounJeong Choi, Jane Park, Meghna Das Thakur, Stephen Simko, Nga Wan Rachel Tam, Andrea Ferrari
BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12-17 years with this tumor type (NCT01519323). PROCEDURE: Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350117/-treating-poisoning-how-do-you-choose-the-best-type-of-gastrointestinal-decontamination
#14
M V Verschueren, F G A Jansman, D J Touw, C Kramers
- A new guideline: 'Intoxication: initial approach in the hospital' will be published this year. This guideline sets out the latest insights on gastrointestinal decontamination in intoxication; the advice is summarized in a flowchart.- The advice is to generally administer activated charcoal, unless there are indications that the toxin will not bind to activated charcoal or that the amount of toxin that the patient has ingested is too great; in these cases gastric lavage can be considered.- Activated charcoal can be administered up to 2 hours after the ingestion of a toxic substance, unless there are contra-indications...
2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29350075/characterization-of-the-proteome-and-lipidome-profiles-of-human-lung-cells-after-low-dose-and-chronic-exposure-to-multiwalled-carbon-nanotubes
#15
Santosh Phuyal, Mayes Kasem, Oskar Knittelfelder, Animesh Sharma, Davi de Miranda Fonseca, Vaineta Vebraite, Sergey Shaposhnikov, Geir Slupphaug, Vidar Skaug, Shanbeh Zienolddiny
The effects of long-term chronic exposure of human lung cells to multi-walled carbon nanotubes (MWCNT) and their impact upon cellular proteins and lipids were investigated. Since the lung is the major target organ, an in vitro normal bronchial epithelial cell line model was used. Additionally, to better mimic exposure to manufactured nanomaterials at occupational settings, cells were continuously exposed to two non-toxic and low doses of a MWCNT for 13-weeks. MWCNT-treatment increased ROS levels in cells without increasing oxidative DNA damage and resulted in differential expression of multiple anti- and pro-apoptotic proteins...
January 19, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29349890/case-report-cytochrome-p450-implications-for-comorbid-adhd-and-ocd-pharmacotherapy
#16
Michaela K Hogan, Nikhil P Rao
TOPIC: This case report details the treatment of an early adolescent already receiving treatment for attention-deficit hyperactivity disorder who presents with recurrent obsessive-compulsive disorder. Potential atomoxetine (Strattera) and fluoxetine (Prozac) interactions via Cytochrome P450 (CYP450) pathways are examined and alternate therapies are recommended. PURPOSE: Provide a discussion of psychopharmacogenomics, especially in the case of combining medications, CYP450 enzymes, and clinical implications in the context of the burgeoning field of precision medicine...
January 19, 2018: Journal of Child and Adolescent Psychiatric Nursing
https://www.readbyqxmd.com/read/29349797/efficacy-and-toxicity-of-praziquantel-in-helminth-infected-barbel-barbus-barbus-l
#17
E Zuskova, V Piackova, J Machova, L Chupani, C Steinbach, A Stara, J Velisek
This study evaluated efficacy and toxicity of the pyrazinoisoquinoline anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant biomarkers and the lipid peroxidation response in juvenile barbel post-treatment. The estimated 96-hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4-day bath treatment. Both concentrations were 100% effective against D...
January 19, 2018: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29349760/advancements-and-personalization-of-breast-cancer-treatment-strategies-in-radiation-therapy
#18
Meena S Moran
Significant technologic advances in radiation treatment delivery now allow for more personalized delivery considerations which incorporate individual patient characteristics (such as tumor location and patient anatomy) and more precise delivery in the breast conservation or post-mastectomy setting. The combined advancements with other treatment modalities (i.e., systemic therapy, surgical management) have had direct effects on local-regional management and outcomes such that currently, local-regional relapses after definitive treatment for localized disease are now rarely experienced...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349737/teratogenic-effects-induced-by-chitosan-oligosaccharide-in-wistar-female-rat-rattus-norvegicus
#19
Amal Abdel Aziz Eisa, Gamal El-Sayed Aboelghar, Ibrahim Mahmoud Ammar, Hala Gabr Metwally, Samah Saied Arafa
The aim of this research is to investigate the teratogenic effects of chitosan oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were administrated orally to Wistar female rats to examine the teratogenic effect during organogenesis period from 6th day to 15th day of gestation. Treated and control rats were sacrificed and their foetuses were examined for external, skeletal and visceral anomalies, number and length of foetuses and their weights...
January 18, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29349603/neoadjuvant-chemoradiation-for-esophageal-cancer-surgery-improves-locoregional-control-while-response-based-on-fdg-pet-ct-predicts-survival
#20
Nina-Sophie Hegemann, Rebecca Koepple, Franziska Walter, David Boeckle, Wolfgang P Fendler, Martin Kurt Angele, Stefan Boeck, Claus Belka, Falk Roeder
INTRODUCTION: To retrospectively analyze the outcome of patients with esophageal cancer treated with neoadjuvant chemoradiation. METHODS: A total of 41 patients received neoadjuvant intent chemoradiation for esophageal cancer. Most patients had a locally advanced disease (T3/4: 82%, N+: 83%, M0: 100%) and squamous cell carcinoma (83%). All patients received concurrent chemotherapy with cisplatin/5-fluorouracil or mitomycin/5-fluorouracil. Median radiation dose was 50...
January 18, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
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