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https://www.readbyqxmd.com/read/28938529/defining-a-therapeutic-window-for-kinase-inhibitors-in-leukemia-to-avoid-neutropenia
#1
Kate McArthur, Akshay A D'Cruz, David Segal, Kurt Lackovic, Andrew F Wilks, Joanne A O'Donnell, Cameron J Nowell, Motti Gerlic, David C S Huang, Christopher J Burns, Ben A Croker
Neutropenia represents one of the major dose-limiting toxicities of many current cancer therapies. To circumvent the off-target effects of cytotoxic chemotherapeutics, kinase inhibitors are increasingly being used as an adjunct therapy to target leukemia. In this study, we conducted a screen of leukemic cell lines in parallel with primary neutrophils to identify kinase inhibitors with the capacity to induce apoptosis of myeloid and lymphoid cell lines whilst sparing primary mouse and human neutrophils. We have utilized a high-throughput live cell imaging platform to demonstrate that cytotoxic drugs have limited effects on neutrophil viability but are toxic to hematopoietic progenitor cells, with the exception of the topoisomerase I inhibitor SN-38...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938525/toxic-effects-of-tripterygium-wilfordii-hook-f-on-the-reproductive-system-of-adolescent-male-rats
#2
Xiaoping Jing, Weiwei Cheng, Sheng Guo, Ya Zou, Ting Zhang, Li He
Tripterygium wilfordii Hook F. (TWHF) is a compound extracted from Lei Gong Teng (Thunder God Vine) that has been used to treat a variety of immune-related diseases in clinical practice, particularly in pediatrics. Nevertheless, clinical data indicated that glycosides from Tripterygium wilfordii Hook F (GTW) are toxic to the male reproductive system, but the mechanism is unknown. Here, the administration of a high dose of GTW for 4 weeks and a low dose for 12 weeks can reduce the body weights and testes weights in adolescent male rats...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938452/dose-specific-effects-of-di-isononyl-phthalate-on-the-endocannabinoid-system-and-on-liver-of-female-zebrafish
#3
Isabel Forner-Piquer, Francesca Maradonna, Giorgia Gioacchini, Stefania Santangeli, Marco Allarà, Fabiana Piscitelli, Hamid R Habibi, Vincenzo Di Marzo, Oliana Carnevali
Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, the Di-isononyl phthalate (DiNP) has been recently used to replace the bis(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an Endocrine Disrupting Chemical (EDC), however little is known about its effects on the Endocannabinoid System (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage...
August 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938148/intestinal-epithelial-cell-injury-induced-by-copper-containing-nanoparticles-in-piglets
#4
Hui Zhang, Xiaoxing Wu, Khalid Mehmood, Zhenyu Chang, Kun Li, Xiong Jiang, Fazul Nabi, Muhammad Ijaz, Mujeeb Ur Rehman, Muhammad Tariq Javed, Donghai Zhou
The nano copper has been widely used in modern clinical medicine practice. However, it has been noticed that nano copper particles induce cell injury and toxicity. The present study was designed to determine the effect of nano copper particles on cell injury of intestinal epithelial cells (IECs) in piglets. The IECs were treated with different doses of nano copper (5, 10, 20 and 40μg/ml) for 24-48h to observe cell injury and toxicity. Cell injury was measured based on morphological and other changes including oxidative stress and genes expression...
September 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28938010/epidermal-growth-factor-receptor-targeted-sonoporation-with-microbubbles-enhances-therapeutic-efficacy-in-a-squamous-cell-carcinoma-model
#5
Fumika Hirabayashi, Kenjiro Iwanaga, Toshinori Okinaga, Osamu Takahashi, Wataru Ariyoshi, Ryo Suzuki, Mutsumi Sugii, Kazuo Maruyama, Kazuhiro Tominaga, Tatsuji Nishihara
Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions. We previously reported that sonoporation with microbubbles (MBs) could achieve effective intracellular drug delivery to human gingival squamous carcinoma Ca9-22 cells. In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated MBs (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28937866/soluble-vascular-adhesion-protein-1-mediates-spermine-oxidation-as-semicarbazide-sensitive-amine-oxidase-possible-role-in-proliferative-diabetic-retinopathy
#6
Miyuki Murata, Kousuke Noda, Akiko Kawasaki, Shiho Yoshida, Yoko Dong, Michiyuki Saito, Zhenyu Dong, Ryo Ando, Shohei Mori, Wataru Saito, Atsuhiro Kanda, Susumu Ishida
Purpose/Aim of the study: To explore the possible role of vascular adhesion protein-1 (VAP-1) via its enzymatic function as a semicarbazide-sensitive amine oxidase (SSAO) in the pathogenesis of proliferative diabetic retinopathy (PDR). MATERIALS AND METHODS: The levels of soluble VAP-1/SSAO and the unsaturated aldehyde acrolein (ACR)-conjugated protein, N(ε)-(3-formyl-3, 4-dehydropiperidino) lysine adduct (FDP-Lys), were measured in vitreous fluid samples of PDR and non-diabetic patients using ELISA...
September 22, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28937522/ambulatory-high-dose-methotrexate-administration-in-pediatric-osteosarcoma-patients-at-a-single-institution-in-argentina
#7
Jose A Villegas Rubio, Walter Cacciavillano, Adriana Rose, Pedro Zubizarreta, Marcelo Scopinaro
BACKGROUND: The purpose of this study was to evaluate the feasibility and safety of ambulatory high-dose methotrexate (HDMTX) administration with oral hydration, alkalinization, and leucovorin rescue. HDMTX (12 g/m) was given intravenously over 4 hours after urine alkalinization. Families and patients were instructed to continue ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment algorithm. Clinical status and MTX levels were controlled every 24 hours, and oral leucovorin dose was adjusted accordingly...
October 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28937324/impact-of-2-staged-stereotactic-radiosurgery-for-treatment-of-brain-metastases-%C3%A2-2-cm
#8
Lilyana Angelov, Alireza M Mohammadi, Elizabeth E Bennett, Mahmoud Abbassy, Paul Elson, Samuel T Chao, Joshua S Montgomery, Ghaith Habboub, Michael A Vogelbaum, John H Suh, Erin S Murphy, Manmeet S Ahluwalia, Sean J Nagel, Gene H Barnett
OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy...
September 22, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28937306/biocompatibility-assessment-of-functionalized-magnetic-mesoporous-silica-nanoparticles-in-human-heparg-cells
#9
Cédric Pisani, Estelle Rascol, Christophe Dorandeu, Clarence Charnay, Yannick Guari, Joël Chopineau, Jean-Marie Devoisselle, Odette Prat
Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized...
September 22, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28937269/dose-escalation-using-contact-x-ray-brachytherapy-papillon-for-rectal-cancer-does-it-improve-the-chance-of-organ-preservation
#10
Arthur Sun Myint, Fraser McLean Smith, Simon William Gollins, Helen Wong, Christopher Rao, Karen Whitmarsh, Raj Sripadam, Paul Rooney, Michael Jeremy Hershman, Zsolt Fekete, Kate Perkins, D Mark Pritchard
OBJECTIVE: A watch and wait policy for patients with a complete clinical response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately a third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact x-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth. METHODS: From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012...
September 20, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28937265/salvage-radiotherapy-for-locoregionally-recurrent-extrahepatic-bile-ducth-cancer-after-radical-surgery
#11
Eunji Kim, Yi-Jun Kim, Kyubo Kim, Changoon Song, Jae-Sung Kim, Do-Youn Oh, Eun Mi Nam, Eui Kyu Chie
OBJECTIVE: This study evaluated the outcome of salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer. METHODS: We performed a retrospective review of 23 extrahepatic bile duct cancer patients who underwent radiotherapy with or without concomitant chemotherapy for isolated locoregional recurrence after radical surgery between August 2001 and September 2013. The median disease-free interval was 11.8 months. Salvage radiotherapy was delivered to the recurrent tumor with or without initial operation bed up to a median dose of 54 Gy (range, 45-60)...
September 13, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28937260/the-effect-of-ht-2-toxin-on-ovarian-steroidogenesis-and-its-response-to-igf-i-leptin-and-ghrelin-in-rabbits
#12
A Kolesarova, N Maruniakova, A Kadasi, M Halenar, M Marak, A V Sirotkin
T-2 toxin and its metabolite HT-2 toxin are one of the most toxic mycotoxins of type A-trichothecenes, which are produced mainly by Fusarium species. Therefore, study of Fusarium toxins T-2 toxin and HT-2 toxin is an essential issue because they could also play role in failures of reproductive functions as well as endocrine system of domestic animals. Assessment of the effect of A-trichothecene mycotoxin HT-2 toxin alone or combined with insulin-like growth factor (IGF-I), leptin and ghrelin on estradiol secretion by rabbit ovarian fragments in vitro was done...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936567/metformin-as-a-repurposed-therapy-in-advanced-non-small-cell-lung-cancer-nsclc-results-of-a-phase-ii-trial
#13
Anish B Parikh, Peter Kozuch, Nicholas Rohs, Daniel J Becker, Benjamin P Levy
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity...
September 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28936374/helical-tomotherapy-for-postmastectomy-radiotherapy-after-immediate-left-breast-reconstruction-a-case-study
#14
Dominique Mathieu, Nazanin Shahvary, Nicolas Côté, Kerianne Boulva, Léamarie Meloche-Dumas, Toni Vu, Erica Patocskai, Christina Bernier, David Roberge, Israel Fortin
A 43-year-old premenopausal female presented with a multicentric infiltrating lobular carcinoma of the left breast with axillary nodes metastasis. She underwent modified radical mastectomy with axillary lymph node dissection (level I and II) followed by a mixed autologous latissimus dorsi flap reconstruction with the addition of prosthesis. The final pathological analysis revealed a 6 cm invasive lobular carcinoma pT3N2aM0, grade III/III, estrogen and progesterone positive, human epidermal growth factor receptor 2 (HER2) negative, with 5/16 positive lymph nodes...
July 12, 2017: Curēus
https://www.readbyqxmd.com/read/28936204/modulatory-influence-of-segmented-filamentous-bacteria-on-transcriptomic-response-of-gnotobiotic-mice-exposed-to-tcdd
#15
Robert D Stedtfeld, Benli Chai, Robert B Crawford, Tiffany M Stedtfeld, Maggie R Williams, Shao Xiangwen, Tomomi Kuwahara, James R Cole, Norbert E Kaminski, James M Tiedje, Syed A Hashsham
Environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR), are known to induce host toxicity and structural shifts in the gut microbiota. Key bacterial populations with similar or opposing functional responses to AhR ligand exposure may potentially help regulate expression of genes associated with immune dysfunction. To examine this question and the mechanisms for AhR ligand-induced bacterial shifts, C57BL/6 gnotobiotic mice were colonized with and without segmented filamentous bacteria (SFB) - an immune activator...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28936184/hypothermia-due-to-antipsychotic-medication-a-systematic-review
#16
Cherryl Zonnenberg, Jolien M Bueno-de-Mesquita, Dharmindredew Ramlal, Jan Dirk Blom
BACKGROUND: Hypothermia is a rare, but potentially fatal adverse effect of antipsychotic drug (APD) use. Although the opposite condition, hyperthermia, has been researched extensively in the context of the malignant antipsychotic syndrome, little is known about hypothermia due to APDs. OBJECTIVE: This study aimed to review the literature on hypothermia in the context of APD use, and formulate implications for research and clinical care. METHODS: A systematic search was made in PubMed and Ovid Medline...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#17
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935588/effect-of-methapyrilene-hydrochloride-on-hepatic-intracellular-iron-metabolism-in-vivo-and-in-vitro
#18
Iryna Kindrat, Kostiantyn Dreval, Svitlana Shpyleva, Volodymyr Tryndyak, Aline de Conti, Thilak K Mudalige, Tao Chen, Anna M Erstenyuk, Frederick A Beland, Igor P Pogribny
The liver, a central detoxification organ and main regulator of systemic iron homeostasis, is prone to damage by xenobiotics. In the present study, we investigated the effect of the hepatotoxicant and hepatocarcinogen methapyrilene hydrochloride on iron metabolism in rat liver in a repeat-dose in vivo toxicity study and in human HepaRG cells in vitro. Treatment of male Fischer 344 (F344) rats with methapyrilene at doses 40 and 80mg/kg body weight (bw)/day by gavage for 6 weeks resulted in changes in the expression of classic hepatotoxicity-related marker genes and iron homeostasis-related genes, especially a prominent, dose-dependent down-regulation of the transferrin (Tf) gene and an up-regulation of the ferritin, light chain (Ftl) gene...
September 18, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28935585/developmental-exposure-to-low-concentrations-of-two-brominated-flame-retardants-bde-47-and-bde-99-causes-life-long-behavioral-alterations-in-zebrafish
#19
Lilah Glazer, Corinne N Wells, Meghan Drastal, Kathryn-Ann Odamah, Richard E Galat, Mamta Behl, Edward D Levin
BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints...
September 18, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28935542/phase-i-trial-of-veliparib-a-poly-adp-ribose-polymerase-inhibitor-plus-metronomic-cyclophosphamide-in-metastatic-her2-negative-breast-cancer
#20
Jesus Anampa, Alice Chen, John Wright, Margi Patel, Christine Pellegrino, Karen Fehn, Joseph A Sparano, Eleni Andreopoulou
BACKGROUND: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. METHODS: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer...
September 1, 2017: Clinical Breast Cancer
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