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https://www.readbyqxmd.com/read/28549369/safety-analysis-of-occupational-exposure-of-healthcare-workers-to-residual-contaminations-of-cytotoxic-drugs-using-fmeca-security-approach
#1
Laetitia Minh Mai Le, Delphine Reitter, Sophie He, Franck Té Bonle, Amélie Launois, Diane Martinez, Patrice Prognon, Eric Caudron
Handling cytotoxic drugs is associated with chemical contamination of workplace surfaces. The potential mutagenic, teratogenic and oncogenic properties of those drugs create a risk of occupational exposure for healthcare workers, from reception of starting materials to the preparation and administration of cytotoxic therapies. The Security Failure Mode Effects and Criticality Analysis (FMECA) was used as a proactive method to assess the risks involved in the chemotherapy compounding process. FMECA was carried out by a multidisciplinary team from 2011 to 2016...
May 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28549343/hmgb1-mediated-autophagy-attenuates-gemcitabine-induced-apoptosis-in-bladder-cancer-cells-involving-jnk-and-erk-activation
#2
Hubin Yin, Xiaoyu Yang, Wen Gu, Yan Liu, Xinyuan Li, Xiaolong Huang, Xin Zhu, Yong Tao, Xin Gou, Weiyang He
High-mobility group box 1 (HMGB1) has been found to mediate autophagy during chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy and chemoresistance in bladder cancer is elusive. In this report, HMGB1 expression was found to be increased in 30 primary bladder cancer tissue specimens compared to their matched adjacent non-tumor tissues. While gemcitabine induced apoptotic cell death, it also induced HMGB1 expression and autophagy in bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA strongly potentiated gemcitabine-induced apoptosis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549321/studies-on-free-radical-scavenging-cancer-cell-antiproliferation-and-calf-thymus-dna-interaction-of-schiff-bases
#3
Cleiton M da Silva, Marina M Silva, Fabiano S Reis, Ana Lúcia T G Ruiz, João E de Carvalho, Josué C C Santos, Isis M Figueiredo, Rosemeire B Alves, Luzia V Modolo, Ângelo de Fátima
Thirty-nine Schiff bases were synthesized by performing microwave-assisted condensation of the corresponding aldehydes and aromatic amines. Their reactive nitrogen species (RNS) scavenging activity and inhibitory effects against cancer cell growth were then subsequently investigated. Additionally, the interaction between the calf thymus DNA (ctDNA) and selected Schiff bases was evaluated using fluorescence spectroscopy, and their binding parameters were determined. The yields of the various compounds ranged from moderate to excellent (43-99%) after only a 2-min reaction...
May 17, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28549296/formation-mechanism-of-%C3%AE-lactalabumin-oleic-acid-complex-characterized-by-2d-correlation-analysis
#4
Yeonju Park, Yeseul Kim, Yujeong Park, Sila Jin, Hoon Hwang, Young Mee Jung
Partially unfolded α-lactalbumin (ALA) forms a complex with oleic acid (OA) that exhibits cytotoxic activity. In this study, for the first time, the pH-induced formation mechanism for ALA/OA complexes with two different molar ratios was investigated at the molecular level. For a deeper understanding of the formation mechanism of the two different ALA/OA complexes with decreasing pH, principal component analysis (PCA) and two-dimensional (2D) correlation spectroscopy were used to examine the pH-dependent IR spectra of ALA/OA complexes...
May 17, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28549219/design-synthesis-and-properties-of-a-potent-inhibitor-of-pseudomonas-aeruginosa-deacetylase-lpxc
#5
Grazia Piizzi, David T Parker, Yunshan Peng, Markus Rolf Dobler, Anup Patnaik, Som Wattanasin, Eugene Liu, Francois Lenoir, Jill Nunez, John Kerrigan, David McKenney, Colin S Osborne, Donghui Yu, Leanne Lanieri, Jade Bojkovic, JoAnne Dzink-Fox, Maria-Dawn Lilly, Elizabeth R Sprague, Yipin Lu, Hongming Wang, Srijan Ranjitkar, Bing Wang, Meir Glick, Lawrence G Hamann, Ruben Tommasi, Xia Yang, Charles R Dean
Over the past several decades the frequency of antibacterial resistance in hospitals, including multi-drug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28548962/prognostic-implication-of-leucocyte-subpopulations-in-diffuse-large-b-cell-lymphoma
#6
Xiao Han, Jing Ruan, Wei Zhang, Daobin Zhou, Dongsheng Xu, Qiang Pei, Mingqi Ouyang, Mengxuan Zuo
BACKGROUND: Recent studies have suggested that variables related to host adaptive immunity and the tumor microenvironment may predict the outcome in patients with non-Hodgkin's lymphoma. This study was undertaken to determine the prognostic value of peripheral blood leucocyte subpopulations in diffuse large-B-cell lymphoma patients. METHODS: We prospectively analyzed the 16 leukocyte subpopulations using Cytodiff flow cytometric technique in a cohort of 45 diffuse large-B-cell lymphoma patients at a single institution between February and December 2014...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548955/exploring-brusatol-as-a-new-anti-pancreatic-cancer-adjuvant-biological-evaluation-and-mechanistic-studies
#7
Zheng Lu, Zheng-Quan Lai, Albert W N Leung, Po Sing Leung, Zhao-Shen Li, Zhi-Xiu Lin
Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#8
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548928/crosstalk-between-tongue-carcinoma-cells-extracellular-vesicles-and-immune-cells-in-in-vitro-and-in-vivo-models
#9
Ahmed Al-Samadi, Shady Adnan Awad, Katja Tuomainen, Yue Zhao, Abdelhakim Salem, Mataleena Parikka, Tuula Salo
The crosstalk between immune cells, cancer cells, and extracellular vesicles (EVs) secreted by cancer cells remains poorly understood. We created three-dimensional (3D) cell culture models using human leiomyoma discs and Myogel to study the effects of immune cells on highly (HSC-3) and less (SCC-25) invasive oral tongue squamous cell carcinoma (OTSCC) cell lines. Additionally, we studied the effects of EVs isolated from these cell lines on the cytotoxicity of CD8+ T and NK cells isolated from three healthy donors...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548926/preclinical-study-of-cc223-as-a-potential-anti-ovarian-cancer-agent
#10
Zhenzhen Jin, Huanfu Niu, Xuenan Wang, Lei Zhang, Qin Wang, Aijun Yang
Aberrant activation of mTOR contributes to ovarian cancer progression. CC223 is a novel and potent mTOR kinase inhibitor. The current study tested its activity against human ovarian cancer cells. We showed that CC223, at nM concentrations, inhibited survival and proliferation of established/primary human ovarian cancer cells. Further, significant apoptosis activation was observed in CC223-treated ovarian cancer cells. CC223 disrupted assembly of mTOR complex 1 (mTORC1) and mTORC2 in SKOV3 cells. Meanwhile, activation of mTORC1 and mTORC2 was almost completely blocked by CC223...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548826/protein-nanocage-based-photo-controlled-nitric-oxide-releasing-platform
#11
Xiao Li, Yajie Zhang, Jian Sun, Weijian Chen, Xuewei Wang, Fenli Shao, Yuyu Zhu, Fude Feng, Yang Sun
A photoactive NO releasing system was constructed by incorporation of NO-bound Fe-S clusters into horse spleen apoferritin cavities with high loading efficacy. The composites retained intact core-shell structure and indicated advantages such as enhanced stability, reduced cytotoxicity, efficient cellular uptake, and photo-controlled NO releasing property.
May 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28548825/nepetaefolins-a-j-cytotoxic-chinane-and-abietane-diterpenoids-from-caryopteris-nepetaefolia
#12
Cheng-Gang Zhang, Gui-Xin Chou, Xu-Dong Mao, Qing-Shan Yang, Jian-Li Zhou
Nepetaefolins A-J (1-10) and seven known compounds were isolated from the whole plant of Caryopteris nepetaefolia. The absolute configurations of 1-3 were determined from single-crystal X-ray diffraction and spectroscopic data. Compounds 6 and 7, with IC50 values of 6.3-9.0 μM, showed higher cytotoxicity than paclitaxel in one non-small-cell lung cancer, patient-derived xenograft (PDX) model when tested using PDX models and the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA).
May 26, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28548677/destabilization-of-human-insulin-fibrils-by-peptides-of-fruit-bromelain-derived-from-ananas-comosus-pineapple
#13
Sromona Das, Debasish Bhattacharyya
Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers...
May 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#14
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28548167/light-induced-antibiotic-release-from-a-coumarin-caged-compound-on-the-ultrafast-timescale
#15
L-M Herzig, I Elamri, H Schwalbe, J Wachtveitl
A synthesis route for puromycin caged with the photo-responsive 7-diethylaminocoumarinyl protecting group carbamate was developed. The inactivation and recovery of the cytotoxic effect of puromycin was tested with a XTT cell viability assay. The uncaging mechanism was studied by ultrafast transient absorption spectroscopy and by time-correlated single photon counting. The combination of these results with quantum-chemical calculations provided detailed insights in dynamics upon excitation. Interestingly, a change of the dipole moment due to structural rearrangements of the amino moiety led to an intermolecular charge transfer on the picosecond time-scale...
May 26, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28548102/replicating-viral-vector-platform-exploits-alarmin-signals-for-potent-cd8-t-cell-mediated-tumour-immunotherapy
#16
Sandra M Kallert, Stephanie Darbre, Weldy V Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A Luther, Alfred Zippelius, Doron Merkler, Daniel D Pinschewer
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL(eff)) responses. Conversely, the induction of protective tumour-specific CTL(eff) and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548029/digital-assays-part-ii-digital-protein-and-cell-assays
#17
Amar S Basu
A digital assay is one in which the sample is partitioned into many containers such that each partition contains a discrete number of biological entities (0, 1, 2, 3, . . .). A powerful technique in the biologist's toolkit, digital assays bring a new level of precision in quantifying nucleic acids, measuring proteins and their enzymatic activity, and probing single-cell genotype and phenotype. Where part I of this review focused on the fundamentals of partitioning and digital PCR, part II turns its attention to digital protein and cell assays...
May 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28547940/cytotoxic-activity-of-propolis-extracts-from-the-stingless-bee-trigona-sirindhornae-against-primary-and-metastatic-head-and-neck-cancer-cell-lines
#18
Kusumawadee Utispan, Bordin Chitkul, Sittichai Koontongkaew
Background: Propolis, a resinous substance produced by the honeybee, has a wide spectrum of potent biological activities. However, anti-cancer activity of propolis obtained from Trigona sirindhornae, a new species of stingless bee, has not yet been reported. This study concerned cytotoxicity of propolis extracts from T. sirindhornae against two head and neck squamous cell carcinoma (HNSCC) cell lines. Materials and Methods: A dichloromethane extract of propolis (DMEP) was prepared generating 3 fractions: DMEP-A, DMEP-B, and DMEP-C...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28547897/mannich-curcuminoids-as-potent-anticancer-agents
#19
Márió Gyuris, László Hackler, Lajos I Nagy, Róbert Alföldi, Eszter Rédei, Annamária Marton, Tibor Vellai, Nóra Faragó, Béla Ózsvári, Anasztázia Hetényi, Gábor K Tóth, Péter Sipos, Iván Kanizsai, László G Puskás
A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen-Schmidt condensation sequence. Structure-activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model...
May 26, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28547389/anti-inflammation-compounds-from-the-seedpods-of-pongamia-pinnata-l-pierre-guided-by-the-bioactivity-and-uplc-hresims
#20
Hong Guo, Zisong Bai, Yangyang Xu, Xueqin Wu, Ning Li, Yan Zhu, Xiaoming Wang, Peng Zhang
Pongamia pinnata (Linn.) Pierre has anti-inflammatory activity and could significantly decrease serum tumor necrosis factor-α and IL-10 in arthritic rats. Previous research indicated the typical chemical constituent in P. pinnata is furanoflavone. Guided by anti-inflammatory active assay and UPLC-HRESIMS chromatography, 22 compounds were isolated from the ethanol extract of P. pinnata seedpods. One novel furanoflavone, 4'-hydroxypinnatin, was elucidated by HRESIMS, 1D- and 2D-NMR spectra. The 21 known compounds, including 9 furanoflavone, were identified by comparing their NMR data with the previous data in reference...
May 25, 2017: Archives of Pharmacal Research
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