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Cytostatics

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https://www.readbyqxmd.com/read/27920038/tgf-%C3%AE-family-signaling-in-the-control-of-cell-proliferation-and-survival
#1
Yun Zhang, Peter B Alexander, Xiao-Fan Wang
The transforming growth factor β (TGF-β) family controls many fundamental aspects of cellular behavior. With advances in the molecular details of the TGF-β signaling cascade and its cross talk with other signaling pathways, we now have a more coherent understanding of the cytostatic program induced by TGF-β. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated by TGF-β and determine a cell's proliferation and survival, apoptosis, dormancy, autophagy, and senescence...
December 5, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27916939/immunopathogenic-mechanisms-of-autoimmune-hepatitis-how-much-do-we-know-from-animal-models
#2
REVIEW
Urs Christen, Edith Hintermann
Autoimmune hepatitis (AIH) is characterized by a progressive destruction of the liver parenchyma and a chronic fibrosis. The current treatment of autoimmune hepatitis is still largely dependent on the administration of corticosteroids and cytostatic drugs. For a long time the development of novel therapeutic strategies has been hampered by a lack of understanding the basic immunopathogenic mechanisms of AIH and the absence of valid animal models. However, in the past decade, knowledge from clinical observations in AIH patients and the development of innovative animal models have led to a situation where critical factors driving the disease have been identified and alternative treatments are being evaluated...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27912948/therapeutic-efficacy-of-traditional-chinese-medicine-kuan-sin-yin-in-patients-undergoing-chemotherapy-for-advanced-colon-cancer-a-controlled-trial
#3
Tsai-Ju Chien, Chia-Yu Liu, Ruey-Hwa Lu, Chin-Wei Kuo, Yang-Chao Lin, Chung-Hua Hsu
BACKGROUND: Traditional Chinese Medicine (TCM) has been used increasingly as complementary medicine in cancer care. Kuan-Sin-Yin (KSY) is a TCM decoction containing seven herbs known to cause immunomodulation or anticancer activity, and which are associated with the TCM concept of Qi and energy supply. Kuan-Sin-Yin has cytostatic effects on cancer cells in animal models. OBJECTIVE: The aim of this study is to evaluate the level of improvement in meridian energy and heart-rate variability (HRV) and to assess whether these observations are compatible with TCM theory...
December 2016: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/27912174/synthesis-and-cytostatic-properties-of-polyfunctionalized-furanoallocolchicinoids
#4
Iuliia A Gracheva, Iuliia V Voitovich, Vladimir I Faerman, Nikolay S Sitnikov, Ekaterina V Myrsikova, Hans-Gunther Schmalz, Elena V Svirshevskaya, Alexey Yu Fedorov
A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine-step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect)...
November 16, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27911980/cell-based-dna-demethylation-detection-system-for-screening-of-epigenetic-drugs-in-2d-3d-and-xenograft-models
#5
Khushboo Agrawal, Viswanath Das, Miroslav Otmar, Marcela Krečmerová, Petr Džubák, Marián Hajdúch
Aberrant DNA methylation that results in silencing of genes has remained a significant interest in cancer research. Despite major advances, the success of epigenetic therapy is elusive due to narrow therapeutic window. A wide variety of naturally occurring epigenetic agents and synthetic molecules that can alter methylation patterns exist, however, their usefulness in epigenetic therapy remains unknown. This underlines the need for effective tumor models for large-scale screening of drug candidates with potent hypomethylation activity...
December 2, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/27909727/anti%C3%A2-proliferative-activity-of-epigallocatechin%C3%A2-3%C3%A2-gallate-and-silibinin-on-soft-tissue-sarcoma-cells
#6
Kamran Harati, Björn Behr, Christoph Wallner, Adrien Daigeler, Tobias Hirsch, Frank Jacobsen, Marcus Renner, Ali Harati, Marcus Lehnhardt, Mustafa Becerikli
Disseminated soft tissue sarcomas (STS) present a therapeutic dilemma. The first-line cytostatic doxorubicin demonstrates a response rate of 30% and is not suitable for elderly patients with underlying cardiac disease, due to its cardiotoxicity. Well‑tolerated alternative treatment options, particularly in palliative situations, are rare. Therefore, the present study assessed the anti‑proliferative effects of the natural compounds epigallocatechin-3-gallate (EGCG), silibinin and noscapine on STS cells. A total of eight different human STS cell lines were used in the study: Fibrosarcoma (HT1080), liposarcoma (SW872, T778 and MLS‑402), synovial sarcoma (SW982, SYO1 and 1273) and pleomorphic sarcoma (U2197)...
November 28, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#7
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27901050/the-use-of-the-nedd8-inhibitor-mln4924-pevonedistat-in-a-cyclotherapy-approach-to-protect-wild-type-p53-cells-from-mln4924-induced-toxicity
#8
Lara J Bou Malhab, Simon Descamps, Benedicte Delaval, Dimitris P Xirodimas
Targetting the ubiquitin pathway is an attractive strategy for cancer therapy. The inhibitor of the ubiquitin-like molecule NEDD8 pathway, MLN4924 (Pevonedistat) is in Phase II clinical trials. Protection of healthy cells from the induced toxicity of the treatment while preserving anticancer efficacy is a highly anticipated outcome in chemotherapy. Cyclotherapy was proposed as a promising approach to achieve this goal. We found that cytostatic activation of p53 protects cells against MLN4924-induced toxicity and importantly the effects are reversible...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900869/-evaluation-of-five-years-of-treatment-of-erdheim-chester-disease-with-anakinra-case-report-and-overview-of-literature
#9
Zdeněk Adam, Hana Petrášová, Zdeněk Řehák, Renata Koukalová, Marta Krejčí, Luděk Pour, Eva Vetešníková, Aleš Čermák, Sabina Ševčíková, Petr Szturz, Zdeněk Král, Jiří Mayer
: Erdheim-Chester disease is a histiocytic neoplasm of diseases from the group of non-Langerhans-cell histiocytoses, formed by infiltrates of foamy histiocytes. These pathological histiocytes produce pro-inflammatory cytokines. Therefore Erdheim-Chester disease is called inflammatory histiocytary neoplasm. The disease is accompanied by clinical symptoms of systemic inflammatory response, i.e. B symptoms. Imaging examinations detect typical osteosclerotic changes affecting diaphyses and metaphyses of the lower long bones and fibrotic changes which affect the aorta wall and the vessels leading from it...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27900099/effect-of-cytostatic-proline-rich-polypeptide-1-on-tumor-suppressors-of-inflammation-pathway-signaling-in-chondrosarcoma
#10
Karina Galoian, Shihua Luo, Amir Qureshi, Parthik Patel, Rachel Price, Ashlyn S Morse, Gor Chailyan, Silva Abrahamyan, H T Temple
Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1). Western blot experiments demonstrated that the levels of suppressor of cytokine signaling 3 (SOCS3) were upregulated in chondrocytes compared with chondrosarcoma cells...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27895480/synthesis-of-three-arm-block-copolymer-poly-lactic-co-glycolic-acid-poly-ethylene-glycol-with-oxalyl-chloride-and-its-application-in-hydrophobic-drug-delivery
#11
Xiaowei Zhu, Chao Liu, Jianwei Duan, Xiaoyu Liang, Xuanling Li, Hongfan Sun, Deling Kong, Jing Yang
PURPOSE: Synthesis of star-shaped block copolymer with oxalyl chloride and preparation of micelles to assess the prospect for drug-carrier applications. MATERIALS AND METHODS: Three-arm star block copolymers of poly(lactic-co-glycolic acid) (3S-PLGA)-polyethylene glycol (PEG) were synthesized by ring-opening polymerization, then PEG as the hydrophilic block was linked to the terminal hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR) spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic resonance ((1)H-NMR) spectra, and differential scanning calorimetry were employed to identify the structure and properties of 3S-PLGA-PEG...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27894689/occupational-exposure-to-cytostatic-antineoplastic-drugs-and-cytogenetic-damage-measured-using-the-lymphocyte-cytokinesis-block-micronucleus-assay-a-systematic-review-of-the-literature-and-meta-analysis
#12
REVIEW
M Villarini, V Gianfredi, S Levorato, S Vannini, T Salvatori, M Moretti
Many studies have reported the occurrence of work-environment contamination by antineoplastic drugs (ANPD), with significant incorporation of trace amounts of these hazardous drugs in hospital personnel. Given the ability of most ANPD to actively bind DNA, thus inducing genotoxic effects, it is of pivotal importance to assess the degree of genotoxic damage (i.e., residual genotoxic risk) in occupationally exposed subjects. The lymphocyte cytokinesis-block micronucleus (L-CBMN) assay is largely used for biological effect monitoring in subjects occupationally exposed to ANPD...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27894589/discovery-and-preclinical-evaluation-of-7-benzyl-n-substituted-pyrrolo-3-2-d-pyrimidin-4-amines-as-single-agents-with-microtubule-targeting-effects-along-with-triple-acting-angiokinase-inhibition-as-antitumor-agents
#13
Roheeth Kumar Pavana, Shruti Choudhary, Anja Bastian, Michael A Ihnat, Ruoli Bai, Ernest Hamel, Aleem Gangjee
The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of AA with microtubule targeting agents (MTAs) have been particularly successful. The discovery, synthesis and biological evaluations of a series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR), along with microtubule targeting in single molecules are described...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27894231/evidence-of-exposure-to-cytostatic-drugs-in-healthcare-staff-a-review-of-recent-literature
#14
Pablo Martín Lancharro, Nuria De Castro-Acuña Iglesias, Francisco-Javier González-Barcala, José Domingo Moure González
OBJECTIVE: Provide updated evidence and learn about the actions that must be implemented in order to prevent the occupational exposure to cytostatic drugs. METHOD: A bibliographic search was carried out on the MEDLINE, COCHRANE PLUS and WEB OF SCIENCE databases, with the terms "surface contamination", "cytostatic drug", "drug preparation", "occupational exposure", "safe handling" and "closed-system transfer device", within the 2010-2015 period. RESULTS: Thirteen articles were selected for review...
November 1, 2016: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/27894224/comparative-study-of-preparation-of-hazardous-drugs-with-different-closed-system-drug-transfer-devices-by-means-of-simulation-with-fluorescein
#15
Eva González-Haba Peña, Silvia Manrique Rodríguez, Ana Mª Herranz Alonso, Patricia Pérez Castán, Mónica Moreno Gálvez, Irene Iglesias Peinado, María Sanjurjo Saez
OBJECTIVES: The level of environmental contamination generated during preparation and administration of hazardous drugs using different valve closed-systems and their combinations was compared. The actual impact on the overall time of preparation of cytostatics and the economic cost of the different modalities were also compared. METHODS: Comparative study of the preparation of fluorescein mixtures with different modalities of valve closed-system combinations. Environmental contamination was detected in critical points of connection, and in splashes produced at any other points...
November 1, 2016: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/27894189/ziprasidone-induces-cytotoxicity-and-genotoxicity-in-human-peripheral-lymphocytes
#16
Haluk Kefelioğlu, Zülal Atlı Şekeroğlu, Gamze Coşguner, Seval Kontaş Yedier, Vedat Şekeroğlu
It has been stated that some antipsychotic drugs might cause genotoxic and carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug. However, its genotoxicity and carcinogenicity data are very limited. The cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with 50, 75 and 100 μg/ml of ZIP in the presence and absence of a metabolic activator (S9 mix)...
November 29, 2016: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/27886555/overcoming-multidrug-resistance-via-simultaneous-delivery-of-cytostatic-drug-and-p-glycoprotein-inhibitor-to-cancer-cells-by-hpma-copolymer-conjugate
#17
Ladislav Sivak, Vladimir Subr, Jakub Tomala, Blanka Rihova, Jiri Strohalm, Tomas Etrych, Marek Kovar
Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. MDR is either acquired as a result of previous repeated exposure to cytostatic drugs (P388/MDR cells) or naturally, as some tumors are congenitally resistant to chemotherapy (CT26 cells). One of the most common mechanisms of MDR is upregulation of P-glycoprotein (P-gp) expression. Here, we used HPMA copolymer conjugates, whereby the cytostatic drug doxorubicin (Dox) or the derivative of the P-gp inhibitor reversin 121 (R121) or both were covalently bound through a degradable pH-sensitive hydrazone bond...
November 12, 2016: Biomaterials
https://www.readbyqxmd.com/read/27882559/lipiodol-does-not-affect-the-tissue-distribution-of-intravenous-doxorubicin-infusion-in-pigs
#18
Elsa Lilienberg, Ilse R Dubbelboer, Erik Sjögren, Hans Lennernäs
OBJECTIVES: In liver cancer treatment, lipiodol is used as a pharmaceutical excipient to improve delivery of the cytostatic drug doxorubicin (DOX). As DOX and its metabolite doxorubicinol (DOXol) cause serious off-target adverse effects, we investigated the effects of drug-free lipiodol or ciclosporin (CsA) on the tissue distribution (Kp ) of DOX and DOXol in relevant pig tissues. METHODS: Four treatment groups (TI-TIV) all received an intravenous DOX solution at 0 and 200 min...
November 23, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27880045/koelreuteria-formosana-extract-induces-growth-inhibition-and-cell-death-in-human-colon-carcinoma-cells-via-g2-m-arrest-and-lc3-ii-activation-dependent-autophagy
#19
Chi-Ting Horng, Yueh-Jung Wu, Pei-Ni Chen, Shu-Chen Chu, Chun-Miao Tsai, Yih-Shou Hsieh
Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death...
November 23, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27879007/drotaverine-a-concealed-cytostatic
#20
Ioana Z Pavel, Lucie Heller, Sven Sommerwerk, Anne Loesche, Ahmed Al-Harrasi, René Csuk
Drotaverine (also known as dihydroperparine or No-Spa(®) ) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50 values as low as 3.0 μM were observed in SRB assays for HT-29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was observed after 24 h...
November 23, 2016: Archiv der Pharmazie
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