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Cytostatics

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https://www.readbyqxmd.com/read/28738256/p53-and-mitf-bcl-2-identified-as-key-pathways-in-the-acquired-resistance-of-nras-mutant-melanoma-to-mek-inhibition
#1
Ahmad Najem, Mohammad Krayem, François Salès, Nader Hussein, Bassam Badran, Caroline Robert, Ahmad Awada, Fabrice Journe, Ghanem E Ghanem
Activating mutations in Neuroblastoma RAS viral oncogene homolog (NRAS) are found in 15-30% of melanomas and are associated with a poor prognosis. Although MAP kinase kinase (MEK) inhibitors used as single agents showed a limited clinical benefit in patients with NRAS-mutant melanoma due to their rather cytostatic effect and high toxicity, their combination with other inhibitors of pathways known to cooperate with MEK inhibition may maximise their antitumour activity. Similarly, in a context where p53 is largely inactivated in melanoma, hyperexpression of Microphthalmia associated transcription factor (MITF) and its downstream anti-apoptotic targets may be the cause of the restraint cytotoxic effects of MEK inhibitors...
July 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28737348/-handling-of-cytostatics-in-oncology-wards-of-an-algerian-university-hospital
#2
Nadia Tigha Bouaziz, Djamel Tourab, Abdelmalek Nezzal
In the light of this study, it appears relevant to improve cytostatic handling conditions by setting up a medical and environmental surveillance programme with the participation of all prevention personnel.</ce:para>.
April 27, 2017: Santé Publique: Revue Multidisciplinaire Pour la Recherche et L'action
https://www.readbyqxmd.com/read/28732643/development-and-internal-validation-of-a-prediction-model-to-estimate-the-probability-of-needing-aggressive-immunosuppressive-therapy-with-cytostatics-in-de-novo-lupus-nephritis-patients
#3
Mauricio Restrepo-Escobar, Paula Andrea Granda-Carvajal, Fabián Jaimes
OBJECTIVE: To develop a multivariable clinical prediction model for the requirement of aggressive immunosuppression with cytostatics, based on simple clinical record data and lab tests. The model is defined in accordance with the result of the kidney biopsies. METHODS: Retrospective study conducted with data from patients 16 years and older, with SLE and nephritis with less than 6 months of evolution. An initial bivariate analysis was conducted to select the variables to be included in a multiple logistic regression model...
July 18, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28726193/regenerative-potential-of-spermatogonial-stem-cells-endothelial-progenitor-cells-and-epithelial-progenitor-cells-of-c57bl-6-male-mice-with-metabolic-disorders
#4
E G Skurikhin, A V Pakhomova, O V Pershina, L A Ermolaeva, V A Krupin, N N Ermakova, E S Pan, A I Kudryashova, O Yu Rybalkina, T B Pavlovskaya, N V Litvyakov, V E Goldberg, A M Dygai
The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90(+) and epithelial progenitors CD45-CD31-Sca-1(+)CD49f(+) derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28725488/generation-and-analysis-of-spheroids-from-human-primary-skin-myofibroblasts-an-experimental-system-to-study-myofibroblasts-deactivation
#5
Giuseppina Granato, Maria R Ruocco, Antonino Iaccarino, Stefania Masone, Gaetano Calì, Angelica Avagliano, Valentina Russo, Claudio Bellevicine, Gaetano Di Spigna, Giuseppe Fiume, Stefania Montagnani, Alessandro Arcucci
Myofibroblasts are activated fibroblasts involved in tissue repair and cancer. They are characterized by de novo expression of α-smooth muscle actin (α-SMA), immunoregulatory phenotype and paracrine interaction with normal and tumorigenic cells leading to cell proliferation. At the end of wound-healing myofibroblasts undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also subjected to a programmed necrosis-like cell death, termed nemosis, associated with cyclooxygenase-2 (COX-2) expression induction and inflammatory response...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28724165/cytogenotoxicity-of-inclusion-complexes-of-diazepam-with-2-hydroxypropyl-%C3%AE-cyclodextrin
#6
Jasmina Hadžiabdić, Nevenka Kopjar, Davor Želježić, Selma Špirtović-Halilović, Davorka Završnik
Background Diazepam, as one of the most frequent prescribed drug from 1,4-benzodiazepine group, has certain limitations in pharmaceutical technology due to its poor solubility in water. By forming inclusion complexes with 2-hydroxypropyl-β-cyclodextrin, diazepam's biopharmaceutical properties can be greatly improved. Aim Aim of this research was to in vitro evaluate genotoxicity of prepared novel complexes of diazepam and their influence on proliferation of human peripheral blood lymphocytes. Methods For identification of possible genotoxicity of diazepam inclusion complexes, cytokinesis-block micronucleus assay has been chosen...
July 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28723571/emi2-is-essential-for-mouse-spermatogenesis
#7
Lakshmi Gopinathan, Radoslaw Szmyd, Diana Low, M Kasim Diril, Heng-Yu Chang, Vincenzo Coppola, Kui Liu, Lino Tessarollo, Ernesto Guccione, Ans M M van Pelt, Philipp Kaldis
The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2-in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720209/the-influence-of-oxazaphosphorine-agents-on-kidney-function-in-rats
#8
Łukasz Dobrek, Beata Skowron, Agnieszka Baranowska, Klaudia Płoszaj, Dorota Bądziul, Piotr Thor
BACKGROUND AND OBJECTIVE: The application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of our study was to assess the influence of CP and IF on the kidney histology and function in rats intraperitoneally treated with four doses of either CP or IF. MATERIALS AND METHODS: A total of 30 rats were divided into three groups (10 in each group): group 1 (control), sham treated with saline solution, group 2 (treated with 75mg/kg b...
July 2, 2017: Medicina
https://www.readbyqxmd.com/read/28714904/brd9-inhibition-alone-or-in-combination-with-cytostatic-compounds-as-a-therapeutic-approach-in-rhabdoid-tumors
#9
Katja F Krämer, Natalia Moreno, Michael C Frühwald, Kornelius Kerl
Rhabdoid tumors (RT) are malignant neoplasms of early childhood. Despite intensive therapy, survival is poor and new treatment approaches are required. The only recurrent mutations in these tumors affect SMARCB1 and less commonly SMARCA4, both subunits of the chromatin remodeling complex SWItch/Sucrose Non-Fermentable (SWI/SNF). Loss of these two core subunits alters the function of the SWI/SNF complex, resulting in tumor development. We hypothesized that inhibition of aberrant SWI/SNF function by selective blockade of the BRD9 subunit of the SWI/SNF complex would reduce tumor cell proliferation...
July 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28713162/abt-263-induces-g1-g0-phase-arrest-apoptosis-and-autophagy-in-human-esophageal-cancer-cells-in-vitro
#10
Qing-Huan Lin, Fu-Chang Que, Chun-Ping Gu, De-Sheng Zhong, Dan Zhou, Yi Kong, Le Yu, Shu-Wen Liu
Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28710231/tuberin-regulates-prostaglandin-receptor-mediated-viability-via-rheb-in-mtorc1-hyperactive-cells
#11
Chenggang Li, Xiaolei Liu, Yang Liu, Erik Zhang, Kantha Medepalli, Kohei Masuda, Na Li, Elizabeth J Kopras, David J Kwiatkowski, Michael T Borchers, Kathryn A Wikenheiser-Brokamp, Andrew Osterburg, Maxwell Mays, Yang Sun, David R Plas, Julia L Sun, David N Franz, Jamie K Capal, Anya Alayev, Marina K Holz, Darcy A Krueger, Brian J Siroky, Jane J Yu
Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome affecting multiple organs, including the brain, skin, kidneys, heart, and lungs. TSC is associated with mutations in TSC1 or TSC2 resulting in hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1). Clinical trials demonstrate that mTORC1 inhibitors decrease tumor volume and stabilize lung function in TSC patients; however, mTOR inhibitors are cytostatic not cytocidal, and long-term benefits and toxicities are uncertain. Previously, we identified rapamycin-insensitive upregulation of cyclooxygenase 2 (PTGS2/COX2) and prostaglandin E2 (PGE2) production in TSC2-deficient cells and postulate that the action of excess PGE2 and its cognate receptors (EPs) contribute to cell survival...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28706010/clinical-management-of-potential-toxicities-and-drug-interactions-related-to-cyclin-dependent-kinase-4-6-inhibitors-in-breast-cancer-practical-considerations-and-recommendations
#12
REVIEW
Laura M Spring, Mark L Zangardi, Beverly Moy, Aditya Bardia
Aberrations of the cell cycle are pervasive in cancer, and selective cell cycle inhibition of cancer cells is a target of choice for a number of novel cancer therapeutics. Cyclin-dependent kinases (CDKs) are key regulatory enzymes that control cell cycle transitions and the commitment to cell division. Palbociclib and ribociclib are both orally active, highly selective reversible inhibitors of CDK4 and CDK6 that are approved by the U.S. Food and Drug Administration (FDA) for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies...
July 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28705408/superior-in-vitro-and-in-vivo-activity-of-trastuzumab-emtansine-t-dm1-in-comparison-to-trastuzumab-pertuzumab-and-their-combination-in-epithelial-ovarian-carcinoma-with-high-her2-neu-expression
#13
Gulden Menderes, Elena Bonazzoli, Stefania Bellone, Gary Altwerger, Jonathan D Black, Katherine Dugan, Francesca Pettinella, Alice Masserdotti, Francesco Riccio, Anna Bianchi, Luca Zammataro, Christopher de Haydu, Natalia Buza, Pei Hui, Serena Wong, Gloria S Huang, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
BACKGROUND: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. The objective of this study was to compare the anti-tumor activity of HER2/neu-targeting monoclonal antibodies, trastuzumab (T), pertuzumab (P), combination of trastuzumab and pertuzumab (T+P) and trastuzumab-emtansine (T-DM1) in EOC with high HER2/neu expression. METHODS: Primary EOC cell lines were established and cell blocks were analyzed for HER2/neu expression. Cytostatic, apoptotic and antibody-dependent cell-mediated cytotoxicity (ADCC) activities of T, P, T+P and T-DM1 were evaluated in vitro...
July 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28704934/functioning-of-fluorescent-proteins-in-aggregates-in-anthozoa-species-and-in-recombinant-artificial-models
#14
Natalia V Povarova, Natalia D Petri, Anna E Blokhina, Alexey M Bogdanov, Nadya G Gurskaya, Konstantin A Lukyanov
Despite great advances in practical applications of fluorescent proteins (FPs), their natural function is poorly understood. FPs display complex spatio-temporal expression patterns in living Anthozoa coral polyps. Here we applied confocal microscopy, specifically, the fluorescence recovery after photobleaching (FRAP) technique to analyze intracellular localization and mobility of endogenous FPs in live tissues. We observed three distinct types of protein distributions in living tissues. One type of distribution, characteristic for Anemonia, Discosoma and Zoanthus, is free, highly mobile cytoplasmic localization...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28704436/platinum-nanoparticles-induce-damage-to-dna-and-inhibit-dna-replication
#15
Lukas Nejdl, Jiri Kudr, Amitava Moulick, Dagmar Hegerova, Branislav Ruttkay-Nedecky, Jaromir Gumulec, Kristyna Cihalova, Kristyna Smerkova, Simona Dostalova, Sona Krizkova, Marie Novotna, Pavel Kopel, Vojtech Adam
Sparsely tested group of platinum nanoparticles (PtNPs) may have a comparable effect as complex platinum compounds. The aim of this study was to observe the effect of PtNPs in in vitro amplification of DNA fragment of phage λ, on the bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts and erythrocytes. In vitro synthesized PtNPs were characterized by dynamic light scattering (PtNPs size range 4.8-11.7 nm), zeta potential measurements (-15 mV at pH 7.4), X-ray fluorescence, UV/vis spectrophotometry and atomic absorption spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/28699738/a-molecular-combination-of-zinc-ii-phthalocyanine-and-tamoxifen-derivative-for-dual-targeting-photodynamic-therapy-and-hormone-therapy
#16
Feng-Ling Zhang, Mei-Ru Song, Gan-Kun Yuan, Huan-Nian Ye, Ye Tian, Ming-Dong Huang, Jin-Ping Xue, Zhi-Hong Zhang, Jian-Yong Liu
The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells...
July 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28689428/long-survival-in-a-patient-with-metastatic-colorrectal-carcinoma-reality-or-utopia
#17
Andrea Illán, Jonathan Aires, Laura Quintana
We report the case of a 42-year-old male patient with mucinous-type metastatic colorectal carcinoma of eight years of evolution. He has received multiple lines of cytostatic treatment with acceptable tolerance and without significant impairment in his quality of life. At present, it is estimated that the overall survival of metastatic colon cancer in cytostatic treatment is around 24 months. However, a small subset of patients may present prolonged survivals of 5 to 10 years after diagnosis, revealing heterogeneity of tumor behavior and response to treatment...
July 10, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28683700/degree-of-technological-implementation-in-intravenous-chemotherapy-management-in-hospitals-of-the-autonomous-community-of-madrid
#18
Belén Ortiz-Martín, Silvia Peña-Cabia
OBJECTIVE: To understand the degree of technological implementation in the processes of preparation and administration of cytostatics drugs that is available in those hospitals of the Autonomous Community of Madrid where intravenous chemotherapy is prepared. METHOD: A descriptive observational study through the completion of a survey targeted to the staff responsible for the preparation of this type of treatments. RESULTS: The degree of implementation of assisted electronic prescription is high, there is a medium degree in the case of bar code reading technology, and low in terms of vial re-labelling and gravimetric and voice control for preparation...
July 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28678928/the-diterpene-sclareol-vascular-effect-in-normotensive-and-hypertensive-rats
#19
Debora Ribeiro Campos, Andrea Carla Celotto, Agnes Afrodite S Albuquerque, Luciana Garros Ferreira, Ariadne Santana E Neves Monteiro, Eduardo Barbosa Coelho, Paulo Roberto Barbosa Evora
Background: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg)...
June 29, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28678764/antitumor-activity-of-gemcitabine-against-high-grade-meningioma-in-vitro-and-in-vivo
#20
Hiroyuki Takeda, Masashi Okada, Kenta Kuramoto, Shuhei Suzuki, Hirotsugu Sakaki, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Hirofumi Hirano, Kazunori Arita, Chifumi Kitanaka
Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possible antitumor activity in high-grade meningioma and discovered that high-grade meningioma cells show a preferential sensitivity to antimetabolites, in particular, to gemcitabine. In vitro, gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death...
June 29, 2017: Oncotarget
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