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https://www.readbyqxmd.com/read/28432813/targeting-on-poly-adp-ribose-polymerase-activity-with-dna-damaging-hybrid-lactam-steroid-alkylators-in-wild-type-and-brca1-mutated-ovarian-cancer-cells
#1
Dimitrios T Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas, Vassiliki Sarli
Conjugated lactam-steroid alkylators (LSA), have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemotherapy. Hybrid LSAs combine two active compounds in a single molecule and incorporate modified steroids bearing lactam moiety in one or more steroid rings functioning as vectors for cytotoxic agents. We first describe a novel class of LSAs that generate excellent anticancer activity against UWB1.289 and UWB1.289+BRCA1 human ovarian cancer cell lines...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28431896/pressurized-intraperitoneal-aerosol-chemotherapy-%C3%A2-practical-aspects
#2
M Hübner, F Grass, H Teixeira-Farinha, B Pache, P Mathevet, N Demartines
INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has been introduced as novel treatment for peritoneal carcinomatosis. Only proper patient selection, stringent safety protocol and careful surgery allow for a secure procedure. We hereby report the essentials for safe implementation. METHODS: All consecutive procedures within 20 months after PIPAC implementation were analyzed with regards to practical and surgical aspects. Special emphasis was laid on modifications of technique and safety measures during the implementation process with systematic use of a dedicated checklist...
April 8, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28429112/testicular-cancer-patients-undergoing-cisplatin-based-chemotherapy-exhibit-temporary-olfactory-threshold-scores-changes
#3
Ute Walliczek-Dworschak, Volker Gudziol, Claudia Mitzschke, Michael Froehner, Thomas Hummel
Testicular cancer is the most frequent malignant disease in young males between 15 and 35 years. Platinum based chemotherapy regimen is the therapy of choice in advanced disease. This treatment has also adverse effects caused by the cytostatic active substances, such as olfactory dysfunctions. The aim of this study was, therefore, to monitor olfactory function of testicular cancer patients during and 6 months after chemotherapy. A total of 17 patients (mean age 31.06 ± 10.26 years), which underwent chemotherapy (mean 2...
April 20, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28419480/characterization-of-neutropenia-in-advanced-cancer-patients-following-palbociclib-treatment-using-a-population-pharmacokinetic-pharmacodynamic-modeling-and-simulation-approach
#4
Wan Sun, Peter J O'Dwyer, Richard S Finn, Ana Ruiz-Garcia, Geoffrey I Shapiro, Gary K Schwartz, Angela DeMichele, Diane Wang
Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was developed to describe the time course of absolute neutrophil count (ANC) and quantify the exposure-response relationship for neutropenia. These analyses help in understanding neutropenia associated with palbociclib and its comparison with chemotherapy-induced neutropenia...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28415776/targeting-protein-homeostasis-with-nelfinavir-salinomycin-dual-therapy-effectively-induces-death-of-mtorc1-hyperactive-cells
#5
Elaine A Dunlop, Charlotte E Johnson, Marie Wiltshire, Rachel J Errington, Andrew R Tee
Uncontrolled cell growth in Tuberous Sclerosis Complex occurs due to inappropriate activation of mechanistic (mammalian) target of rapamycin complex 1 (mTORC1). The current therapy, rapamycin, produced promising clinical trial results, but patient tumours regrow if treatment is discontinued, revealing rapamycin has cytostatic properties rather than a cytotoxic effect. Taking advantage of the enhanced levels of endoplasmic reticulum (ER) stress present in TSC2-null cells, we investigated drug combinations producing a cytotoxic response...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415547/effect-of-polymer-degradation-on-prolonged-release-of-paclitaxel-from-filomicelles-of-polylactide-poly-ethylene-glycol-block-copolymers
#6
Katarzyna Jelonek, Suming Li, Janusz Kasperczyk, Xiaohan Wu, Arkadiusz Orchel
Paclitaxel is one of the most efficient anticancer agents, but the conventional dosage formulations cause many side effects. PLA-PEG filomicelles are promising carriers of paclitaxel because high loading capacity and long term release can be achieved. Slow release of cytostatic drugs is very advantageous due to prolonged exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for prolonged delivery of paclitaxel...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28411366/anticancer-activity-of-some-polyamine-derivatives-on-human-prostate-and-breast-cancer-cell-lines
#7
Marta Szumilak, Malgorzata Galdyszynska, Kamila Dominska, Andrzej Stanczak, Agnieszka Piastowska-Ciesielska
The aim of this study was to expand our knowledge about anticancer activity of some polyamine derivatives with quinoline or chromane as terminal moieties. Tested compounds were evaluated in vitro towards metastatic human prostate adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma (MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial metabolic activity using water-soluble tetrazolium WST1 to establish effective concentrations of the tested compounds under experimental conditions...
April 14, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28403076/diffuse-melanosis-cutis-related-to-dermal-micrometastases-as-the-first-clinical-symptom-of-distant-metastatic-malignant-melanoma-case-report
#8
Joanna Maj, Alina Jankowska-Konsur, Joanna Gruber, Zdzisław Woźniak, Piotr Nockowski, Anita Hryncewicz-Gwóźdź
RATIONALE: Diffuse melanosis cutis (DMC) is a very rare sign of malignant melanoma progression. The condition usually develops after approximately one year from melanoma diagnosis in a patient with metastatic tumors and after anticancer treatment with cytostatic medications. PATIENT CONCERNS: A 72-year old Caucasian man was admitted to the Department of Dermatology with DMC for 4 months and the history of two melanomas treated surgically 30 years and 9 months before present hospitalization...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28391184/thioredoxin-1-modulates-apoptosis-induced-by-bioactive-compounds-in-prostate-cancer-cells
#9
Aida Rodriguez-Garcia, David Hevia, Juan C Mayo, Pedro Gonzalez-Menendez, Lucia Coppo, Jun Lu, Arne Holmgren, Rosa M Sainz
Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3...
March 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28391026/radiopharmaceuticals-in-the-elderly-cancer-patient-practical-considerations-with-a-focus-on-prostate-cancer-therapy-a-position-paper-from-the-international-society-of-geriatric-oncology-task-force
#10
John O Prior, Silke Gillessen, Manfred Wirth, William Dale, Matti Aapro, Wim J G Oyen
Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e...
April 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28386264/factors-associated-with-mortality-in-patients-with-autoimmune-diseases-admitted-to-the-intensive-care-unit-in-bogota-colombia
#11
Jorge Armando Carrizosa, Jorge Aponte, Diego Cartagena, Ricard Cervera, Maria Teresa Ospina, Alexander Sanchez
Patients with autoimmune diseases (ADs) are a challenge for the intensivist; it is hard to differentiate among infection, disease activity, and combinations of both, leading to high mortality. This study is a retrospective analysis of 124 critically ill patients admitted to the intensive care unit (ICU) in a university hospital between 2008 and 2016. Bivariate case-control analysis was performed, using patients who died as cases; later, analysis using a logistic regression model with variables that were associated with mortality was conducted...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28385782/inhibition-of-monocarboxylate-transporter-1-by-azd3965-as-a-novel-therapeutic-approach-for-the-treatment-of-diffuse-large-b-cell-lymphoma-and-burkitt-lymphoma
#12
Richard A Noble, Natalie Bell, Helen Blair, Arti Sikka, Huw Thomas, Nicole Phillips, Sirintra Nakjang, Satomi Miwa, Rachel Crossland, Vikki Rand, Despina Televantou, Anna Long, Hector C Keun, Chris M Bacon, Simon Bomken, Susan E Critchlow, Stephen R Wedge
Inhibition of monocarboxylate transporter 1 has been proposed as a therapeutic approach to perturb lactate shuttling in tumor cells that lack monocarboxylate transporter 4. We examined the monocarboxylate transporter 1 inhibitor AZD3965, currently in phase I clinical studies, as a potential therapy for diffuse large B-cell lymphoma and Burkitt lymphoma. Whilst extensive monocarboxylate transporter 1 protein was found in 120 diffuse large B-cell lymphoma and 10 Burkitt lymphoma patient tumors, monocarboxylate transporter 4 protein expression was undetectable in 73% of the diffuse large B-cell lymphoma samples and undetectable or negligible in each Burkitt lymphoma sample...
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28384546/in%C3%A2-vitro-biological-evaluation-of-new-antimycobacterial-salicylanilide-tuftsin-conjugates
#13
Zsuzsa Baranyai, Martin Krátký, Rudolf Vosátka, Eleonóra Szabó, Zsuzsanna Senoner, Sándor Dávid, Jiřina Stolaříková, Jarmila Vinšová, Szilvia Bősze
Tuberculosis is caused by Mycobacterium tuberculosis, an intracellular pathogen that can survive in host cells, mainly in macrophages. An increase of multidrug-resistant tuberculosis qualifies this infectious disease as a major public health problem worldwide. The cellular uptake of the antimycobacterial agents by infected host cells is limited. Our approach is to enhance the cellular uptake of the antituberculars by target cell-directed delivery using drug-peptide conjugates to achieve an increased intracellular efficacy...
March 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28376402/metapristone-ru486-derivative-inhibits-cell-proliferation-and-migration-as-melanoma-metastatic-chemopreventive-agent
#14
Ning Zheng, Jiahang Chen, Weiqun Liu, Jichuang Wang, Jian Liu, Lee Jia
Uncontrolled cell proliferation and metastasis are the two well-known manifestations of melanoma. We hypothesized that metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486), had a dual function to fight cancer. In the present study, our findings clearly demonstrated that metapristone had modest cytostatic effect in melanoma cells. Metapristone inhibited cell viability and induced both early and late apoptosis in B16F10 and A375 cells in a time- and concentrate-dependent manner...
April 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28373209/fludarabine-resistance-mediated-by-aminoglycoside-3-phosphotransferase-iia-and-the-structurally-related-eukaryotic-camp-dependent-protein-kinase
#15
Dámaso Sánchez-Carrera, Sara Bravo-Navas, Elena Cabezón, Ignacio Arechaga, Matilde Cabezas, Lucrecia Yáñez, Carlos Pipaón
While working with G418-resistant stably transfected cells, we realized the neomycin resistance gene (NeoR), which encodes the aminoglycoside-3'-phosphotransferase-IIa [APH(3')-IIa], also confers resistance to the nucleoside analog fludarabine. Fludarabine is a cytostatic drug widely used in the treatment of hematologic and solid tumors as well as in the conditioning of patients before transplantation of hematopoietic progenitors. We present evidence that NeoR-transfected cells do not incorporate fludarabine, thus avoiding DNA damage caused by the drug, evidenced by a lack of FANCD2 monoubiquitination and impaired apoptosis...
April 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28371597/role-of-proton-pumps-in-tumorigenesis
#16
REVIEW
V A Kobliakov
One of the differences between normal and cancer cells is lower pH of the extracellular space in tumors. Low pH in the extracellular space activates proteases and stimulates tumor invasion and metastasis. Tumor cells display higher level of the HIF1α transcription factor that promotes cell switch from mitochondrial respiration to glycolysis. The terminal product of glycolysis is lactate. Lactate formation from pyruvate is catalyzed by the specific HIF1α-dependent isoform of lactate dehydrogenase A. Because lactate accumulation is deleterious for the cell, it is actively exported by monocarboxylate transporters...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28365849/impairment-of-human-neural-crest-cell-migration-by-prolonged-exposure-to-interferon-beta
#17
Giorgia Pallocca, Johanna Nyffeler, Xenia Dolde, Marianna Grinberg, Gerhard Gstraunthaler, Tanja Waldmann, Jörg Rahnenführer, Agapios Sachinidis, Marcel Leist
Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the 'migration inhibition of neural crest' (MINC) assay...
April 1, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28365838/n-p-coumaroyl-serotonin-inhibits-glioblastoma-cells-growth-through-triggering-s-phase-arrest-and-apoptosis
#18
Diamanto Lazari, George A Alexiou, Georgios S Markopoulos, Evrysthenis Vartholomatos, Entela Hodaj, Ieremias Chousidis, Ioannis Leonardos, Vasiliki Galani, Athanasios P Kyritsis
Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. N-(p-coumaroyl) serotonin (CS) is an indole alkaloid with antioxidant, cardioprotective effects after ischemia and antitumor activity. In the present study we sought to determine whether could exert cytotoxic and cytostatic effects in glioma cells in vitro. CS was tested for toxicity in zebrafish. We investigated the effect of CS in U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay and the xCELLigence system...
April 1, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28365318/pronounced-anti-proliferative-activity-and-tumor-cell-selectivity-of-5-alkyl-2-amino-3-methylcarboxylate-thiophenes
#19
Joice Thomas, Alenka Jecic, Els Vanstreels, Lizette van Berckelaer, Romeo Romagnoli, Wim Dehaen, Sandra Liekens, Jan Balzarini
5-(2-(4-Methoxyphenyl)ethyl)-2-amino-3-methylcarboxylate thiophene (TR560) is the prototype drug of a recently discovered novel class of tumor-selective compounds that preferentially inhibit the proliferation of specific tumor cell types (e.g. leukemia/lymphoma). Here, we further increased tumor selectivity by simplification of the molecule through replacing the 4-methoxyphenyl moiety by an alkyl chain. Several 2-amino-3-methylcarboxylate thiophene derivatives containing at C-5 an alkyl group consisting of at least 6 (hexyl) to 9 (nonyl) carbon units showed pronounced anti-proliferative activity in the mid-nanomolar range with 500- to 1000-fold tumor cell selectivity...
March 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28364708/evaluation-of-buffers-toxicity-in-tobacco-cells-homopiperazine-1-4-bis-2-ethanesulfonic-acid-is-a-suitable-buffer-for-plant-cells-studies-at-low-ph
#20
Lucélia Borgo
Low pH is an important environmental stressor of plant root cells. Understanding the mechanisms of stress and tolerance to acidity is critical; however, there is no widely accepted pH buffer for studies of plant cells at low pH. Such a buffer might also benefit studies of Al toxicity, in which buffering at low pH is also important. The challenge is to find a buffer with minimal cellular effects. We examined the cytotoxicity and possible metabolic disturbances of four buffers that have adequate pKa values and potential use for studies in the pH range of 4...
March 19, 2017: Plant Physiology and Biochemistry: PPB
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