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Michael K Krapf, Jennifer Gallus, Sahel Vahdati, Michael Wiese
Multidrug resistance occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome multidrug resistance, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized...
March 16, 2018: Journal of Medicinal Chemistry
A V Petrayevsky, K S Trishkin
Pterygium is one of the modern problems of ophthalmology. The exact etiology and pathogenesis of this disease has not been reliably established and, as a result, there is no universal method for its recurrence-free treatment. The literature data on various methods of pterygium surgical treatment such as 'bare sclera', conjunctival autograft, limbal stem cells transplantation techniques, amniotic membrane plasty and other methods was analyzed. The advantages and disadvantages of those surgery methods were identified...
2018: Vestnik Oftalmologii
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
Irena R Štenglová-Netíková, Luboš Petruželka, Martin Šťastný, Václav Štengl
Nanostructured titanium(IV) oxide was used for the destructive adsorption and photocatalytic degradation of mitoxantrone (MTX), a cytostatic drug from the group of anthracycline antibiotics. During adsorption on a titania dioxide surface, four degradation products of MTX, mitoxantrone dicarboxylic acid, 1,4-dihydroxy-5-((2-((2-hydroxyethyl)amino)ethyl)amino)-8-((2-(methylamino)ethyl)amino)anthracene-9,10-dione, 1,4-dihydroxy-5,8-diiminoanthracene-9,10(5H,8H)-dione and 1,4-dihydroxy-5-imino-8-(methyleneamino)anthracene-9,10(5H,8H)-dione, were identified...
2018: PloS One
Seong Ji Park, Seung Koo Lee, Chae Rin Lim, Hye Won Park, Fang Liu, Seong-Jin Kim, Byung-Chul Kim
Heme oxygenase-1 (HO-1) has been implicated in tumor progression, but the underlying molecular mechanisms remain largely unknown. Transforming growth factor-β1 (TGF-β1) exhibits cytostatic and apoptotic effects in hepatocytes and several types of hepatocellular carcinoma (HCC) cell lines, and deregulation of its signaling pathway is linked to hepatic tumorigenesis. In the present study, we observed that HO-1 is expressed at higher levels in HCC tissues than in paired normal tissues. Moreover, TGF-β1-induced cell cycle arrest and up-regulation of cyclin-dependent kinase inhibitors in HCC cell lines were significantly attenuated by overexpression of HO-1 or treatment with tricarbonyldichlororuthenium(II) dimer ([Ru(CO)3 Cl2 ]2 , suggesting an inhibitory role of the HO-1/CO axis in TGF-β signaling to growth inhibition in HCC cell lines...
March 7, 2018: Biochemical and Biophysical Research Communications
Christoph Oing, Christoph Seidel, Carsten Bokemeyer
Most germ cell cancer patients with metastatic disease are cured by cisplatin-based combination chemotherapy. 30% of metastatic patients will develop relapse or progress despite adequate first-line treatment and will require salvage therapy, with about 10% of metastasized patients ultimately developing platinum-resistant and fatal disease. Areas covered: Based on a comprehensive literature search of MEDLINE, EMBASE and conference proceedings of ESMO, ASCO and EAU meetings, this review provides an overview on current and potential future treatment options for platinum-refractory germ cell cancer patients including cytostatics and molecularly targeted therapies...
March 8, 2018: Expert Review of Anticancer Therapy
Andrea Vazanova, Jana Jurecekova, Tomas Balharek, Juraj Marcinek, Jan Stasko, Anton Dzian, Lukas Plank, Pavol Zubor, Peter Racay, Jozef Hatok
Background: Apoptosis plays an important role in the development and homeostasis of multicellular organisms and its deregulation may result in many serious diseases, including cancer. Now it is clear that some oncogenic mutations disrupt apoptosis, leading to tumour initiation, progression or metastasis. Here, expression of apoptotic genes in context of drug resistance was investigated. Methods: We examined total of 102 samples from leukemic patients (n = 60) and patients with solid tumours (n = 42)...
2018: Cancer Cell International
Tom Tg Nieskens, Janny Gp Peters, Dina Dabaghie, Daphne Korte, Katja Jansen, Alexander H Van Asbeck, Neslihan N Tavraz, Thomas Friedrich, Frans Russel, Rosalinde Masereeuw, Martijn J Wilmer
Cisplatin is a cytostatic drug used for treatment of solid organ tumors. The main adverse effect is organic cation transporter 2 (OCT2)-mediated nephrotoxicity, observed in 30% of patients. The contribution of other renal drug transporters is elusive. Here, cisplatin-induced toxicity was evaluated in human-derived proximal tubule epithelial cells (ciPTEC) expressing renal drug transporters, including OCT2 and organic anion transporter 1 (OAT1) or 3 (OAT3). Parent ciPTEC demonstrated OCT2-dependent cisplatin toxicity (TC50 34±1 μM after 24 h exposure), as determined by cell viability...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Marzena Matejczyk, Renata Swislocka, Monika Kalinowska, Grzegorz Swidersk, Wlodzimierz Lewandowsk, Agata Jablonska-Trypuo
Caffeic acid and its derivatives because of its biological activities, including antioxidants, antithrombosis, antihypertensive, antifibrosis, antiviral, and anti-tumor properties are good candidates as adjuvants in anticancer therapy. The aim of this study was the examination of cyto- and genotoxic effect of caffeic acid on Escherichia coli K-12 recA::gfp strain treated with dacarbazine. Obtained results indicate that dacarbazine and caffeic acid influenced the reactivity of recA promoter and modulate the level of gfp expression in genetic construct rrcA::gfpmut2 in E...
May 2017: Acta Poloniae Pharmaceutica
Zhenqin Zhang, Zhenzhu Zhu, Cheng Luo, Chengcheng Zhu, Changli Zhang, Zijian Guo, Xiaoyong Wang
Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH3 )2 Cl]NO3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography...
March 7, 2018: Inorganic Chemistry
Thomas S Zajonz, Michael Sander, Winfried Padberg, Andreas Hecker, Ruediger Hörbelt, Christian Koch, Emmanuel Schneck
Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) poses a widely used and accepted treatment option for patients with peritoneal carcinomatosis of gastrointestinal tumors. In contrast to the well-described risks and complications of intravenous cytostatic drugs, literature offers only scarce information of serious complications following HIPEC. To our knowledge no other description of rapid progressive pulmonary hypertension (PH) and consecutive respiratory failure following HIPEC have been described in current literature...
March 2018: Annals of Medicine and Surgery
Ida K Myhrvold, Andrea Cremaschi, Johanne U Hermansen, Geir E Tjønnfjord, Ludvig A Munthe, Kjetil Taskén, Sigrid S Skånland
Chronic lymphocytic leukemia (CLL) has a high incidence and a steeply growing prevalence in the Western world. The heterogeneity of the disease necessitates individual mapping of biology and predicted drug response in each patient as basis for administration of tailored treatments. Cell signaling aberrations may serve as biological indicators for suitable therapy. By applying phospho-specific flow cytometry, we mapped basal and induced phosphorylation levels of 20 phospho-epitopes on proteins relevant to B-cell signaling in B cells from 22 CLL patients and 25 normal controls...
February 6, 2018: Oncotarget
Xiangsheng Huang, Stefan Wiehr, Anna-Maria Wild, Patrick Voßberg, Wolfgang Hoffmann, Beate Grüner, Carsten Köhler, Peter T Soboslay
Cytostatic drugs used in cancer therapy were evaluated for their capacity to inhibit Echinococcus multilocularis metacestode growth and proliferation. Metacestode tissues were exposed in vitro to docetaxel, doxorubicin, navelbine, paclitaxel, and vorinostat for 1 week, then incubated in drug-free culture, and thereafter metacestodes were injected into the peritoneum of Meriones unguiculatus . Magnetic resonance imaging (MRI) and simultaneous positron emission tomography (PET) were applied to monitor in vivo growth of drug-exposed E...
February 6, 2018: Oncotarget
Witold Owczarek, Monika Słowińska, Aleksandra Lesiak, Magdalena Ciążyńska, Aldona Maciąg, Elwira Paluchowska, Luiza Marek-Józefowicz, Rafał Czajkowski
Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them...
October 2017: Postȩpy Dermatologii i Alergologii
E V Koldysheva, M G Klinnikova, D B Nikityuk, E K Ivleva, N A Listvyagova, E L Lushnikova
Immunohistochemical assay was employed to determine localization of MMP-2 in cardiomyocytes of WAG rats and changes in MMP-2 expression during modeled cardiomyopathy induced by single intraperitoneal injection of cyclophosphamide (125 mg/kg) alone or in combination with preventive intraperitoneal administration of an equal dose of asparcam-L (potassium-magnesium asparaginate) 30 min prior to the cytostatic. In the myocardium of control and experimental rats, MMP-2 was mostly located in cardiomyocyte nuclei...
March 5, 2018: Bulletin of Experimental Biology and Medicine
Jaroslav Kalous, Anna Tetkova, Michal Kubelka, Andrej Susor
Although the involvement of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the regulation of cytostatic factor (CSF) activity; as well as in microtubules organization during meiotic maturation of oocytes; has already been described in detail; rather less attention has been paid to the role of ERK1/2 in the regulation of mRNA translation. However; important data on the role of ERK1/2 in translation during oocyte meiosis have been documented. This review focuses on recent findings regarding the regulation of translation and the role of ERK1/2 in this process in the meiotic cycle of mammalian oocytes...
March 1, 2018: International Journal of Molecular Sciences
Anders R Holmberg, Marcela Marquez, Lena Lennartsson, Lennart Meurling, Sten Nilsson
BACKGROUND/AIM: Prostate-specific membrane antigen (PSMA) is emerging as a target for treatment of castration-resistant prostate cancer (CRPC) while its up-regulated in the majority of CRPC tumors. The most common approach is targeted radionuclide therapy. MATERIALS AND METHODS: The PSMA binding pharmacophore Glu-Urea-Lysine (GUL) and lysine were conjugated to oxidized dextran with reductive amination and subsequently labelled with fluorosceinisothiocyanate (FITC)...
March 2018: Anticancer Research
Zülal Atlı Şekeroğlu, Vedat Şekeroğlu, Ebru Uçgun, Seval Kontaş Yedier, Birsen Aydın
Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100 µg/ml of CHN in the presence (3 h treatment) and absence (48 h treatment) of S9 mix...
February 26, 2018: Drug and Chemical Toxicology
Raquel Azevedo, Eleazar Rodriguez, Rafael José Mendes, Nuno Mariz-Ponte, Sara Sario, José Carlos Lopes, José Miguel P Ferreira de Oliveira, Conceição Santos
Inorganic Mercury (Hg) contamination persists an environmental problem, but its cyto- and genotoxicity in plants remains yet unquantified. To determine the extent of Hg-induced cyto- and genotoxicity, and assess most sensitive endpoints in plants, Pisum sativum L. seedlings were exposed for 14 days to different HgCl2 concentrations up to 100 μM. Shoots and roots from hydroponic exposure presented growth impairment and/or morphological disorders for doses >1 μM, being the roots more sensitive. Plant growth, ploidy changes, clastogenicity (HPCV), cell cycle dynamics (G1 -S-G2 ), Comet-tail moment (TM), Comet-TD, Mitotic-index (MI) and cell proliferation index (CPI) were used to evaluate Hg-induced cyto/genotoxicity...
February 16, 2018: Plant Physiology and Biochemistry: PPB
Eulália M L da Silva, Susannah Rankin
Chromosome structure in both interphase and M-phase cells is strongly influenced by the action of the cohesin and condensin protein complexes. The cohesin complex tethers the identical copies of each chromosome, called sister chromatids, together following DNA replication and promotes normal interphase chromosome structure and gene expression. In contrast, condensin is active largely in M phase and promotes the compaction of individual chromosomes. The Xenopus egg extract system is uniquely suited to analyze the functions of both complexes...
February 23, 2018: Cold Spring Harbor Protocols
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