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  • resistance
  • The dGuo-R cell line showed an increased level of resistance to 2-fluoro-2'-deoxyadenosine and 2-fluoroadenine arabinoside (11-14-fold), but essentially no increase in resistance to deoxyadenosine or adenine arabinoside. (ecu.edu)
  • To establish the role of GSH/GSTs towards inactivity and/or resistance of tumor cells to cytotoxic drugs, two major experimental approaches have been followed. (allindianpatents.com)
  • The first of them involved studies in which elevated levels or expression and activity of GSH/GSTs were correlated with increased levels of drug resistance. (allindianpatents.com)
  • This approach also included modulation of GSH/GSTs activity by means of GSH inhibitors such as BSO (buthionine sulphoximine), in order to circumvent or reverse drug resistance. (allindianpatents.com)
  • Recently, the role of GSH in dmg resistance has been linked to the regulation of the activity of the multi-drug resistance-associated proteins (IVIRP) which confer resistance to different cytotoxics including anthracyclines (e.g. doxorubicin, idarubicin, epirubicin and donatives thereof), epidophyllotoxins (e.g. etoposide and teniposide), Vince alkaloids (e.g. vinblastine and vincrisdne) and tisanes (e.g. paclitaxel and docetaxel) [Eur. (allindianpatents.com)
  • Moreover, a growing body of evidence implies that a variety of miRNAs suppress malignant phenotypes of pancreatic cancer cells including drug resistance through the down-regulation of RUNX2. (beds.ac.uk)
  • Cell lines defective in NER, which show an increased sensitivity to classical alkylating agents, display a three-four fold resistance to nemorubicin. (aacrjournals.org)
  • Studies are in progress to determine the methylation status of the XPG gene in the nemorubicin-resistant cell line.In conclusion, these results further corroborate the unique mechanism of action of nemorubicin and identify a novel mechanism of drug resistance through the genetic silencing of a DNA repair gene. (aacrjournals.org)
  • These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction. (biomedcentral.com)
  • Export of folates from a Chinese hamster ovary Pyr R100 cell line is markedly impaired, resulting in expansion of cellular folate pools and high-level antifolate resistance. (aspetjournals.org)
  • We now report that MRP1 expression is absent in Pyr R100 cells along with a marked decrease in MRP5 expression with 3-fold cross-resistance to thiopurines. (aspetjournals.org)
  • Transfection of MRP5 into Pyr R100 cells did not alter sensitivity to pyrimethamine or MTX but restored sensitivity to mercaptopurines, indicating that decreased MRP5 expression did not play a role in antifolate resistance. (aspetjournals.org)
  • Chronic lymphocytic leukemia (CLL) lymphocytes respond to DNA alkylation by excision repair, with the extent of repair increasing as the cells acquire resistance to alkylating agents. (aacrjournals.org)
  • vitro
  • Pharmacokinetic analysis using this dosing schedule demonstrated patient plasma concentrations in the micromolar range that are consistent with concentrations required in vitro for inhibition of cell growth and induction of PCD. (aacrjournals.org)
  • There is abundant evidence of critical cytoskeletal differences involving microfilaments between normal and neoplastic cells, and a variety of natural products and semi-synthetic derivatives are available to exploit these differences in vitro. (jove.com)
  • Lymphocytes from 50 patients with CLL that were not refractory to alkylators were treated in vitro with 4-hydroperoxycyclophosphamide (4-HC) with or without prior incubation with fludarabine nucleoside (F-ara-A) or with clofarabine (Cl-F-ara-A). DNA damage repair kinetics were determined by the single-cell gel electrophoresis (comet) assay. (aacrjournals.org)
  • cytotoxic activity
  • In addition, these cells are not able to repair UV-induced damage on transfected DNA (host -cell reactivation assay), suggesting that the NER system might be involved in mediating the cytotoxic activity of nemorubicin. (aacrjournals.org)
  • Furthermore, whereas many agents currently entering clinical trials are said to be cytostatic, the data to be presented show that many if not all of these compounds possess cytotoxic activity that is at least as important if not more so than any cytostatic property. (aacrjournals.org)
  • Analogues
  • Camptothecin analogues showing more potent anti-tumor activity than a naturally occurring alkaloid camptothecin, which also exhibit an immunosuppressive activity, in which the 1-ethyl of camptothecin is replaced by various members of substitutents such as alkyls (except ethyl), alkenyls, alkynyls, aralkyls. (google.com)
  • More particularly, it relates to novel camptothecin analogues showing potent anti-tumor and immunosuppressive activities, and to a process for producing them. (google.com)
  • The ability of polyamine analogues to alter activity of cytotoxic chemotherapeutic agents in breast cancer models has not been evaluated. (aacrjournals.org)
  • They were able to synergize with one or both polyamine analogues in most of the breast cancer cell lines. (aacrjournals.org)
  • Because incorporation of nucleotide analogues into the repair patches elicits death signals in quiescent cells, the increased capacity for excision repair in alkylator-resistant cells could facilitate incorporation of nucleotide analogues. (aacrjournals.org)
  • We hypothesized that the mechanism-based interaction of nucleoside analogues with alkylating agents could elicit greater than additive killing of CLL cells. (aacrjournals.org)
  • Recently, purine nucleoside analogues have been shown to be efficacious in the therapy of CLL and other indolent B-cell malignancies. (aacrjournals.org)
  • kinase
  • when cytosine arabinoside or deoxyguanosine was used as the substrate, the kinase activity in the extracts from the dGuo-R cells was only 10% of the enzyme activity in the extracts from the wild-type cells. (ecu.edu)
  • By use of high-performance liquid chromatography, the kinase activities in the extracts from the wild-type and resistant cells could be resolved. (ecu.edu)
  • There was the specific loss of kinase activity toward cytosine arabinoside and deoxyguanosine as substrates. (ecu.edu)
  • These data indicate that the dGuo-R cells have decreased levels of a specific deoxyribonucleoside kinase activity. (ecu.edu)
  • Cory, Ann H. and Shibley, Ivan A. and Chalovich, Joseph M. and Cory, Joseph G., "Deoxyguanosine-resistant Leukemia L1210 Cells: Loss of Specific Deoxyribonecleoside Kinase Activity," Journal of Biological Chemistry 268, no. 1 (January 1993), http://hdl.handle.net/10342/3245 (accessed September 20, 2018). (ecu.edu)
  • mechanisms
  • Therefore, it is urgent to develop novel treatment options against pancreatic cancer, and also to understand the precise molecular mechanisms how pancreatic cancer cells could acquire and maintain GEM-resistant phenotype. (beds.ac.uk)
  • We concluded that if CSCs are the main driving force behind tumor support and growth then understanding the molecular mechanisms and the immunological properties directing these cells for immune tolerance is of great clinical significance. (springer.com)
  • Although the existence of NK cells has been known for more than 20 years, many of the basic issues concerning these cells, such as their developmental pathway, their mechanisms of recognition, and their physiologic function, are still poorly understood. (jimmunol.org)
  • Even less is understood about the mechanisms of positive recognition used by NK cells. (jimmunol.org)
  • Molecular mechanisms of cytostasis will be analyzed, including interference with the cell cycle as well as putative links with necrosis and autophagy. (aacrjournals.org)
  • induce
  • Given that both lovastatin and paclitaxel are used in the clinic and are capable of inducing cell cycle-specific effects, it is of great interest to determine whether combinations of these agents induce additive or supra-additive effects that may be harnessed for novel therapeutic applications. (aacrjournals.org)
  • mechanism
  • Drug stimulation of topoisomerase II-mediated DNA cleavage is remarkably attenuated in the aza-bioisosteric derivatives, suggesting that other non-enzyme-mediated cytotoxic mechanism(s), possibly connected with free radical production, are responsible for efficient cell killing. (aspetjournals.org)
  • 1976
  • 1976. Identification of the cell-multiplication-inhibitory factors in interferon preparations as interferons. (springer.com)
  • molecular
  • Thus, it is urgent to understand the precise molecular basis behind the drug-resistant property of pancreatic cancer and also to develop a novel strategy to overcome this deadly disease. (beds.ac.uk)
  • Since p53, which monitors and ensures the genomic integrity, is an essential molecular barrier against carcinogenesis [ 8 , 9 ], it is possible that loss of function mutation of p53 leads to the accumulation of genetic damage within pancreatic cancer cells, and thus they might acquire GEM-resistant property as well as metastatic potential. (beds.ac.uk)
  • analogs
  • In addition these analogs promote accumulation of cells in S-phase which appears to be necessary for radiosensitization. (springer.com)
  • sensitivity
  • Indeed, certain p53 mutants render pancreatic cancer cells much more resistant to GEM, implying that p53 mutation is one of the critical determinants of GEM sensitivity. (beds.ac.uk)
  • Recently, we have found for the first time that forced depletion of RUNX2 significantly increases GEM sensitivity of p53 -null as well as p53 -mutated pancreatic cancer cells through the stimulation of p53 family TAp63/TAp73-dependent cell death pathway. (beds.ac.uk)
  • Preliminary experiments performed using a hypomethylating compound showed that pre-treatment of resistant cells with these molecule can restore the sensitivity to nemorubicin. (aacrjournals.org)
  • Sinclair, W. K., and Morton, R. A. X-ray sensitivity during cell generation cycle of cultured Chinese hamster cells. (springer.com)
  • drug-resistant
  • Accumulating evidence strongly suggests that p53 mutations contribute to the acquisition and/or maintenance of drug-resistant property of pancreatic cancer. (beds.ac.uk)
  • concentrations
  • In view of previous works, these results suggest a relationship between alterations in ALDH iso-enzymes activities and cytosolic aldehyde concentrations with respect to normal or tumoral cell growth. (springer.com)
  • ascites
  • Bachrach U, Abzug S, Bekierkunst A: Cytotoxic effect of oxidized spermine in Ehrlich ascites cells. (springer.com)
  • Translation of nonviral and viral mrna's in extracts from uninfected and infected ehrlich ascites tumor cells. (jax.org)
  • Cancer
  • Cancer stem cells (CSCs) need to survive cancer treatments with a specific end goal to provide new, more differentiated, metastatic-prone cancerous cells. (springer.com)
  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. (springer.com)
  • A steadily increasing number of subsequent studies described aberrant expression and function of GSLs and related enzymes in cancer cells and tissues. (frontiersin.org)
  • High aldehyde dehydrogenase (ALDH hi ) activity has been reported in normal and cancer stem cells. (frontiersin.org)
  • By definition, cytostatic drugs do not kill cancer cells but instead stop cancer cells from proliferating. (aacrjournals.org)
  • Prolonged time to progression and improved overall survival have been recently reported using novel targeted therapies, and it has been argued that this effect is totally or partially mediated by cancer cell cytostasis without direct cytotoxic effects. (aacrjournals.org)
  • molecule
  • Both the frequency of cells expressing a given Ly49 molecule and the level of expression are influenced by host MHC genes ( 6 , 7 , 8 ). (jimmunol.org)