[ biopathway.org | BioIE ]

---

Test corpus 1

1. Surface plasmon resonance experiments, performed with DNA hairpin oligomers, indicate that NB-506 binds almost equally well to both AT and GC base pairs, and the binding affinity (K = 10(5) M(-1)) is similar to that of certain classical intercalators such as amsacrine and bisantrene.
2. The trithiophene derivative interacts preferentially with AT-rich sequences at low concentrations, but can accomodate GC sites at higher concentrations.
3. NB-506 completely inhibits the capacity of topoisomerase I to phosphorylate, in vitro, the human splicing factor 2/alternative splicing factor (SF2/ASF).
4. Following exposure to BNP1350, increased binding of 14-3-3 proteins to chk1 occurred in both cell lines, with more being observed in the A253/vec cell line.
5. Camptothecin-induced apoptosis was associated with redistribution of BAX from cytosol to organelle membranes.
6. DA-125, a novel anthracycline derivative showing high-affinity DNA binding and topoisomerase II inhibitory activities, exerts cytotoxicity via c-Jun N-terminal kinase pathway.
7. Intracellular polyamines are constitutive components of mammalian cells and their availability is critical for cell proliferation.
8. This agent also allowed partial dissociation of enzyme from the DNA in the absence of religation, indicating unique interactions between 1, enzyme and DNA in the ternary complexes.
9. Structural homology between DNA binding sites of DNA polymerase beta and DNA topoisomerase II.
10. HTLV-1 Tax oncoprotein exerts pleiotropic effects on cellular regulatory systems, trans-activation and trans-repression of transcription and promotion of the cell cycle, through interaction with various cellular factors.
11. Subfractionation analyses showed that the N-terminal LAP2 alpha fragment was extracted from intranuclear structures in detergent/salt buffers, whereas the C-terminal fragment remained associated with a residual framework devoid of chromatin.
12. A number of cytotoxic bisdioxopiperazines such as ICRF-193 target topoisomerase II by binding and trapping the closed enzyme clamp.
13. Although the peptides bind DNA, their inhibitory activity appears to be more specifically targeted to the Int-substrate complex, insofar as inhibition is resistant to high levels of non-specific competitor DNA and the peptides have higher levels of affinity for the Int-DNA substrate complex than for DNA alone.
14. F 11782 appeared to act by inhibiting the binding of topoisomerases I and II to DNA in a manner dependent both on drug and enzyme concentrations, via a mechanism not previously described or shared by other known topoisomerase 'poisons' or inhibitors.
15. TopoIIalpha gene amplification and deletion are common in ErbB-2-amplified breast cancer and are associated with increased or decreased sensitivity to topoII inhibitors in vitro, respectively.
16. Furthermore, the observed increase of antitumor activity in A253/Bax tumors was associated with an enhanced induction of apoptosis in vivo.
17. Many nuclear functions, including multidrug resistance, and others which lead to cell death, have been shown to be compromised when these anticancer agents interact with the nuclear matrix.
18. TAS-103 cytotoxicity is not affected by the presence of Pgp, MRP, LRP or mutations in the CAM binding region of the topo-I enzyme and its growth-inhibitory effect appears to be weakly dependent on exposure duration.
19. BRCA1 may also enhance chemosensitivity and repair of DNA damage through binding to and coactivation of p53.
20. These data are consistent with alpha-helix 4 being a distinct portion of the quinolone-binding site of GyrA.
21. The DNA binding of daunorubicin was slightly higher in HL-60 cells, but there was no notable variance between the cell lines for aclarubicin.
22. Thus, our studies provide further support to the hypothesis that XPD and p53 can functionally interact in a p53-mediated apoptotic pathway.
23. Using mass spectrometry, we found that, similar to Chk1, Chk2 can phosphorylate serine 216 in Cdc25C, a site known to be involved in negative regulation of Cdc25C.
24. (d) both of the classic integrin receptors that bind VN (alpha(v)beta3,=alpha(v)beta5) were capable of mediating this protective effect, because ligation of either of the two classic integrins conferred chemoresistance to Topo; and (e) chemoresistance observed with VN was associated with an increase in expression of two antiapoptotic proteins, Bcl-2 and Bcl-X(L), with a
25. Collectively, the evidence presented suggests the existence of an atypical interaction between Topo II and paclitaxel that may disrupt the normal functioning of the enzyme.
26. It binds tightly to sites composed of at least four adjacent AT base pairs, such as 5'-TAAT, AATT and TTTT.
27. Understanding how these proteins interact to regulate the cell cycle has become increasingly important to researchers and clinicians with the discovery that many of the genes that encode cell cycle regulatory activities are targets for alterations that underlie the development of cancer.
28. We set out to elucidate the molecular basis of their interaction with duplex DNA, with particular emphasis on the role of the carbohydrate residue.
29. Overexpression of TGF-alpha and/or its receptor (EGFR) has been associated with a more aggressive disease and a poor prognosis.
30. Presently, five analogues of camptothecin that differ only at C-20 have been evaluated for their ability to bind to the topoisomerase I-DNA binary complex and thereby inhibit enzyme function.
31. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities.
32. In each case, the glycoside residue plays a significant role in the interaction of the drug with the DNA double helix.
33. This led us to speculate that maternal exposure during pregnancy to environmental agents that inhibit DNA topo 2 may be associated with the development of leukemia in infants.
34. The selective cytotoxicity is associated with the presence of an imminium ion and other structural features of protoberberines, and is not shared by drugs such as camptothecin, doxorubicin, vinblastine, and etoposide, which are either equally or more cytotoxic against RPMI 8402 cells than SF-268 cells.
35. High-performance liquid chromatography revealed that SN-38 treatment was associated with increased levels of the deoxynucleotide dTTP and decreased levels of dUTP.
36. Our finding of differential expression of Topo II alpha between SCLC and NSCLC also suggests that the Topo II alpha expression level is associated with sensitivity to Topo II inhibitors.
37. Topoisomerase II appears to have a close association with the SMC (stable maintenance of chromosomes) family of proteins involved in organisation of the chromatin in a series of loops on the proteinaceous chromosomal scaffold.
38. Genistein induced expression of p21, and the increased levels of p21 were associated with increased binding of p21 with cdc2 and cdk2.
39. Genistein induced expression of p21, and the increased levels of p21 were associated with increased binding of p21 with cdc2 and cdk2.
40. The core domain encompasses residues approximately 198 to approximately 651, is involved in catalysis, and is important for the preferential binding of the enzyme to supercoiled DNA.
41. Lamin B phosphorylation by protein kinase calpha and proteolysis during apoptosis in human leukemia HL60 cells.
42. Because up-regulation of topo IIalpha in vitro and in clinical specimens is associated with increased response to doxorubicin (presumptively by an increase in drug substrate), this may be the mechanism of the increased sensitivity to doxorubicin seen in heregulin beta-2-transfected cells.
43. These results support models in which both quinolones and antitumor agents bind to a conserved site that overlaps the active site of the enzyme.
44. Treatment of murine SV3T3 cells with IC261 specifically blocked phosphorylation in vivo of the CK1delta/epsilon phosphorylation sites in p53, indicating that p53 interacts physiologically with CK1delta and/or CK1epsilon.
45. [Cytotoxicity and interaction of amsacrine derivatives with topoisomerase II.
46. Irinotecan is 65% bound to plasma proteins.
47. Finally, competition studies indicate that azatoxin interacts with topoisomerase II in the enzyme domain utilized by etoposide and ellipticine.
48. alternatively, it could modify the chromatin-association functions of MLL.
49. DNA methylation and the association between genetic and epigenetic changes.
50. The results suggest that the inhibition of topoisomerase I by indolocarbazoles arises in part from their ability to interact with DNA.
51. The potentiation of etoposide-induced apoptosis by staurosprine was associated with a significant increase in cyclin A-dependent kinase activity.
52. Rather, BQ most probably inhibits the SH-dependent topo II by binding to an essential SH group.
53. CPT induces well-defined alterations of the oligo structure, whereas CPT11 interacts with oligonucleotides more weakly and in another manner than CPT.
54. Internucleosomal DNA fragmentation, triggered by either VP-16 or an anti-Fas antibody, was associated with proteolytic cleavage of the poly(ADP-ribose)polymerase (PARP), a decrease in the level of 32 kDa CPP32 proenzyme and the appearance of the CPP32 p17 active subunit.
55. A synergistic interaction between topotecan and melphalan was observed only in the cell lines expressing low levels of topoisomerase I even if all cell lines exhibited a comparable sensitivity to this agent.
56. These results suggest that Trp-P-1 changes DNA conformation by intercalation, causing inhibition of binding of repair enzymes to UV-damaged DNA, and this in turn leads to inhibition of DNA excision repair and to co-mutagenic effects.
57. This novel regulation of topo I mRNA by topo I-targeting agents could be associated with acquirement of drug resistance to saintopin or SN-38/CPT-11 in KB/STP-2 cells.
58. Topoisomerase II plays a role in the attachment of 50-kilobase domains of DNA to the nuclear matrix; fragments of this size are cleaved during apoptosis.
59. The first is the inhibition of the enzyme's binding to its DNA substrate as seen with intercalating drugs such as chloroquine and aclarubicin; a second, more specific, interaction is elicited by bisdioxopiperazines, which are thought to lock the homodimeric topoisomerase II in the form of a closed bracelet surrounding the DNA at the postreligation step.
60. Compounds 7-9, which contain a basic C-terminus function such as (dimethylamino)propyl and bind to DNA with C(50) values of 200, 160, and 135 microM, respectively, exhibited inhibition of topoisomerase I in a concentration dependent manner.
61. Intoplicine (RP 60475F; NSC 645008) is a novel 7H-benzo[e]pyrido[4,3-b]indole derivative which interacts with both topoisomerases I and II .
62. Addition of a stoichiometric amount of DNA to a performed coumermycin-topoisomerase complex quantitatively displaces the drug, indicating that coumermycin binding and DNA binding to topoisomerase are mutually exclusive.
63. Camptothecin resistance of the human leukemia CEM/C2 cells is associated with a topoisomerase I (top1) mutation.
64. We constructed multi-AT hook (MATH) proteins and demonstrate that they specifically bind the clustered A tracts of SARs in chromatin and chromosomes.
65. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity.
66. Assessing the interaction of irradiation with etoposide or idarubicin.
67. These results suggest that the inhibitory effect of XPAC on DNA replication probably occurs through its interaction with RPA.
68. Preferential binding of histones H3 and H4 to highly positively coiled DNA.
69. In addition, cell proliferation was associated with increased DNA topoisomerase I protein levels in both nuclear and cytosol fractions.
70. Seven dicationic 2,5-diarylfurans have been synthesized, and their interactions with poly(dA-dT) and the duplex oligomer d(CGCCAATTCGCG)2 were evaluated by Tm measurements.
71. The effects of ATA on DNA-protein complex formation in living cells appear to be due to the direct interaction of the drug with topoisomerase II, since similar results are found when nuclei from untreated DC-3F cells are exposed to amsacrine after a short preincubation with ATA.
72. Physical studies have further defined interactions of quinolones with their principal target, DNA gyrase.
73. In vivo interaction between cytokines and cytotoxic agents involves an additional layer of complexity because of the effects of cytokines on the host immune system and on drug-metabolizing enzymes.
74. The differences observed in the subnuclear distribution and DNA binding pattern of the topoisomerase II isozymes support the hypotheses that each isozyme has a distinct cellular function.
75. A camptothecin-resistant top1 with a mutation (Asn722-->Ser) next to the catalytic tyrosine (Tyr723) was cross-resistant to STP, suggesting that both STP and camptothecin interact with the protein near the catalytic tyrosine.
76. The two DNA intercalators, actinomycin D and 2-methyl-9-hydroxy-ellipticine, and the DNA minor groove ligant DAPI inhibited the growth of the haloarchaeon Halobacterium sp. GRB and bind to its plasmid pGRB-1.
77. The acute toxicity of batracyclin has been associated with the formation of its N-acetyl metabolite which is a potent inducer of unscheduled DNA synthesis in rat hepatocytes.
78. Taken together, these results indicate that resistance to VP-16 in a K562 subline is associated with a quantitative reduction in topoisomerase II protein and, in addition, a distinct qualitative alteration in topoisomerase II affecting the stability of drug-induced DNA-topoisomerase II complexes.
79. ICRF-193 can bind to the closed-clamp form of the enzyme and prevents its conversion to the open-clamp form.
80. The discovery that this phenomenon is associated with the overexpression of a membrane glycoprotein, P-glycoprotein, which acts as a drug efflux pump, has provided a new target for drug development.
81. Doses greater than 1.5 mg/m2 were associated with nadirs that developed after one to three weekly treatments.
82. We propose that the direct interaction of beta-lapachone with topoisomerase I does not affect the assembly of the enzyme-DNA complex but does inhibit the formation of cleavable complex.
83. Specific interaction of camptothecin, a topoisomerase I inhibitor, with guanine residues of DNA detected by photoactivation at 365 nm.
84. Since apoptosis has been associated with potential involvement of intracellular signaling linked to the Ca2+/calmodulin and protein kinase C transduction pathways, we also investigated the effects of signaling modulators on camptothecin- and teniposide-induced secondary DNA fragmentation in HL-60 cells.
85. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan.
86. In order to define the biochemical basis for its antitumor activity and to enhance suramin's chemotherapeutic potential while decreasing its toxicity, we have examined interactions of suramin with topoisomerase I and II and several clinically active anticancer drugs against the human prostate (PC3 and LNCaP) cancer cell line.
87. Recent results using single-stranded conformational polymorphism analysis reveals the presence of a mutation in the motif B/nucleotide binding site of the topo II alpha gene in CEM at-MDR cells and in another leukemic cell line selected for resistance to m-AMSA.
88. Intermolecular nuclear Overhauser effects (NOE) between the ligand and the DNA receptor fragment confirm that the ligand binds in the minor groove of the DNA, interacting with the centrally located 5'-GGCCA segment.
89. As an inhibitor of DNA repair, it can potentially interact with DNA-damaging agents such as alkylating agents or inhibitors of topoisomerase II.
90. VM-26 and m-AMSA appear to interact specifically with nuclear matrix topoisomerase II, and one mechanism of cellular resistance to these agents is associated with depletion of the matrix enzyme.
91. Transcription is associated with a substantial increase in the binding of anti-Z-DNA antibodies, paralleling the increased level of RNA synthesized as the level of ribonucleoside triphosphate in the medium is increased.
92. The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation.
93. Synergistic interactions between tumor necrosis factor and inhibitors of DNA topoisomerase I and II.
94. Membrane filtration and spin-column techniques were used to study the binding of [3H]norfloxacin to purified plasmid DNA, DNA gyrase, and complexes formed by adding gyrase to different forms of plasmid DNA.
95. The increased NMHE cellular concentration in the multidrug resistant cells was associated with an 8-fold increased toxicity.
96. The association of topoisomerase II enzymes with papovavirus-chromatin has been described recently.
97. These results suggest that the selection of the mature mRNAs for nucleocytoplasmic transport occurs at the release stage from the matrix (i.e. before translocation through the nuclear pore) and that reactions hitherto known to cause changes in the DNA secondary structure are associated with the detachment of mRNA from the nuclear substructure.
98. It is known that where DNA topoisomerase is acting on DNA, the addition of sodium dodecyl sulphate will result in cleavage of the DNA and covalent attachment of the enzyme to the cut DNA end.
99. DNA binding of bithiazole derivatives has also been studied by two complementary topological methods.
100. Studies suggest that the anticancer drugs VP16-213 and VM26 produce cytotoxicity by inducing protein-associated DNA breakage in vivo through interaction with a yet unknown nuclear component.
101. We suggest that these results reflect allosteric interactions between the subunits of a multienzyme DNA-synthesizing complex, which can be modulated by the specific inhibitors of individual enzyme activities in intact cells.