The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
A. G. Kudrev - One of the best experts on this subject based on the ideXlab platform.
-
Stabilization of Double-Stranded Poly(A)·Poly(U) with ZnTMPyP4 Metalloporphyrin in Aqueous Solution
Russian Journal of General Chemistry, 2020Co-Authors: A. G. KudrevAbstract:UV-Vis absorption spectra of aqueous solutions containing both metalloporphyrin Zn(X)TMPyP4 [H_2TMPyP4—5,10,15,20-tetrakis(1-methylpyridin-4-yl)-21 H ,23 H -porphyrin] and synthetic Polyadenylic-Polyuridylic Acid Poly(A)·Poly(U) over the temperature range from 20 to 70°C (pH = 7.0, I = 0.15 M.) have been analyzed. Deconvolution of the spectrometric data matrix, without postulating a physicochemical equilibrium model, has allowed estimation of the contribution of the Poly(A)·Poly(U)·(ZnTMPyP4)_ n complex to the total change in the spectra. Chemometric analysis has shown an increase in the melting temperature of this ternary complex by 9.4°С compared to pure polyribonucleotide, which indicates the stabilization of the bonds between nucleic bases in the Poly(A)·Poly(U) polynucleotide under the influence of bound porphyrin.
-
thermal unwinding of Polyadenylic Polyuridylic Acid complex with tmpyp4 porphyrin in aqueous solutions
Journal of Molecular Structure, 2020Co-Authors: M Ivanov, V Sizov, A. G. KudrevAbstract:Abstract The molecular mechanism of Poly(A)•Poly(U) (Polyadenylic•Polyuridylic Acid) polyribonucleotide denaturation was studied through a combination of molecular dynamics (MD) simulations and UV–Vis-melting experiments. UV–Vis absorption spectra of Poly(A)•Poly(U) were measured at different temperatures (20–70 °C) both in the absence and presence of porphyrin-ligand TMPyP4 in equilibrated aqueous solutions (pH 7.0). Thermal behavior of double-stranded structure of Poly(A)•Poly(U) altered by formation of the ternary [Poly(A)•Poly(U)]*(TMPyP4)n complexes was studied with the help of a new semi-soft chemometrics procedure, based on the analyses of fractions of species in solution versus temperature. The melting temperature in the presence of porphyrin is 1.2 °C higher than that for pure polyribonucleotide, which indicates that porphyrin binding contributes to the suppression of transition between the native ordered structure of Poly(A)•Poly(U) and disordered state. MD simulations were performed for the binding of TMPyP4 to (rA)12•(rU)12 oligonucleotide to provide molecular-level insight into the mechanism of duplex dsRNA melting in the presence of TMPyP4. The results of MD simulations suggest a molecular mechanism of thermal stabilization of the native structure through the accommodation of TMPyP4 in double-stranded structure of (rA)12•(rU)12 oligonucleotide groove close to the end of the ordered region of stacked nucleobase pairs.
-
Thermal unwinding of Polyadenylic·Polyuridylic Acid complex with TMPyP4 porphyrin in aqueous solutions
Journal of Molecular Structure, 2020Co-Authors: M Ivanov, V Sizov, A. G. KudrevAbstract:Abstract The molecular mechanism of Poly(A)•Poly(U) (Polyadenylic•Polyuridylic Acid) polyribonucleotide denaturation was studied through a combination of molecular dynamics (MD) simulations and UV–Vis-melting experiments. UV–Vis absorption spectra of Poly(A)•Poly(U) were measured at different temperatures (20–70 °C) both in the absence and presence of porphyrin-ligand TMPyP4 in equilibrated aqueous solutions (pH 7.0). Thermal behavior of double-stranded structure of Poly(A)•Poly(U) altered by formation of the ternary [Poly(A)•Poly(U)]*(TMPyP4)n complexes was studied with the help of a new semi-soft chemometrics procedure, based on the analyses of fractions of species in solution versus temperature. The melting temperature in the presence of porphyrin is 1.2 °C higher than that for pure polyribonucleotide, which indicates that porphyrin binding contributes to the suppression of transition between the native ordered structure of Poly(A)•Poly(U) and disordered state. MD simulations were performed for the binding of TMPyP4 to (rA)12•(rU)12 oligonucleotide to provide molecular-level insight into the mechanism of duplex dsRNA melting in the presence of TMPyP4. The results of MD simulations suggest a molecular mechanism of thermal stabilization of the native structure through the accommodation of TMPyP4 in double-stranded structure of (rA)12•(rU)12 oligonucleotide groove close to the end of the ordered region of stacked nucleobase pairs.
-
Interactions of Copper(I) Phenanthroline Chelate with Polyadenylic-Polyuridylic Acid in Aqueous Dioxane
Russian Journal of General Chemistry, 2004Co-Authors: A. G. KudrevAbstract:Acid-base transformations in the system copper(I) phenanthroline chelate [Cu(phen)_2]^+aq-poly-adenylic-Polyuridylic Acid in aqueous dioxane were studied by spectrophotometry. Changes in band intensi-ties, positions were revealed in the visible, near UV regions, dependent on the pH of the solution.Factor analysis was used to show that the absorption variance on titration of copper(I) bisphenanthrolinechelate is determined by mutual transformations of three spectral forms of complexes. Concentration profiles were calculated for compounds prevailing in the solution. In the presence of Polyadenylic-Polyuridylic Acid, an additional spectral form appears as a result of a short-wave shift of the d -π* MLCT transition in the copper(I) chelate complex. Analysis of the calculated concentration profiles established that the new complex is formed at pH 5.2-5.6 from the bisphenanthroline chelate and the double-helix rod-like form of the polymer.
-
study of the Acid base equilibria and conformational changes of double stranded Polyadenylic Polyuridylic Acid in aqueous solution
Analytica Chimica Acta, 1998Co-Authors: A. G. Kudrev, Raimundo Gargallo, Romà Tauler, A Izquierdoridorsa, Enric CasassasAbstract:Abstract UV-absorption and circular dichroism (CD) spectroscopy have been applied to the study of the Acid–base properties of the heteropolynucleotide riboPolyadenylic–Polyuridylic Acid (poly(A)–poly(U)) and to the study of the possible interaction of this polynucleotide with 2,2′-bipyridyl (bipy) in aqueous solutions as a function of pH. Using soft modelling chemometric procedures based on factor analysis and multivariate curve resolution, the individual absorption spectra and pH–concentration profiles of all the species detected under equilibrium conditions are estimated for the systems studied. From these results, chemical models are proposed, which include the protonation of the adenine base of poly(A)–poly(U) on the transition from neutral to Acidic solutions and the deprotonation of the uridine base of poly(A)–poly(U) on the transition from neutral to basic solutions. The conformational changes accompanying Acid–base equilibria of poly(A)–poly(U) are deduced from the UV and CD spectral data. Under the experimental conditions of this work, no interaction was detected between the heteropolynucleotide poly(A)–poly(U) and bipy. Similarly, the interaction between the monomers cUMP, cAMP and bipy was proved not to be significant.
Hyun Cheol Chung - One of the best experts on this subject based on the ideXlab platform.
-
Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up
Annals of oncology : official journal of the European Society for Medical Oncology, 2007Co-Authors: Hei Cheul Jeung, Yong Wha Moon, Sun Young Rha, Nae Choon Yoo, Jaekyung Roh, Sung Hoon Noh, Jin Sik Min, Bong Seog Kim, Hyun Cheol ChungAbstract:Abstract Background This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. Patients and methods From 1984 to 1989, patients who had D2–3 curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. Results A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2–T4a), and lymph node status (N0–N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. Conclusions These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.
-
phase iii trial of adjuvant 5 fluorouracil and adriamycin versus 5 fluorouracil adriamycin and Polyadenylic Polyuridylic Acid poly a u for locally advanced gastric cancer after curative surgery final results of 15 year follow up
Annals of Oncology, 2007Co-Authors: Hei Cheul Jeung, Yong Wha Moon, Sun Young Rha, Nae Choon Yoo, Sung Hoon Noh, Jin Sik Min, Bong Seog Kim, J K Roh, Hyun Cheol ChungAbstract:Abstract Background This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. Patients and methods From 1984 to 1989, patients who had D2–3 curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. Results A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2–T4a), and lymph node status (N0–N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. Conclusions These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.
Laurence Zitvogel - One of the best experts on this subject based on the ideXlab platform.
-
Anticancer effects of Polyadenylic-Polyuridylic Acid (poly[A:U]) and uncoupling of chemokine receptor signaling: Role of CCR5 and CXCR3
Journal of Clinical Oncology, 2009Co-Authors: Rosa Conforti, Yannis Morel, Carine Paturel, Magali Terme, Sophie Viaud, Nathalie Chaput, F. Andre, Guido Kroemer, Laurence ZitvogelAbstract:3063 Background: Several tumor cells express toll-like receptors (TLRs) which constitute putative therapeutic targets. Methods: To dissect the clinical outcome of the host versus cell autonomous effects of the TLR3 agonist poly(A:U), we took advantage of two murine TLR3 expressing tumor models (melanoma and glioblastoma) that produced large amounts of CCL5 (a CCR5 ligand) and CXCL10 (a CXCR3 ligand) in response to the poly(A:U) and type I IFN in vitro and in vivo. We tested in vivo a triple combination based on vaccine against tumor antigens (V), chemotherapy (C), and TLR3 agonist (poly[A:U]) (T). Results: Single agents (V, C, or T) and combinations of two agents (VC, VT, or CT) failed to improve tumor progression. However, the sequential tritherapy (VCT) significantly retarded tumor growth and prolonged the survival of tumor-bearing C57BL/6 mice. The antitumor effects of VCT (immunochemotherapy) failed to be observed in nu/nu and TRIF-/- mice, indicating the contribution of T cells and TRIF-dependent sig...
-
Toll like receptor 3 expression and efficacy of adjuvant treatment with Polyadenylic-Polyuridylic Acid in patients with axillary node positive breast cancer: Results from two randomized trials
Journal of Clinical Oncology, 2006Co-Authors: Fabrice Andre, Christophe Massard, Hazem I. Assi, Benjamin Besse, Jean-christophe Sabourin, Laurence ZitvogelAbstract:10563 Background: Toll like receptor 3 (TLR3) are transmembrane receptors involved in the cellular response to danger signal and specifically activated by double stranded RNA. Based on these data, we hypothesized that the TLR3 expression by tumor cells is associated with the efficacy of a treatment with double stranded RNA in cancer patients. Patients and Methods: TLR3 expression was assessed by immunohistochemistry in 336 patients with axillary node positive breast cancer. These patients were selected to have been included in two randomized trials that compared a post-operative administration of Polyadenylic-Polyuridylic Acid (polyAU) to either no treatment (n = 174, trial I) or an adjuvant chemotherapy by CMF regimen (n = 162, trial II). In the trial II, locoregional and pelvic radiotherapy were given in the polyAU arm. Results: TLR3 was found to be overexpressed in 45 tumors (13%). Median follow-up were 23 and 17 years for living patients included in the trials I and II respectively. When the analysis ...
Rosa Conforti - One of the best experts on this subject based on the ideXlab platform.
-
Opposing effects of toll-like receptor (TLR3) signaling in tumors can be therapeutically uncoupled to optimize the anticancer efficacy of TLR3 ligands.
Cancer Research, 2010Co-Authors: Rosa Conforti, Yannis Morel, Carine Paturel, Magali Terme, Sophie Viaud, Bernard Ryffel, Maria Ferrantini, Ravindra Uppaluri, Robert Schreiber, Christophe CombadièreAbstract:Many cancer cells express Toll-like receptors (TLR) that offer possible therapeutic targets. Polyadenylic-Polyuridylic Acid [poly(A:U)] is an agonist of the Toll-like receptor TLR3 that displays anticancer properties. In this study, we illustrate how the immunostimulatory and immunosuppressive effects of this agent can be uncoupled to therapeutic advantage. We took advantage of two TLR3-expressing tumor models that produced large amounts of CCL5 (a CCR5 ligand) and CXCL10 (a CXCR3 ligand) in response to type I IFN and poly(A:U), both in vitro and in vivo. Conventional chemotherapy or in vivo injection of poly(A:U), alone or in combination, failed to reduce tumor growth unless an immunochemotherapeutic regimen of vaccination against tumor antigens was included. CCL5 blockade improved the efficacy of immunochemotherapy, whereas CXCR3 blockade abolished its beneficial effects. These findings show how poly(A:U) can elicit production of a range of chemokines by tumor cells that reinforce immunostimulatory or immunosuppressive effects. Optimizing the anticancer effects of TLR3 agonists may require manipulating these chemokines or their receptors.
-
Anticancer effects of Polyadenylic-Polyuridylic Acid (poly[A:U]) and uncoupling of chemokine receptor signaling: Role of CCR5 and CXCR3
Journal of Clinical Oncology, 2009Co-Authors: Rosa Conforti, Yannis Morel, Carine Paturel, Magali Terme, Sophie Viaud, Nathalie Chaput, F. Andre, Guido Kroemer, Laurence ZitvogelAbstract:3063 Background: Several tumor cells express toll-like receptors (TLRs) which constitute putative therapeutic targets. Methods: To dissect the clinical outcome of the host versus cell autonomous effects of the TLR3 agonist poly(A:U), we took advantage of two murine TLR3 expressing tumor models (melanoma and glioblastoma) that produced large amounts of CCL5 (a CCR5 ligand) and CXCL10 (a CXCR3 ligand) in response to the poly(A:U) and type I IFN in vitro and in vivo. We tested in vivo a triple combination based on vaccine against tumor antigens (V), chemotherapy (C), and TLR3 agonist (poly[A:U]) (T). Results: Single agents (V, C, or T) and combinations of two agents (VC, VT, or CT) failed to improve tumor progression. However, the sequential tritherapy (VCT) significantly retarded tumor growth and prolonged the survival of tumor-bearing C57BL/6 mice. The antitumor effects of VCT (immunochemotherapy) failed to be observed in nu/nu and TRIF-/- mice, indicating the contribution of T cells and TRIF-dependent sig...
Hei Cheul Jeung - One of the best experts on this subject based on the ideXlab platform.
-
Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up
Annals of oncology : official journal of the European Society for Medical Oncology, 2007Co-Authors: Hei Cheul Jeung, Yong Wha Moon, Sun Young Rha, Nae Choon Yoo, Jaekyung Roh, Sung Hoon Noh, Jin Sik Min, Bong Seog Kim, Hyun Cheol ChungAbstract:Abstract Background This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. Patients and methods From 1984 to 1989, patients who had D2–3 curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. Results A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2–T4a), and lymph node status (N0–N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. Conclusions These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.
-
phase iii trial of adjuvant 5 fluorouracil and adriamycin versus 5 fluorouracil adriamycin and Polyadenylic Polyuridylic Acid poly a u for locally advanced gastric cancer after curative surgery final results of 15 year follow up
Annals of Oncology, 2007Co-Authors: Hei Cheul Jeung, Yong Wha Moon, Sun Young Rha, Nae Choon Yoo, Sung Hoon Noh, Jin Sik Min, Bong Seog Kim, J K Roh, Hyun Cheol ChungAbstract:Abstract Background This phase III trial was to compare 5-fluorouracil (5-FU), adriamycin, and Polyadenylic–Polyuridylic Acid (poly A:U) against 5-fluorouracil plus adriamycin (FA) for operable gastric cancer. Patients and methods From 1984 to 1989, patients who had D2–3 curative resection were randomly assigned to receive chemotherapy or chemoimmunotherapy. Chemotherapy consisted of 12 mg/kg 5-FU every week for 18 months and 40 mg/m2 adriamycin every 3 weeks for 12 cycles. Chemoimmunotherapy consisted of FA plus 100 mg of poly A:U weekly for six cycles and was followed 6 months later by six weekly 50-mg booster injections. Results A total of 292 patients were enrolled. After excluding 12 ineligible patients, 142 and 138 patients were allocated to each treatment. Patients were balanced with prognostic variables: age, sex, tumor location, differentiation, degree of tumor invasion (T2–T4a), and lymph node status (N0–N2). During the 15-year follow-up, chemoimmunotherapy significantly prolonged overall (P = 0.013) and recurrence-free (P = 0.005) survivals compared with chemotherapy alone. The survival benefits were prominent in the subset of patients with T3/T4a, N2, or stage III. Treatments were generally well tolerated in both arms. Conclusions These results indicate a survival advantage of chemoimmunotherapy with a regimen of FA and poly A:U in curatively resected gastric adenocarcinoma.