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1. Saponin is Essential for the Isolation of Proteins and RNA from Biological Nanoparticles

Author

Brezgin, Sergey, Frolova, Anastasia, Bayurova, Ekaterina, Slatinskaya, Olga, Ponomareva, Natalia, Parshina, Evgeniia, Bochkova, Zhanna, Kachanov, Artyom, Tikhonov, Andrey, Kostyusheva, Anastasiya, Karandashov, Ivan, Demina, Polina, Latyshev, Oleg, Eliseeva, Olesja, Belikova, Maria, Pokrovsky, Vadim S., Gegechkory, Vladimir, Khaydukov, Evgeny, Silachev, Denis, Zamyatnin Jr, Andrey A., Maksimov, Georgy, Lukashev, Alexander, Gordeychuk, Ilya, Chulanov, Vladimir, and Kostyushev, Dmitry

Abstract

Extracellular vesicles (EVs), biomimetics, and other biological nanoparticles (BNs) produced from human cells are gaining increasing attention in the fields of molecular diagnostics and nanomedicine for the delivery of therapeutic cargo. In particular, BNs are considered prospective delivery vehicles for different biologics, including protein and RNA therapeutics. Moreover, EVs are widely used in molecular diagnostics for early detection of disease-associated proteins and RNA. Technical approaches for measuring biologics mostly originated from the field of EVs and were later adopted for other BNs, such as extracellular vesicle-mimetic nanovesicles, membrane nanoparticles (nanoghosts), and hybrid nanoparticles, with minimal modifications. Here, we demonstrate that BNs are highly resistant to protocols that severely underestimate the protein and RNA content of BNs, and provide the relevance of these data both for general BNs characterization and practical applications of CRISPR/Cas-based therapies. We demonstrate that the addition of saponin leads to an ∼2- to 7-fold enhancement in protein isolation and an ∼2- to 242-fold improvement in RNA recovery rates and detection efficiency. Differences in the proteolipid contents of BNs, measured by Raman and surface-enhanced Raman spectroscopy, correlate with their susceptibility to saponin treatment for cargo extraction. Finally, we develop a unified protocol using saponin to efficiently isolate proteins and RNA from the BNs. These data demonstrate that previously utilized protocols underestimate BN cargo contents and offer gold standard protocols that can be broadly adopted into the field of nanobiologics, molecular diagnostics, and analytical chemistry.

Published
2024
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2. Design, in silicostudies, synthesis, and in vitroanticancer assessment of new naphthylidene isoxazolidinedione derivatives

Author

Upadhyay, Neha, Tilekar, Kalpana, Oak, Aditi, Pokrovsky, Vadim S., and Subramanian Chelakara, Ramaa

Abstract

Cancer is the most destructive and fatal disease, representing an urgent medical challenge to the world. The discovery of a new anticancer candidate may help reduce or eliminate this alarming disease to a greater extent. On similar lines, in silico research was carried out on novel naphthylidene isoxazolidinedione derivatives that were logically conceived, synthesized, purified, and structurally characterized. In vitrobiological evaluation revealed the most active compound 4d with an inhibitory concentration of 42.87 µmagainst K562 and 47.42 µmon A549 cells. The anticancer activity of this naphthylidene isoxazolidinedione derivative was evident by cell cycle and apoptosis assays, which showed arrest of the G2/M phase (65.6%) of the K562 cells and induction of apoptosis with 21.47% apoptotic cells as compared to 0.2% of untreated cells, respectively.

Published
2024
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3. Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials

Author

Orkin, Chloe, Molina, Jean-Michel, Cahn, Pedro, Lombaard, Johannes, Supparatpinyo, Khuanchai, Kumar, Sushma, Campbell, Havilland, Wan, Hong, Teal, Valerie, Jin Xu, Zhi, Asante-Appiah, Ernest, Sklar, Peter, Teppler, Hedy, Lahoulou, Rima, Martins, Marcelo D, Cahn, Pedro E, Lopardo, Gustavo D, Porteiro, Norma, Bloch, Mark Theo, Baker, David Alfred, Roth, Norman, Moore, Richard J, Finlayson, Robert James, McMahon, James, Rieger, Armin, Zoufaly, Alexander, Schmied, Brigitte, Hartl, Sylvia, Zangerle, Robert, Smaill, Fiona, Walmsley, Sharon L, Conway, Brian, Rachlis, Anita, Smith, Graham H R, Perez Cortes, Carlos, Afani, Alejandro, Campos Barker, Maria Isabel E, Chahin Anania, Carolina Eugenia, Reyes, Marcelo J. Wolff, Gerstoft, Jan, Weis, Nina, Laursen, Alex Lund, Molina, Jean-Michel, Yazdanpanah, Yazdan, Cotte, Laurent, Raffi, Francois, Slama, Laurence, Morlat, Philippe, Girard, Pierre-Marie, Katlama, Christine, Rockstroh, Juergen K, Arasteh, Keikawus, Esser, Stefan, Stoehr, Albrecht, Stellbrink, Hans-Juergen, Stoll, Matthias, Schuermann, Dirk, Faetkenheuer, Gerd, Bogner, Johannes Richard, Lutz, Thomas, Baumgarten, Axel, Jaeger, Hans, Wiese, Carmen, Gori, Andrea, Migliorino, Guglielmo Marco, Coltan, Gabriel, Constandis, Felicia, Erscoiu, Simona M, Prisacariu, Liviu-Jany, Rugina, Sorin, Streinu-Cercel, Adrian, Pokrovsky, Vadim V, Zakharova, Natalia, Shuldyakov, Andrey Anatolyevich, Ryamova, Elena Pavlovna, Kulagin, Valeriy Viktorovich, Tsybakova, Olga Aleksandrovna, Orlova-Morozova, Elena, Nagimova, Firaya, Voronin, Evgeniy, Shimonova, Tatiana Evgenyevna, Kozyrev, Oleg Anatolyevich, Orrell, Catherine, Lombaard, Johannes Jurgens, Botes, Margaretha Elizabeth, de Jager, Marleen, Segorb, Joaquin Portilla, Gatell Artigas, Josep Maria, Mallolas Masferrer, Josep, Guillen, Santiago Moreno, Perez Elias, Maria Jesus, Arribas Lopez, Jose R, Puigmal, Eugenia Negredo, Podzamczer Palter, Daniel, Ortega, Frederico Pulido, Garcia, Jesus Troya, de los Santos Gil, Ignacio, Berenguer, Juan, Nelson, Mark Richard, Williams, Ian G, Johnson, Margaret A, Khoo, Saye, Schembri, Gabriel, Clarke, Amanda, Gompels, Mark, Fox, Julie Meriel, Lwanga, Julianne, Taylor, Steven John, Dockrell, David Harold, Kegg, Stephen, Hagins, Debbie P, Osiyemi, Olayemi O, Prelutsky, David James, Ramgopal, Moti N, Scarsella, Anthony J, Dretler, Robin, DeJesus, Edwin, Bettacchi, Christopher J, Sims III, James, Clay, Patrick G, Bellos, Nicholaos C, Thompson, Melanie A, Montero, Jose, McDonald, Cheryl K, Creticos, Catherine, Shamblaw, David, Terrelonge, Antonio E, Valdes, Martin, Tashima, Karen T, Robbins, William J, Elion, Richard A, Goldstein, Deborah, Slim, Jihad, Lalezari, Jacob Paul, Pushkin, Richard, Lalla-Reddy, Sujata N, Win, Sanda S, Ruane, Peter Jerome, Mills, Anthony Martin, Cade, Jerry L, Campo, Rafael, Dietz, Craig A, Hoffman-Terry, Margaret, Blick, Gary, Rubin, David Scott, Mayer, Cynthia, Rondon, Juan Carlos, Cook, Paul P, Daar, Eric, Kumar, Princy N, Swindells, Susan, Castro, Jose Guillermo, Morales-Ramirez, Javier O, Santiago, Lizette, Santana-Bagur, Jorge L, Vandekerckhove, Linos, Florence, Eric, De Wit, Stephane, Derdelinckx, Inge, Vandercam, Bernard, Belkhir, Leila, De Wet, Joseph, Lebouche, Bertrand, Trottier, Benoit, Longpre, Daniele, Szabo, Jason, LeBlanc, Roger P, Jensen, Werner, Gonzalez, Alvaro Rojas, Beltran, Carlos, Sussmann, Otto Alberto, Velez, Juan Diego, Onate, Jose Millan, Nielsen, Henrik, Degen, Olaf, Stephan, Christoph, Arathoon, Eduardo, Lopez, Rudy Manuel, Rojas Alvarado, Evelyn Michelle, Gonzalez Patzan, Luis Demetrio, Meija, Carlos R, Pinzon, Rodolfo, Parchment, Charles, Sthoeger, Zev, Chowers, Michal, Riesenberg, Klaris, Shahar, Eduardo, Levy, Itzchak, Quintero Perez, Nora Patricia, Andrade-Villanueva, Jaime Federico, Crabtree Ramirez, Brenda Eloisa, Rijnders, Bart, den Hollander, Jan G, Handy, Rupert, Morales, Nilo Bonifacio, Hidalgo, Jose Alfredo, Infante, Rosa Mercedes, Matos Prado, Eduardo Demetrio, Campos, Pablo E, Ticona Chaves, Eduardo Romulo, Pinedo, Yvett, Pacheco, Patricia, Maltez, Fernando Manuel, Cunha, Jose, Neves, Isabel, Serrao, Rosario, Melendez-Rivera, Ivan, Mendoza-Rodriguez, Rafael O, Maldonado-Rivera, Sandra, Ortiz-Lasanta, Grisell, Kizhlo, Svetlana, Freud, Hernando Knobel, Moreno, Jose Sanz, Mendez, Francisco Vera, Mohapi, Lerato, Mitha, Essack Aziz, Mahomed, Akbar Anvar, Fouche, Leon Frederik, Kaplan, Richard, Siddique, Naeem, Hoosen, Farzana, Rassool, Mohammed Siddique, Baraldi, Ezio, Calmy, Alexandra, Cavassini, Matthias, Fehr, Jan, Tsai, Hung-Chin, Lin, Hsi-Hsun, Huang, Chun-Kai, Ko, Wen-Chien, Lin, Yu-Hui, Chen, Su-Jung, Hung, Chien-Ching, Avihingsanon, Anchalee, Kiertiburanakul, Sasisopin, Ratanasuwan, Winai, Supparatpinyo, Khuanchai, Chetchotisakd, Ploenchan, Changpradub, Dhitiwat, Orkin, Chloe, Fox, Ashini, Winston, Alan, Ustianowski, Andrew, Yangco, Bienvenido G, Asmuth, David Michael, Vigil, Karen J, Berger, Daniel S, Bhatti, Laveeza, Campbell, Thomas, Casey, Kathleen K, Liu, Edward, Crofoot, Gordon E, Cunningham, Douglas, Feinberg, Judith, Fichtenbaum, Carl, Balamban Felizarta, Franco Antonio, Jefferson, Thomas T, Johnson, Marc Alexander, Lewis, Stanley T, Luque, Amneris E, Novak, Richard M, Sloan, Louis, Sweet, Donna E, Towner, William J, Zane, Ryan, Riedel, David J, Loftus, Richard Anton, Shon, Alyssa So Young, Mogyoros, Miguel, Tebas, Pablo, Scott, Mia Louise, Parenti, David M, and Inciarte Portillo, Alexy

Abstract

In two phase 3 trials for first-line therapy in adults with HIV-1, doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks. Here we report 192-week results from both studies.

Published
2024
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4. Clinical significance of HIV DNA in polymorphonuclear neutrophils from patients with HIV infection

Author

Gabrilovich, Dmitry I., Vassilev, Ventzislav, Nosikov, Valery V., Serebrovskaya, Lidia V., Ivanova, Larisa A., and Pokrovsky, Vadim V.

Subjects
Neutrophils -- Physiological aspects, HIV (Viruses) -- Genetic aspects, Pneumocystis carinii pneumonia -- Physiological aspects, Neutropenia -- Health aspects, Health
Abstract

DNA from the human immunodeficiency virus (HIV) was detected in the neutrophils of HIV-infected patients. Neutrophils are cells which play a part in immune responses. The breakdown of neutrophil activity is part of the process of infection with HIV. This decrease in functioning may play a role in the susceptibility of AIDS patients to diseases. Neutrophils were isolated from blood samples from 37 HIV-infected patients. HIV DNA was most often found in the neutrophils of patients who had symptoms of HIV infection. HIV DNA was found more often in patients with low blood levels of neutrophils. HIV DNA was also found more often in patients with Pneumocystis carinii pneumonia.

Published
1993

5. Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones

Author

Krasnovskaya, Olga O., Guk, Dmitry A., Naumov, Alexey E., Nikitina, Vita N., Semkina, Alevtina S., Vlasova, Kseniya Yu., Pokrovsky, Vadim, Ryabaya, Oksana O., Karshieva, Saida S., Skvortsov, Dmitry A., Zhirkina, Irina V., Shafikov, Radik R., Gorelkin, Petr V., Vaneev, Alexander N., Erofeev, Alexander S., Mazur, Dmitrii M., Tafeenko, Viktor A., Pergushov, Vladimir I., Melnikov, Mikhail Ya., Soldatov, Mikhail A., Shapovalov, Victor V., Soldatov, Alexander V., Akasov, Roman. A., Gerasimov, Vasily M., Sakharov, Dmitry A., Moiseeva, Anna A., Zyk, Nikolay V., Beloglazkina, Elena K., and Majouga, Alexander G.

Abstract

A series of 73 ligands and 73 of their Cu+2and Cu+1copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure–activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40–60 μm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1redox potential. A nontoxic in vivosingle-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2redox-active coordination compounds, 72kand 61k,was conducted.

Published
2020
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6. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial

Author

Molina, Jean-Michel, Squires, Kathleen, Sax, Paul E, Cahn, Pedro, Lombaard, Johan, DeJesus, Edwin, Lai, Ming-Tain, Rodgers, Anthony, Lupinacci, Lisa, Kumar, Sushma, Sklar, Peter, Hanna, George J, Hwang, Carey, Martin, Elizabeth Anne, Hagins, Debbie P., Osiyemi, Olayemi O., Prelutsky, David James, Ramgopal, Moti N., Scarsella, Anthony John, Dretler, Robin, DeJesus, Edwin, Bettacchi, Christopher J., Sims, James, Clay, Patrick G., Bellos, Nicholaos C., Thompson, Melanie A., Montero, Jose, McDonald, Cheryl K., Creticos, Catherine, Shamblaw, David, Mogyoros, Miguel, Terrelonge, Antonio E., Valdes, Martin, Tashima, Karen T., Robbins, William J., Felizarta, Franco Antonio, Elion, Richard A., Slim, Jihad, Win, Sandra S., Lalla-Reddy, Sujata N., Ruane, Peter Jerome, Mills, Anthony, Cade, Jerry L., Dietz, Craig A., Rubin, David Scott, Mayer, Cynthia, Rondon, Juan Carlos, Cook, Paul P., Daar, Eric, Kumar, Princy N., Swindells, Susan, Castro, Jose Guillermo, Melendez-Rivera, Ivan, Morales-Ramirez, Javier O., Santiago, Lizette, Santana-Bagur, Jorge L., Martins, Marcelo, Cahn, Pedro Enrique, Lopardo, Gustavo D., Porteiro, Norma, Bloch, Mark Theo, Baker, David Alfred, Roth, Norman, Moore, Richard James, Finlayson, Robert James, McMahon, James, Rieger, Armin, Zoufaly, Alexander, Hartl, Sylvia, Zangerle, Robert, Smaill, Fiona, Walmsley, Sharon L., Conway, Brian, Rachlis, Anita, Smith, Graham H.R., Perez, Carlos, Afani, Alejandro, Campos, Maria Isabel, Chahin, Carolina Eugenia, Wolff Reyes, Marcelo, Gerstoft, Jan, Weis, Nina, Laursen, Alex Lund, Molina, Jean-Michel, Yazdanpanah, Yazdan, Cotte, Laurent, Raffi, Francois, Morlat, Philippe, Girard, Pierre-Marie, Katlama, Christine, Rockstroh, Juergen K., Arasteh, Keikawus, Esser, Stefan, Stoehr, Albrecht, Stellbrink, Hans-Juergen, Stoll, Matthias, Schuermann, Dirk, Faetkenheuer, Gerd, Bogner, Johannes, Lutz, Thomas, Baumgarten, Axel, Jaeger, Hans, Gori, Andrea, Coltan, Gabriel, Constandis, Felicia, Erscoiu, Simona Manuela, Prisacariu, Liviu-Jany, Rugina, Sorin, Streinu-Cercel, Adrian, Pokrovsky, Vadim Valentinovich, Zakharova, Natalia V., Shuldyakov, Andrey Anatolyevich, Ryamova, Elena Pavlovna, Kulagin, Valeriy Viktorovich, Tsybakova, Olga Aleksandrovna, Orlova-Morozova, Elena, Nagimova, Firaya, Voronin, Evgeniy, Shimonova, Tatyana Evgenyevna, Kozyrev, Oleg Anatolyevich, Orrell, Catherine, Lombaard, Johannes Jurgens, de Jager, Marleen, Portilla Segorb, Joaquin, Mallolas, Josep, Perez Elias, Maria Jesus, Gatell, Josep M., Arribas Lopez, Jose Ramon, Negredo Puigmal, Eugenia, Podzamczer Palter, Daniel, Pulido Ortega, Federico, Troya Garcia, Jesus, De los Santos Gil, Ignacio, Berenguer Berenguer, Juan, Williams, Ian G., Johnson, Margaret A., Schembri, Gabriel, Clarke, Amanda, Gompels, Mark, Fox, Julie Meriel, Taylor, Steven John, Dockrell, David Harold, and Kegg, Stephen

Abstract

Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor that has shown non-inferior efficacy to ritonavir-boosted darunavir, with a superior lipid profile, in adults with HIV who were treatment naive at week 48 in the phase 3 DRIVE-FORWARD trial. Here we present the 96-week data for the study.

Published
2020
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7. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials

Author

Cahn, Pedro, Madero, Juan Sierra, Arribas, José Ramón, Antinori, Andrea, Ortiz, Roberto, Clarke, Amanda E, Hung, Chien-Ching, Rockstroh, Jürgen K, Girard, Pierre-Marie, Sievers, Jörg, Man, Choy, Currie, Alexander, Underwood, Mark, Tenorio, Allan R, Pappa, Keith, Wynne, Brian, Fettiplace, Anna, Gartland, Martin, Aboud, Michael, Smith, Kimberly, Cassetti, Lidia, David, Daniel, Figueras, Laura, Losso, Marcelo, Lopardo, Gustavo, Lupo, Sergio, Porteiro, Norma, Sánchez, Marisa, Bloch, Mark, Cooper, David, Finlayson, Robert, Kelleher, Anthony, Koh, Kenneth, Lewis, David, McMahon, James, Moore, Richard, Roth, Norman, Shields, Matthew, De Wit, Stephane, Florence, Eric, Goffard, Jean-Christophe, Demeester, Remy, Lacor, Patrick, Vandercam, Bernard, Vandekerckhove, Linos, Angel, Jonathan, Baril, Jean-Guy, Conway, Brian, De Pokomandy, Alexandra, Szabo, Jason, Walmsley, Sharon, Bouchaud, Olivier, Chidiac, Christian, Delobel, Pierre, Goujard, Cecile, Katlama, Christine, Molina, Jean-Michel, Pialoux, Gilles, Philibert, Patrick, Bogner, Johannes, Esser, Stefan, Krznaric, Ivanka, Lehmann, Clara, Spinner, Christoph, Stellbrink, Hans-Jurgen, Stephan, Christoph, Stoehr, Albrecht, Barchi, Enrico, Caramello, Pietro, Castelli, Francesco, Cattelan, Anna Maria, D'Arminio Monforte, Antonella, Di Biagio, Antonio, Di Perri, Giovanni, Gori, Andrea, Maggiolo, Franco, Menzaghi, Barbara, Migliorino, Guglielmo, Mussini, Cristina, Penco, Giovanni, Puoti, Massimo, Rizzardini, Giuliano, Gulminetti, Roberto, Lazzarin, Adriano, Quirino, Tiziano, Sighinolfi, Laura, Viale, Pierluigi, Amaya Tapia, Gerardo, Andrade Villanueva, Jaime, Granados Reyes, Enrique R, Perez Rios, Alma, Santoscoy Gomez, Mario, Den Hollander, Jan, Rijnders, Bart, Hidalgo, José A, Hercilla Vasquez, Luis, Illescas, Luis, Olczak, Anita, Mansinho, Kamal, Correia Pacheco, Patricia Paula, Teófilo, Eugénio, Saraiva da Cunha, Jose, Sarmento e Castro, Rui, Serrão, Rosário, Arbune, Manuela, Jianu, Cristian, Oprea, Anca, Preotescu, Liliana, Prisacariu, Liviu-Jany, Belonosova, Elena, Borodkina, Olga, Chernova, Oxana, Gankina, Natalia, Kizhlo, Svetlana, Kulagin, Valeriy, Kurina, Nadezhda, Nagimova, Firaya, Pokrovsky, Vadim, Ryamova, Elena, Voronin, Evgeny, Yakovlev, Alexey, Kaplan, Richard, Lee, Sun Hee, Kim, Shin-Woo, Kim, Sang-Il, Kim, Woo Joo, Antela Lopez, Antonio, Casado Osorio, Jose L, Castaño Carracedo, Manuel A, De Los Santos Gil, Ignacio, Estrada Perez, Vicente, Falco Ferrer, Vicenç, Force, Luis, Galinda Puerto, Maria Jose, Garcia Deltoro, Miguel, Gatell, Josep M, Goenaga Sanchez, Miguel A, González Cordón, Ana, Knobel, Hernando, Lopez Bernaldo de Quiros, Juan Carlos, Losa Garcia, Juan E, Masia, Mar, Montero-Alsonso, Marta, Ocampo Hermida, Antonio, Pasquau Liaño, Juan, Portilla Sogorb, Joaquin, Pulido Ortega, Federico, Rivera Roman, Antonio, Santos Fernandez, Jose Ramon, Torres Perea, Rafael, Troya Garcia, Jesus, Viciana Fernandez, Pompeyo, Calmy, Alexandra, Hauser, Christoph, Fehr, Jan, Cheng, Shu-Hsing, Ko, Wen-Chien, Lin, Hsi-Hsun, Lu, Po-Liang, Tseng, Yu-Ting, Wang, Ning-Chi, Wong, Wing-Wai, Yang, Chia-Jui, Arduino, Roberto, Benson, Paul, Berhe, Mezgebe, Bredeek, Fritz, Brinson, Cynthia, Campbell, Thomas, Crofoot, Gordon, Cunningham, Douglas, DeJesus, Edwin, Dretler, Robin, Eron, Joseph, Fife, Kenneth, Fichtenbaum, Carl, Flamm, Jason, Goldstein, Deborah, Gupta, Samir, Hagins, Debbie, Hoffman-Terry, Margaret, Jayaweera, Dushyantha, Kinder, Clifford, Klein, Daniel, McDonald, Cheryl, Mills, Anthony, Nahass, Ronald, Osiyemi, Olayemi, Overton, Edgar, Parks, David, Prelutsky, David, Ramgopal, Moti, Schrader, Shannon, Sha, Beverly, Simon, Gary, Sims, James, Skiest, Daniel, Slim, Jihad, Tashima, Karen, Thedinger, Blair, Gazzard, Brian, Fox, Julie, Johnson, Margaret, Kegg, Stephen, Khoo, Saye, Mazhude, Charles, Orkin, Chloe, Schembri, Gabriel, and Ustianowski, Andrew

Abstract

Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults.

Published
2019
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8. Amino Acid Degrading Enzymes and their Application in Cancer Therapy

Author

Pokrovsky, Vadim S., Chepikova, Olga E., Davydov, Denis Zh., Jr, Andrey A. Zamyatnin, Lukashev, Alexander N., and Lukasheva, Elena V.

Abstract

Background: Amino acids are essential components in various biochemical pathways. The deprivation of certain amino acids is an antimetabolite strategy for the treatment of amino acid-dependent cancers which exploits the compromised metabolism of malignant cells. Several studies have focused on the development and preclinical and clinical evaluation of amino acid degrading enzymes, namely L-asparaginase, L-methionine γ-lyase, L-arginine deiminase, L-lysine α-oxidase. Further research into cancer cell metabolism may therefore define possible targets for controlling tumor growth. Objective: The purpose of this review was to summarize recent progress in the relationship between amino acids metabolism and cancer therapy, with a particular focus on Lasparagine, L-methionine, L-arginine and L-lysine degrading enzymes and their formulations, which have been successfully used in the treatment of several types of cancer. Methods: We carried out a structured search among literature regarding to amino acid degrading enzymes. The main aspects of search were in vitro and in vivo studies, clinical trials concerning application of these enzymes in oncology. Results: Most published research are on the subject of L-asparaginase properties and it’s use for cancer treatment. L-arginine deiminase has shown promising results in a phase II trial in advanced melanoma and hepatocellular carcinoma. Other enzymes, in particular Lmethionine γ-lyase and L-lysine α-oxidase, were effective in vitro and in vivo. Conclusion: The findings of this review revealed that therapy based on amino acid depletion may have the potential application for cancer treatment but further clinical investigations are required to provide the efficacy and safety of these agents.

Published
2019
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9. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial

Author

Molina, Jean-Michel, Squires, Kathleen, Sax, Paul E, Cahn, Pedro, Lombaard, Johan, DeJesus, Edwin, Lai, Ming-Tain, Xu, Xia, Rodgers, Anthony, Lupinacci, Lisa, Kumar, Sushma, Sklar, Peter, Nguyen, Bach-Yen, Hanna, George J, Hwang, Carey, Martins, Marcelo, Cahn, Pedro Enrique, Lopardo, Gustavo D., Porteiro, Norma, Bloch, Mark Theo, Baker, David Alfred, Roth, Norman, Moore, Richard James, Finlayson, Robert James, McMahon, James, Rieger, Armin, Zoufaly, Alexander, Hartl, Sylvia, Zangerle, Robert, Smaill, Fiona, Walmsley, Sharon L., Conway, Brian, Rachlis, Anita, Smith, Graham H.R., Perez, Carlos, Afani, Alejandro, Campos Barker, Maria Isabel E., Chahin, Carolina Eugenia, Wolff Reyes, Marcelo, Gerstoft, Jan, Weis, Nina, Laursen, Alex Lund, Molina, Jean-Michel, Yazdanpanah, Yazdan, Cotte, Laurent, Raffi, Francois, Morlat, Philippe, Girard, Pierre-Marie, Katlama, Christine, Rockstroh, Juergen K., Arasteh, Keikawus, Esser, Stefan, Stoehr, Albrecht, Stellbrink, Hans-Juergen, Stoll, Matthias, Schuermann, Dirk, Faetkenheuer, Gerd, Bogner, Johannes, Lutz, Thomas, Baumgarten, Axel, Jaeger, Hans, Gori, Andrea, Coltan, Gabriel, Constandis, Felicia, Erscoiu, Simona Manuela, Prisacariu, Liviu-Jany, Rugina, Sorin, Streinu-Cercel, Adrian, Pokrovsky, Vadim Valentinovich, Zakharova, Natalia V., Shuldyakov, Andrey Anatolyevich, Ryamova, Elena Pavlovna, Kulagin, Valeriy Viktorovich, Tsybakova, Olga Aleksandrovna, Orlova-Morozova, Elena, Nagimova, Firaya, Voronin, Evgeniy, Shimonova, Tatyana Evgenyevna, Kozyrev, Oleg Anatolyevich, Orrell, Catherine, Lombaard, Johannes Jurgens, Botes, Margaretha Elizabeth, Portilla, Joaquin, Gatell, Josep Maria, Perez, Maria Jesus, Arribas, Jose Ramon, Negredo, Eugenia, Podzamczer, Daniel, Pulido, Federico, Troya, Jesus, De los Santos, Ignacio, Berenguer, Juan, Williams, Ian G., Johnson, Margaret A., Schembri, Gabriel, Clarke, Amanda, Gompels, Mark, Fox, Julie Meriel, Taylor, Steven John, Kegg, Stephen, Hagins, Debbie P., Osiyemi, Olayemi O., Prelutsky, David James, Ramgopal, Moti N., Dretler, Robin, DeJesus, Edwin, Sloan, Louis, Lewis, Stanley T., Clay, Patrick G., Bellos, Nicholaos C., Thompson, Melanie A., Montero, Jose, McDonald, Cheryl K., Creticos, Catherine, Shamblaw, David, Terrelonge, Antonio E., Valdes, Martin, Tashima, Karen T., Robbins, William J., Felizarta, Franco Antonio, Elion, Richard A., Slim, Jihad, Lalezari, Jacob Paul, Lalla-Reddy, Sujata N., Ruane, Peter Jerome, Mills, Anthony, Cade, Jerry L., Campo, Rafael E., Dietz, Craig A., Blick, Gary, Mayer, Cynthia, Rondon, Juan Carlos, Cook, Paul P., Daar, Eric, Kumar, Princy N., Swindells, Susan, Castro, Jose Guillermo, Morales-Ramirez, Javier O., Santiago, Lizette, and Santana-Bagur, Jorge L.

Abstract

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection.

Published
2018
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10. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study

Author

Orrell, Catherine, Hagins, Debbie P, Belonosova, Elena, Porteiro, Norma, Walmsley, Sharon, Falcó, Vicenç, Man, Choy Y, Aylott, Alicia, Buchanan, Ann M, Wynne, Brian, Vavro, Cindy, Aboud, Michael, Smith, Kimberly Y, Cahn, Pedro Enrique, Cassetti, Lidia Isabel, Porteiro Barreira, Norma, Angel, Jonathan Benjamin, de Pokomandy, Alexandra, Harris, Marianne, Rachlis, Anita R., Walmsley, Sharon L., Allavena, Clotilde, Bouchaud, Oliver, Gatey, Caroline, Rami, Agathe, Casari, Salvatore, Di Perri, Giovanni, Lazzarin, Adriano, Maggiolo, Franco, Penco, Giovanni, Quirino, Tiziana, Rizzardini, Giuliano, Andrade-Villanueva, Jaime-Federico, Sierra-Madero, Juan G., Branco, Teresa, Serrao, Rosario, Teofilo, Eugenio JR., Melendez-Rivera, Ivan, Santiago, Lizette, Zorrilla, Carmen D., Belonosova, Elena, Chernova, Oksana E., Pokrovsky, Vadim, Rakhmanova, Aza Gasanovna, Tsybakova, Olga, Voronin, Eugene, Orrell, Catherine, Vally, Tasneem, Farisani, Livhuwani ML., Sebopa, Boitumelo Lucrecia, Barros, Carlos Aguado, Cano Sánchez, Alfredo, Castaño, Manuel, Falcó Ferrer, Vicens, González García, Juan J., Hernandez-Quero, Jose, Negredo Puigmal, Eugenia, Pérez Elías, María Jesús, Podzamczer Palter, Daniel, Portilla, Joaquin Sogorb, Viciana Fernández, Pompeyo, Manosuthi, Weerawat, Ruxrungtham, Kiat, Dockrell, David H., Hay, Phillip E., Johnson, Margaret A., Mackie, Nicola E., Orkin, Chloe M., Taylor, Steve, Bhatti, Laveeza, Brar, Indira, Brennan, Robert Owen, Cade, Jerry L., Casanas, Beata, Casey, Kathleen, Cunningham, Douglas, DeJesus, Edwin, Dietz, Craig, Dretler, Robin Henry, Eron, Joseph J., Felizarta, Franco Antoni B., Fife, Kenneth H., Hagins, Debbie P., Hoffman-Terry, Margaret, Jain, Mamta, Johnson, Marc Alexander, Kinder, Clifford A., Kumar, Princy N., Lewis, Stanley T., McDonald, Cheryl Kay, Meza, Armando D., Mounzer, Karam C., Newman, Cheryl L., Osiyemi, Olayemi O., Poblete, Ronald, Presti, Rachel M., Ramgopal, Moti, Rosenstock, Joel, Samuel, Rafik, Sandkovsky, Uriel Sebastian, Shon, Alyssa So Young, Skiest, Daniel J., Sloan, Louis M., Small, Catherine B., Tebas, Pablo, and Van Dam, Cornelius N.

Abstract

Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1.

Published
2017
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12. Enzymatic properties and anticancer activity of L-lysine -oxidase from Trichodermacf. aureovirideRifai BKMF-4268D

Author

Pokrovsky, Vadim S., Treshalina, Helen M., Lukasheva, Elena V., Sedakova, Ludmila A., Medentzev, Alexander G., Arinbasarova, Anna Yu., and Berezov, Temirbolat T.

Abstract

L-Lysine -oxidase (LO) from a novel Trichoderma strain: Trichodermacf. aureovirideRifai shows favorable biochemical and kinetic properties (Kmfor L-lysine of 17.9 µmoll, optimum pH 8.0, high stability) and significant antiproliferative activity both in vitroand in vivo. The molecular weight of LO was determined to be 115–116 kDa; the active dimer consists of two identical 57–58 kDa subunits. LO shows considerable cytotoxicity against the following tumor cell lines: K562, LS174T, HT29, SCOV3, PC3, and MCF7, with the inhibition concentration (IC50) ranging from 3.0×10–6to 7.8×10–2Uml (3.2×10–8to 8.2×10–4mgml). Two human colon cancer xenografts HCT116 and LS174T and breast adenocarcinoma T47D implanted subcutaneously into Balbc nude mice showed high sensitivity to LO with a TCof 12, 37, and 36, respectively (P<0.05). The antitumor efficacy of LO was observed in the absence of pronounced morbidity or toxicity in vivo. Taken together, these data suggest that LO may be considered as an effective anticancer agent for the treatment of solid tumors in vivo. This study presents promising data on the possible application of LO in clinical oncology for patients with colorectal cancer.

Published
2013
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13. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study

Author

Raffi, Francois, Rachlis, Anita, Stellbrink, Hans-Jürgen, Hardy, W David, Torti, Carlo, Orkin, Chloe, Bloch, Mark, Podzamczer, Daniel, Pokrovsky, Vadim, Pulido, Federico, Almond, Steve, Margolis, David, Brennan, Clare, and Min, Sherene

Abstract

Dolutegravir (S/GSK1349572) is a once-daily HIV integrase inhibitor with potent antiviral activity and a favourable safety profile. We compared dolutegravir with HIV integrase inhibitor raltegravir, as initial treatment for adults with HIV-1.

Published
2013
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14. Unboosted atazanavir-based therapy maintains control of HIV type-1 replication as effectively as a ritonavir-boosted regimen

Author

Ghosn, Jade, Carosi, Giampiero, Moreno, Santiago, Pokrovsky, Vadim, Lazzarin, Adriano, Pialoux, Gilles, Sanz-Moreno, Jose, Balogh, Agnes, Vandeloise, Eric, Biguenet, Sophie, Leleu, Ghislaine, and Delfraissy, Jean-Francois

Abstract

Background Triple combination therapy based on a ritonavir (RTV)-boosted protease inhibitor plus two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) has improved outcomes in HIV type-1 (HIV-1)-infected patients. For patients unable to tolerate these regimens, alternative therapeutic approaches are needed.Methods We report a comparative, open-label study in treatment-naive patients who underwent initial induction treatment with a triple combination including RTV-boosted atazanavir (ATV; 300/100 mg once daily). Patients who achieved an HIV-1 viral load <50 copies/ml after the induction period were then randomized in the maintenance phase either to continue on current treatment or to switch to unboosted ATV 400 mg once daily (plus two NRTIs unchanged).Results A total of 252 patients entered the induction phase, of whom 172 were eligible for randomization in the maintenance phase (ATV/RTV n=85 and ATV n=87). The unboosted ATV regimen demonstrated non-inferior efficacy to the ATV/RTV regimen with 78% and 75% of patients, respectively, maintaining virological suppression (HIV-1 RNA <50 copies/ml) up to week 48 after randomization (difference estimate 2.9, 95% confidence interval -9.8–15.5). Time to virological failure and change from the end of the induction phase in mean CD4+T-cell counts were also similar between the treatment arms. Although both regimens were well-tolerated, unboosted ATV was associated with fewer adverse events, fewer total bilirubin abnormalities and an improved lipid profile compared with ATV/RTV.Conclusions An HIV-1 combined treatment regimen based on unboosted ATV is a feasible treatment option for patients with established virological control who are unable to tolerate triple combination therapy including ATV/RTV.

Published
2010
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15. Temporal trends in the HIV‐1 epidemic in Russia: Predominance of subtype A

Author

Bobkov, Aleksei F., Kazennova, Elena V., Selimova, Ludmila M., Khanina, Tatyana A., Ryabov, Grigory S., Bobkova, Marina R., Sukhanova, Anna L., Kravchenko, Aleksei V., Ladnaya, Natalia N., Weber, Jonathan N., and Pokrovsky, Vadim V.

Abstract

During the period 1996–1997, three highly homogeneous variants of HIV‐1 were identified, circulating among injecting drug users (IDUs) in the former Soviet Union republics. One of these belonged to HIV‐1 genetic subtype A (IDU‐A), another belonged to HIV‐1 genetic subtype B (IDU‐B) and the third was a recombinant between the first two variants (CRF03_AB). However, since 1997, the HIV‐1 epidemic has affected an increasing number of geographic regions in Russia. This study was undertaken to survey the prevailing genetic variants and to estimate the current proportions of these three HIV‐1 genetic subtypes in Russia. Blood samples were taken in 1999–2003 from 1090 HIV‐infected individuals and analysed by gag/envHMA. The IDU‐A variant was found to be the majority variant (89.7–100%) in 44 of 45 regions of the Russian Federation studied. The IDU‐A variant was also found to spreading rapidly through heterosexual transmission in 1999–2003 (30/34, 88%). CRF03_AB predominates in the Kaliningrad region only (28/29, 96.6%). The IDU‐B variant is currently of minor importance in the IDU epidemic but other European subtype B variants predominate among men having sex with men (18/18, 100%). Sequence analysis of the envV3 encoding regions derived from HIV‐1 infected individuals in Yekaterinburg (the main centre of the HIV‐1 epidemic in Russia in 2002–2003) showed that the IDU‐A variant is still highly homogeneous. The mean pairwise nucleotide distance (n = 9) was 2.89 ± 1.14 (range 1.36–6.14). However, the mean genetic distance between each sequence within the samples collected from the Yekaterinburg IDU‐A variant subset and the IDU‐A consensus is 2.51 ± 1.06 (range 1.36–4.66) and considerably higher than in South Russia in 1996 (0.79 ± 0.51, range 0.38–1.90). The current HIV‐1 epidemic in Russia is almost entirely caused by a highly homogeneous A‐subtype strain, which will influence vaccine development strategies and must be taken into account in the quality control of molecular tests for the diagnosis of HIV‐1. J. Med. Virol. 74:191–196, 2004. © 2004 Wiley‐Liss, Inc.

Published
2004
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16. An HIV Type 1 Subtype A Strain of Low Genetic Diversity Continues to Spread among Injecting Drug Users in Russia: Study of the New Local Outbreaks in Moscow and Irkutsk

Author

Bobkov, Aleksei, Kazennova, Elena, Khanina, Tatyana, Bobkova, Marina, Selimova, Ludmila, Kravchenko, Aleksei, Pokrovsky, Vadim, and Weber, Jonathan

Abstract

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among injecting drug users (IDUs) in the former Soviet Union republics. In 1999, the two largest local IDU outbreaks of HIV-1 infection in the Russian Federation were registered in the Moscow and Irkutsk regions, where 13,004 HIV-1 cases were identified (44% of the total number of HIV-1 infections in Russia in 1999). To study the prevailing genetic variants and to estimate the genetic diversity of HIV-1 in these outbreaks, 60 samples from Moscow (n = 36) and from Irkutsk (n = 24) were analyzed using the gag/env heteroduplex mobility assay, and the env gp120 V3 encoding regions obtained from 23 individuals were sequenced. Both virus populations were highly homogeneous (the means of pairwise nucleotide distance were 1.75 ± 0.83 and 2.35 ± 1.59 for Irkutsk and Moscow, respectively), and similar to the subtype A viruses obtained earlier from IDUs in the former Soviet Union. The subtype A HIV-1 variant thus dominates in the largest HIV-1 outbreaks among IDUs in the Russian Federation.

Published
2001
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17. An AB Recombinant and Its Parental HIV Type 1 Strains in the Area of the Former Soviet Union: Low Requirements for Sequence Identity in Recombination

Author

Liitsola, Kirsi, Holm, Kirsi, Bobkov, Aleksei, Pokrovsky, Vadim, Smolskaya, Tatjana, Leinikki, Pauli, Osmanov, Saladin, and Salminen, Mika

Abstract

In the former Soviet Union (SU) increasing numbers of HIV-1 infections among injecting drug users (IDU) have been reported, especially in the Ukraine. The main subtype transmitted among the IDUs seems to be subtype A, but limited numbers of subtype B cases have also been reported. In Kaliningrad, Russia, an AB recombinant strain was earlier shown to be responsible for the local outbreak. Here we describe the genetic relationship of HIV-1 strains circulating among IDUs in the former SU. For subtype A and the AB recombinant strains nearly full-length genomes were sequenced, and for one subtype B strain the entire envelope gene was cloned. The relationship between the AB recombinant strain and the subtype A and subtype B strains and the mosaic structure of the recombinant was studied by phylogenetic analysis. Ukrainian A and B strains were shown to be the probable parental viruses of the Kaliningrad AB recombinant strain. In the envelope gene the recombination breakpoint could also be precisely mapped to a region of similarity of only 14 base pairs. This suggests that only short stretches of absolute sequence identity may be needed for efficient RNA recombination between HIV-1 subtypes.

Published
2000
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18. Clinical Significance of Neutrophil Functional Activity in HIV Infection

Author

Gabrilovich, Dmitry, Ivanova, Larisa, Serebrovskaya, Lidia, Shepeleva, Galina, and Pokrovsky, Vadim

Abstract

Functional activity of polymorphonuclear neutrophils (PMN) was tested in 63 HIV-1 infected patients. PMN chemiluminescence (CL) and intracellular enzyme activity were both depressed in patients at all stages of infection, though this depression was more pronounced in AIDS patients. We found no such depression when cells were incubated in the presence of autologous serum. PMN phagocytosis in the presence of serum was reduced in the early stage of HIV infection (LAS) but was in the normal range in AIDS patients. No differences in PMN functional activity between patients with LAS and those with dermatological disorders were found. The appearance of recurrent upper respiratory tract infection was associated with reduced PMN CL. The most pronounced changes in PMN activity were observed in patients with severe, recurrent bacterial pneumonia and Pneumocystis carinii pneumonia. A lower level of PMN activity was found in patients with infection progressing rapidly towards AIDS than in patients with a relatively stable course of infection. Thus, PMN CL may be regarded as a predictive factor for the progression of HIV infection.

Published
1994
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19. Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate

Author

Machulkin, Aleksei E., Uspenskaya, Anastasia A., Zyk, Nikolay U., Nimenko, Ekaterina A., Ber, Anton P., Petrov, Stanislav A., Polshakov, Vladimir I., Shafikov, Radik R., Skvortsov, Dmitry A., Plotnikova, Ekaterina A., Pankratov, Andrei A., Smirnova, Galina B., Borisova, Yulia A., Pokrovsky, Vadim S., Kolmogorov, Vasilii S., Vaneev, Alexander N., Khudyakov, Alexander D., Chepikova, Olga E., Kovalev, Sergey, Zamyatnin Jr, Andrey A., Erofeev, Alexander, Gorelkin, Petr, Beloglazkina, Elena K., Zyk, Nikolay V., Khazanova, Elena S., and Majouga, Alexander G.

Abstract

Prostate cancer is the second most common type of cancer among men. Its main method of treatment is chemotherapy, which has a wide range of side effects. One of the solutions to this challenge is targeted delivery to prostate cancer cells. Here we synthesized a novel small-molecule PSMA-targeted conjugate based on the monomethyl auristatin E. Its structure and conformational properties were investigated by NMR spectroscopy. Cytotoxicity, intracellular reactive oxygen species induction, and stability under liver microsomes and P450-cytochrome species were investigated for this conjugate. The conjugate demonstrated 77–85% tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared with a 37% inhibition level on PC-3 (PSMA (−)) xenografts, in a single dose of 0.3 mg/kg and a sufficiently high therapeutic index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics have shown that the synthesized conjugate is a promising potential agent for the chemotherapy of prostate cancer.

Published
2021
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20. Mechanisms of the Antiproliferative and Antitumor Activity of Novel Telomerase–Carbonic Anhydrase Dual-Hybrid Inhibitors

Author

Plyasova, Anna A., Berrino, Emanuela, Khan, Irina I., Veselovsky, Alexander V., Pokrovsky, Vadim S., Angeli, Andrea, Ferraroni, Marta, Supuran, Claudiu T., Pokrovskaya, Marina V., Alexandrova, Svetlana S., Gladilina, Yulia A., Sokolov, Nikolay N., Hilal, Abdullah, Carta, Fabrizio, and Zhdanov, Dmitry D.

Abstract

Human (h) telomerase (TL; EC 2.7.7.49) plays a key role in sustaining cancer cells by means of elongating telomeric repeats at the 3′ ends of chromosomes. Since TL-inhibitor (TI) stand-alone cancer therapy has been proven to be remarkably challenging, a polypharmacological approach represents a valid alternative. Here we consider a series of compounds able to inhibit both hTL and the tumor-associated carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII. Compounds 7and 9suppressed hTL activity in both cell lysates and human colon cancer cell lines, and prolonged incubation with either 7or 9resulted in telomere shortening, cell cycle arrest, replicative senescence, and apoptosis. Enzyme kinetics showed that 7and 9are mixed-type inhibitors of the binding of DNA primers and deoxynucleoside triphosphate (dNTP) to the TL catalytic subunit hTERT, which is in agreement with docking experiments. Compound 9showed antitumor activity in Colo-205 mouse xenografts and suppressed telomerase activity by telomere reduction.

Published
2021
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21. Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

Author

Machulkin, Aleksei E., Shafikov, Radik R., Uspenskaya, Anastasia A., Petrov, Stanislav A., Ber, Anton P., Skvortsov, Dmitry A., Nimenko, Ekaterina A., Zyk, Nikolay U., Smirnova, Galina B., Pokrovsky, Vadim S., Abakumov, Maxim A., Saltykova, Irina V., Akhmirov, Rauf T., Garanina, Anastasiia S., Polshakov, Vladimir I., Saveliev, Oleg Y., Ivanenkov, Yan A., Aladinskaya, Anastasiya V., Finko, Alexander V., Yamansarov, Emil U., Krasnovskaya, Olga O., Erofeev, Alexander S., Gorelkin, Petr V., Dontsova, Olga A., Beloglazkina, Elena K., Zyk, Nikolay V., Khazanova, Elena S., and Majouga, Alexander G.

Abstract

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitroevaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivobiodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5and PSMA-SulfoCy7conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7demonstrated the absence of any explicit toxicity up to 87.9 mg/kg.

Published
2021
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22. Human Immunodeficiency Virus Type 1 in Illicit-Drug Solutions Used Intravenously Retains Infectivity

Author

Bobkov, Aleksei F., Selimova, Ludmila M., Khanina, Tatyana A., Zverev, Sergey Y., Pokrovsky, Vadim V., Weber, Jonathan N., Bobkov, Eugene N., and Rylkov, Andrey V.

Abstract

ABSTRACTThe stability of the human immunodeficiency virus type 1 (HIV-1) strain IIIB in drug solutions was studied. The data demonstrate that HIV-1 infectivity can be retained in drug solutions (e.g. , heroin, “Khanka,” and “Vint”) for long periods of time. This fact must be taken into account when designing health education programs for the prevention of HIV and AIDS in Eastern Europe.

Published
2005
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23. An HIV Type 1 Subtype A Outbreak among Injecting Drug Users in Kazakhstan

Author

Bobkov, Aleksei F., Kazennova, Elena V., Sukhanova, Anna L., Bobkova, Marina R., Pokrovsky, Vadim V., Zeman, Victoria V., Kovtunenko, Natalia G., and Erasilova, Isidora B.

Abstract

Kazakhstan experienced the start of the HIV-1 outbreak among intravenous drug users (IDUs) in 1997. To characterize genetically HIV-1 strains circulating in this country, peripheral blood mononuclear cells (PBMCs) DNA samples (1999–2002) derived from HIV-infected IDUs and their sexual partners in Pavlodar (n = 19), Shymkent (n = 6), and Qaraghandy (n = 18) regions were analyzed by the gag/env heteroduplex mobility assay (HMA). The 366-bp proviral env gene fragments encoding the gp120 C2–V3 region obtained from 16 individuals were sequenced. The results of HMA revealed that all 43 HIV-1 strains studied belonged to gag/env subtype A. The nucleotide sequence analysis showed a marked genetic homogeneity with the mean genetic distance being 3.63 ± 2.39 (range 0.00–12.13). The mean genetic distance between each sequence within the Kazakhstan set and the East-European IDU subtype A consensus was 2.94 ± 1.92 (range 0.79–8.48). The data presented thus confirm the spreading of the same IDU subtype A virus in the former Soviet Union.

Published
2004
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