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1. Transcriptomic classification of diffuse large B-cell lymphoma identifies a high-risk activated B-cell-like subpopulation with targetable MYC dysregulation

Author

Stokes, Matthew E., Wenzl, Kerstin, Huang, C. Chris, Ortiz, María, Hsu, Chih-Chao, Maurer, Matthew J., Stong, Nicholas, Nakayama, Yumi, Wu, Lei, Chiu, Hsiling, Polonskaia, Ann, Danziger, Samuel A., Towfic, Fadi, Parker, Joel, King, Rebecca L., Link, Brian K., Slager, Susan L., Sarangi, Vivekananda, Asmann, Yan W., Novak, Joseph P., Sudhindra, Akshay, Ansell, Stephen M., Habermann, Thomas M., Hagner, Patrick R., Nowakowski, Grzegorz S., Cerhan, James R., Novak, Anne J., and Gandhi, Anita K.

Published
2024
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2. Transcriptomic classification of diffuse large B-cell lymphoma identifies a high-risk activated B-cell-like subpopulation with targetable MYC dysregulation

Author

Matthew E. Stokes, Kerstin Wenzl, C. Chris Huang, María Ortiz, Chih-Chao Hsu, Matthew J. Maurer, Nicholas Stong, Yumi Nakayama, Lei Wu, Hsiling Chiu, Ann Polonskaia, Samuel A. Danziger, Fadi Towfic, Joel Parker, Rebecca L. King, Brian K. Link, Susan L. Slager, Vivekananda Sarangi, Yan W. Asmann, Joseph P. Novak, Akshay Sudhindra, Stephen M. Ansell, Thomas M. Habermann, Patrick R. Hagner, Grzegorz S. Nowakowski, James R. Cerhan, Anne J. Novak, and Anita K. Gandhi

Subjects
Science
Abstract

Abstract Immunochemotherapy has been the mainstay of treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL) yet is inadequate for many patients. In this work, we perform unsupervised clustering on transcriptomic features from a large cohort of ndDLBCL patients and identify seven clusters, one called A7 with poor prognosis, and develop a classifier to identify these clusters in independent ndDLBCL cohorts. This high-risk cluster is enriched for activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations. We compare and contrast our methodology with recent DLBCL classifiers to contextualize our clusters and show improved prognostic utility. Finally, using pre-clinical models, we demonstrate a mechanistic rationale for IKZF1/3 degraders such as lenalidomide to overcome the low immune infiltration phenotype of A7 by inducing T-cell trafficking into tumors and upregulating MHC I and II on tumor cells, and demonstrate that TCF4 is an important regulator of MYC-related biology in A7.

Published
2024
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3. Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study

Author

Anton V. Snegovoy, Inessa B. Kononenko, Irina M. Radiukova, Svetlana A. Orlova, Alexander V. Sultanbaev, Daria M. Dubovichenko, Aleksandr S. Dergunov, Aleksandra F. Saidullaeva, Nadezhda N. Repina, Iuliia A. Gronskaia, Elena I. Rossokha, Tatiana V. Starostina, Oksana V. Akimova, Iuliia A. Vasil'eva, Zarina A. Godzhieva, Ol'ga Iu. Garanina, Khava I. Gorchkhanova, Iuliia S. Machekhina, Aleksandra S. Gracheva, Anastasiia E. Danilova, Tat'iana N. Dmitrakova, Vadim N. Dmitriev, Marina V. Dmitrochenko, Olga V. Dylinova, Viktoriia O. El'kova, Alla V. Zhelezniak, Irina V. Zubova, Aleksandr N. Ivanov, Liliia P. Kaleikina, Iuliia V. Komoza, Dmitrii N. Korolev, Liudmila N. Lebedeva, Andrei A. Lebedinets, Naira N. Mamedguseinova, Valeriia S. Miagkova, Elena I. Matiushina, Kristina V. Narovenkova, Valentina M. Nikolaeva, Denis V. Novikov, Galina E. Polonskaia, Olesia V. Rebrina, Mariia A. Safronova, Anna S. Semenova, Inessa A. Semenova, Roman A. Skotnikov, Ekaterina P. Solov'eva, Anna N. Tat'ianenko, Antonina A. Teterich, Vladimir N. Timin, Irina A. Tolmacheva, Iana A. Tiugina, Aleksandra V. Khodkevich, Fatima V. Tsarakhova, Iana S. Chapko, Margarita M. Shegurova, Nadezhda R. Shakurova, Anna I. Shalina, Elena A. Shumilkina, Daria V. Iakuba, Tansylu M. Ibragimova, Polina S. Feoktistova, Irina V. Sorokina, Anna M. Berezina, Polina V. Kiseleva, Olga N. Mironenko, and Oxana N. Prosianikova

Subjects
myeloproliferative relative dose-intensity, neutropenia, granulocyte colony-stimulating factors, chemotherapy, malignancies, empegfilgrastim, extimia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aim. To evaluate the effectiveness and safety of Extimia® (empegfilgrastim, JSC "BIOCAD") in reducing the frequency, duration of neutropenia, the incidence of febrile neutropenia (FN) and infections caused by FN in patients with solid tumors receiving myelosuppressive therapy. Materials and methods. The paper presents the final results of a multicenter prospective observational post-marketing study of the safety and effectiveness of Extimia® (empegfilgrastim) in patients with solid tumors receiving cytotoxic therapy. For the primary prevention of FN, all patients received empegfilgrastim at 7.5 mg subcutaneously once per course of chemotherapy (CT) 24 hours after the end of CT administration. The primary endpoint included an assessment of the relative dose-intensity (RDI) of the CT courses administered. The endpoints of interest included the assessment of the RDI of CT courses by nosology and CT regimen, the frequency of dose-limiting neutropenia, and the incidence of all adverse events (AEs) in patients who received at least one dose of the study medication, including serious AEs. Results. From February 2021 to December 2022, 3218 patients with various malignancies were included in 41 study centers of the Russian Fede- ration. Of these, 3217 (99.97%) patients received at least one dose of the study drug, and 2663 (82.8%) patients were included in the RDI evaluation population according to the study protocol. The mean age in this group was 56.9 (18–84) years. RDI ≥85% was achieved in 2,415 (90.7%) patients. The mean RDI was 96.2%, with a median of 100%. FN risk factors were present in 1216 (45.7%) patients, with age ≥65 years being the most common risk factor at 761/2663 (28.6%). It should be noted that in patients younger than 65 years, the RDI was 91.5%, and in elderly patients (≥65 years) 88.7%. Dose-limiting neutropenia was reported in 19 (0.7%) patients. There were 74 cases of grade 3–4 AEs (according to CTCAE v.5) in 59 (1.8%) patients. The most common were neutropenia, anemia, and diarrhea in 19 (0.7%), 7 (0.2%), and 6 (0.2%) patients, respectively. Serious AEs were reported in 17 patients (0.5%). Conclusion. Primary prophylaxis of FN with long-acting granulocyte colony-stimulating factor empegfilgrastim effectively maintains RDI in various nosological and therapeutic groups of patients with different CT regimens in real-world clinical practice.

Published
2024
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4. Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi studyResearch in context

Author

Ragda Abdalla-Aslan, Pierluigi Bonomo, Dorothy Keefe, Nicole Blijlevens, Katrina Cao, Yin Ting Cheung, Eduardo Rodrigues Fregnani, Robert Miller, Judith Raber-Durlacher, Joel Epstein, Ysabella Van Sebille, Elisa Kauark-Fontes, Abhishek Kandwal, Emma McCurdy-Franks, Joel Finkelstein, Victoria McCarvell, Yehuda Zadik, Giulia Ottaviani, Rui Amaral Mendes, Caroline Margina Speksnijder, Hannah Rose Wardill, Paolo Bossi, Alexa Laheij, Arghavan Tonkaboni, Jacqui Scott, Rania Abasaeed, Adel Kauzman, Adriana Do Socorro Lima Flato, Adwaita Gore, Anne-Marie Hardman, Agnes Horvath, Allan Hovan, Aisha Al-Jamaei, Aya koizumi, Alan Santos-Silva, Alessandra Majorana, Alexandre Giannini, Aléxia Teixeira, Muhammad Ali Shazib, Alison Melvin, Aluísio Miranda Filho, Amanda Gruza, Amber Brown-Dahl, Amit Harilall, Amr El Maghrabi, Ana Andabak Rogulj, Ana Raphaela Curvo, Ana Laura Soares, Andrea Stringer, Andréa Moreira, Andy Kurtzweil, Angelyn Salaberry, Anne Blazy, Anne Margrete Gussgard, Anne Marie Lynge Pedersen, Annette Freidank, Anura Ariyawardana, Adrian Ramseier, Jann Arends, Ariel Blanchard, Adriana Sesti Paz, Angela Thermann, Augusto Poropat, Azael Freites-Martinez, Abdul Rahman Al-Azri, Bente Brokstad Herlofson, Sitaraman BalajiSubramanian, Barbara Ballantyne, Kivanc Bektas-Kayhan, Bengt Hasséus, Benjamin Kaffenberger, Bernar Benites, Bernice Kwong, Beth Test, Fernando Chiantia, Bo Pettersson, Bomi Framroze, Božana Lončar Brzak, Brittany Dulmage, Sorin Buga, Caroline Spekssnijder, Carlton Brown, Antonio Carlos Moura de Melo, Ana Carolina Ribeiro, Caroline Silva, Caroline Fulop, Carryn Anderson, Catherine Flaitz, Cathy Massoud, Cesar Migliorati, Callie Gross, Chiara Gandini, Charles Loprinzi, Charlotte de Mooij, Catherine Hong, Ying Chu Choi, Maria Choy, Christine Boers-Doets, Leonard Schmeel, Cibele Nagano, Maria Coeli Franco, Courtney Subramaniam, Carolyn Patrick, Catherine Poh, Cristina Neuenschwander, Cesar Virgen, Dorothea Riesenbeck, Dale Weaver, Daniel Cohen Goldemberg, Daniel Sundaresan, Daniela Nunes, Danyel Perez, Daphine Travassos, David Yang, Daniela Ribeiro, Dean Kolbinson, Deborah Buick, Deborah Saunders, Juliane De Bortolli, Deepika Chugh, Denise Markstrom, Denise Travassos, Dianna Weikel, Dimitra Galiti, Dinusha Peiris, Fedja Djordjevic, Pankaj Singhai, Douglas Peterson, Douglas Fonseca, Doreen Pon, Iuliia Kovalenko, Aleksandra Polonskaia, Rogério Caldas, Kevin Saganski, Julia Néri, Dennis Abbott, Abhijna Vithal Yergolkar, Cristina Del Conte, Januaria Passos, Katia Uezu, Paula Silva, Steven Gilbert, Keng Yeoh, Kunal Jain, Madhup Rastogi, Satheeshkumar Poolakkad Sankaran, Deborah Manne, Evgeniya Shatokhina, Esther Adebayo-Olojo, Eszter Somogyi-Ganss, Eli Ehrenpreis, Wilber Bernaola-Paredes, Eduardo Fregnani, Elaci Cardoso, Elena Bardellini, Eleni Arvanitou, Elisa Kauark Fontes, Elise Bruning, Eloise Neumann, Elsa Madureira, Marcia Ramires, Erofili Papadopoulou, Etiene Munhoz, Fred Spijkervet, Fabiana Granzotto, Fabiana Martins, Fabio Alves, Farah Mougeot, Federica Aielli, Fernanda Pigatti, Fernanda Fonseca, Firoozeh Samim, Flavia Carvalho, Florence Cuadra Zelaya, Cesar Freytes, Gabriela da Silveira, Gabriela Torino, Gabriela Martins, Geisa Silva, Gemma Caro, Gemma Bryan, Georgette Radford, Ghanyah Al-Qadami, Giorgia Albini, Gisele Mainville, Georgios Gkardiakos, Gleidston Potter, Gulbin Hoeberechts, Gordon Howarth, Grace Bradley, Gunjan Verma, Gustavo dos Santos, Margaret Randles-Guzzardi, Hanlie Engelbrecht, Hannah Wardill, Heidi Hansen, Iquebal Hasan, Hironobu Hata, Helena Ullgren, Heliton Spindola Antunes, Heloísa Laís dos Santos, Howard Weld, Helen McInnes, Hans Peter Jungbluth, Hsiaofen Weng, Ian Hewson, Ingrid Santos, Jorge Illarramendi, Ines Semendric, Rol Menge, Inger Von Bultzingslowen, Maria da Gloria de Melo, Iona Leong, Isabella Fonseca, Isadora Kalif, James Carroll, Janet Coller, Johann Beck-Mannagetta, Joanne Bowen, Jose Meurer, Ricky McCullough, Jennifer Powers, Jesus Gomez, Jimma Lenjisa, jaya Vangara, Jasna Leko, Jane Fall-Dickson, Jean-Luc Mougeot, Joan Fox, Jolien Robijns, Jonn Wu, Patricio Palma, Jaya Amaram-Davila, Jim Siderov, Juliana Dantas, Juliana Jasper, Juliana Monteiro, Julia Bruno, julie pfeffer, Julija Jovanovic Ristivojevic, Juliana Brito, Jyothsna Kuriakose, Yuji Kabasawa, Kanan Dave, Karin Barczyszyn, Karol Sartori Lima, Kate Secombe, Kate White, Kate Cooper, Kouji Katsura, Karen Biggs, Katharine Ciarrocca, Kristopher Dennis, Ken Tomizuka, Kevin Hendler, Ikuko Komo, Kristina Skallsjö, Kristy Hodgins, Katia Rupel, Keiko Tanaka, Seema Kurup, Luiz Gueiros, Larissa Agatti, Laura Garzona-Navas, Letícia Guerra, Leila Portela, Leilani Iossi, Linda Elting, Lene Baad-Hansen, Leslie Reeder, Leticia Lang, Liciane Menezes, Liliana Braun, Liliane Grando, Mathew Lim, Lina Fernandez, Lucy McKeage, Luana Campos, Luciana Simonato, Luciana Muniz, Leah van Draanen, Mieko Mizutani, Tsai-Wei Huang, Mahfujul Riad, Mahnoor Nazar, Maíra Souza, Mariana Minamisako, Manoela Pereira, Carlos Mantelato, Márcio Diniz-Freitas, Marco Montezuma, Marco Andrade, Marcos Santos, Margherita Gobbo, Maria Caterina Fortuna, Mariana Vitor, Joana Marinho, Alina Markova, Marlyse Knuchel, Marta Carlesimo, Marta Neves, Andrew Mazar, Maria Cristina Gomez Amarilla, Mark Chambers, Melissa de Araujo, Alexandre Melo, Melody Cole, Mohamed Elsayed, Monica Fliedner, Martin Hauer-Jensen, Micaela Bouchacourt, Michael Brennan, Michael Thirlwell, Michio Nakamura, Midori Nakagaki, Camila Rossi, Mireille Kaprilian, Michael Kase, Michael Dougan, Monique Stokman, Ragnhild Monsen, Alisha Morgan, Jocelyn Harding, Maryam Taleghani, Marie-Therese Genot, Mukund Seshadri, Brian Muzyka, Nancy Batista, Nancy Gadd, Naoko Tanda, Narmin Nasr, Natália Garcia, Nathan Lee, Natalia Palmier, Norman Brito-Dellan, Nancy Corbitt, Neli Pieralisi, Verônica Serrano, Nicola Alessandro Iacovelli, Norma Lúcia Sampaio, Nour Karra, Niveditha Venkatesh, Noam Yarom, Renata Cristina Borin, Olivia Lemenchick, Ondina Mendes, Ourania Nicolatou-Galitis, Vasiliy Shchitka, Paula Reis, Paulo Sérgio Santos, Paz Fernandez-Ortega, Ira Parker, Raquel García, Peter Fritz, Edmund Peters, Pamela Gardner, Pierre Saint Girons, Priya Tiwari, Pravin Chaturvedi, Tais de Moraes, Priscila Andrade, Raj Nair, Rachel Gibson, Rachita Gururaj, Raghu Thota, Rajesh Lalla, Raquel Almeida Prado, Ravikiran Ongole, George Taybos, Regina Mackey, Renata Rego, Renata Camilotti, Renata Ferrari, Renato Junior, Rene-Jean Bensadoun, Richard Logan, Roberta Sales, Roberta Zanicotti, Roberta Tunes, Rodolfo Mauceri, Rosiene Feitoza, Kathryn Ruddy, Cynthia Rybczyk, Stephanie Trager, Sachiyo Mitsunaga, Sahani Gunathilake, Rajan Saini, Viola Salvestrini, Sandip Mukhopadhyay, Sandrina Angeloz, Pramod Sankar S, Luciana S Barbosa Barbosa, Elena Volkova, Sharon Elad, Sergio Cantoreggi, Sharon Gordon, Shelly Brown, Shu Yie Janine Tam, Sibelle Faleiro, Silmara da Silva, Silvia de Oliveira, Siri Beier Jensen, Ivana Skrinjar, Sophie Beaumont, Felipe Sperandio, Sandra Reese, Steven Roser, Sachiko Seo, Stephanie van Leeuwen, Stephen Sonis, Stephen Bernard, Stephen Rajan Samuel, Stuart Taylor, Suranjan Maitra, Susanne Skulski, Suzanne Carlisle, Sylvie Louise Avon, Tomoya Yokota, Takashi Yurikusa, Tabata Santos Polvora, Tabitha Kelock, Tauana Fernandes, Taylor Wain, Timothy Brown, Tetsuhito konishi, Thalyta Amanda Ferreira, Tomoko Kataoka, Thomas Kelly, Takehiko Mori, Tomoko Higuchi, Toshiaki Saeki, Nikolaos Tsoukalas, Typhaine Maupoint De Vandeul, Masatoshi Usubuchi, Vanessa Lacerda, Vanessa Tilly, Emmanuelle Vigarios, Alessandro Villa, Vinicius Torregrossa, Vinodh Kumar Selvaraj, Viviane Sarmento, Vivien Heng, Wagner Gomes-Silva, Petter Wilberg, Wanessa Miranda e Silva, Wan Nor I'zzah Wan Mohamad Zain, Wonse Park, Wim Tissing, Yoshihiko Soga, Bella Van Sebille, and Yuhei Matsuda

Subjects
Oral mucositis, Gastrointestinal mucositis, Mucositis assessment tools, Patient-reported outcome measures, Medicine (General), R5-920
Abstract

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Published
2024
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5. Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi study

Author

Laheij, Alexa, Tonkaboni, Arghavan, Scott, Jacqui, Abasaeed, Rania, Kauzman, Adel, Flato, Adriana Do Socorro Lima, Gore, Adwaita, Hardman, Anne-Marie, Horvath, Agnes, Hovan, Allan, Al-Jamaei, Aisha, koizumi, Aya, Santos-Silva, Alan, Majorana, Alessandra, Giannini, Alexandre, Teixeira, Aléxia, Shazib, Muhammad Ali, Melvin, Alison, Filho, Aluísio Miranda, Gruza, Amanda, Brown-Dahl, Amber, Harilall, Amit, El Maghrabi, Amr, Rogulj, Ana Andabak, Curvo, Ana Raphaela, Soares, Ana Laura, Stringer, Andrea, Moreira, Andréa, Kurtzweil, Andy, Salaberry, Angelyn, Blazy, Anne, Gussgard, Anne Margrete, Lynge Pedersen, Anne Marie, Freidank, Annette, Ariyawardana, Anura, Ramseier, Adrian, Arends, Jann, Blanchard, Ariel, Paz, Adriana Sesti, Thermann, Angela, Poropat, Augusto, Freites-Martinez, Azael, Al-Azri, Abdul Rahman, Herlofson, Bente Brokstad, BalajiSubramanian, Sitaraman, Ballantyne, Barbara, Bektas-Kayhan, Kivanc, Hasséus, Bengt, Kaffenberger, Benjamin, Benites, Bernar, Kwong, Bernice, Test, Beth, Chiantia, Fernando, Pettersson, Bo, Framroze, Bomi, Bonomo, Pierluigi, Brzak, Božana Lončar, Dulmage, Brittany, Buga, Sorin, Spekssnijder, Caroline, Brown, Carlton, Melo, Antonio Carlos Moura de, Ribeiro, Ana Carolina, Silva, Caroline, Fulop, Caroline, Anderson, Carryn, Flaitz, Catherine, Massoud, Cathy, Migliorati, Cesar, Gross, Callie, Gandini, Chiara, Loprinzi, Charles, de Mooij, Charlotte, Hong, Catherine, Choi, Ying Chu, Choy, Maria, Boers-Doets, Christine, Schmeel, Leonard, Nagano, Cibele, Franco, Maria Coeli, Subramaniam, Courtney, Patrick, Carolyn, Poh, Catherine, Neuenschwander, Cristina, Virgen, Cesar, Riesenbeck, Dorothea, Weaver, Dale, Goldemberg, Daniel Cohen, Sundaresan, Daniel, Nunes, Daniela, Perez, Danyel, Travassos, Daphine, Yang, David, Ribeiro, Daniela, Kolbinson, Dean, Buick, Deborah, Saunders, Deborah, De Bortolli, Juliane, Chugh, Deepika, Markstrom, Denise, Travassos, Denise, Weikel, Dianna, Galiti, Dimitra, Peiris, Dinusha, Djordjevic, Fedja, Singhai, Pankaj, Keefe, Dorothy, Peterson, Douglas, Fonseca, Douglas, Pon, Doreen, Kovalenko, Iuliia, Polonskaia, Aleksandra, Caldas, Rogério, Saganski, Kevin, Néri, Julia, Abbott, Dennis, Yergolkar, Abhijna Vithal, Del Conte, Cristina, Passos, Januaria, Uezu, Katia, Silva, Paula, Gilbert, Steven, Yeoh, Keng, Jain, Kunal, Rastogi, Madhup, Sankaran, Satheeshkumar Poolakkad, Manne, Deborah, Shatokhina, Evgeniya, Adebayo-Olojo, Esther, Somogyi-Ganss, Eszter, Ehrenpreis, Eli, Bernaola-Paredes, Wilber, Fregnani, Eduardo, Cardoso, Elaci, Bardellini, Elena, Arvanitou, Eleni, Fontes, Elisa Kauark, Bruning, Elise, Neumann, Eloise, Madureira, Elsa, Ramires, Marcia, Papadopoulou, Erofili, Munhoz, Etiene, Spijkervet, Fred, Granzotto, Fabiana, Martins, Fabiana, Alves, Fabio, Mougeot, Farah, Aielli, Federica, Pigatti, Fernanda, Fonseca, Fernanda, Samim, Firoozeh, Carvalho, Flavia, Zelaya, Florence Cuadra, Freytes, Cesar, da Silveira, Gabriela, Torino, Gabriela, Martins, Gabriela, Silva, Geisa, Caro, Gemma, Bryan, Gemma, Radford, Georgette, Al-Qadami, Ghanyah, Albini, Giorgia, Mainville, Gisele, Gkardiakos, Georgios, Potter, Gleidston, Hoeberechts, Gulbin, Howarth, Gordon, Ottaviani, Giulia, Bradley, Grace, Verma, Gunjan, Santos, Gustavo dos, Randles-Guzzardi, Margaret, Engelbrecht, Hanlie, Wardill, Hannah, Hansen, Heidi, Hasan, Iquebal, Hata, Hironobu, Ullgren, Helena, Antunes, Heliton Spindola, Laís dos Santos, Heloísa, Weld, Howard, McInnes, Helen, Jungbluth, Hans Peter, Weng, Hsiaofen, Hewson, Ian, Santos, Ingrid, Illarramendi, Jorge, Semendric, Ines, Menge, Rol, Von Bultzingslowen, Inger, Melo, Maria da Gloria de, Leong, Iona, Fonseca, Isabella, Kalif, Isadora, Carroll, James, Coller, Janet, Beck-Mannagetta, Johann, Bowen, Joanne, Meurer, Jose, McCullough, Ricky, Powers, Jennifer, Gomez, Jesus, Lenjisa, Jimma, jaya Vangara, Leko, Jasna, Fall-Dickson, Jane, Mougeot, Jean-Luc, Fox, Joan, Epstein, Joel, Robijns, Jolien, Wu, Jonn, Palma, Patricio, Amaram-Davila, Jaya, Siderov, Jim, Raber-Durlacher, Judith, Dantas, Juliana, Jasper, Juliana, Monteiro, Juliana, Bruno, Julia, julie pfeffer, Ristivojevic, Julija Jovanovic, Brito, Juliana, Kuriakose, Jyothsna, Kabasawa, Yuji, Dave, Kanan, Barczyszyn, Karin, Lima, Karol Sartori, Secombe, Kate, White, Kate, Cooper, Kate, Katsura, Kouji, Biggs, Karen, Ciarrocca, Katharine, Dennis, Kristopher, Tomizuka, Ken, Hendler, Kevin, Komo, Ikuko, Skallsjö, Kristina, Hodgins, Kristy, Rupel, Katia, Tanaka, Keiko, Kurup, Seema, Gueiros, Luiz, Agatti, Larissa, Garzona-Navas, Laura, Guerra, Letícia, Portela, Leila, Iossi, Leilani, Elting, Linda, Baad-Hansen, Lene, Reeder, Leslie, Lang, Leticia, Menezes, Liciane, Braun, Liliana, Grando, Liliane, Lim, Mathew, Fernandez, Lina, McKeage, Lucy, Campos, Luana, Simonato, Luciana, Muniz, Luciana, van Draanen, Leah, Mizutani, Mieko, Huang, Tsai-Wei, Riad, Mahfujul, Nazar, Mahnoor, Souza, Maíra, Minamisako, Mariana, Pereira, Manoela, Mantelato, Carlos, Diniz-Freitas, Márcio, Montezuma, Marco, Andrade, Marco, Santos, Marcos, Gobbo, Margherita, Fortuna, Maria Caterina, Vitor, Mariana, Marinho, Joana, Markova, Alina, Knuchel, Marlyse, Carlesimo, Marta, Neves, Marta, Mazar, Andrew, Gomez Amarilla, Maria Cristina, Chambers, Mark, Araujo, Melissa de, Melo, Alexandre, Cole, Melody, Elsayed, Mohamed, Fliedner, Monica, Hauer-Jensen, Martin, Bouchacourt, Micaela, Brennan, Michael, Thirlwell, Michael, Nakamura, Michio, Nakagaki, Midori, Rossi, Camila, Miller, Robert, Kaprilian, Mireille, Kase, Michael, Dougan, Michael, Stokman, Monique, Monsen, Ragnhild, Morgan, Alisha, Harding, Jocelyn, Taleghani, Maryam, Genot, Marie-Therese, Seshadri, Mukund, Muzyka, Brian, Batista, Nancy, Gadd, Nancy, Tanda, Naoko, Nasr, Narmin, Garcia, Natália, Lee, Nathan, Palmier, Natalia, Brito-Dellan, Norman, Corbitt, Nancy, Pieralisi, Neli, Serrano, Verônica, Iacovelli, Nicola Alessandro, Blijlevens, Nicole, Sampaio, Norma Lúcia, Karra, Nour, Venkatesh, Niveditha, Yarom, Noam, Borin, Renata Cristina, Lemenchick, Olivia, Mendes, Ondina, Nicolatou-Galitis, Ourania, Shchitka, Vasiliy, Bossi, Paolo, Reis, Paula, Santos, Paulo Sérgio, Fernandez-Ortega, Paz, Parker, Ira, García, Raquel, Fritz, Peter, Peters, Edmund, Gardner, Pamela, Girons, Pierre Saint, Tiwari, Priya, Chaturvedi, Pravin, de Moraes, Tais, Andrade, Priscila, Nair, Raj, Gibson, Rachel, Gururaj, Rachita, Abdalla-Aslan, Ragda, Thota, Raghu, Lalla, Rajesh, Mendes, Rui Amaral, Prado, Raquel Almeida, Ongole, Ravikiran, Taybos, George, Mackey, Regina, Rego, Renata, Camilotti, Renata, Ferrari, Renata, Junior, Renato, Bensadoun, Rene-Jean, Logan, Richard, Sales, Roberta, Zanicotti, Roberta, Tunes, Roberta, Mauceri, Rodolfo, Feitoza, Rosiene, Ruddy, Kathryn, Rybczyk, Cynthia, Trager, Stephanie, Mitsunaga, Sachiyo, Gunathilake, Sahani, Saini, Rajan, Salvestrini, Viola, Mukhopadhyay, Sandip, Angeloz, Sandrina, Sankar S, Pramod, Barbosa, Luciana S Barbosa, Volkova, Elena, Elad, Sharon, Cantoreggi, Sergio, Gordon, Sharon, Brown, Shelly, Janine Tam, Shu Yie, Faleiro, Sibelle, da Silva, Silmara, de Oliveira, Silvia, Jensen, Siri Beier, Skrinjar, Ivana, Beaumont, Sophie, Sperandio, Felipe, Reese, Sandra, Roser, Steven, Seo, Sachiko, van Leeuwen, Stephanie, Sonis, Stephen, Bernard, Stephen, Samuel, Stephen Rajan, Taylor, Stuart, Maitra, Suranjan, Skulski, Susanne, Carlisle, Suzanne, Avon, Sylvie Louise, Yokota, Tomoya, Yurikusa, Takashi, Polvora, Tabata Santos, Kelock, Tabitha, Fernandes, Tauana, Wain, Taylor, Brown, Timothy, Tetsuhito konishi, Ferreira, Thalyta Amanda, Kataoka, Tomoko, Kelly, Thomas, Mori, Takehiko, Higuchi, Tomoko, Saeki, Toshiaki, Tsoukalas, Nikolaos, De Vandeul, Typhaine Maupoint, Usubuchi, Masatoshi, Lacerda, Vanessa, Tilly, Vanessa, Vigarios, Emmanuelle, Villa, Alessandro, Torregrossa, Vinicius, Selvaraj, Vinodh Kumar, Sarmento, Viviane, Heng, Vivien, Gomes-Silva, Wagner, Kandwal, Abhishek, Wilberg, Petter, Miranda e Silva, Wanessa, I'zzah Wan Mohamad Zain, Wan Nor, Park, Wonse, Tissing, Wim, Soga, Yoshihiko, Van Sebille, Bella, Matsuda, Yuhei, Zadik, Yehuda, Cao, Katrina, Cheung, Yin Ting, Fregnani, Eduardo Rodrigues, Van Sebille, Ysabella, Kauark-Fontes, Elisa, McCurdy-Franks, Emma, Finkelstein, Joel, McCarvell, Victoria, Amaral Mendes, Rui, Speksnijder, Caroline Margina, and Wardill, Hannah Rose

Published
2024
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6. Automated Evolutionary Approach for the Design of Composite Machine Learning Pipelines

Author

Nikitin, Nikolay O., Vychuzhanin, Pavel, Sarafanov, Mikhail, Polonskaia, Iana S., Revin, Ilia, Barabanova, Irina V., Maximov, Gleb, Kalyuzhnaya, Anna V., and Boukhanovsky, Alexander

Subjects
Computer Science - Machine Learning
Abstract

The effectiveness of the machine learning methods for real-world tasks depends on the proper structure of the modeling pipeline. The proposed approach is aimed to automate the design of composite machine learning pipelines, which is equivalent to computation workflows that consist of models and data operations. The approach combines key ideas of both automated machine learning and workflow management systems. It designs the pipelines with a customizable graph-based structure, analyzes the obtained results, and reproduces them. The evolutionary approach is used for the flexible identification of pipeline structure. The additional algorithms for sensitivity analysis, atomization, and hyperparameter tuning are implemented to improve the effectiveness of the approach. Also, the software implementation on this approach is presented as an open-source framework. The set of experiments is conducted for the different datasets and tasks (classification, regression, time series forecasting). The obtained results confirm the correctness and effectiveness of the proposed approach in the comparison with the state-of-the-art competitors and baseline solutions.

Published
2021
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7. Multi-Objective Evolutionary Design of Composite Data-Driven Models

Author

Polonskaia, Iana S., Nikitin, Nikolay O., Revin, Ilia, Vychuzhanin, Pavel, and Kalyuzhnaya, Anna V.

Subjects
Computer Science - Neural and Evolutionary Computing, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

In this paper, a multi-objective approach for the design of composite data-driven mathematical models is proposed. It allows automating the identification of graph-based heterogeneous pipelines that consist of different blocks: machine learning models, data preprocessing blocks, etc. The implemented approach is based on a parameter-free genetic algorithm (GA) for model design called GPComp@Free. It is developed to be part of automated machine learning solutions and to increase the efficiency of the modeling pipeline automation. A set of experiments was conducted to verify the correctness and efficiency of the proposed approach and substantiate the selected solutions. The experimental results confirm that a multi-objective approach to the model design allows achieving better diversity and quality of obtained models. The implemented approach is available as a part of the open-source AutoML framework FEDOT.

Published
2021

8. Skin microbiome in cancer patients with pruritus and other skin toxic reactions related to anticancer therapy: A review

Author

Aleksandra S. Polonskaia, Anna V. Michenko, Larisa S. Kruglova, Evgeniya A. Shatokhina, and Andrey N. Lvov

Subjects
skin microbiome, skin toxicity, toxic skin reactions, skin neoplasms, actinic keratosis, squamous cell carcinoma, lymphoma, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Modern antitumor therapy includes novel targeted and immunotherapeutic options specifically targeting tumor targets. However, many of these targets are also expressed in the constantly proliferating epidermis of the skin, leading to derangement of proliferation and differentiation of keratinocytes, inflammatory responses, skin barrier dysfunction, inhibition of antimicrobial peptides' synthesis, and toxic skin reactions. The article presents an overview of current data on microbiome disorders associated with toxic skin reactions. The potential mechanisms of skin microbiome changes inducing the occurrence and persistence of rashes during anticancer therapy are addressed.

Published
2023
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9. The multi-objective optimisation of breakwaters using evolutionary approach

Author

Nikitin, Nikolay O., Polonskaia, Iana S., Kalyuzhnaya, Anna V., and Boukhanovsky, Alexander V.

Subjects
Computer Science - Neural and Evolutionary Computing
Abstract

In engineering practice, it is often necessary to increase the effectiveness of existing protective constructions for ports and coasts (i. e. breakwaters) by extending their configuration, because existing configurations don't provide the appropriate environmental conditions. That extension task can be considered as an optimisation problem. In the paper, the multi-objective evolutionary approach for the breakwaters optimisation is proposed. Also, a greedy heuristic is implemented and included to algorithm, that allows achieving the appropriate solution faster. The task of the identification of the attached breakwaters optimal variant that provides the safe ship parking and manoeuvring in large Black Sea Port of Sochi has been used as a case study. The results of the experiments demonstrated the possibility to apply the proposed multi-objective evolutionary approach in real-world engineering problems. It allows identifying the Pareto-optimal set of the possible configuration, which can be analysed by decision makers and used for final construction

Published
2020

10. Extended exposure to low doses of azacitidine induces differentiation of leukemic stem cells through activation of myeloperoxidase

Author

Danny V. Jeyaraju, Maryam Alapa, Ann Polonskaia, Alberto Risueño, Prakash Subramanyam, Amit Anand, Kaushik Ghosh, Charalampos Kyriakopoulos, Daiane Hemerich, Rose Hurren, Xiaoming Wang, Marcela Gronda, Aarif Ahsan, Hsiling Chiu, Geethu Thomas, Evan F. Lind, Daniel L Menezes, Aaron D. Schimmer, Patrick R. Hagner, Anita Gandhi, and Anjan G. Thakurta

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Oral azacitidine (oral-Aza) treatment results in longer median overall survival (OS) (24.7 vs. 14.8 months in placebo) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy. The dosing schedule of oral-Aza (14 days/28-day cycle) allows for low exposure of Aza for an extended duration thereby facilitating a sustained therapeutic effect. However, the underlying mechanisms supporting the clinical impact of oral-Aza in maintenance therapy remain to be fully understood. In this preclinical work, we explore the mechanistic basis of oral-Aza/extended exposure to Aza through in vitro and in vivo modeling. In cell lines, extended exposure to Aza results in sustained DNMT1 loss, leading to durable hypomethylation, and gene expression changes. In mouse models, extended exposure to Aza, preferentially targets immature leukemic cells. In leukemic stem cell (LSC) models, the extended dose of Aza induces differentiation and depletes CD34+CD38- LSC. Mechanistically, LSC differentiation is driven in part by increased myeloperoxidase (MPO) expression. Inhibition of MPO activity either by using an MPO-specific inhibitor or blocking oxidative stress, a known mechanism of MPO, partly reverses the differentiation of LSC. Overall, our preclinical work reveals novel mechanistic insights into oral-Aza and its ability to target LSC.

Published
2023
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14. Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem

Author

A. S. Polonskaia, E. A. Shatokhina, and L. S. Kruglova

Subjects
dermatologic adverse events, targeted cancer therapy, acneiform rash, paronychia, supportive care, epidermal growth factor receptor inhibitors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Epidermal growth factor receptor inhibitors (EGFR) have a high rate of class-specific dermatologic adverse events. Supportive treatment of dermatologic adverse events decreases their severity, minimizes the need for dose de-escalation / discontinuation of targeted therapy, improves commitment to anticancer treatment and patient’s quality of life. Close interdisciplinary cooperation between oncologists and dermatologists is a key to the successful management of patients treated with EGFR. This article highlights current approaches to classification, concepts of pathogenesis and clinical course of EGFR-associated dermatologic adverse events, current and promising prophylactic and therapeutic strategies to manage these adverse events.

Published
2022
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17. Evolutionary Algorithms for the Design of Neural Network Classifiers for the Classification of Pain Intensity

Author

Mamontov, Danila, Polonskaia, Iana, Skorokhod, Alina, Semenkin, Eugene, Kessler, Viktor, Schwenker, Friedhelm, Hutchison, David, Editorial Board Member, Kanade, Takeo, Editorial Board Member, Kittler, Josef, Editorial Board Member, Kleinberg, Jon M., Editorial Board Member, Mattern, Friedemann, Editorial Board Member, Mitchell, John C., Editorial Board Member, Naor, Moni, Editorial Board Member, Pandu Rangan, C., Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Terzopoulos, Demetri, Editorial Board Member, Tygar, Doug, Editorial Board Member, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Schwenker, Friedhelm, editor, and Scherer, Stefan, editor

Published
2019
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18. Management of acneiform rash associated with anti-EGFR monoclonal antibody treatment

Author

E. A. Shatokhina, L. S. Kruglova, and A. S. Polonskaia

Subjects
acneiform rash, targeted cancer therapy, dermatologic adverse events, supportive care, anti-egfr monoclonal antibodies, Medicine
Abstract

Introduction. Dermatologic adverse events (DAEs) occur in 50-90% of cases during anti-EGFR monoclonal antibody treatment. Positive correlation between the severity of acneiform rash (AR) and the effectiveness of anti-EGFR management is established. Low effectiveness of traditional treatment for AR impairs patients’ compliance, leads to dose reduction or drug discontinuation, affecting treatment results.Objective. To assess the effectiveness of traditional and proposed combined treatment for AR associated with anti-EGFR monoclonal antibody therapy.Materials and methods. 44 patients with grade I-II acneiform rash were included in a 12-week study. Patients were divided into 3 equal groups and received different treatment: group 1a – traditional therapy, group 1b – combined continuous therapy, and group 1c – combined intermittent therapy. Assessment of clinical outcomes was performed with DLQI, IGA score, and the NCI CTCAE v. 4.03.Results. The severity of AR in groups 1b and 1c improved by the end of week 1, and this trend was kept until the end of the study. The improvement was more prominent in group 1c comparing to group 1b. The severity of AR in group 1a improved by the end of week 1. During weeks 2 and 3 there was no significant change. At week 4 a deterioration of the evaluated parameters was registered, and the treatment regimen in group 1a was changed according to the treatment protocols of group 1c with rapid improvement of AR.Conclusion. Combined intermittent therapy with systemic doxycycline and topical therapy with metronidazole 1% gel and cream with hydrocortisone acetate 1% and fusidic acid 2% showed the best effectiveness and tolerability in patients with anti-EGFR monoclonal antibody-related AR.

Published
2020
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22. P412: LOW EXPOSURE, EXTENDED DOSING MIMICKING CLINICAL EXPOSURES OF ORAL AZACITIDINE SYNERGIZES WITH VENETOCLAX IN PRECLINICAL AML MODELS

Author

D. Jeyaraju, M. Alapa, A. Polonskaia, A. Risueno Perez, R. Hurren, X. Wang, M. Gronda, A. Ahsan, C. Wang, P. Subramanyam, J. Sriganesh, A. Anand, M. Bysani Reddy, K. Ghosh, C. Kyriakopoulos, N. Lailler, C. Hartl, D. Lopes de Menezes, A. Schimmer, P. Hagner, A. Gandhi, and A. Thakurta

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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27. Extended exposure to low doses of azacitidine induces differentiation of leukemic stem cells through activation of myeloperoxidase

Author

Jeyaraju, Danny V., primary, Alapa, Maryam, additional, Polonskaia, Ann, additional, Risueño, Alberto, additional, Subramanyam, Prakash, additional, Anand, Amit, additional, Ghosh, Kaushik, additional, Kyriakopoulos, Charalampos, additional, Hemerich, Daiane, additional, Hurren, Rose, additional, Wang, Xiaoming, additional, Gronda, Marcela, additional, Ahsan, Aarif, additional, Chiu, Hsiling, additional, Thomas, Geethu, additional, Lind, Evan F., additional, Menezes, Daniel L, additional, Schimmer, Aaron D., additional, Hagner, Patrick R., additional, Gandhi, Anita, additional, and Thakurta, Anjan G., additional

Published
2023
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31. Analysis of Interaction Parameter Levels in Interaction Quality Modelling for Human-Human Conversation

Author

Spirina, Anastasiia, Vaskovskaia, Olesia, Karaseva, Tatiana, Skorokhod, Alina, Polonskaia, Iana, Sidorov, Maxim, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Karpov, Alexey, editor, Potapova, Rodmonga, editor, and Mporas, Iosif, editor

Published
2017
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32. Significance of Interaction Parameter Levels in Interaction Quality Modelling for Human-Human Conversation

Author

Spirina, Anastasiia, Skorokhod, Alina, Karaseva, Tatiana, Polonskaia, Iana, Sidorov, Maxim, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Ekštein, Kamil, editor, and Matoušek, Václav, editor

Published
2017
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33. Evaluation of effectiveness of combined supportive treatment for paronychia and pyogenic granulomas, associated with targeted anticancer therapy

Author

L.S. Kruglova, Evgeniya Shatokhina, and Aleksandra Polonskaia

Subjects
Applied Mathematics, General Mathematics
Abstract

BACKGROUND: Paronychia and pyogenic granulomas occur in 1050% of patients treated with epidermal growth receptor (EGFR) inhibitors. Supportive therapy for periungual lesions is challenging, since these adverse reactions are prone to torpidity and frequent relapses. AIM: to evaluate the effectiveness of supportive treatment for paronychia and pyogenic granulomas ― dermatologic adverse events of EGFR inhibitors, with a combined cream with betamethasone dipropionate, clotrimazole, gentamicin, and betaxolol solution. MATERIALS AND METHODS: 16 patients with paronychia and pyogenic granulomas associated with EGFR inhibitor therapy were included in a 12-week open-label prospective study. Paronychia and pyogenic granulomas severity assessment was performed with the NCI-CTCAE v. 5.0, a developed 10-point scale. The intensity of pain was assessed with a visual-analogue scale (VAS). The quality of life was assessed with the Dermatology Life Quality Index (DLQI). RESULTS: A significant improvement of all parameters (p 0.05) was evaluated from week 1, indicating the effective reduction of dermatologic adverse event objective and subjective symptoms, improvement of patients quality of life. By the end of the study, 37.5% of patients had complete resolution of lesions, 62.5% of patients had minimal residual erythema. Decrease of pain sensation in the affected periungual folds was observed throughout the study (p 0.05). DLQI score indicated the "small effect" of paronychia and pyogenic granulomas on patients life by the end of the study. CONCLUSIONS: Supportive treatment of paronychia and pyogenic granulomas with a combined cream with betamethasone dipropionate, clotrimazole and gentamicin and a betaxolol 0.25% solution is effective in the management of paronychia and pyogenic granulomas objective and subjective symptoms, has a high tolerability, allows to improve patients quality of life and continue targeted therapy without dose reduction. Long-term maintenance of pain sensation after paronychia and pyogenic granulomas resolution underlines the need for additional treatment options that will improve the effectiveness of pain management.

Published
2023

34. Low-level laser therapy in the supportive treatment of dermatologic adverse events in oncology

Author

L.S. Kruglova, Aleksandra Polonskaia, and Evgeniya Shatokhina

Subjects
General Medicine
Abstract

Supportive treatment plays an important role in oncology nowadays. The main aims of oncologic supportive treatment are management of cancer symptoms and adverse events of cancer treatment. In terms of dermatologic adverse events the most important types of reaction are oral mucositis during radiation therapy, chemotherapy and during hematopoetic stem cell transplantation, palmoplantar syndrome during chemotherapy, palmoplantar skin reaction, acneiform paronychia and pyogenic granulomas during targeted therapy, immune-related dermatologic adverse events during immunotherapy. During recent years, special attention has been paid to low level laser therapy for the prophylaxis and management of cancer therapy dermatologic adverse events. The effects of low level laser therapy may have a beneficial effect on many conditions that play important roles in the pathogenesis of radiation and chemotherapy-induced complications in oncologic patients. Therapeutic effects of low level laser therapy are attributed to the stimulation of adaptive processes and to the increase of nonspecific resistance. The latter develop due to the close interaction of the immune, humoral and nervous systems. When choosing a method for the supportive treatment of cancer therapy adverse events, it is extremely important to establish safety in terms of the tumor process and absence of negative effects on cancer treatment. Effects of low level laser therapy on the proliferative and invasive activity of an existing malignancy remains a matter of debate due to conflicting results from in vitro studies. At the same time, according to the results of numerous clinical studies, the use of this method is assumed to be safe for cancer patients.

Published
2022

35. P997: FEDRATINIB IS EFFECTIVE IN RUXOLITINIB-RESISTANT CELLS: CLINICAL AND PRECLINICAL CORRELATIONS

Author

Jeyaraju, Danny, primary, Hayati, Sheida, additional, Polonskaia, Ann, additional, Browne, Andrew, additional, Risueño, Alberto, additional, Hagner, Patrick, additional, Gupta, Vikas, additional, Talpaz, Moshe, additional, Hernandez, Christopher, additional, Chia, Vincent, additional, Brown, Patrick, additional, De Menezes, Daniel Lopes, additional, La Motte-Mohs, Ross, additional, Nvs Suragani, Rajasekhar, additional, and Gandhi, Anita, additional

Published
2023
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36. Loss of COP9 signalosome genes at 2q37 is associated with IMiD resistance in multiple myeloma

Author

Sarah Gooding, Naser Ansari-Pour, Mohammad Kazeroun, Kubra Karagoz, Ann Polonskaia, Mirian Salazar, Evie Fitzsimons, Korsuk Sirinukunwattana, Selina Chavda, Maria Ortiz Estevez, Fadi Towfic, Erin Flynt, William Pierceall, Daniel Royston, Kwee Yong, Karthik Ramasamy, Paresh Vyas, and Anjan Thakurta

Subjects
Ubiquitin-Protein Ligases, Immunology, Humans, Cell Biology, Hematology, RNA, Small Interfering, Multiple Myeloma, Lenalidomide, Biochemistry, Adaptor Proteins, Signal Transducing, Peptide Hydrolases
Abstract

The acquisition of a multidrug refractory state is a major cause of mortality in myeloma. Myeloma drugs that target the cereblon (CRBN) protein include widely used immunomodulatory drugs (IMiDs), and newer CRBN E3 ligase modulator drugs (CELMoDs), in clinical trials. CRBN genetic disruption causes resistance and poor outcomes with IMiDs. Here, we investigate alternative genomic associations of IMiD resistance, using large whole-genome sequencing patient datasets (n = 522 cases) at newly diagnosed, lenalidomide (LEN)-refractory and lenalidomide-then-pomalidomide (LEN-then-POM)-refractory timepoints. Selecting gene targets reproducibly identified by published CRISPR/shRNA IMiD resistance screens, we found little evidence of genetic disruption by mutation associated with IMiD resistance. However, we identified a chromosome region, 2q37, containing COP9 signalosome members COPS7B and COPS8, copy loss of which significantly enriches between newly diagnosed (incidence 5.5%), LEN-refractory (10.0%), and LEN-then-POM-refractory states (16.4%), and may adversely affect outcomes when clonal fraction is high. In a separate dataset (50 patients) with sequential samples taken throughout treatment, we identified acquisition of 2q37 loss in 16% cases with IMiD exposure, but none in cases without IMiD exposure. The COP9 signalosome is essential for maintenance of the CUL4-DDB1-CRBN E3 ubiquitin ligase. This region may represent a novel marker of IMiD resistance with clinical utility.

Published
2022

37. Balneotherapy as a promising method for the correction of dermatologic adverse events of cancer therapy

Author

L.S. Kruglova, Aleksandra Polonskaia, and Evgeniya Shatokhina

Subjects
General Medicine
Abstract

Cancer treatment with chemotherapy, targeted and immunotherapy is associated with a wide spectrum of dermatologic adverse events. Xerosis (dryness) of the skin is the most prevalent skin side effect in oncologic patients, which occurs both during treatment with "classic" chemotherapy drugs and modern cancer drugs, such as targeted therapy and immunotherapy. Despite the high prevalence of this side effect, current approaches to the correction of skin xerosis in cancer patients are very limited. At the same time, in the absence of adequate supportive treatment of xerosis, the formation of persistent fissures, eczematization and secondary infection is observed, which may lead to antitumor therapy regimen modification. Thus, optimization of prophylactic and treatment strategies for xerosis in patients treated with anticancer drugs remain an important interdisciplinary problem. Balneotherapy is a promising method for the correction of skin xerosis due to a complex positive effect on the level of skin hydration, a decrease in the intensity of inflammatory processes, a beneficial effect on the state of the skin barrier function, as well as an increase in antimicrobial protection. Available data on the use of balneotherapy in the supportive treatment of skin xerosis as a dermatological adverse event of anticancer therapy confirms the high efficacy and safety, as well as good tolerability of this method in cancer patients.

Published
2022

38. New techniques and models for assessing ischemic heart disease risks

Author

I.N. Yakovina, N.A. Bannova, E.V. Kashtanova, Ya.V. Polonskaia, and Yu.I. Ragino

Subjects
risk assessment, ischemic heart disease, laboratory and diagnostic complex, biochemical parameters, logic and mathematic model, program module, questioning as per Rose, Medicine
Abstract

The paper focuses on tasks of creating and implementing a new technique aimed at assessing ischemic heart diseases risk. The techniques is based on a laboratory-diagnostic complex which includes oxidative, lipid-lipoprotein, inflammatory and metabolic biochemical parameters; s system of logic-mathematic models used for obtaining numeric risk assessments; and a program module which allows to calculate and analyze the results. we justified our models in the course of our re-search which included 172 patients suffering from ischemic heart diseases (IHD) combined with coronary atherosclerosis verified by coronary arteriography and 167 patients who didn't have ischemic heart diseases. Our research program in-cluded demographic and social data, questioning on tobacco and alcohol addiction, questioning about dietary habits, chronic diseases case history and medications intake, cardiologic questioning as per Rose, anthropometry, 3-times meas-ured blood pressure, spirometry, and electrocardiogram taking and recording with decoding as per Minnesota code. We detected biochemical parameters of each patient and adjusted our task of creating techniques and models for assessing ischemic heart disease risks on the basis of inflammatory, oxidative, and lipid biological markers. We created a system of logic and mathematic models which is a universal scheme for laboratory parameters processing allowing for dissimilar data specificity. The system of models is universal, but a diagnostic approach to applied biochemical parameters is spe-cific. The created program module (calculator) helps a physician to obtain a result on the basis of laboratory research data; the result characterizes numeric risks of coronary atherosclerosis and ischemic heart disease for a patient. It also allows to obtain a visual image of a system of parameters and their deviation from a conditional «standard – pathology» boundary. The complex is implemented into practice by the Scientific Research Institute for Therapy and Preventive Medicine.

Published
2017
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50. Data from Inactivation of Mirk/Dyrk1b Kinase Targets Quiescent Pancreatic Cancer Cells

Author

Eileen A. Friedman, John F. Boylan, Karen Zipf, Ann F. Hoffman, Ann Polonskaia, Kin-chun Luk, Xiaobing Deng, Maria Vilenchik, Jing Hu, and Daina Z. Ewton

Abstract

A major problem in the treatment of cancer arises from quiescent cancer cells that are relatively insensitive to most chemotherapeutic drugs and radiation. Such residual cancer cells can cause tumor regrowth or recurrence when they reenter the cell cycle. Earlier studies showed that levels of the serine/theronine kinase Mirk/dyrk1B are elevated up to 10-fold in quiescent G0 tumor cells. Mirk uses several mechanisms to block cell cycling, and Mirk increases expression of antioxidant genes that decrease reactive oxygen species (ROS) levels and increase quiescent cell viability. We now show that a novel small molecule Mirk kinase inhibitor blocked tumor cells from undergoing reversible arrest in a quiescent G0 state and enabled some cells to exit quiescence. The inhibitor increased cycling in Panc1, AsPc1, and SW620 cells that expressed Mirk, but not in HCT116 cells that did not. Mirk kinase inhibition elevated ROS levels and DNA damage detected by increased phosphorylation of the histone protein H2AX and by S-phase checkpoints. The Mirk kinase inhibitor increased cleavage of the apoptotic proteins PARP and caspase 3, and increased tumor cell kill several-fold by gemcitabine and cisplatin. A phenocopy of these effects occurred following Mirk depletion, showing drug specificity. In previous studies Mirk knockout or depletion had no detectable effect on normal tissue, suggesting that the Mirk kinase inhibitor could have a selective effect on cancer cells expressing elevated levels of Mirk kinase. Mol Cancer Ther; 10(11); 2104–14. ©2011 AACR.

Published
2023

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