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5. Exploring uterine involvement in hysterectomy samples following conization for adenocarcinoma in situ of the uterine cervix: Insights from a multicenter study by the FRANCOGYN group

Author

Marjolaine, Le Gac, Louise, Benoit, Meriem, Koual, Enrica, Bentivegna, Pierre-Adrien, Bolze, Yohan, Kerbage, Emilie, Raimond, Lise, Lecointre, Xavier, Carcopino, Geoffroy, Canlorbe, Charles-André, Philip, Huyen-Thu, Nguyen-Xuan, Anne-Sophie, Bats, and Henri, Azaïs

Published
2024
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6. Clinical, pathological, and comprehensive molecular analysis of the uterine clear cell carcinoma: a retrospective national study from TMRG and GINECO network

Author

Nigon, Elsa, Lefeuvre-Plesse, Claudia, Martinez, Alejandra, Chauleur, Céline, Lortholary, Alain, Favier, Laure, Bats, Anne-Sophie, Guille, Arnaud, AdélaÏde, José, Finetti, Pascal, de Casteljac, Victoire, Provansal, Magali, Mamessier, Emilie, Bertucci, François, Ray-Coquard, Isabelle, and Sabatier, Renaud

Published
2023
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7. A design space for event-centric displays in public libraries

Author

Alix Ducros, Aurélien Tabard, Peter Dalsgaard, Raphaelle Bats, and Eva Eriksson

Subjects
public library, HCI, design, public displays, design space, Electronic computers. Computer science, QA75.5-76.95
Abstract

We present a design space for displays in public libraries; more specifically public displays related to events taking place in the library. The design space is developed from the perspective of the librarians and is intended to support libraries in rethinking, developing, and employing displays to communicate and support the events they host. It is based on a study of 18 concepts co-designed in eight participatory workshops scaling participation to a total of 88 professional librarians. By analyzing the concepts through inductive and iterative analysis, we have defined a design space consisting of 12 aspects, categorized in four themes: interaction-, content-, event-, and display-centric. We argue that the design space can both serve as (1) an analytical tool for understanding and categorizing information displays and identifying overarching design considerations and (2) a generative framework to inspire design across a wide variety of libraries.

Published
2024
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13. Clinical, pathological, and comprehensive molecular analysis of the uterine clear cell carcinoma: a retrospective national study from TMRG and GINECO network

Author

Elsa Nigon, Claudia Lefeuvre-Plesse, Alejandra Martinez, Céline Chauleur, Alain Lortholary, Laure Favier, Anne-Sophie Bats, Arnaud Guille, José AdélaÏde, Pascal Finetti, Victoire de Casteljac, Magali Provansal, Emilie Mamessier, François Bertucci, Isabelle Ray-Coquard, and Renaud Sabatier

Subjects
Uterine cancer, Clear cell carcinoma, Tissue micro-array, Genomics, Gene expression profiling, Medicine
Abstract

Abstract Background Uterine clear cell carcinomas (CCC) represent less than 5% of uterine cancers. Their biological characteristics and clinical management remain uncertain. A multicenter study to explore both clinical and molecular features of these rare tumors was conducted. Methods This multicenter retrospective national study was performed within the French TMRG (Rare Gynecologic Malignant Tumors) network. Clinical data and, when available, FFPE blocks were collected. Clinical features, treatments, and outcome (progression-free survival (PFS) and overall survival (OS)) were analyzed and correlated to the protein (tissue micro-array), RNA (Nanostring nCounter® technology), and DNA (array-Comparative Genomic hybridization and target-next generation sequencing) levels using the tumor samples available. Results Sixty-eight patients with uterine CCC were enrolled, 61 from endometrial localization and 5 with cervix localization. Median age at diagnosis was 68.9 years old (range 19–89.7). Most tumors were diagnosed at an early stage (78% FIGO stage I–II). Hysterectomy (performed in 90%) and lymph node dissection (80%) were the most frequent surgical treatment. More than 70% of patients received external beam radiotherapy and 57% received brachytherapy. Nearly half (46%) of the patients received chemotherapy. After a median follow-up of 24.7 months, median PFS was 64.8 months (95 CI [5.3–124.4]) and median OS was 79.7 (IC95 [31.0–128.4]). Low hormone receptor expression (13% estrogen-receptor positive), frequent PI3K pathway alterations (58% PTEN loss, 50% PIK3CA mutations), and P53 abnormalities (41%) were observed. Mismatch repair deficiency was identified in 20%. P16 expression was associated with shorter PFS (HR = 5.88, 95 CI [1.56–25], p = 0.009). Transcriptomic analyzes revealed a specific transcriptomic profile notably with a high expression of immune response-associated genes in uterine CCC displaying a very good overall prognosis. Conclusions Uterine CCC reported to be potentially MSI high, hormone receptors negative, and sometimes TP53 mutated. However, some patients with immune response-associated features and better prognosis may be candidate to treatment de-escalation and immunotherapy.

Published
2023
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14. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials

Author

Cole, Abosede O, Gerstenblith, Adam T, Kotagiri, Ajay, Edwards, Albert O, Zambrano, Alberto D, Eaton, Alexander M, Rubowitz, Alexander, Lyon, Alice T, Chiang, Allen, Ho, Allen, Hu, Allen Y, Guerami, Amir H, Dessouki, Amr L, de Carvalho, André Corrêa Maia, Emanuelli, Andrés, Chang, Andrew A, Antoszyk, Andrew N, Francone, Anibal Andrés, Prasad, Anita, Wolf, Armin, Khanani, Arshad M, Abbey, Ashkan Michael, Moulana, Asma, Wihelm, Barbara, Sikorski, Bartosz L, Kuppermann, Baruch D, Wolff, Benjamin, Jewart, Brian H, Do, Brian K, Chan-Kai, Brian T, Mein, Calvin, Hoyng, Carel B, Awh, Carl C, Regillio, Carl, Zeolite, Carlos, Baumal, Caroline R, Creuzot-Garcher, Catherine, Maury, Catherine Français, Wykoff, Charles C, Newell, Charles K, Jhaveri, Chirag, Lohmann, Chris P, Dinah, Christiana B, Ma, Colin, Crawford, Courtney, Parke, D Wilkin, Lavinsky, Daniel, Roth, Daniel, Pieramici, Dante J, Moshfeghi, Darius M, Levin, Darrin, Saperstein, David A, Brown, David, Gaucher, David, Lally, David R, Liao, David S, Brown, David Warren, Goldstein, Debra, Marcus, Dennis, Chan, Derek G, Dhoot, Dilsher, Tacite, Domingo, Zalewski, Dominik, Espana, Edgar M, Lad, Eleonora M, Souied, Eric H, Suan, Eric P, Eting, Eva, Sola, Federico Furno, de Bats, Flore, Bandello, Francesco, Gómez-Ulla, Francisco, Devin, François, Holz, Frank G, Chen, Fred K, Makkouk, Fuad, Dyer, Gawain, Spital, George, Staurenghi, Giovanni, Stoller, Glenn, Cousins, Gwen, Salehi-Had, Hani, Agostini, Hansjürgen, Eleftheriadis, Haralabos, Weiss, Harold, Sultan, Harris C, Massé, Hélène, Pearce, Ian, Dias, Indra, Barbazetto, Irene, Rosenblatt, Irit, Suñer, Ivan J, Kovach, Jaclyn L, Kaluzny, Jakub, Borthwick, James, Howard, James G, Wong, James, Ernest, Jan, Němčanský, Jan, Ysasaga, Jason Edward, Handza, Jason M, Moreno, Javier Antonio Montero, Korobelnik, Jean-François, Heier, Jeffrey S, Arnold, Jennifer J, Brown, Jeremiah, Bafalluy, Joaquin, Pearlman, Joel, Pitcher, John D, Kitchens, John, Carlson, John P, Gilhotra, Jolly, Fein, Jordana, Monés, Jordi M, Luna, José Domingo, Moreno, José María Ruiz, Coney, Joseph M, Sallum, Juliana Maria Ferraz, Olsen, Karl R, Blobner, Katharina, Macoul, Katherine A, Oh, Kean T, Malik, Khurram Javed, Hattenbach, Lars-Olof, Kodjikian, Laurent, Neto, Laurentino Biccas, Singerman, Lawrence J, Altay, Lebriz, Sheck, Leo-H, Feiner, Leonard, Harris, Lindsey D, Chishold, Lionel D, Rao, Llewelyn J, Nehemy, Márcio Bittar, Elizalde, Maria Jose Capella, Gamulescu, Maria-Andreea, Saravia, Mario J, Johnson, Mark W, McKibbin, Martin, Maccumber, Mathew, Vidosevich, Matko, Ohr, Matthew P, Samuel, Michael A, Singer, Michael A, Cassell, Michael, Dollin, Michael, Elman, Michael J, Ip, Michael S, Goldstein, Michaella, Busquets, Miguel, Mititelu, Mihai, Shah, Milan, Veith, Miroslav, Fineman, Mitchell, Varano, Monica, Christmas, Nancy, Steinle, Nathan C, Chaudhry, Nauman, Chinskey, Nicholas D, Eter, Nicole, London, Nikolas J S, Mathalone, Nurit, Schlottmann, Patricio G, Coady, Patrick, Higgins, Patrick M, Raskauskas, Paul A, Yates, Paul A, Bernstein, Paul, Mitchell, Paul, Monsour, Paul, Raphaelian, Paul V, Stanga, Paulo E, Stodulka, Pavel, Issa, Peter Charbel, Pavan, Peter, Ferrone, Phil J, Oleksy, Piotr, Abraham, Prema, Mruthyunjaya, Prithvi, Nguyen, Quan Dong, Reddy, Rahul K, Khurana, Rahul N, Tuli, Raman, Tadayoni, Ramin, Katz, Randy Steven, Arora, Rashi, Schlingemann, Reinier O, Rosen, Richard B, Gale, Richard, Scartozzi, Richard, Isernharge, Ricky, Singh, Rishi P, Stoltz, Robert A, Avery, Robert L, Wirthlin, Robert S, Guymer, Robyn, Goldberg, Roger A, Frenkel, Ronald, Belfort, Rubens Jr, Mohand-Said, Saddek, Grisanti, Salvatore, Razavi, Sam, Fraser-Bell, Samantha, Shah, Sandeep N, Wickremasinghe, Sanjeewa, Haug, Sara Joy, Adrean, Sean D, Priglinger, Siegfried G, Esposti, Simona Degli, Guest, Stephen, Huddleston, Stephen, Itty, Sujit, Moon, Suk Jin, Bhatia, Sumit P, Gupta, Sunil, Patel, Sunil S, Garg, Sunir J, Joshi, Sunir, Nghiem-Buffet, Sylvia, Johnson, T Mark, Jaouni, Tareq, Ach, Thomas, Williams, Thomas R, Sheidow, Thomas, Cleland, Timothy P, You, Timothy T, Peto, Tunde, Konidaris, Vasileios, Gonzalez, Victor H, Korda, Vladimir, Freeman, William R, Bridges, William Z, Barak, Yoreh, Zagorski, Zbigniew, Yehoshua, Zohar, Dubska, Zora, Rosenfeld, Philip J, Guymer, Robyn H, Boyer, David, Grossi, Federico, Korobelnik, Jean-Francois, Slakter, Jason S, Waheed, Nadia K, Metlapally, Ravi, Steinle, Nathan, Francone, Anibal A, Hu, Allen, Deschatelets, Pascal, Francois, Cedric, Bliss, Caleb, Monés, Jordi, and Ribeiro, Ramiro

Published
2023
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15. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial

Author

Alezzandrini, Arturo, Francone, Anibal Andres, Bafalluy, Joaquín, Bainttein, Silvina, Luna Pinto, Jose, Saravia, Mario, Vidosevich, Matko, Zeolite, Carlos, Furno Sola, Federico, Chang, Andrew, Cornish, Elisa Eleanor Guida, Nguyen, Thanh, Findl, Oliver, Haas, Anton, Kralinger, Martina, Sacu, Stefan, Postelmans, Laurence Dominique, Farah, Michel, Maia, Mauricio, Nehemy, Marcio, Ali, Fareed, Brent, Michael, Dollin, Michael, Gonder, John, Kherani, Amin, Merkur, Andrew, Tuli, Raman, Lopera, Monica Marie, Rodriguez, Francisco, Bradvica, Mario, Ernest, Jan, Kalijurand, Kuldar, Noor, Kai, Cohen, Yves, Creuzot-Garcher, Catherine, De Bats, Flore, Devin, François, Français-Maury, Catherine, Kodjikian, Laurent, Korobelnik, Jean François, Le Mer, Yannick, Quaranta El Maftouhi, Maddalena, Razavi, Sam, Souied, Eric, Tadayoni, Ramin, Weber, Michel, Eter, Nicole, Feltgen, Nicolas, Grisanti, Salvatore, Walter, Peter, Liegl, Raffael, Lorenz, Katrin, Spital, Georg, Priglinger, Siegfried, Spitzer, Martin, Volker, Michael, Krohne, Tim, Jochmann, Claudia, Lohmann, Chris Patrick, Framme, Carsten, Kerenyi, Agnes, Papp, Andras, Seres, Andras, Toth-Molnar, Edit, Tsorbatzoglou, Alexis, Vajas, Atilla, Varsanyi, Balázs, Vogt, Gabor, Bar, Asaf, Eting, Eva, Hauser, David, Levy, Jamie, Mathalone, Nurit, Morori-Katz, Haia, Rosenblatt, Irit, Soudry-Zayit, Shiri, Trivizky, Omert, Bandello, Francesco, Ciardella, Antonio Pasquale, Figus, Michele, Giansanti, Fabrizio, Lanzetta, Paolo, Mariotti, Cesare, Mastropasqua, Leonardo, Midena, Edoardo, Parmeggiani, Francesco, Ricci, Federico, Simonelli, Francesca, Staurenghi, Giovanni, Viola, Francesco, Varano, Monica, Laganovska, Guna, Cisiecki, Sławomir, Jedrzejewski, Wojciech, Kaluzny, Jakub, Misiuk-Hojło, Marta, Abengoechea, Santiago, Iribarren, Javier Araiz, Ascaso, Franciso Javier, Cubero, Juan Manuel, Gallego-Pinazo, Roberto, Gomez-Ulla De Irazazabal, Francisco, Mestre, Ignasi Jürgens, Mones I Carilla, Jordi Manel, Montero Moreno, Javier, María Ruiz Moreno, José, Sararols Ramsay, Laura, Garcia Layana, Alfredo, Downey, Louise, Abraham, Prema, Alfaro, Daniel Virgil, Bagheri, Nika, Barbazetto, Irene, Benevento, Joseph, Bernstein, Paul, Bertolucci, George, Bhavsar, Abdhish, Bridges, William, Brooks, Jr, Harold Logan, Brown, Jamin, Brucker, Alexander, Calvo, Charles M., Capone, Antonio, Carlson, John, Chan, Clement, Chang, Emmanuel, Chan-Kai, Brian, Chaudhry, Nauman, Chen, Sanford, Csaky, Karl, Cummings, Howard, Danzig, Carl, Dessouki, Amr, Dyer, David, Eaton, Alexander, Eichenbaum, David, Faber, David, Feldman, Robert, Finnen, Neil, Freeman, William, Frenkel, Ronald, Gonzales, Christine, Gonzalez, Victor, Gross, John, Gupta, Sunil, Hall, Edward, Han, Min-Kyu, Heier, Jeffrey, Hershberger, Vrinda, Higgins, Patrick, Hsu, Jason, Ip, Michael, Jablon, Eric, Jewart, Brian, John, Vishak, Jonisch, Jonathan, Joondeph, Brian, Kay, Christine, Khanani, Arshad, Kokame, Gregg T., Kwun, Robert, Lai, Michael, Lally, David, Laud, Ketan, Lavina, Adrian, Lee, Michael, Lin, Phoebe, Lin, Haijiang, Manoharan, Niranjan, Marcus, Dennis, Martidis, Adam, McCabe, Frank, Nielsen, Jared, Osher, James, Palmer, James, Patel, Sunil, Pearlman, Joel, Perkins, Stephen, Pirouz, Ashkan, Qureshi, Jawad, Randolph, John, Piri, Niloofar, Rosenfeld, Phillip, Saperstein, David, Scartozzi, Richard, Schwartz, Steven, Sharma, Ashish, Sharma, Atul, Sheth, Veeral, Singer, Michael, Spinak, David, Suan, Eric, Tabandeh, Homayoun, Tabassian, Ali, Uchiyama, Eduardo, Varenhorst, Michael, Wagner, Alan, Warrow, David, Wells, III, John, Wong, Robert, Wong, Keye, Wykoff, Charles, Xavier, Samantha, Ysasaga, Edward, Khanani, Arshad M, Patel, Sunil S, Danzig, Carl J, Eichenbaum, David A, Wykoff, Charles C, Heier, Jeffrey S, Lally, David R, Monés, Jordi, Nielsen, Jared S, Sheth, Veeral S, Kaiser, Peter K, Clark, Julie, Zhu, Liansheng, Patel, Hersh, Tang, Justin, Desai, Dhaval, and Jaffe, Glenn J

Published
2023
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20. TRANSLACOL project: Nodal human papillomavirus tumoral DNA detection by ddPCR for survival prediction in early cervical cancer patients without pelvic lymph node invasion

Author

Montero-Macías, Rosa, Veyer, David, Bruneau, Thomas, Robillard, Nicolas, Le Frère-Belda, Marie-Aude, Rigolet, Pascal, Boulhic, Mélanie, Stankovic, Ivana, Bélec, Laurent, Angeles, Martina Aida, Mery, Eliane, Badoual, Cécile, Coronado, Pluvio J, Bats, Anne-Sophie, Mathevet, Patrice, Taly, Valérie, Lécuru, Fabrice, and Péré, Hélène

Published
2023
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22. Discovery and validation of a transcriptional signature identifying homologous recombination-deficient breast, endometrial and ovarian cancers

Author

Beinse, Guillaume, Just, Pierre-Alexandre, Le Frere Belda, Marie-Aude, Laurent-Puig, Pierre, Jacques, Sebastien, Koual, Meriem, Garinet, Simon, Leroy, Karen, Delanoy, Nicolas, Blons, Helene, Gervais, Claire, Durdux, Catherine, Chapron, Charles, Goldwasser, François, Terris, Benoit, Badoual, Cecile, Taly, Valerie, Bats, Anne-Sophie, Borghese, Bruno, and Alexandre, Jérôme

Published
2022
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26. Treatment of Multisystem Inflammatory Syndrome in Children: Understanding Differences in Results of Comparative Effectiveness Studies

Author

Michael Melgar, Eleanor G. Seaby, Andrew J. McArdle, Cameron C. Young, Angela P. Campbell, Nancy L. Murray, Manish M. Patel, Michael Levin, Adrienne G. Randolph, Mary Beth F. Son, and BATS Consortium and the Overcoming COVID‐19 Investigators

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Objective Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS‐C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS‐C definitions and differing disease severity between cohorts underlay discrepant results. Methods The Overcoming COVID‐19 Public Health Surveillance Registry (OC‐19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS‐C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC‐19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. Results Of 349 OC‐19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC‐19 patients had WHO‐defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC‐19 patients were more often admitted to intensive care (61.0% vs 44.8%, P

Published
2022
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27. Helicobacter pylori Modulates Heptose Metabolite Biosynthesis and Heptose-Dependent Innate Immune Host Cell Activation by Multiple Mechanisms

Author

Martina Hauke, Felix Metz, Johanna Rapp, Larissa Faass, Simon H. Bats, Sandra Radziej, Hannes Link, Wolfgang Eisenreich, and Christine Josenhans

Subjects
ADP-heptose, ALPK1-TIFA, Helicobacter pylori, mass spectrometry, NMR, bacterial metabolites, Microbiology, QR1-502
Abstract

ABSTRACT Heptose metabolites including ADP-d-glycero-β-d-manno-heptose (ADP-heptose) are involved in bacterial lipopolysaccharide and cell envelope biosynthesis. Recently, heptoses were also identified to have potent proinflammatory activity on human cells as novel microbe-associated molecular patterns. The gastric pathogenic bacterium Helicobacter pylori produces heptose metabolites, which it transports into human cells through its Cag type 4 secretion system. Using H. pylori as a model, we have addressed the question of how proinflammatory ADP-heptose biosynthesis can be regulated by bacteria. We have characterized the interstrain variability and regulation of heptose biosynthesis genes and the modulation of heptose metabolite production by H. pylori, which impact cell-autonomous proinflammatory human cell activation. HldE, a central enzyme of heptose metabolite biosynthesis, showed strong sequence variability between strains and was also variably expressed between strains. Amounts of gene transcripts in the hldE gene cluster displayed intrastrain and interstrain differences, were modulated by host cell contact and the presence of the cag pathogenicity island, and were affected by carbon starvation regulator A (CsrA). We reconstituted four steps of the H. pylori lipopolysaccharide (LPS) heptose biosynthetic pathway in vitro using recombinant purified GmhA, HldE, and GmhB proteins. On the basis of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, the structures of major reaction products were identified as β-d-ADP-heptose and β-heptose-1-monophosphate. A proinflammatory heptose-monophosphate variant was also identified for the first time as a novel cell-active product in H. pylori bacteria. Separate purified HldE subdomains and variant HldE allowed us to uncover additional strain variation in generating heptose metabolites. IMPORTANCE Bacterial heptose metabolites, intermediates of lipopolysaccharide (LPS) biosynthesis, are novel microbe-associated molecular patterns (MAMPs) that activate proinflammatory signaling. In the gastric pathogen Helicobacter pylori, heptoses are transferred into host cells by the Cag type IV secretion system, which is also involved in carcinogenesis. Little is known about how H. pylori, which is highly strain variable, regulates heptose biosynthesis and downstream host cell activation. We report here that the regulation of proinflammatory heptose production by H. pylori is strain specific. Heptose gene cluster activity is modulated by the presence of an active cag pathogenicity island (cagPAI), contact with human cells, and the carbon starvation regulator A. Reconstitution with purified biosynthesis enzymes and purified bacterial lysates allowed us to biochemically characterize heptose pathway products, identifying a heptose-monophosphate variant as a novel proinflammatory metabolite. These findings emphasize that the bacteria use heptose biosynthesis to fine-tune inflammation and also highlight opportunities to mine the heptose biosynthesis pathway as a potential therapeutic target against infection, inflammation, and cancer.

Published
2023
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29. Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM

Author

Ian Coombs, Cécile Bats, Craig A Sexton, Dorota Studniarczyk, Stuart G Cull-Candy, and Mark Farrant

Subjects
AMPA-type glutamate receptor, excitatory postsynaptic current, TARP, spermine, NASPM, rectification, Medicine, Science, Biology (General), QH301-705.5
Abstract

Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent channel block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits – including transmembrane AMPAR regulatory proteins, cornichons, and GSG1L – which are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here, we show that the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution results in a complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, completely blocks outward synaptic currents. Thus, our results identify a functional measure of CP-AMPARs, that is unaffected by their auxiliary subunit content.

Published
2023
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37. Impact of mixtures of persistent organic pollutants on breast cancer aggressiveness

Author

Louise Benoit, Meriem Koual, Céline Tomkiewicz, Anne-Sophie Bats, Jean-Philippe Antignac, Xavier Coumoul, Robert Barouki, and German Cano-Sancho

Subjects
Adipose tissue, Mammary cancer, Endocrine disrupting chemicals, Environmental exposure, Metastasis, Environmental sciences, GE1-350
Abstract

Introduction: Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness. Methods: Patients undergoing surgery for their BC were prospectively included in the METAPOP cohort. Forty-two POPs were extracted, among them 17 dioxins (PCDD/F), 16 polychlorobiphenyls (PCB), 8 polybromodiphenylethers (PBDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (PBB153) were measured in the adipose tissue surrounding the tumor. BC aggressiveness was defined using tumor size and metastasis (distant or lymph nodes). Two complementary models were used to evaluate the impact of the mixture of pollutants: the BKMR (Bayesian Kernel machine regression) and WQS (weighted quantile sum regression) models. The WQS estimates the weight (positive or negative) of a certain chemical based on its quantile and the BKMR model applies a kernel-based approach to estimate posterior inclusion probabilities. The sub-group of patients with a body mass index (BMI) > 22 kg/ m2 was also analyzed. Results: Ninety-one patients were included. Of these, 38 patients presented a metastasis, and the mean tumor size was 25.4 mm. The mean BMI was 24.5 kg/m2 (+/- 4.1). No statistical association was found in the general population. However, in patients with a BMI > 22 kg/ m2, our mixture was positively associated with tumor size (OR: 9.73 95 %CI: 1.30–18.15) and metastasis (OR = 3.98 95 %CI = 1.09–17.53) using the WQS model. Moreover, using the BKMR model on chemical families, dioxin like chemicals and PCDD were associated with a higher risk of metastasis. Discussion: These novel findings identified a mixture associated with breast cancer aggressiveness in patients with a BMI > 22 kg/ m2.

Published
2022
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41. Complete pathological response to olaparib and bevacizumab in advanced cervical cancer following chemoradiation in a BRCA1 mutation carrier: a case report

Author

Rosa Montero-Macias, Meriem Koual, Céline Crespel, Marie Aude Le Frére-Belda, Hélène Blons Hélène, Huyen-Thu Nguyen-Xuan, Simon Garinet, Géraldine Perkins, Vincent Balay, Catherine Durdux, Marie Florin, Hélène Péré, and Anne-Sophie Bats

Subjects
Advanced cervical cancer, BRCA1, PARP inhibitor, Olaparib, Precision oncology, Medicine
Abstract

Abstract Background Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer. Case presentation Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence. Conclusion Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.

Published
2021
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44. Environmental chemicals, breast cancer progression and drug resistance

Author

Meriem Koual, Céline Tomkiewicz, German Cano-Sancho, Jean-Philippe Antignac, Anne-Sophie Bats, and Xavier Coumoul

Subjects
Breast cancer, Environmental exposure, Organochlorine pesticides, Endocrine disrupting chemicals, Polychlorinated biphenyls, Perfluoroalkyl acid, Industrial medicine. Industrial hygiene, RC963-969, Public aspects of medicine, RA1-1270
Abstract

Abstract Breast cancer (BC) is one of the most common causes of cancer in the world and the second leading cause of cancer deaths among women. Mortality is associated mainly with the development of metastases. Identification of the mechanisms involved in metastasis formation is, therefore, a major public health issue. Among the proposed risk factors, chemical environment and pollution are increasingly suggested to have an effect on the signaling pathways involved in metastatic tumor cells emergence and progression. The purpose of this article is to summarize current knowledge about the role of environmental chemicals in breast cancer progression, metastasis formation and resistance to chemotherapy. Through a scoping review, we highlight the effects of a wide variety of environmental toxicants, including persistent organic pollutants and endocrine disruptors, on invasion mechanisms and metastatic processes in BC. We identified the epithelial-to-mesenchymal transition and cancer-stemness (the stem cell-like phenotype in tumors), two mechanisms suspected of playing key roles in the development of metastases and linked to chemoresistance, as potential targets of contaminants. We discuss then the recently described pro-migratory and pro-invasive Ah receptor signaling pathway and conclude that his role in BC progression is still controversial. In conclusion, although several pertinent pathways for the effects of xenobiotics have been identified, the mechanisms of actions for multiple other molecules remain to be established. The integral role of xenobiotics in the exposome in BC needs to be further explored through additional relevant epidemiological studies that can be extended to molecular mechanisms.

Published
2020
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