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5. 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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11. 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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12. 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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13. 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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18. 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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19. 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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25. 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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26. 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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27. 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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35. 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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36. 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

Le gac, Marjolaine, primary, Benoit, Louise, additional, Koual, Meriem, additional, Bentivegna, Enrica, additional, Bolze, Pierre Adrien, additional, kerbage, yohan, additional, Raimond, Emilie, additional, Lecointre, Lise, additional, Carcopino, Xavier, additional, Canlorbe, Geoffroy, additional, Philip, Charles Andre, additional, Nguyen-Xuan, Huyen-thu, additional, Bats, Anne-Sophie, additional, and Azais, Henri, additional

Published
2024
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40. HPV Molecular Genotyping as a Differential Diagnosis Tool in Cervical Cancer Metastasis

Author

Rosa Montero-Macías, Pluvio J. Coronado, Nicolas Robillard, David Veyer, Vincent Villefranque, Marie-Aude Le Frére-Belda, Elisabeth Auberger, Pauline Bitolog, Ivana Stankovic, Laurent Bélec, Anne-Sophie Bats, Fabrice Lécuru, and Hélène Péré

Subjects
HPV, cervical cancer, metastasis, HPV commercial genotyping assays, differential diagnostic tool, Medicine
Abstract

Background: Differentiating metastatic cervical cancer from another primary tumor can be difficult in patients with a history of cervical cancer and a distant lesion. The use of routine HPV molecular detection and genotyping tests could help in these cases. The objective of this study was to identify if an easy-to-use HPV molecular genotyping assay would allow differentiating between HPV tumor metastasis and a new independent primary non-HPV-induced tumor. Materials and Methods: Between 2010 and 2020, we identified patients with a primary cervical carcinoma who also had another secondary lesion. This identification included a clinical and histologic differential diagnosis of metastatic cervical cancer versus a new primary cancer or metastatic cancer from another site. We used a routine multiplex real-time PCR (rt-PCR) AnyplexTM II HPV28 (Seegene, Seoul, Republic of Korea) to detect the high-risk (HR)-HPV genome in the distant lesions in these patients. Results: Eight cases of cervical cancer with a new secondary lesion were identified. In seven, HR-HPV DNA was detected in the biopsy of the distant lesion, which confirmed the diagnosis of cervical cancer metastasis. In the remaining case, no HPV was detected in the secondary lung biopsy, confirming the diagnosis of new primary lung cancer. Conclusion: Our results pave the way for HPV molecular genotyping use in cases of newly diagnosed distant lesions in patients with a history of HPV cervical neoplasia by using a routine diagnosis process to complete the clinical and histologic differential diagnosis when confronted with ambiguous situations.

Published
2023
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41. A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer

Author

Marie Métairie, Louise Benoit, Meriem Koual, Enrica Bentivegna, Henri Wohrer, Pierre-Adrien Bolze, Yohan Kerbage, Emilie Raimond, Cherif Akladios, Xavier Carcopino, Geoffroy Canlorbe, Jennifer Uzan, Vincent Lavoué, Camille Mimoun, Cyrille Huchon, Martin Koskas, Hélène Costaz, François Margueritte, Yohann Dabi, Cyril Touboul, Sofiane Bendifallah, Lobna Ouldamer, Nicolas Delanoy, Huyen-Thu Nguyen-Xuan, Anne-Sophie Bats, and Henri Azaïs

Subjects
epithelial ovarian cancer, FIGO stage IV, metastatic patterns, prognosis, pleural involvement, overall survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

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

Author

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

Published
2023
Full Text
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48. A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration

Author

Timothy L. Jackson, Jason Slakter, Marc Buyse, Kun Wang, Pravin U. Dugel, Charles C. Wykoff, David S. Boyer, Michael Gerometta, Megan E. Baldwin, Clare F. Price, Bohdan Kousal, Jan Studnicka, Michal Veith, Catherine Creuzot-Garcher, Flore De Bats, David Gaucher, Martine Mauget-Faysse, Eric Souied, Ramin Tadayoni, Andrea Facsko, Agnes Kerénvi, Andras Papp, Alexis Tsorbatzoglou, Gabor Vogt, Yoreh Barak, Itay Chowers, Michaella Goldstein, Joel Hanhart, Haya Morori-Katz, Irit Rosenblatt, Alexander Rubowitz, Oren Tomkins Netzer, Francesco Bandello, Antonio Ciardella, Federico Ricci, Giovanni Staurenghi, Gianni Virgili, Kristine Baumane, Guna Laganovska, Signe Ozolina, Ilze Strautmane, Bartlomiej Kaluzny, Jerzy Mackiewicz, Marta Misiuk-Hoilo, Ewa Mrukwa-Kominek, Piotr Oleksy, Krystyna Raczynska, Tomasz Zarnowski, Alfredo Adan, Javier Araiz, Anna Boixadera, Alvaro Fernández-Vega, Alfredo Garcia Layana, Francisco Gomez-Ulla, Javier Montero, Jose Maria Ruiz Moreno, David Gilmour, Timothy Jackson, Sidath Liyanage, Luke Membrey, Geeta Menon, Niro Narendran, Sobha Sivaprasad, Daniel Alfaro, Andrew Antoszyk, Carl Baker, Ivan Batille, Brian Berger, David Boyer, William Bridges, Harold Brooks, David Brown, Margaret Chang, Daniel Chao, Sanford Chen, Courtney Crawford, Pravin Dugel, Alexander Eaton, David Eichenbaum, Jordana Fein, Leonard Feiner, Christina Flaxel, Frank Garber, Alan Gordon, Sunil Gupta, Curtis Haegedorn, George Hampton, Thomas Hanscom, Vrinda Hershberger, Peter Kaiser, Randy Katz, Arshad Khanani, Erik Kruger, Denis Marcus, Matthew Ohr, Sunil Patel, Joel Pearlman, Richard Pesavento, Dante Pieramici, John Pitcher, Jay Prensky, John Randolf, Carl Regillo, Steven Rose, Michael Samuel, Todd Schneiderman, Sumit Shah, Michael Singer, Nathan Steinle, Glenn Stoller, Alan Thach, John Thompson, Michael Varenhorst, Alan Wagner, Joseph Walker, John Wells, Jonathan Williams, Robert Wong, and Charles Wykoff

Subjects
Ophthalmology
Published
2023

50. #876 Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: the chipor randomised phase III trial

Author

Classe, Jean-Marc, primary, Meeus, Pierre, additional, Leblanc, Eric, additional, Wernert, Romuald, additional, Quenet, François, additional, Marchal, Frédéric, additional, Houvenaeghel, Gilles, additional, Bats, Anne-Sophie, additional, Lécuru, Fabrice, additional, Ferron, Gwenaël, additional, Brigand, Cécile, additional, Berton, Dominique, additional, Gladieff, Laurence, additional, Joly, Florence, additional, Coquard, Isabelle Ray, additional, Durand-Fontanier, Sylvaine, additional, Brument, Emilie, additional, Asselain, Bernard, additional, Campion, Loïc, additional, and Glehen, Olivier, additional

Published
2023
Full Text
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