2,282 results on '"Bachelot A"'
Search Results
2. Comparative analysis of molecular signatures suggests the use of gabapentin for the management of endometriosis-associated pain
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Bellessort B, Bachelot A, Grouthier V, De Lombares C, Narboux-Neme N, Garagnani P, Pirazzini C, Astigiano S, Mastracci L, Fontaine A, Alfama G, Duvernois-Berthet E, and Levi G
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endometriosis ,gabapentin ,CACNA2D3 ,Dlx5 ,pain ,Medicine (General) ,R5-920 - Abstract
Brice Bellessort,1 Anne Bachelot,1,2 Virginie Grouthier,2 Camille De Lombares,1 Nicolas Narboux-Neme,1 Paolo Garagnani,3,4 Chiara Pirazzini,3,4 Simonetta Astigiano,5 Luca Mastracci,6,7 Anastasia Fontaine,1 Gladys Alfama,1 Evelyne Duvernois-Berthet,1 Giovanni Levi1 1Evolution of Endocrine Regulations, Department AVIV, National Museum of Natural History, Paris, France; 2AP-HP, Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases, Pitié-Salpêtrière Hospital, UPMC, Paris, France; 3Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 4Interdepartmental Center “L. Galvani”, University of Bologna, Bologna, Italy; 5Department of Integrated Oncological Therapies, San Martino Hospital, Genova, Italy; 6Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genoa, Genova, Italy; 7Division of Anatomic Pathology, Department of Surgical Science and Integrated Diagnostics, University of Genoa, Genova, Italy Background: It has been repetitively shown that the transcription factors DLX5 and DLX6 are drastically downregulated in endometriotic lesions when compared with eutopic endometrium. These findings suggest that regulatory cascades involving DLX5/6 might be at the origin of endometriosis symptoms such as chronic pelvic pain (CPP). We have shown that inactivation of Dlx5 and Dlx5/6 in the mouse uterus results in an endometrial phenotype reminiscent of endometriosis. Methods: We focused on genes that present a similar deregulation in endometriosis and in Dlx5/6-null mice in search of new endometriosis targets. Results: We confirmed a strong reduction of DLX5 expression in endometriosis implants. We identified a signature of 30 genes similarly deregulated in human endometriosis implants and in Dlx5/6-null mouse uteri, reinforcing the notion that the downregulation of Dlx5/6 is an early event in the progress of endometriosis. CACNA2D3, a component of the α2δ family of voltage-dependent calcium channel complex, was strongly overexpressed both in mutant mouse uteri and in endometriosis implants, were also CACNA2D1 and CACNA2D2, other members of the α2δ family involved in nociception, are upregulated. Conclusion: Comparative analysis of gene expression signatures from endometriosis and mouse models showed that calcium channel subunits α2δ involved in nociception can be targets for the treatment of endometriosis-associated pain. CACNA2D3 has been associated with pain sensitization and heat nociception in animal models. In patients, CACNA2D3 variants were associated with reduced sensitivity to acute noxious stimuli. As α2δs were targets of gabapentinoid analgesics, the results suggested the use of these drugs for the treatment of endometriosis-associated pain. Indeed, recent small-scale clinical studies have shown that gabapentin could be effective in women with CPP. The findings of this study reinforce the need for a large definitive trial. Keywords: endometriosis, gabapentin, CACNA2D3, Dlx5, pain
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- 2018
3. Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors
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Sablin, Marie-Paule, Gestraud, Pierre, Jonas, Sarah Flora, Lamy, Constance, Lacroix-Triki, Magali, Bachelot, Thomas, Filleron, Thomas, Lacroix, Ludovic, Tran-Dien, Alicia, Jézéquel, Pascal, Mauduit, Marjorie, Barros Monteiro, Janice, Jimenez, Marta, Michiels, Stefan, Attignon, Valery, Soubeyran, Isabelle, Driouch, Keltouma, Servant, Nicolas, Le Tourneau, Christophe, Kamal, Maud, André, Fabrice, and Bièche, Ivan
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- 2024
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4. Machine learning approach to assess the association between anthropometric, metabolic, and nutritional status and semen parameters
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Guillaume Bachelot, Antonin Lamaziere, Sebastien Czernichow, Celine Faure, Chrystelle Racine, Rachel Levy, Charlotte Dupont, and Nutrition and Fertility (ALIFERT) Group
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lifestyle ,machine learning ,metabolism ,nutrition ,sperm dna fragmentation ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Many lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.
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- 2024
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5. Low to moderate dose 137Cs (γ) radiation promotes M2 type macrophage skewing and reduces atherosclerotic plaque CD68+ cell content in ApoE(−/−) mice
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Rey, N., Ebrahimian, T., Gloaguen, C., Kereselidze, D., Christelle, E., Brizais, C., Bachelot, F., Riazi, G., Monceau, V., Demarquay, C., Zineddine, I. Garali, Klokov, D., Lehoux, S., and Ebrahimian, Teni G.
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- 2024
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6. p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane
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Vanacker, Hélène, Treilleux, Isabelle, Schiffler, Camille, Bieche, Ivan, Campone, Mario, Patsouris, Anne, Arnedos, Monica, Cottu, Paul H., Jacquin, Jean-Philippe, Dalenc, Florence, Pinton, Antoine, Servant, Nicolas, Attignon, Valéry, Rouleau, Etienne, Morel, Alain, Legrand, François, Jimenez, Marta, Andre, Fabrice, and Bachelot, Thomas
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- 2024
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7. Low to moderate dose 137Cs (γ) radiation promotes M2 type macrophage skewing and reduces atherosclerotic plaque CD68+ cell content in ApoE(−/−) mice
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N. Rey, T. Ebrahimian, C. Gloaguen, D. Kereselidze, E. Christelle, C. Brizais, F. Bachelot, G. Riazi, V. Monceau, C. Demarquay, I. Garali Zineddine, D. Klokov, S. Lehoux, and Teni G. Ebrahimian
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Medicine ,Science - Abstract
Abstract The effects of low doses of ionizing radiation on atherosclerosis remain uncertain, particularly as regards the generation of pro- or anti-inflammatory responses, and the time scale at which such effects can occur following irradiation. To explore these phenomena, we exposed atheroprone ApoE(−/−) mice to a single dose of 0, 0.05, 0.5 or 1 Gy of 137Cs (γ) administered at a 10.35 mGy min−1 dose rate and evaluated short-term (1–10 days) and long-term consequences (100 days). Bone marrow-derived macrophages were derived from mice 1 day after exposure. Irradiation was associated with a significant skewing of M0 and M2 polarized macrophages towards the M2 phenotype, as demonstrated by an increased mRNA expression of Retnla, Arg1, and Chil3 in cells from mice exposed to 0.5 or 1 Gy compared with non-irradiated animals. Minimal effects were noted in M1 cells or M1 marker mRNA. Concurrently, we observed a reduced secretion of IL-1β but enhanced IL-10 release from M0 and M2 macrophages. Effects of irradiation on circulating monocytes were most marked at day 10 post-exposure, when the 1 Gy dose was associated with enhanced numbers of both Ly6CHigh and Ly6Low cells. By day 100, levels of circulating monocytes in irradiated and non-irradiated mice were equivalent, but anti-inflammatory Ly6CLow monocytes were significantly increased in the spleen of mice exposed to 0.05 or 1 Gy. Long term exposures did not affect atherosclerotic plaque size or lipid content, as determined by Oil red O staining, whatever the dose applied. Similarly, irradiation did not affect atherosclerotic plaque collagen or smooth muscle cell content. However, we found that lesion CD68+ cell content tended to decrease with rising doses of radioactivity exposure, culminating in a significant reduction of plaque macrophage content at 1 Gy. Taken together, our results show that short- and long-term exposures to low to moderate doses of ionizing radiation drive an anti-inflammatory response, skewing bone marrow-derived macrophages towards an IL-10-secreting M2 phenotype and decreasing plaque macrophage content. These results suggest a low-grade athero-protective effect of low and moderate doses of ionizing radiation.
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- 2024
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8. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial
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Rugo, Hope S, Im, Seock-Ah, Cardoso, Fatima, Cortes, Javier, Curigliano, Giuseppe, Musolino, Antonino, Pegram, Mark D, Bachelot, Thomas, Wright, Gail S, Saura, Cristina, Escrivá-de-Romaní, Santiago, De Laurentiis, Michelino, Schwartz, Gary N, Pluard, Timothy J, Ricci, Francesco, Gwin, William R, Levy, Christelle, Brown-Glaberman, Ursa, Ferrero, Jean-Marc, de Boer, Maaike, Kim, Sung-Bae, Petráková, Katarína, Yardley, Denise A, Freedman, Orit, Jakobsen, Erik H, Gal-Yam, Einav Nili, Yerushalmi, Rinat, Fasching, Peter A, Kaufman, Peter A, Ashley, Emily J, Perez-Olle, Raul, Hong, Shengyan, Rosales, Minori Koshiji, Gradishar, William J, and Group, on behalf of the SOPHIA Study
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Cancer ,Clinical Research ,Breast Cancer ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Humans ,Female ,Trastuzumab ,Breast Neoplasms ,Receptor ,ErbB-2 ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Combined Chemotherapy Protocols ,SOPHIA Study Group ,Receptor ,erbB-2 ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.
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- 2023
9. Insights adjusting for non-adherence in randomized clinical trials: a reanalysis of an adjuvant trial of tamoxifen duration in early breast cancer
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Giudici, Fabiola, Pistilli, Barbara, Vaz-Luis, Ines, Karimi, Maryam, Delaloge, Suzette, Bachelot, Thomas, Michiels, Stefan, and Bardet, Aurelie
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- 2023
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10. Using imaging spectroscopy to assess the impacts of invasive plants on aboveground and belowground characteristics
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M. Ny Aina Rakotoarivony, Hamed Gholizadeh, Kianoosh Hassani, Shelby McMahan, Elizabeth Struble, Samuel Fuhlendorf, Robert Hamilton, and Benedicte Bachelot
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Invasive plants ,imaging spectroscopy ,plant functional traits ,belowground characteristics ,Mathematical geography. Cartography ,GA1-1776 ,Environmental sciences ,GE1-350 - Abstract
Invasive plants are threats to biodiversity, ecosystem functioning, and services. Previous studies have reported that the impacts of biological invasions on ecosystem characteristics can be scale- and ecosystem-dependent. Current methods to assess the impacts of biological invasions have mainly focused on traditional field observations, limiting the scale at which biological invasions can be studied. With its synoptic view, remote sensing can contribute to improving our understanding of the impacts of biological invasions across large spatial scales. However, the application of remote sensing to determine the impacts of invasive plants on ecosystem characteristics, including aboveground and belowground, has not yet been explored. Therefore, our goals were to (1) determine the impacts of invasive plants on aboveground functional traits and productivity, (2) assess the underlying mechanisms through which species invasion impacts belowground characteristics, and (3) determine the capability of remotely-sensed data to capture the impacts of species invasion on aboveground and belowground characteristics. To address our goals, we focused on Lespedeza cuneata (L. cuneata), an invasive legume at the Joseph H. Williams Tallgrass Prairie Preserve in Oklahoma, U.S. We measured percent cover of L. cuneata, quantified aboveground biomass, collected top-of-canopy foliage samples and soil samples in the field, and collected airborne imaging spectroscopy. We used remotely-sensed spectral data and in situ-measured traits to estimate plant functional traits and aboveground biomass. We then assessed the impacts of L. cuneata invasion on aboveground functional traits and biomass using generalized additive models. We also identified the mechanisms through which L. cuneata impacted belowground characteristics using structural equation models. We developed generalized joint attribute models using in situ aboveground and belowground characteristics and predicted belowground characteristics throughout our study site by applying the developed model to remotely-sensed aboveground characteristics. Our findings showed that L. cuneata invasion shifted aboveground functional traits toward those of L. cuneata by significantly increasing community-weighted mean (CWM) foliar nitrogen and phosphorus concentrations. Moreover, L. cuneata significantly increased aboveground biomass, a proxy for aboveground productivity. We also showed that imaging spectroscopy captured the impacts of species invasion on aboveground functional traits and productivity. More importantly, we provided substantial evidence suggesting that imaging spectroscopy can be used to predict belowground characteristics through the aboveground-belowground linkages. These findings can significantly advance our understanding of the impacts of biological invasions on belowground characteristics across large scales which is often challenging to quantify using field methods.
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- 2024
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11. Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trialResearch in context
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Sylvie Giacchetti, Enora Laas, Thomas Bachelot, Jérome Lemonnier, Fabrice André, David Cameron, Judith Bliss, Sylvie Chabaud, Anne-Claire Hardy- Bessard, Magali Lacroix-Triki, Jean-Luc Canon, Marc Debled, Mario Campone, Paul Cottu, Florence Dalenc, Annabelle Ballesta, Frederique Penault-Llorca, Bernard Asselain, Elise Dumas, Fabien Reyal, Paul Gougis, Francis Lévi, and Anne-Sophie Hamy
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Breast cancer ,Endocrine therapy ,Tamoxifen ,Aromatase inhibitors ,Circadian rhythm ,Intake timing ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). Methods: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00–11:59 (morning), 12:00–17:59 (afternoon), 18:00–23:59 (evening), or 24:00–05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. Findings: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53–1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22–0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68–1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16–0.91]). Interpretation: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. Funding: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.
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- 2024
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12. Trastuzumab deruxtecan in previously treated HER2‐positive metastatic or unresectable breast cancer: Real‐life data from the temporary use authorization program in France
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Thierry Petit, Nawale Hajjaji, Eric‐Charles Antoine, Marc‐Antoine Benderra, Michel Gozy, Cyril Foa, Jean‐Loup Mouysset, Julien Grenier, Mireille Mousseau, Audrey Mailliez, Mahasti Saghatchian, Emma Lachaier, Isabelle Desmoulins, Audrey Hennequin, Patricia Maes, Delphine Loirat, Francesco Ricci, Véronique Diéras, Dominique Berton, Florence Lai Tiong, Luis Teixeira, Nadine Dohollou, Christelle Lévy, Thomas Bachelot, and Jean‐Yves Pierga
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breast cancer ,early‐access program ,HER2‐positive ,metastatic cancer ,trastuzumab deruxtecan ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T‐DXd) in France based on DESTINY‐Breast01 trial which demonstrated its efficacy and safety in HER2‐positive metastatic/unresectable breast cancer after ≥2 anti‐HER2‐based regimens received at metastatic stage. Methods This multicenter real‐world early access program included HER2‐positive metastatic/unresectable breast patients pretreated with at least two lines of anti‐HER2 regimens who received T‐DXd 5.4 mg/kg intravenously in monotherapy every 3 weeks. Results Four hundred and fifty‐nine patients (median age, 58 years; hormone receptor‐positive, 67%; brain metastases, 28.1%) received T‐DXd. Before inclusion, 81.7% of patients had radiation therapy and 76.5% had undergone surgery. Median number of prior metastatic treatment lines was four (range, 2–22); 99.8% patients had received trastuzumab, 94.8% trastuzumab emtansine and 79.3% pertuzumab. Follow‐up was performed from September 30, 2020 to March 30, 2021; when the early access program stopped, the median duration of T‐DXd treatment was 3.4 (range, 0–7.8) months. In 160 patients with available tumor assessment, objective response rate was 56.7% and 12.1% had progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was reported for 35.7% patients and 5.4% had progression. A total of 17 (3.7%) patients with interstitial lung disease (ILD) was reported with no cases of ILD‐related death. Conclusions In this early access program in patients with heavily pretreated HER2‐positive metastatic/unresectable breast cancer, T‐DXd had antitumor activity with a similar response to that reported in previous clinical studies. T‐DXd was well tolerated and no new safety signals were observed.
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- 2024
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13. Long-term outcomes in non-CAH 46,XX DSD
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Virginie Grouthier and Anne Bachelot
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disorders of sex development ,non-CAH 46,XX DSD ,quality of life ,gender identity ,fertility ,sexuality ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.
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- 2024
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14. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
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Mosele, Fernanda, Deluche, Elise, Lusque, Amelie, Le Bescond, Loïc, Filleron, Thomas, Pradat, Yoann, Ducoulombier, Agnes, Pistilli, Barbara, Bachelot, Thomas, Viret, Frederic, Levy, Christelle, Signolle, Nicolas, Alfaro, Alexia, Tran, Diep T. N., Garberis, Ingrid Judith, Talbot, Hugues, Christodoulidis, Stergios, Vakalopoulou, Maria, Droin, Nathalie, Stourm, Aurelie, Kobayashi, Maki, Kakegawa, Tomoya, Lacroix, Ludovic, Saulnier, Patrick, Job, Bastien, Deloger, Marc, Jimenez, Marta, Mahier, Celine, Baris, Vianney, Laplante, Pierre, Kannouche, Patricia, Marty, Virginie, Lacroix-Triki, Magali, Diéras, Veronique, and André, Fabrice
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- 2023
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15. Local Optical Chirality Induced by Near-Field Mode Interference in Achiral Plasmonic Metamolecules
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Horrer, Andreas, Zhang, Yinping, Gérard, Davy, Béal, Jérémie, Kociak, Mathieu, Plain, Jérôme, and Bachelot, Renaud
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Physics - Optics - Abstract
When circularly polarized light interacts with a nanostructure, the optical response depends on the geometry of the structure. If the nanostructure is chiral (i.e., it cannot be superimposed on its mirror image), then its optical response, both in near-field and far-field, depends on the handedness of the incident light. In contrast, achiral structures exhibit identical far-field responses for left- and right-circular polarization. Here, we show that a perfectly achiral nanostructure, a plasmonic metamolecule with trigonal D3h symmetry, exhibits a near-field response that is sensitive to the handedness of light. This effect stems from the near-field interference between the different plasmonic modes sustained by the plasmonic metamolecule under circularly polarized light excitation. The local chirality in a plasmonic trimer is then experimentally evidenced with nanoscale resolution using a molecular probe. Our experiments demonstrate that the optical near-field chirality can be imprinted into the photosensitive polymer, turning an optical chirality into a geometrical chirality that can be imaged using atomic force microscopy. These results are of interest for the field of polarization-sensitive photochemistry.
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- 2021
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16. X-ray Radiotherapy Impacts Cardiac Dysfunction by Modulating the Sympathetic Nervous System and Calcium Transients
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Justyne Feat-Vetel, Nadine Suffee, Florence Bachelot, Morgane Dos Santos, Nathalie Mougenot, Elise Delage, Florian Saliou, Sabrina Martin, Isabelle Brunet, Pierre Sicard, and Virginie Monceau
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breast cancer ,cardiovascular disease ,radiotherapy ,ionizing radiation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC.
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- 2024
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17. The Dirac Sea for the Non-Separable Hilbert Spaces
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Bachelot, Alain
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Mathematical Physics ,81Q, 81T - Abstract
We give a rigorous construction of the Dirac Sea for the fermionic quantization in the non-separable Hilbert spaces. These CAR-representations depend on the Axiom of Choice, hence are not unique, nevertheless they are unitarily equivalent to the classic Fock representation.
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- 2021
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18. Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial
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Giacchetti, Sylvie, Laas, Enora, Bachelot, Thomas, Lemonnier, Jérome, André, Fabrice, Cameron, David, Bliss, Judith, Chabaud, Sylvie, Hardy- Bessard, Anne-Claire, Lacroix-Triki, Magali, Canon, Jean-Luc, Debled, Marc, Campone, Mario, Cottu, Paul, Dalenc, Florence, Ballesta, Annabelle, Penault-Llorca, Frederique, Asselain, Bernard, Dumas, Elise, Reyal, Fabien, Gougis, Paul, Lévi, Francis, and Hamy, Anne-Sophie
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- 2024
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19. Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial
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Penault-Llorca, F., Dalenc, F., Chabaud, S., Cottu, P., Allouache, D., Cameron, D., Grenier, J., Venat Bouvet, L., Jegannathen, A., Campone, M., Debled, M., Hardy-Bessard, A.-C., Giacchetti, S., Barthelemy, P., Kaluzinski, L., Mailliez, A., Mouret-Reynier, M.-A., Legouffe, E., Cayre, A., Martinez, M., Delbaldo, C., Mollon-Grange, D., Macaskill, E.J., Sephton, M., Stefani, L., Belgadi, B., Winter, M., Orfeuvre, H., Lacroix-Triki, M., Bonnefoi, H., Bliss, J., Canon, J.-L., Lemonnier, J., Andre, F., and Bachelot, T.
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- 2024
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20. Incidence and outcome of brain and/or leptomeningeal metastases in HER2-low metastatic breast cancer in the French ESME cohort
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Epaillard, N., Lusque, A., Jacot, W., Mailliez, A., Bachelot, T., Arnedos, M., Le Du, F., Brain, E., Ferrero, J.M., Massard, V., Desmoulins, I., Mouret-Reynier, M.A., Levy, C., Gonçalves, A., Leheurteur, M., Petit, T., Filleron, T., Bosquet, L., Pistilli, B., and Frenel, J.S.
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- 2024
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21. Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database
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Courtinard, Coralie, Gourgou, Sophie, Jacot, William, Carton, Matthieu, Guérin, Olivier, Vacher, Laure, Bertaut, Aurélie, Le Deley, Marie-Cécile, Pérol, David, Marino, Patricia, Levy, Christelle, Uwer, Lionel, Perrocheau, Geneviève, Schiappa, Renaud, Bachelot, Florence, Parent, Damien, Breton, Mathias, Petit, Thierry, Filleron, Thomas, Loeb, Agnès, Mathoulin-Pélissier, Simone, Robain, Mathieu, Delaloge, Suzette, and Bellera, Carine
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- 2023
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22. Long-term response to sequential anti-HER2 therapies including trastuzumab-deruxtecan in a patient with HER2-positive metastatic breast cancer with leptomeningeal metastases: a case report and review of the literature
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Axel de Bernardi, Thomas Bachelot, and Louis Larrouquère
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leptomeningeal metastasis ,breast cancer ,HER2 ,trastuzumab-deruxtecan ,tucatinib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The incidence of leptomeningeal metastases (LM) is increasing among breast cancer patients, but their prognosis remains dismal. Many therapeutic options are now available to treat HER2-positive (HER2+) metastatic breast cancer (MBC) involving the central nervous system (CNS). This case report illustrates a long-lasting response of more than 2 years in a patient with HER2+ MBC with LM after sequential administration of systemic and intrathecal (IT) anti-HER2 therapies and highlights that an appropriate treatment of HER2+ LM can result in durable survival.
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- 2024
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23. Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation
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Frenel, J.-S., Lusque, A., Delaloge, S., Ferrero, J.-M., Bachelot, T., Desmoulins, I., Levy, C., Eymard, J.-C., Gonçalves, A., Patsouris, A., Reynier, M. A. Mouret, Thery, M. J.-C., Petit, T., Cabel, L., Uwer, L., Debled, M., Chevrot, M., Mailliez, A., Jacot, W., and de La Motte Rouge, T.
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- 2023
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24. Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated with Metronomic Cyclophosphamide: A Clinical and Translational Prospective Study
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Mery B, Ménétrier-Caux C, Montané L, Heudel PE, Ray-Coquard I, Bachelot T, Derbel O, Augereau P, Treilleux I, Berthet J, Nkodia A, Bardin-Dit-Courageot C, Attignon V, Ferrari A, Garin G, Perol D, Caux C, Dubois B, and Trédan O
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metastatic breast cancer ,lymphopenia ,immunotherapy ,chemotherapy ,immunomonitoring ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Benoîte Mery,1,2,* Christine Ménétrier-Caux,2,3,* Laure Montané,4 Pierre-Etienne Heudel,1 Isabelle Ray-Coquard,1 Thomas Bachelot,1 Olfa Derbel,5 Paule Augereau,6 Isabelle Treilleux,2,7 Justine Berthet,2,3 Axelle Nkodia,3 Christine Bardin-Dit-Courageot,3 Valery Attignon,8 Anthony Ferrari,9 Gwenaele Garin,4 David Perol,4 Christophe Caux,2,3 Bertrand Dubois,2,3,* Olivier Trédan1,2,* 1Department of Medical Oncology, Centre Léon Bérard, Lyon, France; 2Inserm U1052, CNRS 5286, Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, Lyon, France; 3Laboratory of Cancer Immunotherapy of LYON (LICL), Centre Léon Bérard, Lyon, France; 4Clinical Research Platform (DRCI), Centre Léon Bérard, Lyon, France; 5Department of Medical Oncology, Hôpital Privé Jean-Mermoz, Lyon, France; 6Department of Medical Oncology, Institut de Cancérologie de L’ouest- Paul Papin, Angers, France; 7Biopathology Department, Centre Léon Bérard, Lyon, France; 8Genomic of Cancer Platform, Centre Léon Bérard, Lyon, France; 9Gilles Thomas Bioinformatics Platform, Synergie Lyon Cancer Foundation, Centre Léon Bérard, Lyon, France*These authors contributed equally to this workCorrespondence: Benoîte Mery, Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France, Tel +33 4 78 78 26 44, Fax +33 4 78 78 27 15, Email Benoite.mery@lyon.unicancer.frPurpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide.Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon’s minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS).Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4+ T cells and higher CD8+ T cells to macrophage ratios in the tumor. This impact on CD4+ and CD8+ T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4+ and CD8+ memory T cells was observed in other patients.Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations.Keywords: metastatic breast cancer, lymphopenia, immunotherapy, chemotherapy, immunomonitoring
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- 2023
25. Hybrid plasmonic nano-emitters with controlled single quantum emitter positioning on the local excitation field
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Ge, Dandan, Marguet, Sylvie, Issa, Ali, Jradi, Safi, Nguyen, Tien Hoa, Nahra, Mackrine, Béal, Jéremie, Deturche, Régis, Chen, Hongshi, Blaize, Sylvain, Plain, Jérôme, Fiorini, Céline, Douillard, Ludovic, Soppera, Olivier, Dinh, Xuan Quyen, Dang, Cuong, Yang, Xuyong, Xu, Tao, Wei, Bin, Sun, Xiao Wei, Couteau, Christophe, and Bachelot, Renaud
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Physics - Optics ,Condensed Matter - Materials Science ,Quantum Physics - Abstract
Hybrid plasmonic nanoemitters based on the combination of quantum dot emitters (QD) and plasmonic nanoantennas open up new perspectives in the control of light. However, precise positioning of any active medium at the nanoscale constitutes a challenge. Here, we report on the optimal overlap of antenna's near-field and active medium whose spatial distribution is controlled via a plasmon-triggered 2-photon polymerization of a photosensitive formulation containing QDs. Au nanoparticles of various geometries are considered. The response of these hybrid nano-emitters is shown to be highly sensitive to the light polarization. Different light emission states are evidenced by photoluminescence measurements. These states correspond to polarization-sensitive nanoscale overlap between the exciting local field and the active medium distribution. The decrease of the QD concentration within the monomer formulation allows trapping of a single quantum dot in the vicinity of the Au particle. The latter objects show polarization-dependent switching in the single-photon regime.
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- 2020
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26. Propagation of Massive Scalar Fields in Pre-Big Bang Cosmologies
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Bachelot, Alain
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Mathematical Physics ,35Q75, 35Q40 - Abstract
We investigate the linear and semilinear massive Klein-Gordon equations in geometrical frameworks of type "Conformal Cyclic Cosmology" of R. Penrose, or "Singular Bouncing Scenario" as well. We give sufficient conditions on the decay of the mass to the fields be able to propagate across the Big-Bang.
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- 2020
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27. Rs867228 in FPR1 accelerates the manifestation of luminal B breast cancer
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Vincent Carbonnier, Julie Le Naour, Thomas Bachelot, Erika Vacchelli, Fabrice André, Suzette Delaloge, and Guido Kroemer
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Cancer screening ,immunodeficiency ,immunosurveillance ,mammary carcinoma ,polygenic risk score ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ABSTRACTFormyl peptide receptor-1 (FPR1) is a pathogen recognition receptor involved in the detection of bacteria, in the control of inflammation, as well as in cancer immunosurveillance. A single nucleotide polymorphism in FPR1, rs867228, provokes a loss-of-function phenotype. In a bioinformatic study performed on The Cancer Genome Atlas (TCGA), we observed that homo-or heterozygosity for rs867228 in FPR1 (which affects approximately one-third of the population across continents) accelerates age at diagnosis of specific carcinomas including luminal B breast cancer by 4.9 years. To validate this finding, we genotyped 215 patients with metastatic luminal B mammary carcinomas from the SNPs To Risk of Metastasis (SToRM) cohort. The first diagnosis of luminal B breast cancer occurred at an age of 49.2 years for individuals bearing the dysfunctional TT or TG alleles (n = 73) and 55.5 years for patients the functional GG alleles (n = 141), meaning that rs867228 accelerated the age of diagnosis by 6.3 years (p=0.0077, Mann & Whitney). These results confirm our original observation in an independent validation cohort. We speculate that it may be useful to include the detection of rs867228 in breast cancer screening campaigns for selectively increasing the frequency and stringency of examinations starting at a relatively young age.
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- 2023
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28. Marie-Anne Dujarier (dir.), Idées reçues sur le travail. Emploi, activité, organisation
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Mathis Bachelot
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Labor. Work. Working class ,HD4801-8943 ,Sociology (General) ,HM401-1281 - Published
- 2023
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29. Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database
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Coralie Courtinard, Sophie Gourgou, William Jacot, Matthieu Carton, Olivier Guérin, Laure Vacher, Aurélie Bertaut, Marie-Cécile Le Deley, David Pérol, Patricia Marino, Christelle Levy, Lionel Uwer, Geneviève Perrocheau, Renaud Schiappa, Florence Bachelot, Damien Parent, Mathias Breton, Thierry Petit, Thomas Filleron, Agnès Loeb, Simone Mathoulin-Pélissier, Mathieu Robain, Suzette Delaloge, and Carine Bellera
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Real-word data ,Breast cancer ,Overall survival ,Progression-free survival ,Association ,Surrogacy ,Medicine - Abstract
Abstract Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). Methods We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan–Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman’s correlation coefficient. Analyses were conducted by tumor subtype. Results 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8–6.2) for HR-/HER2 − subtype to 13.3 months (36% CI 12.7–14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR − /HER2 − mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. Conclusions Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.
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- 2023
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30. Changes in the clinical management of 5α-reductase type 2 and 17β-hydroxysteroid dehydrogenase type 3 deficiencies in France
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Estelle Bonnet, Mathias Winter, Delphine Mallet, Ingrid Plotton, Claire Bouvattier, Maryse Cartigny, Laetiti Martinerie, Michel Polak, Anne Bachelot, Frédéric Huet, Sabine Baron, Muriel Houang, Sylvie Soskin, Anne Lienhardt, Jérôme Bertherat, Cyril Amouroux, Aurore Bouty, Lise Duranteau, Rémi Besson, Alaa El Ghoneimi, Dinane Samara-Boustani, François Becmeur, Nicolas Kalfa, Françoise Paris, François Medjkane, Aude Brac de la Perrière, Patricia Bretones, Hervé Lejeune, Marc Nicolino, Pierre Mouriquand, Daniela-Brindusa Gorduza, and Claire-Lise Gay
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5α-reductase type 2 deficiency ,17β-hydroxysteroid dehydrogenase type 3 deficiency ,46 ,xy disorders of sex development ,sex assignment ,change in practices ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objectives: To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available. Methods: Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994–2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth. Results: Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients’ age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0–53.2) years for patients born before 2007 and 0.4 (0–9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood. Conclusion: This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.
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- 2023
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31. Two-photon photopolymerization directly initiated by spiropyran photochromic molecules
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Dandan Ge, Jean Aubard, Erell Bodinier, Safi Jradi, Stéphanie Lau-Truong, Nordin Felidj, Renaud Bachelot, and Anne-Laure Baudrion
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spiropyran ,direct laser writing ,two-photon-photopolymerization ,photochromism ,Manufactures ,TS1-2301 ,Applied optics. Photonics ,TA1501-1820 - Abstract
Here, we report the ability of spiropyrans to initiate two-photon polymerization (TPP) for the first time in the literature. The comparison and synergies between the spiropyran photochromic molecule of interest, namely 6-nitro-BIPS, and well-known photoinitiators of radical photopolymerization have been studied. The spiropyran (SPy) molecule can initiate TPP in the presence of trifunctional acrylic monomers and create true 3D structures. The comparison with Irgacure 819, a well-known Type-I photoinitiator, shows that SPy has a comparable capability for TPP. In addition, the combination of SPy with methyl diethanolamine increased the reactivity of both one- and two-photon polymerizations. In the last section, we discuss which SPy isomer is the active photochromic species capable of generating radicals for initiating two-photon polymerization.
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- 2023
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32. Soluble endoglin reduces thrombus formation and platelet aggregation via interaction with αIIbβ3 integrin
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Rossi, Elisa, Pericacho, Miguel, Kauskot, Alexandre, Gamella-Pozuelo, Luis, Reboul, Etienne, Leuci, Alexandre, Egido-Turrion, Cristina, El Hamaoui, Divina, Marchelli, Aurore, Fernández, Francisco J., Margaill, Isabelle, Vega, M. Cristina, Gaussem, Pascale, Pasquali, Samuela, Smadja, David M., Bachelot-Loza, Christilla, and Bernabeu, Carmelo
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- 2023
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33. Genomics to select treatment for patients with metastatic breast cancer
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Andre, Fabrice, Filleron, Thomas, Kamal, Maud, Mosele, Fernanda, Arnedos, Monica, Dalenc, Florence, Sablin, Marie-Paule, Campone, Mario, Bonnefoi, Hervé, Lefeuvre-Plesse, Claudia, Jacot, William, Coussy, Florence, Ferrero, Jean-Marc, Emile, George, Mouret-Reynier, Marie-Ange, Thery, Jean-Christophe, Isambert, Nicolas, Mege, Alice, Barthelemy, Philippe, You, Benoit, Hajjaji, Nawale, Lacroix, Ludovic, Rouleau, Etienne, Tran-Dien, Alicia, Boyault, Sandrine, Attignon, Valery, Gestraud, Pierre, Servant, Nicolas, Le Tourneau, Christophe, Cherif, Linda Larbi, Soubeyran, Isabelle, Montemurro, Filippo, Morel, Alain, Lusque, Amelie, Jimenez, Marta, Jacquet, Alexandra, Gonçalves, Anthony, Bachelot, Thomas, and Bieche, Ivan
- Published
- 2022
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34. EPAC1 inhibition protects the heart from doxorubicin-induced toxicity
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Marianne Mazevet, Anissa Belhadef, Maxance Ribeiro, Delphine Dayde, Anna Llach, Marion Laudette, Tiphaine Belleville, Philippe Mateo, Mélanie Gressette, Florence Lefebvre, Ju Chen, Christilla Bachelot-Loza, Catherine Rucker-Martin, Frank Lezoualch, Bertrand Crozatier, Jean-Pierre Benitah, Marie-Catherine Vozenin, Rodolphe Fischmeister, Ana-Maria Gomez, Christophe Lemaire, and Eric Morel
- Subjects
doxorubicin ,cardiotoxicity ,EPAC1 ,cardiology ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the exchange protein directly activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered in vivo, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 knock-out (KO) mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.
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- 2023
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35. The role of pneumococcal extracellular vesicles on the pathophysiology of the kidney disease hemolytic uremic syndrome
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Miriana Battista, Bianca Hoffmann, Yann Bachelot, Lioba Zimmermann, Laura Teuber, Aurélie Jost, Susanne Linde, Martin Westermann, Mario M. Müller, Hortense Slevogt, Sven Hammerschmidt, Marc Thilo Figge, Cláudia Vilhena, and Peter F. Zipfel
- Subjects
extracellular vesicles ,immunomodulation ,cytokines ,microbe-host ,Microbiology ,QR1-502 - Abstract
ABSTRACT Streptococcus pneumoniae-induced hemolytic uremic syndrome (Sp-HUS) is a kidney disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. This disease is frequently underdiagnosed and its pathophysiology is poorly understood. In this work, we compared clinical strains, isolated from infant Sp-HUS patients, with a reference pathogenic strain D39, for host cytotoxicity and further explored the role of Sp-derived extracellular vesicles (EVs) in the pathogenesis of an HUS infection. In comparison with the wild-type strain, pneumococcal HUS strains caused significant lysis of human erythrocytes and increased the release of hydrogen peroxide. Isolated Sp-HUS EVs were characterized by performing dynamic light-scattering microscopy and proteomic analysis. Sp-HUS strain released EVs at a constant concentration during growth, yet the size of the EVs varied and several subpopulations emerged at later time points. The cargo of the Sp-HUS EVs included several virulence factors at high abundance, i.e., the ribosomal subunit assembly factor BipA, the pneumococcal surface protein A, the lytic enzyme LytC, several sugar utilization, and fatty acid synthesis proteins. Sp-HUS EVs strongly downregulated the expression of the endothelial surface marker platelet endothelial cell adhesion molecule-1 and were internalized by human endothelial cells. Sp-HUS EVs elicited the release of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6) and chemokines (CCL2, CCL3, CXCL1) by human monocytes. These findings shed new light on the overall function of Sp-EVs, in the scope of infection-mediated HUS, and suggest new avenues of research for exploring the usefulness of Sp-EVs as therapeutic and diagnostic targets. IMPORTANCE Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) is a serious and underdiagnosed deadly complication of invasive pneumococcal disease. Despite the introduction of the pneumococcal vaccine, cases of Sp-HUS continue to emerge, especially in children under the age of 2. While a lot has been studied regarding pneumococcal proteins and their role on Sp-HUS pathophysiology, little is known about the role of extracellular vesicles (EVs). In our work, we isolate and initially characterize EVs from a reference pathogenic strain (D39) and a strain isolated from a 2-year-old patient suffering from Sp-HUS. We demonstrate that despite lacking cytotoxicity toward human cells, Sp-HUS EVs are highly internalized by endothelial cells and can trigger cytokine and chemokine production in monocytes. In addition, this work specifically highlights the distinct morphological characteristics of Sp-HUS EVs and their unique cargo. Overall, this work sheds new light into potentially relevant players contained in EVs that might elucidate about pneumococcal EVs biogenesis or pose as interesting candidates for vaccine design.
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- 2023
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36. Evolving perspectives on the treatment of HR+/HER2+ metastatic breast cancer
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Mark Pegram, Richard Pietras, Chau T. Dang, Rashmi Murthy, Thomas Bachelot, Wolfgang Janni, Priyanka Sharma, Erika Hamilton, and Cristina Saura
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Breast cancer (BC) with expression of the estrogen receptor (ER) and/or progesterone receptor (PR) protein and with overexpression/amplification of the human epidermal growth factor receptor 2 (HER2), termed hormone receptor-positive (HR+)/HER2+ BC, represents ∼10% of all BCs in the United States. HR+/HER2+ BC includes HER2+ BCs that are ER+, PR+, or both ER+ and PR+ (triple-positive BC). Although the current guideline-recommended treatment combination of anti-HER2 monoclonal antibodies plus chemotherapy is an effective first-line therapy for many patients with HER2+ advanced disease, intratumoral heterogeneity within the HR+/HER2+ subtype and differences between the HR+/HER2+ subtype and the HR−/HER2+ subtype suggest that other targeted combinations could be investigated in randomized clinical trials for patients with HR+/HER2+ BC. In addition, published data indicate that crosstalk between HRs and HER2 can lead to treatment resistance. Dual HR and HER2 pathway targeting has been shown to be a rational approach to effective and well-tolerated therapy for patients with tumors driven by HER2 and HR, as it may prevent development of resistance by blocking receptor pathway crosstalk. However, clinical trial data for such approaches are limited. Treatments to attenuate other signaling pathways involved in receptor crosstalk are also under investigation for inclusion in dual receptor targeting regimens. These include cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, based on the rationale that association of CDK4/6 with cyclin D1 may play a role in resistance to HER2-directed therapies, and others such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitors. Herein, we will review the scientific and clinical rationale for combined receptor blockade targeting HER2 and ER for patients with advanced-stage HR+/HER2+ disease.
- Published
- 2023
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37. Hybrid plasmonic nanosystem with controlled position of nanoemitters
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Broussier, Aurelie, Issa, Ali, Cunff, Loic O. Le, Nguyen, Tien Hoa, Quyen, Dinh Xuan, Blaize, Sylvain, Plain, Jérôme, Jradi, Safi, Couteau, Christophe, and Bachelot, Renaud
- Subjects
Condensed Matter - Mesoscale and Nanoscale Physics ,Physics - Optics - Abstract
Quantum dots optically excited in close proximity to a silver nanowire can launch nanowire surface plasmons. The challenge related to this promising hybrid system is to control the position of nanoemitters on the nanowire. We report on the use of two-photon photopolymerization process to strategically position quantum dots on nanowires at controlled sites. A parametric study of the distance between the quantum dots and the nanowire extremity shows that precise control of the position of the launching sites enables control of light intensity at the wire end, through surface plasmon propagation.
- Published
- 2019
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38. Unidirectional frequency conversion of surface plasmon polaritons on metal nanowires
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Broussier, Aurélie, Issa, Ali, Le Cunff, Loïc O., Deturche, Régis, Nguyen, Tien Hoa, Quyen, Dinh Xuan, Xu, Tao, Blaize, Sylvain, Jradi, Safi, Couteau, Christophe, and Bachelot, Renaud
- Published
- 2023
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39. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
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Lin, Nancy U, Borges, Virginia, Anders, Carey, Murthy, Rashmi K, Paplomata, Elisavet, Hamilton, Erika, Hurvitz, Sara, Loi, Sherene, Okines, Alicia, Abramson, Vandana, Bedard, Philippe L, Oliveira, Mafalda, Mueller, Volkmar, Zelnak, Amelia, DiGiovanna, Michael P, Bachelot, Thomas, Chien, A Jo, O’Regan, Ruth, Wardley, Andrew, Conlin, Alison, Cameron, David, Carey, Lisa, Curigliano, Giuseppe, Gelmon, Karen, Loibl, Sibylle, Mayor, JoAl, McGoldrick, Suzanne, An, Xuebei, and Winer, Eric P
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Clinical Trials and Supportive Activities ,Cancer ,Clinical Research ,Neurosciences ,Breast Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Brain Neoplasms ,Breast Neoplasms ,Capecitabine ,Disease Progression ,Double-Blind Method ,Female ,Humans ,Middle Aged ,Oxazoles ,Pyridines ,Quinazolines ,Receptor ,ErbB-2 ,Trastuzumab ,Young Adult ,Receptor ,erbB-2 ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeIn the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs.Patients and methodsPatients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease.ResultsThere were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; P < .0001). Median CNS-PFS was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. Risk of death was reduced by 42% in the tucatinib arm (OS HR, 0.58; 95% CI, 0.40 to 0.85; P = .005). Median OS was 18.1 versus 12.0 months. ORR-IC was higher in the tucatinib arm (47.3%; 95% CI, 33.7% to 61.2%) versus the control arm (20.0%; 95% CI, 5.7% to 43.7%; P = .03).ConclusionIn patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial.
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- 2020
40. Immune Checkpoint Inhibitor-Associated Primary Adrenal Insufficiency: WHO VigiBase Report Analysis.
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Grouthier, Virginie, Lebrun-Vignes, Bénédicte, Moey, Melissa, Johnson, Douglas, Moslehi, Javid, Salem, Joe-Elie, and Bachelot, Anne
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Endocrine toxicity ,Immune checkpoint inhibitors ,Immune-related adverse events ,Immunotherapy ,Primary adrenal insufficiency ,Addison Disease ,Adrenal Insufficiency ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Agents ,Immunological ,Humans ,Immune Checkpoint Inhibitors ,Male ,Middle Aged ,World Health Organization - Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but may also trigger autoimmune adverse drug reactions (ADRs) referred to as immune-related adverse events (irAEs). Although endocrinopathies are among the most common form of irAEs, primary adrenal insufficiency (PAI) is infrequent and has only been published in case reports. The aim of this study was to identify and characterize the main features of PAI-irAE. MATERIALS AND METHODS: Suspected PAI-irAE cases were identified using VigiBase, the World Health Organizations pharmacovigilance database of individual case safety reports. RESULTS: From September 2, 2008, through October 5, 2018, a total of 50,108 ICI-associated ADRs were reported. Since 2008, there were 451 cases of PAI-irAE identified of which 45 were definite PAI and 406 possible PAI. Patients were mainly male (58.1%) with a median age of 66 years (range, 30-95). Indications of ICI were predominantly for melanoma (41.2%) and lung cancer (28.6%). The majority of patients were treated with ICI monotherapy (nivolumab: 44.3%, pembrolizumab: 11.7%, ipilimumab: 23.6%), and 17.9% were treated with ICI combination therapy. These events occurred with a median time to onset of 120 days (range, 6-576). ICI-associated PAI was associated with significant morbidity (≥90% severe) and mortality (7.3%). Fatality rates were similar in the subgroups of combination therapy versus monotherapy. There were no relevant differences in clinical or demographical characteristics and outcomes between definite versus possible PAI group. CONCLUSION: Our study represents the largest clinical description and characterization of PAI-irAE. Although ICI-associated PAI is a rare adverse event, early recognition is important to implement corticosteroid treatment. Further studies are required to elucidate risk factors and reversibility of this rare but severe irAE. Clinical trial identification number. NCT03492242 IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitor (ICI)-associated primary adrenal insufficiency (PAI) is a rare adverse event that is important to recognize because it may be severe and life-threatening, requiring emergent and often lifelong hormonal replacement therapy. Awareness regarding this ICI-related endocrinopathy is strongly encouraged among clinicians in addition to patient education about common PAI symptoms that should prompt urgent medical evaluation. In clinical practice, close monitoring and investigation for PAI is crucial to allow for early management and to further define the pathophysiology and prognosis of ICI-PAI. Corticotrophin (adrenocorticotrophic hormone) circulating level evaluation may be often lacking but should be considered as part of the diagnostic workup to differentiate PAI from secondary (central) adrenal insufficiency.
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- 2020
41. Effects of deletion of the prolactin receptor on ovarian gene expression
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Kelly Paul A, Baran Nathalie, Lucas Aurélie, Bachelot Anne, Grosdemouge Isabelle, and Binart Nadine
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ovary ,fertility ,physiology ,prolactin receptor ,mice ,Gynecology and obstetrics ,RG1-991 ,Reproduction ,QH471-489 - Abstract
Abstract Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.
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- 2003
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42. Turner syndrome: French National Diagnosis and Care Protocol (NDCP; National Diagnosis and Care Protocol)
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Elodie Fiot, Bertille Alauze, Bruno Donadille, Dinane Samara-Boustani, Muriel Houang, Gianpaolo De Filippo, Anne Bachelot, Clemence Delcour, Constance Beyler, Emilie Bois, Emmanuelle Bourrat, Emmanuel Bui Quoc, Nathalie Bourcigaux, Catherine Chaussain, Ariel Cohen, Martine Cohen-Solal, Sabrina Da Costa, Claire Dossier, Stephane Ederhy, Monique Elmaleh, Laurence Iserin, Hélène Lengliné, Armelle Poujol-Robert, Dominique Roulot, Jerome Viala, Frederique Albarel, Elise Bismuth, Valérie Bernard, Claire Bouvattier, Aude Brac, Patricia Bretones, Nathalie Chabbert-Buffet, Philippe Chanson, Regis Coutant, Marguerite de Warren, Béatrice Demaret, Lise Duranteau, Florence Eustache, Lydie Gautheret, Georges Gelwane, Claire Gourbesville, Mickaël Grynberg, Karinne Gueniche, Carina Jorgensen, Veronique Kerlan, Charlotte Lebrun, Christine Lefevre, Françoise Lorenzini, Sylvie Manouvrier, Catherine Pienkowski, Rachel Reynaud, Yves Reznik, Jean-Pierre Siffroi, Anne-Claude Tabet, Maithé Tauber, Vanessa Vautier, Igor Tauveron, Sebastien Wambre, Delphine Zenaty, Irène Netchine, Michel Polak, Philippe Touraine, Jean-Claude Carel, Sophie Christin-Maitre, and Juliane Léger
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Turner’s syndrome ,Childhood ,Adulthood ,Diagnosis ,Recommendation ,Management ,Medicine - Abstract
Abstract Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40–50%) and the 45,X/46,XX mosaic karyotype (15–25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.
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- 2022
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43. A Machine Learning Approach for the Prediction of Testicular Sperm Extraction in Nonobstructive Azoospermia: Algorithm Development and Validation Study
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Guillaume Bachelot, Ferdinand Dhombres, Nathalie Sermondade, Rahaf Haj Hamid, Isabelle Berthaut, Valentine Frydman, Marie Prades, Kamila Kolanska, Lise Selleret, Emmanuelle Mathieu-D’Argent, Diane Rivet-Danon, Rachel Levy, Antonin Lamazière, and Charlotte Dupont
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundTesticular sperm extraction (TESE) is an essential therapeutic tool for the management of male infertility. However, it is an invasive procedure with a success rate up to 50%. To date, no model based on clinical and laboratory parameters is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. ObjectiveThe aim of this study is to compare a wide range of predictive models under similar conditions for TESE outcomes in patients with nonobstructive azoospermia (NOA) to identify the correct mathematical approach to apply, most appropriate study size, and relevance of the input biomarkers. MethodsWe analyzed 201 patients who underwent TESE at Tenon Hospital (Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris), distributed in a retrospective training cohort of 175 patients (January 2012 to April 2021) and a prospective testing cohort (May 2021 to December 2021) of 26 patients. Preoperative data (according to the French standard exploration of male infertility, 16 variables) including urogenital history, hormonal data, genetic data, and TESE outcomes (representing the target variable) were collected. A TESE was considered positive if we obtained sufficient spermatozoa for intracytoplasmic sperm injection. After preprocessing the raw data, 8 machine learning (ML) models were trained and optimized on the retrospective training cohort data set: The hyperparameter tuning was performed by random search. Finally, the prospective testing cohort data set was used for the model evaluation. The metrics used to evaluate and compare the models were the following: sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and accuracy. The importance of each variable in the model was assessed using the permutation feature importance technique, and the optimal number of patients to include in the study was assessed using the learning curve. ResultsThe ensemble models, based on decision trees, showed the best performance, especially the random forest model, which yielded the following results: AUC=0.90, sensitivity=100%, and specificity=69.2%. Furthermore, a study size of 120 patients seemed sufficient to properly exploit the preoperative data in the modeling process, since increasing the number of patients beyond 120 during model training did not bring any performance improvement. Furthermore, inhibin B and a history of varicoceles exhibited the highest predictive capacity. ConclusionsAn ML algorithm based on an appropriate approach can predict successful sperm retrieval in men with NOA undergoing TESE, with promising performance. However, although this study is consistent with the first step of this process, a subsequent formal prospective multicentric validation study should be undertaken before any clinical applications. As future work, we consider the use of recent and clinically relevant data sets (including seminal plasma biomarkers, especially noncoding RNAs, as markers of residual spermatogenesis in NOA patients) to improve our results even more.
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- 2023
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44. Unidirectional frequency conversion of surface plasmon polaritons on metal nanowires
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Aurélie Broussier, Ali Issa, Loïc O. Le Cunff, Régis Deturche, Tien Hoa Nguyen, Dinh Xuan Quyen, Tao Xu, Sylvain Blaize, Safi Jradi, Christophe Couteau, and Renaud Bachelot
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Quantum dots ,Plasmonic ,Nanowire ,Electronics ,TK7800-8360 ,Technology (General) ,T1-995 - Abstract
Hybrid nanoplasmonics is one of the most promising branch of nanophotonics which aims, in particular, to control the energy transfer between donor and acceptor nano-emitters via surface plasmons. Recently, an approach of nano-emitters positioning was introduced. It is based on two-photon polymerization of a photosensitive material which contains quantum dots as nano-emitters. This technique allowed for the integration of green quantum dots on plasmonic silver nanowires. In this article, we report on the use of this approach for integrating both green and red quantum dots on silver nanowires. The coupling between nano-emitters and propagating surface plasmons that are supported by the silver nanowires is reported and observed through their scattering at the nanowire ends. For both colors, a parametric study of the distance between the quantum dots and the nanowire extremity shows that precise control of the position of the launching sites enables control of light intensity at the wire end, through surface plasmon propagation length. More interestingly, by integrating two kinds of quantum dots on the same nanowire, we realized an efficient donor-acceptor hybrid nano-system, where green surface plasmons polaritons (from donors) are transformed into red plasmons (from acceptors) at controlled sites of the plasmonic guides, as a result of a frequency conversion of the plasmons polaritons.
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- 2023
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45. A Digital Solution for an Advanced Breast Tumor Board: Pilot Application Cocreation and Implementation Study
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Khalil Hodroj, David Pellegrin, Cindy Menard, Thomas Bachelot, Thierry Durand, Philippe Toussaint, Armelle Dufresne, Benoite Mery, Olivier Tredan, Thibaut Goulvent, and Pierre Heudel
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundCancer treatment is constantly evolving toward a more personalized approach based on clinical features, imaging, and genomic pathology information. To ensure the best care for patients, multidisciplinary teams (MDTs) meet regularly to review cases. Notwithstanding, the conduction of MDT meetings is challenged by medical time restrictions, the unavailability of critical MDT members, and the additional administrative work required. These issues may result in members missing information during MDT meetings and postponed treatment. To explore and facilitate improved approaches for MDT meetings in France, using advanced breast cancers (ABCs) as a model, Centre Léon Bérard (CLB) and ROCHE Diagnostics cocreated an MDT application prototype based on structured data. ObjectiveIn this paper, we want to describe how an application prototype was implemented for ABC MDT meetings at CLB to support clinical decisions. MethodsPrior to the initiation of cocreation activities, an organizational audit of ABC MDT meetings identified the following four key phases for the MDT: the instigation, preparation, execution, and follow-up phases. For each phase, challenges and opportunities were identified that informed the new cocreation activities. The MDT application prototype became software that integrated structured data from medical files for the visualization of the neoplastic history of a patient. The digital solution was assessed via a before-and-after audit and a survey questionnaire that was administered to health care professionals involved in the MDT. ResultsThe ABC MDT meeting audit was carried out during 3 MDT meetings, including 70 discussions of clinical cases before and 58 such discussions after the implementation of the MDT application prototype. We identified 33 pain points related to the preparation, execution, and follow-up phases. No issues were identified related to the instigation phase. Difficulties were grouped as follows: process challenges (n=18), technological limitations (n=9), and the lack of available resources (n=6). The preparation of MDT meetings was the phase in which the most issues (n=16) were seen. A repeat audit, which was undertaken after the implementation of the MDT application, demonstrated that (1) the discussion times per case remained comparable (2 min and 22 s vs 2 min and 14 s), (2) the capture of MDT decisions improved (all cases included a therapeutic proposal), (3) there was no postponement of treatment decisions, and (4) the mean confidence of medical oncologists in decision-making increased. ConclusionsThe introduction of the MDT application prototype at CLB to support the ABC MDT seemed to improve the quality of and confidence in clinical decisions. The integration of an MDT application with the local electronic medical record and the utilization of structured data conforming to international terminologies could enable a national network of MDTs to support sustained improvements to patient care.
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- 2023
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46. Trastuzumab deruxtecan in previously treated HER2‐positive metastatic or unresectable breast cancer: Real‐life data from the temporary use authorization program in France
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Petit, Thierry, primary, Hajjaji, Nawale, additional, Antoine, Eric‐Charles, additional, Benderra, Marc‐Antoine, additional, Gozy, Michel, additional, Foa, Cyril, additional, Mouysset, Jean‐Loup, additional, Grenier, Julien, additional, Mousseau, Mireille, additional, Mailliez, Audrey, additional, Saghatchian, Mahasti, additional, Lachaier, Emma, additional, Desmoulins, Isabelle, additional, Hennequin, Audrey, additional, Maes, Patricia, additional, Loirat, Delphine, additional, Ricci, Francesco, additional, Diéras, Véronique, additional, Berton, Dominique, additional, Tiong, Florence Lai, additional, Teixeira, Luis, additional, Dohollou, Nadine, additional, Lévy, Christelle, additional, Bachelot, Thomas, additional, and Pierga, Jean‐Yves, additional
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- 2024
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47. Long-term outcomes in non-CAH 46,XX DSD
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Grouthier, Virginie, primary and Bachelot, Anne, additional
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- 2024
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48. Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer
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Frenel, Jean-Sebastien, primary, Zeghondy, Jean, additional, Guérin-Charbonnel, Catherine, additional, Mailliez, Audrey, additional, Volant, Elsa, additional, Poumeaud, François, additional, Patsouris, Anne, additional, Arnedos, Monica, additional, Bailleux, Caroline, additional, Cabal, Julie, additional, Galland, Loick, additional, de Nonneville, Alexandre, additional, Guiu, Séverine, additional, Dalenc, Florence, additional, Pistilli, Barbara, additional, Bachelot, Thomas, additional, Pierga, Jean-Yves, additional, Le Du, Fanny, additional, Bocquet, François, additional, Larrouquere, Louis, additional, and Loirat, Delphine, additional
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- 2024
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49. Shifting the landscape: Dominant C‐terminal rare missense FOXL2 variants in non‐syndromic primary ovarian failure etiology
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Jordan, Pénélope, primary, Verebi, Camille, additional, Hervé, Bérénice, additional, Perol, Sandrine, additional, Chakhtoura, Zeina, additional, Courtillot, Carine, additional, Bachelot, Anne, additional, Karila, Daphné, additional, Renard, Céline, additional, Grouthier, Virginie, additional, de la Croix, Stanislas Mulot, additional, Bernard, Valérie, additional, Fouveaut, Corinne, additional, de la Perrière, Aude Brac, additional, Jonard‐Catteau, Sophie, additional, Touraine, Philippe, additional, Plu‐Bureau, Geneviève, additional, Dupont, Jean Michel, additional, Christin‐Maitre, Sophie, additional, and Bienvenu, Thierry, additional
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- 2024
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50. Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms
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Sébastien Larréché, Aurore Bousquet, Lucie Chevillard, Rabah Gahoual, Georges Jourdi, Anne-Laure Dupart, Christilla Bachelot-Loza, Pascale Gaussem, Virginie Siguret, Jean-Philippe Chippaux, and Bruno Mégarbane
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Bothrops ,coagulation ,venom composition ,ROTEM ,co-factor ,antivenom ,Medicine - Abstract
Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.
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- 2023
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