18 results on '"Goffin, Frédéric"'
Search Results
2. Locally advanced and metastatic endometrial cancer: Current and emerging therapies.
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Salmon, Alixe, Lebeau, Alizée, Streel, Sylvie, Dheur, Adriane, Schoenen, Sophie, Goffin, Frédéric, Gonne, Elodie, Kridelka, Frédéric, Kakkos, Athanasios, and Gennigens, Christine
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[Display omitted] • The therapeutic options for patients with advanced/recurrent EC were limited. • The sequencing and molecular classification by TCGA has revolutionized therapeutic management of endometrial cancer. • The emergence of targeted therapies and immunotherapy represents significant progress. • Several promising therapies: immunotherapy for MMRd, selinexor for p53wt and trastuzumab deruxtecan for high levels of HER2. Until recently, patients diagnosed with locally advanced and metastatic endometrial cancer faced significant challenges in their treatment due to limited options and poor prognostic outcomes. The sequencing of tumors has been a major advancement in its management. It has led to The Cancer Genome Atlas classification currently used in clinical practice and the initiation of several clinical trials for innovative treatments targeting principally signaling pathways, immune checkpoints, DNA integrity, growth factors, hormonal signaling, and metabolism. Numerous clinical trials are investigating a combinatorial approach of these targeted therapies to counter tumoral resistance, cellular compensatory mechanisms, and tumor polyclonality. This review provides a comprehensive overview of historical, current, and promising therapies in advanced and metastatic endometrial cancer. It particularly highlights clinical research on targeted and hormonal therapies, but also immunotherapy, reflecting the evolving landscape of treatment modalities for this disease. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Observational BGOG Study of the Results of Robot-assisted Laparoscopy in 166 Patients with FIGO 2009 Stage IA1-IB1 Cervical Cancer.
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de Bruyn, Anouk, Peeters, Frederik, Smulders, Katrien, Goffin, Frédéric, Traen, Koen, Van Trappen, Philippe, and Vergote, Ignace
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Study Objective: Two recent studies (the Laparoscopic Approach to Cervical Cancer [LACC] trial and a cohort study based on the National Cancer Database) raise the question of whether minimally invasive surgery (conventional and robot-assisted laparoscopy) is inferior to open abdominal surgery in early-stage cervical cancer. In the laparotomy group of the LACC trial, the low rates of recurrence and death are notable. The present study wants to elucidate the current situation of patients with early-stage cervical cancer treated with robot-assisted laparoscopy in hospitals of the Belgium and Luxembourg Gynaecological Oncology Group (BGOG).Design: This is a prospective follow-up study.Setting: The combined data obtained from different BGOG hospitals were analyzed regarding patients similar to those included in the LACC trial in terms of cervical cancer recurrence and survival.Patients: We included patients with stage IA1, IA2, or IB1 cervical cancer with a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.Interventions: All patients were treated with robot-assisted laparoscopy.Measurements and Main Results: The outcomes were disease-free and overall survival at 3 and 5 years after surgery. A total of 270 patients were included, and 166 were found suitable for analysis. The median age was 45 years. Most patients had International Federation of Gynecology and Obstetrics stage IB1 cervical cancer (84.9%) and squamous cell carcinoma as the histologic subtype (71.7%). The median follow-up time was 44 months, with a range of between 1 and 131 months. Twenty-one recurrences and 12 deaths were noted. Of the deaths, 8 were related to cervical cancer. Disease-free survival was 86% at 3 years (95% confidence interval [CI], 78.52-90.80) and 85% at 5 years (95% CI, 77.03-89.95). Overall survival was 96% at 3 years (95% CI, 90.11-98.22) and 91% at 5 years (95% CI, 82.54 95.17).Conclusion: The results of this BGOG study show disease-free and overall survival rates after robot-assisted laparoscopy in early-stage cervical cancer that are at least similar to previous reported recurrence and survival data. We expect that the results of the Robot-assisted Approach to Cervical Cancer trial will elucidate the place of robot-assisted laparoscopy in early-stage cervical cancer. [ABSTRACT FROM AUTHOR]- Published
- 2021
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4. Tumor total lesion glycolysis and number of positive pelvic lymph nodes on pretreatment positron emission tomography/computed tomography (PET/CT) predict survival in patients with locally advanced cervical cancer.
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De Cuypere, Marjolein, Lovinfosse, Pierre, Gennigens, Christine, Hermesse, Johanne, Rovira, Ramon, Duch, Joan, Goffin, Frédéric, Hustinx, Roland, and Kridelka, Frédéric
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Objective The aim of this study was to investigate the prognostic value of metabolic parameters obtained at pretreatment [18F]fluoro-2- deoxy- D- glucose positron emission tomography/computed tomography ([18F] FDG PET/CT) in patients with locally advanced cervical cancer. We hypothesize that these metabolic parameters could optimize the treatment decision and thus favor the outcome of patients suffering locally advanced cervical cancer. Methods Patients with locally advanced cervical cancer underwent pretreatment PET/CT. Standard uptake values (maximum, mean, peak), metabolic tumor volume, and total lesion glycolysis were measured in the tumor and in the hypermetabolic pelvic lymph nodes. The relationship between clinical, pathological, and PET/CT metabolic parameters with recurrence- free survival and overall survival was assessed by Cox regression analysis. Results 115 patients with a median age of 52 years (range 23-77) presented with locally advanced cervical cancer. After a mean follow- up of 33.0 months after initiation of therapy, 26 patients (22.6%) recurred of which 17 patients had distant metastasis; 18 (15.7%) patients died. Recurrence- free survival at 2 and 5 years was 79.2% and 72.2%, respectively. The total lesion glycolysis of the tumor and the delay between diagnosis and treatment were significantly associated with recurrence- free survival in the multivariate analysis (HR 1.00, p=0.004, and HR 2.04, p=0.02, respectively). Only the total lesion glycolysis of the tumor ≥373.54 (HR 2.49, 95% CI 1.15 to 5.38; p=0.02) remained significant after log rank testing. Overall survival at 2 and 5 years was 91.7% and 68.8%, respectively. The number of PET- positive pelvic lymph nodes was the only independent prognostic factor for overall survival in the multivariate analysis (HR 1.43, 95% CI 1.13 to 1.81; p=0.003). Conclusion Tumor total lesion glycolysis and the number of positive pelvic lymph nodes on pretreatment PET/CT appear to be independent prognostic factors for recurrence and survival in patients with locally advanced cervical cancer. This may help to select patients who may benefit from therapeutic optimization and closer surveillance. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Added value of para-aortic surgical staging compared to 18F-FDG PET/CT on the external beam radiation field for patients with locally advanced cervical cancer: An ONCO-GF study.
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De Cuypere, Marjolein, Lovinfosse, Pierre, Goffin, Frédéric, Gennigens, Christine, Rovira, Ramon, Duch, Joan, Fastrez, Maxime, Gebhart, Géraldine, Squifflet, Jean Luc, Luyckx, Mathieu, Charaf, Gabriel, Crener, Kurt, Buxant, Frédéric, Bucella, Dario, Jouret, Mathieu, Hustinx, Roland, and Kridelka, Frédéric
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CERVICAL cancer ,RADIATION ,LYMPH nodes ,FLUORODEOXYGLUCOSE F18 ,DEFINITIONS ,SURGICAL indications - Abstract
Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status. Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis. Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT. Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Quality of surgery and treatment and its association with hospital volume: A population-based study in more than 5000 Belgian ovarian cancer patients.
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Bourgeois, Jolyce, Peacock, Hanna M., Savoye, Isabelle, De Gendt, Cindy, Leroy, Roos, Silversmit, Geert, Stordeur, Sabine, de Sutter, Philippe, Goffin, Frédéric, Luyckx, Mathieu, Orye, Guy, Van Dam, Peter, Van Gorp, Toon, and Verleye, Leen
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LYMPHADENECTOMY ,OVARIAN cancer ,CANCER patients ,OVARIAN epithelial cancer ,CANCER treatment ,GENETIC testing - Abstract
Different sets of quality indicators are used to identify areas for improvement in ovarian cancer care. This study reports transparently on how (surgical) indicators were measured and on the association between hospital volume and indicator results in Belgium, a country setting without any centralisation of ovarian cancer care. From the population-based Belgian Cancer Registry, patients with a borderline malignant or invasive epithelial ovarian tumour diagnosed between 2014 and 2018 were selected and linked to health insurance and vital status data (n = 5119). Thirteen quality indicators on diagnosis and treatment were assessed and the association with hospital volume was analysed using logistic regression adjusted for case-mix. The national results for most quality indicators on diagnosis and systemic therapy were around the predefined target value. Other indicators showed results below the benchmark: genetic testing, completeness of staging surgery, lymphadenectomy with at least 20 pelvic/para-aortic lymph nodes removed, and timely start of chemotherapy after surgery (within 42 days). Ovarian cancer care in Belgium is dispersed over 100 hospitals. Lower volume hospitals showed poorer indicator results compared to higher volume hospitals for lymphadenectomy, staging, timely start of chemotherapy and genetic testing. In addition, surgery for advanced stage tumours was performed less often in lower volume hospitals. The indicators that showed poorer results on a national level were also those with poorer results in lower-volume hospitals compared to higher-volume hospitals, consequently supporting centralisation. International benchmarking is hampered by different (surgical) definitions between countries and studies. • Indicators on quality of surgery for ovarian cancer perform below the benchmark in Belgium. • Quality of care is better in higher volume hospitals, supporting centralisation. • Different (surgical) definitions hamper international comparison. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Interval Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First-Line Treatment for Advanced Ovarian Carcinoma.
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D'Hondt, Véronique, Goffin, Frédéric, Roca, Lise, Dresse, Damien, Leroy, Chantal, Kerger, Joseph, Cordier, Lionel, de Forges, Hélène, Veys, Isabelle, and Liberale, Gabriel
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Objectives: We conducted a phase 2 trial to assess the feasibility of interval cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in patients with stage III and IV pleural ovarian carcinoma in first-line treatment with no macroscopic residual disease after surgery. Methods: Patients could be treated either with primary CS with HIPEC followed by 6 conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles. Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m
2 ) for 60 minutes, only in case of complete cytoreduction. Results: Nineteen patients were included in the study, and they all underwent neoadjuvant chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC procedure did not prevent the administration of the standard first-line treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very good. Conclusion: Our study shows an acceptable toxicity of adding HIPEC to the standard first-line treatment in patients with stage III ovarian carcinoma treated with interval CS. Further studies are needed to confirm the role of HIPEC in the treatment of ovarian carcinoma. [ABSTRACT FROM AUTHOR]- Published
- 2016
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8. Robotically Assisted Para-aortic Lymphadenectomy: Surgical Results.
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Hudry, Delphine, Ahmad, Sarfraz, Zanagnolo, Vanna, Narducci, Fabrice, Fastrez, Maxime, Ponce, Jordi, Tucher, Elisabeth, Lécuru, Fabrice, Conri, Vanessa, Leguevaque, Pierre, Goffin, Frédéric, Holloway, Robert W., and Lambaudie, Eric
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- 2015
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9. Improved computer-assisted analysis of the global lymphatic network in human cervical tissues
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Balsat, Cédric, Signolle, Nicolas, Goffin, Frédéric, Delbecque, Katty, Plancoulaine, Benoit, Sauthier, Philippe, Samouëlian, Vanessa, Béliard, Aude, Munaut, Carine, Foidart, Jean-Michel, Blacher, Silvia, Noël, Agnès, and Kridelka, Frédéric
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Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra- and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells.
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- 2014
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10. Improved computer-assisted analysis of the global lymphatic network in human cervical tissues
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Balsat, Cédric, Signolle, Nicolas, Goffin, Frédéric, Delbecque, Katty, Plancoulaine, Benoit, Sauthier, Philippe, Samouëlian, Vanessa, Béliard, Aude, Munaut, Carine, Foidart, Jean-Michel, Blacher, Silvia, Noël, Agnès, and Kridelka, Frédéric
- Abstract
Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra- and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells.
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- 2014
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11. Current concepts in the pathology and epigenetics of endometrial carcinoma
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Arafa, Mohammad, Somja, Joan, Dehan, Pierre, Kridelka, Frédéric, Goffin, Frédéric, Boniver, Jacques, and Delvenne, Philippe
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In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and is the fourth most common cancer in women. Two different clinicopathological subtypes are recognised: the oestrogenrelated (type I, endometrioid) and the non-oestrogen related (type II, non-endometrioid). This article reviews the epidemiology, risk factors, genetic alterations during endometrial carcinogenesis, features of tumours and precursors and early detection of the disease. Insights into the epigenetic alterations, with emphasis on DNA methylation during endometrial carcinogenesis, and their diagnostic value are also provided.
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- 2010
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12. Aggressive Angiomyxoma of the Vulva or Perineum: Report of Three Patients
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Alobaid, Abdulaziz, Goffin, Frédéric, Lussier, Christian, and Drouin, Pierre
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Background:Aggressive angiomyxoma is a rare, locally aggressive soft tissue tumour that chiefly involves the vulvoperineal region of young female patients. Treatment is wide surgical excision. Frequent relapses are common.
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- 2005
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13. Expression Pattern of Metalloproteinases and Tissue Inhibitors of Matrix-Metalloproteinases in Cycling Human Endometrium1
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Goffin, Frédéric, Munaut, Carine, Frankenne, Francis, Perrier d’Hauterive, Sophie, Béliard, Aude, Fridman, Viviana, Nervo, Patricia, Colige, Alain, and Foidart, Jean-Michel
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The cyclic growth, differentiation, and cell death of endometrium represents the most dynamic example of steroid-driven tissue turnover in human adults. Key effectors in these processes—matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs)—are regulated by ovarian steroids and, locally, by cytokines. We used reverse transcription-polymerase chain reaction to evaluate the expression of both transcriptionally regulated molecules such as estrogen receptor-α, progesterone receptor, and prolactin and a large array of MMPs and TIMPs (MMP-1, -2, -3, -7, -8, -9, -11, -12, -19, -26, MT1-MMP, MT2-MMP, MT3-MMP, TIMP-1, -2, -3). Altogether, three distinct patterns of MMP and two patterns of TIMP expression were detected in cycling endometrium: 1) MMPs restricted to the menstrual period (MMPs-1, -3, -8, -9, -12); 2) MMPs and TIMPs expressed throughout the cycle (MMP-2, MT1-MMP, MT2-MMP, MMP-19, TIMP-1, and TIMP-2); 3) MMPs predominantly expressed during the proliferative phase (MMP-7, MMP-11, MMP-26, and MT3-MMP); and 4) TIMP-3, which, contrary to the other TIMPs, shows significant modulations, with maximum expression during the late secretory and menstrual phases. These specific patterns of MMP expression associated with each phase of the cycle may point to specific roles in the processes of menstruation, housekeeping activities, angiogenesis, tissue growth, and extracellular matrix remodeling.
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- 2003
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14. Diazepaminsensitive GABAAreceptors on postnatal spiral ganglion neurones in culture
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Malgrange, Brigitte, Rigo, Jean-Michel, Lefebvre, Philippe P., Coucke, Paul, Goffin, Frédéric, Xhauflaire, Gaël, Belachew, Shibeshih, Water, Thomas R. Van De, and Moonen, Gustave
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USING dissociated spiral ganglion cell cultures obtained from 3-day-old rat cochlea, we investigated the response of auditory neurones to g-aminobutyric acid (GABA) using patch-clamp techniques. In our recording conditions, GABA elicited inward currents in > 95 of the neurones which reversed around 0 mV. Similar inward currents were measured using isoguvacin, a specific agonist of GABAAreceptors. GABA-gated currents were reversibly inhibited by the channel blocker picrotoxin and the GABA competitive antagonist bicuculline. These functional GABAAreceptors are characterized by an insensitivity to benzodiazepines and a relatively high sensitivity to β-carbolines and barbiturates. These results show that the GABAAreceptor pharmacological properties of spiral ganglion neurones are close to those of cerebellar granule cells.
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- 1997
15. Erratum: Improved computer-assisted analysis of the global lymphatic network in human cervical tissues
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Balsat, Cédric, Signolle, Nicolas, Goffin, Frédéric, Delbecque, Katty, Plancoulaine, Benoit, Sauthier, Philippe, Samouëlian, Vanessa, Béliard, Aude, Munaut, Carine, Foidart, Jean-Michel, Blacher, Silvia, Noël, Agnès, and Kridelka, Frédéric
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Correction to: Modern Pathology (2014) 27, 887–898; published online 06 December 2013; doi:10.1038/modpathol.2013.195 In this paper, Figure 5 is incorrect. The correct version of Figure 5 is provided below. The authors regret the error.
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- 2017
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16. A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer
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Balsat, Cédric, Blacher, Silvia, Herfs, Michael, Van de Velde, Maureen, Signolle, Nicolas, Sauthier, Philippe, Pottier, Charles, Gofflot, Stéphanie, De Cuypere, Marjolein, Delvenne, Philippe, Goffin, Frédéric, Noel, Agnès, and Kridelka, Frédéric
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ABSTRACTThe lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms. An original digital image analysis methodology was used to objectively determine whole slide densities and spatial distributions of immunostained structures. We observed a marked increase in lymphatic vessel density (LVD) and a specific capsular and subcapsular distribution in pre-metastatic SLN when compared with non-sentinel counterparts. Such features persisted in the presence of nodal metastatic colonization. The inflammatory profile attested by CD8+, Foxp3, CD20 and PD-1expression was also significantly increased in pre-metastatic SLN. Remarkably, the densities of CD20+B cells and PD-1 expressing germinal centers were positively correlated with LVD. All together, these data strongly support the existence of a pre-metastatic dialog between the primary tumor and the first nodal relay. Both lymphatic and immune responses contribute to the elaboration of a specific pre-metastatic microenvironment in human SLN. Moreover, this work provides evidence that, in the context of early cervical cancer, a pre-metastatic lymphangiogenesis occurs within the SLN (pre-metastatic niche) and is associated with a specific humoral immune response.
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- 2017
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17. Improved computer-assisted analysis of the global lymphatic network in human cervical tissues
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Balsat, Cédric, Signolle, Nicolas, Goffin, Frédéric, Delbecque, Katty, Plancoulaine, Benoit, Sauthier, Philippe, Samouëlian, Vanessa, Béliard, Aude, Munaut, Carine, Foidart, Jean-Michel, Blacher, Silvia, Noël, Agnès, and Kridelka, Frédéric
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- 2017
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18. Granulosa Cell Tumour: A Recurrence 40 Years After Initial Diagnosis
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East, Nathalie, Alobaid, Abdulaziz, Goffin, Frédéric, Ouallouche, Karim, and Gauthier, Philippe
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Background:Granulosa cell tumours are rare ovarian malignancies accounting for 2% to 5% of ovarian tumours. They are characterized by late recurrences, with the latest recurrence reported 37 years after first diagnosis.
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- 2005
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