M M Dauplat

Centre Jean Perrin, Clermont, Auvergne, France

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Publications (16)24.27 Total impact

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    ABSTRACT: This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PG) of extracellular matrix (ECM).The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm Rat Chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA was increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma.
    Nanomedicine : nanotechnology, biology, and medicine. 06/2014;
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    ABSTRACT: Triple negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the Epithelial Growth Factor Receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane based chemotherapy in patients with operable, stage II-III, TNBC. Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for 8 cycles q.3 weeks combined with 4 cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m(2)) q.3 weeks followed by 4 cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathological complete response (pCR) in evaluable patients was the main endpoint while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. Sixty patients were enrolled with 47 assessable for pathologic response. The pathological complete response (pCR) rates were 46.8% [95% CI: 32.5-61.1] and 55.3% [95% CI: 41.1-69.5] according respectively to Chevallier and Sataloff classifications. The complete clinical response rate (cCR) was 37.5%. Conservative surgery was performed in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC.
    Annals of Oncology 05/2014; · 7.38 Impact Factor
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    ABSTRACT: The sentinel lymph node (SN) status is a crucial parameter in the therapeutic approach to breast cancer. However, there is no consensus established yet with regards to the method of SN assessment. The SN assessment ex tempore determines its status during a surgical procedure, thus allowing complete axillary dissection in case of SN positivity. That analysis is not performed systematically and can be done by cytological, histological (frozen sections) or molecular methods (qRT-PCR). The methods differ in sensitivity; qRT-PCR seems to be the most sensitive. The definitive SN status is also assessable by various approaches, immunohistochemistry (IHC) being the preferred one. However, the primacy of IHC is challenged by molecular biology methods.
    Oncologie 01/2013; 15(6). · 0.10 Impact Factor
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
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    ABSTRACT: Intraoperative imprint cytology (IC) is one of several accurate, proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated with neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. We evaluated the validity of IC for SLN testing in patients after NAC. Patients with infiltrating breast carcinoma receiving NAC (n = 132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. SLN were evaluated using IC in 80 of 132 patients (60%). The results of IC in the adjuvant setting (100 patients) were used for comparison. SLN metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases in SLN (P = .00021; relative risk [RR] = 2.3; 95% confidence interval, 1.37-3.85). The non-NAC group, which contained fewer micrometastatic cases, showed better sensitivity (47.4%) and NPV (88.9%). NAC does not seem to influence the accuracy and sensitivity of IC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.
    Annals of Surgical Oncology 02/2010; 17(8):2132-7. · 4.12 Impact Factor
  • M.-M. Dauplat, F. Penault-Llorca
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    ABSTRACT: Sentinel lymph node (SLN) biopsy is the most used practice in breast cancer, in absence of clinical or radiological evidence of node metastasis for stage T0, T1 and T2 until 3cm tumours. About 20,000 patients each year could benefit from a SLN biopsy in France. Nevertheless, the mean rate of second surgical procedure is of 10 to 17%. Two techniques (OSNA® et GeneSearch™) are actually available in France. Their principle is based upon an intraoperative diagnosis of the presence or absence of metastasis in the SLN, using a rapid, quantitative, accurate molecular assay. The literature shows that those tests have the advantage of being more sensitive (frequently greater than 95%) than the classical techniques of frozen section diagnosis. The concordance with histopathological examination is high too (>90%). For some of the patients, these techniques avoid a second surgery, reduce the cost of the management and shorten the initiation of treatment. In the future, this approach could become a standard.
    Medecine Nucleaire-imagerie Fonctionnelle Et Metabolique - MED NUCL. 01/2010; 34(1):23-26.
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    ABSTRACT: Ovarian epithelial dysplasia (OED) was first described after prophylactic oophorectomy for genetic risk of ovarian cancer. In light of Fathalla's incessant ovulation theory, this study was set up to describe the presence of ovarian abnormalities (dysplasia) after ovulation induction and to compare dysplasia profiles in stimulated and genetic risk ovaries. One-hundred and twenty-four patients who had undergone salpingo-oophorectomies or ovarian cystectomies between 1990 and 2005 were reviewed. They were divided into three groups: (1) previous in vitro fertilisation (n=35); (2) prophylactic oophorectomies for genetic risk (n=27) and (3) fertile non-cancerous controls (n=62). Eleven cytological and architectural epithelial features were defined and a dysplasia score was calculated to quantify ovarian epithelial abnormalities. Mean dysplasia score was significantly higher in the genetic risk and stimulated ovary groups than in controls (9.55 versus 3.62, p<0.0001; 7.51 versus 3.62, p<0.0002, respectively). Cytological and architectural abnormalities were more frequent in the genetic risk group, while the profile of abnormalities was different in the genetic risk and stimulated groups. These findings support a possible relationship between OED and the use of ovulation-stimulating drugs. The increased dysplasia score in stimulated and genetic risk ovaries might be consistent with progression towards neoplastic transformation, and may justify the use of the term dysplasia or intraepithelial ovarian neoplasia. The observation of dysplasia in the stimulated group may differentiate women at risk. Conversely, the fact that the dysplasia profile after stimulation differs from that in genetic risk ovaries suggests that ovarian stimulation may predispose to a different evolution.
    European journal of cancer (Oxford, England: 1990) 10/2009; 45(17):2977-83. · 4.12 Impact Factor
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    ABSTRACT: Ovarian epithelial dysplasia was first described after prophylactic oophorectomies for genetic risk. Ovarian stimulation has been considered as a risk factor of ovarian cancer by Fathalla's incessant ovulation theory. In this study, we have investigated the risk of ovarian dysplasia after ovulation induction. We reviewed 99 oophorectomies or cystectomies between 1990 and 2005 divided them into two groups: previous in vitro fertilization (n = 37) and a panel of fertile controls (n = 62). Eleven epithelial cytological and architectural features were defined and an ovarian epithelial dysplasia score was calculated to quantify the degree of ovarian epithelial abnormalities. All the ovaries were macroscopically non-cancerous except in two patients (one endometrioid cancer and one borderline tumour). The mean ovarian dysplasia score was significantly higher in the ovulation induction group than in the control group (7.64 versus 3.62, P = 0.0002). We also found a relationship between the number of ovulation-inducted cycles and the severity of ovarian dysplasia ('dose-effect') and a relationship between time after the end of ovulation induction (over 7 years) and the severity of ovarian dysplasia ('time-effect'). There is probably a relationship between ovarian epithelial dysplasia and either ovulation inducing drugs or infertility. By Fathalla's incessant ovulation theory, 'the dose effect and the time effect' of ovarian stimulation may explain ovarian dysplasia formation.
    Human Reproduction 10/2008; 24(1):132-8. · 4.67 Impact Factor
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    ABSTRACT: Ovarian epithelial dysplasia has been described in the ovarian surface epithelium by histologic, morphometric and nuclear profile studies. It could represent a potential precursor of ovarian malignancy in patients with genetic risk of ovarian cancer, although its natural history and progression to carcinoma are unpredictable. Diagnosis and identification of ovarian dysplasia would certainly be useful to understand the early steps of ovarian carcinogenesis. However, dysplasia in relation with ovulation induction seems to have a different pattern. We report dysplasia definitions and the current clinical management.
    Gynecologie Obstetrique & Fertilite - GYNECOL OBSTET FERTIL. 01/2008; 36(7):800-807.
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    ABSTRACT: To evaluate the clinical significance of tumour metastases detected using real-time reverse transcription-PCR (RT-PCR) in sentinel lymph nodes (SLN) of breast cancer patients. Sixty-seven patients with T1-T2 primary breast cancer were included in a prospective study. SLN were analysed for the presence of metastatic tumour cells using standard histopathology staining, immunochemistry (IHC) and multimarker real-time RT-PCR assay for mammaglobin (MMG), carcinoembryonic antigen (CEA) and cytokeratin-19 (CK19) mRNA expression. Correlations between molecular metastases and traditional clinicopathological prognostic factors, including St Gallen risk categories were studied. Of the 67 patients, 15 (22.3%) had one or more pathology-positive SLN. Five (9.6%) pathology-negative SLN were positive by IHC and 19 (36.5%) by RT-PCR. Of note, RT-PCR analysis was also positive in all cases with pathology- or IHC-positive SLN. MMG was the most informative tumour marker in the panel. Molecularly detected metastases were significantly associated with intermediate St Gallen risk category (p=0.023). Molecular staging of SLN using real-time RT-PCR for early breast cancer could serve as a useful complement to standard clinicopathological risk factors. Studies with long-term follow-up are necessary to define the impact of molecular metastases on disease free survival and overall survival.
    European Journal of Surgical Oncology 03/2007; 33(1):16-22. · 2.61 Impact Factor
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    ABSTRACT: Background Nephrogenic fibrosing dermopathy is a cutaneous and systemic sclerosis affecting patients with renal failure.Case-reportA 68-year-old man with renal insufficiency and on dialysis developed hardening of the skin and severe joint contractions. He had previously undergone angiography with gadolinium-containing contrast agents. A skin biopsy confirmed nephrogenic fibrosing dermopathy. The patient was treated by oral steroids followed by extracorporeal photopheresis. An improvement was seen after 12 cycles.DiscussionTreatment of nephrogenic systemic fibrosis is not codified and is normally based on the methods used for other forms of systemic sclerosis. Six cases of patients showing improvement under extracorporeal photopheresis have been published. The physiopathology of the disease is unknown. Gadolinium could act as a triggering agent by attracting circulating fibrocytes in the dermis of patients. Medical authorities recommend avoidance of gadolinium in patients with advanced kidney failure unless strictly necessary.
    Annales de Dermatologie et de Vénéréologie 01/2007; 134:667-671. · 0.60 Impact Factor
  • Annales de Pathologie 32(5):S131. · 0.24 Impact Factor
  • M. -M. Dauplat, F. Penault-Llorca
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    ABSTRACT: Oncology research, and particularly breast pathology, is undergoing a revolution with the advent of molecular signatures. These tools are complementary to the classical clinicopathological parameters commonly used in routine. The intrinsic signature brings, via a new taxonomy of breast cancer, a fresh look at the tumor beyond the histopathological type, grade and classic parameters of the tumor burden. Other prognostic signatures are Mammaprint®, Oncotype Dx®, and MapQant Dx®. Some of these signatures are available for formalin-fixed paraffin-embedded tissues opening the door for an use in routine setting. However, pathological evaluation is still cornerstone for the optimal management of patients with breast cancer, with the back up of molecular signatures particularly for Hormone receptor positive, HER2 negative patients. Furthermore, true predictive signature are highly awaited.
    Oncologie 14(9). · 0.10 Impact Factor
  • Actualités en sénologie - Formation médicale continue, 2009 ; p. 26-28.
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    ABSTRACT: Le traitement conservateur est actuellement la référence dans la prise en charge des cancers du sein de stades I et II. L’obtention de marges saines est un facteur primordial pour la diminution du taux de récidives locales. Elle ne fait l’objet d’aucun consensus tant pour la technique d’évaluation des berges chirurgicales que pour la valeur seuil limite d’une marge d’exérèse de sécurité. Diverses approches ont été évaluées dans la littérature, depuis la prise en charge macroscopique de la pièce à sa réception par le pathologiste à l’emploi de méthodes cytologiques et histologiques d’évaluation des berges. De telles pratiques sont évidemment à replacer dans un contexte radioclinique et doivent faire l’objet d’une collaboration étroite entre les différents spécialistes. Les perspectives sont une amélioration de l’évaluation des limites et/ou des marges tumorales à l’aide de techniques de médecine nucléaire, et/ou de biologie moléculaire afin de diminuer le nombre de reprises chirurgicales. Conservative surgery is the actual gold standard for the management of low-stages (i.e. I and II) breast cancers. The completion of clearmargins isaprerequisite for a complete local treatment and a decrease of local recurrences. Atight collaboration between pathologists and surgeons is mandatory. There is no consensus for the definition of the cut of a clear margin. Different management processes have been reported through the literature, ranging fromgrossmanagement to cytologic or histopathologic methods for margin evaluation. Such approaches have to be correlated to the clinical and radiological setting. They have to be performed in line with tumor characteristics, and treatment plans. The perspectives are a better evaluation of surgical margins using nuclear medicine or molecular biology tools to decrease the number of second surgical procedures.
    Oncologie 12(1):19-23. · 0.10 Impact Factor
  • Annales de Pathologie 32(5):S129. · 0.24 Impact Factor