Reig Jofre Group

Barcelona, Spain

Reig Jofre Group

Barcelona, Spain

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Perez-Sanchez C.,Oryzon Genomics | Colas E.,Autonomous University of Barcelona | Cabrera S.,Autonomous University of Barcelona | Fernandez-De-Castillo L.,University of Barcelona | And 23 more authors.
International Journal of Cancer | Year: 2013

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase- polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double-blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases. What's new? Many studies report biomarker discovery using omics approaches, but few survive the translation into clinically validated diagnostic assays. Using previously identified biomarkers, here the authors set to improve the early diagnosis of endometrial cancer (EC) based on minimally invasive samples: endometrial aspirates. Current sensitivity and failure rate of histological diagnosis limit the success of aspirate-based diagnosis and subsequent hysteroscopy is often necessary. The authors developed and clinically validated a novel molecular test, which increases the efficacy, sensitivity and negative predictive value of aspirate-based diagnosis and has the potential to reduce the average time and cost for EC diagnosis. Copyright © 2013 UICC.


Colas E.,University of Barcelona | Colas E.,Autonomous University of Barcelona | Perez C.,Oryzon Genomics | Cabrera S.,University of Barcelona | And 25 more authors.
International Journal of Cancer | Year: 2011

Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs. Copyright © 2011 UICC.


Florez Borges P.,University of Barcelona | Perez Lozano P.,University of Barcelona | Garcia Montoya E.,University of Barcelona | Minarro M.,University of Barcelona | And 3 more authors.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences | Year: 2014

BACKGROUND: A new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride.METHODS: For RP-HPLC analysis it was used an Eclipse XDB C8 column 150 mm × 4.6 mm, 5 μm (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2 M K2HPO4 pH 7.00 and acetonitrile (65:35, v/v) at a flow rate of 1 mL min (-1). Detection was performed at 230 nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification.RESULTS: The method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products. Regression analysis showed r(2) > 0.999 for cetirizine dihydrochloride in the concentration range of 650 μg mL (-1) to 350 μg mL(-1) for drug substance assay and a r(2) > 0.999 in the concentration range of 0.25 μg mL(-1) to 5 μg mL(-1) for degradation products. The method presents a limit of detection of 0.056 μg mL (-1) and a limit of quantification of 0.25 μg mL(-1). The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method.CONCLUSIONS: The proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development.


PubMed | University of Barcelona and Reig Jofre Group
Type: | Journal: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences | Year: 2015

A new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride.For RP-HPLC analysis it was used an Eclipse XDB C8 column 150mm 4.6mm, 5m (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2M K2HPO4 pH7.00 and acetonitrile (65:35, v/v) at a flow rate of 1mLmin (-1). Detection was performed at 230nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification.The method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products. Regression analysis showed r(2)>0.999 for cetirizine dihydrochloride in the concentration range of 650gmL (-1) to 350gmL(-1) for drug substance assay and a r(2)>0.999 in the concentration range of 0.25gmL(-1) to 5gmL(-1) for degradation products. The method presents a limit of detection of 0.056gmL (-1) and a limit of quantification of 0.25gmL(-1). The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method.The proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development.

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