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1.
Future Oncol ; 10(2): 195-209, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24490606

RESUMEN

AIMS: Following the introduction of new adjuvant therapies we wanted to reappraise the prognostic and predictive value of uPA/PAI-1 in early breast cancer. PATIENTS & METHODS: This monocentric retrospective study included 652 patients who had curative surgery between 2006 and 2011 and adjuvant treatment decision-making, taking into account uPA/PAI-1 tumor levels. RESULTS: uPA and PAI-1 levels were associated with classical clinicopathological parameters and adjuvant chemotherapy decision, but not with peritumoral vascular invasion (PVI; also known as peritumoral vascular emboli). HER2 overexpression, PVI and uPA/PAI-1 levels were not significantly associated with relapse-free survival in univariate analysis. In multivariate analysis, T stage, N stage and progesterone receptors were the only independent relapse-free survival predictive factors. CONCLUSION: The absence of an association between uPA/PAI-1 and PVI allows their concomitant consideration in adjuvant treatment discussion. The overall good prognosis of patients with high uPA/PAI-1 levels might be linked to the uPA/PAI-1 predictive value and the inclusion of these parameters in adjuvant guidelines.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Inhibidor 1 de Activador Plasminogénico/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Toma de Decisiones , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos
2.
Clin Chem Lab Med ; 51(9): 1833-41, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23787470

RESUMEN

BACKGROUND: Anemia, a frequent and deleterious condition in patients with cancer, is mainly caused by chemotherapy toxicity, iron deficiency, or inflammation. We evaluated the baseline iron metabolism biomarkers and their association with anemia occurrence during chemotherapy in patients with early breast cancer (EBC). METHODS: In this monocentric retrospective study, classical iron metabolism markers and new biomarkers as well as sTfR and hepcidin were assessed at baseline in 347 patients with EBC who received a sequential taxane and anthracycline-based regimen between April 2007 and October 2009. Hemoglobin level was measured every 21 days. RESULTS: Thirty-five patients had baseline iron deficiency and 13 inflammatory iron sequestration. In multivariate analysis, only high sTfR (OR=27.6, p<0.001, 95% CI 8.74-87) and pre-menopausal status (OR=7.3, 95% CI 0.04-0.43, p=0.001) remained statistically associated with iron deficiency. High hepcidin values and inflammatory iron sequestration were significantly associated (p=0.032). In total 6.1% patients had baseline anemia and 86.2% patients developed anemia during chemotherapy (41 had grade ≥2 anemia). Baseline hemoglobin below 13 g/dL and low hepcidin levels were the two independent predictive factors of severe anemia. CONCLUSIONS: In early breast cancer treated by chemotherapy, only baseline hemoglobin and hepcidin levels are independent predictive factors of anemic syndrome occurrence.


Asunto(s)
Anemia Ferropénica/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Hemoglobinas/metabolismo , Hepcidinas/sangre , Receptores de Transferrina/sangre , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
3.
Ann Biol Clin (Paris) ; 68(3): 325-9, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20478777

RESUMEN

Human epididymis protein 4 (HE4) is a novel marker for ovarian cancer. HE4 exhibits a high sensitivity to detect ovarian cancer and can be used with CA125 as a predictor of malignancy. Additional uses of HE4 are as an aid of monitoring response to therapy for patients with invasive ovarian cancer and as a marker to detect recurrences in the follow-up after treatment of the primary tumor. The HE4 EIA, an enzyme immunoassay for the quantitative determination of HE4 in human serum developed by Fujirebio Diagnostic Inc. (Tokyo, Japan), is now available with a CE-IVD label in Europe (Diasource, Nivelles, Belgium). The aim of the study was to evaluate according to the COFRAC LAB GTA 04 guide, the analytical performance of the test, using 4 standardized samples (target values: 49.8, 140.4, 167.6 and 415.2 pmol/L) and serum samples from patients with ovarian cancer treated in our institution. Intra- and inter-assay precisions showed coefficients of variation less than 10%. The low limit of detection (4 pmol/L) and the limit of quantitation (8 pmol/L) are suitable for clinical samples assessment. The assay mean dilution linearity is 100 +/- 10% (90 to 107% of recovery). Globally, the uncertainty varied from 13.1% (low values) to 28.1% (elevated values). We conclude that the HE4 EIA from Fujirebio Diagnostic Inc. displayed convenient analytical performances that allows its use it clinical practice.


Asunto(s)
Proteínas Secretorias del Epidídimo/genética , Neoplasias Ováricas/genética , Ensayo de Inmunoadsorción Enzimática , Proteínas Secretorias del Epidídimo/análisis , Femenino , Marcadores Genéticos , Humanos , beta-Defensinas
4.
J Mol Diagn ; 17(4): 366-73, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25952101

RESUMEN

The detection of the BRAF V600E mutation in melanoma samples is used to select patients who should respond to BRAF inhibitors. Different techniques are routinely used to determine BRAF status in clinical samples. However, low tumor cellularity and tumor heterogeneity can affect the sensitivity of somatic mutation detection. Digital PCR (dPCR) is a next-generation genotyping method that clonally amplifies nucleic acids and allows the detection and quantification of rare mutations. Our aim was to evaluate the clinical routine performance of a new dPCR-based test to detect and quantify BRAF mutation load in 47 paraffin-embedded cutaneous melanoma biopsies. We compared the results obtained by dPCR with high-resolution melting curve analysis and pyrosequencing or with one of the allele-specific PCR methods available on the market. dPCR showed the lowest limit of detection. dPCR and allele-specific amplification detected the highest number of mutated samples. For the BRAF mutation load quantification both dPCR and pyrosequencing gave similar results with strong disparities in allele frequencies in the 47 tumor samples under study (from 0.7% to 79% of BRAF V600E mutations/sample). In conclusion, the four methods showed a high degree of concordance. dPCR was the more-sensitive method to reliably and easily detect mutations. Both pyrosequencing and dPCR could quantify the mutation load in heterogeneous tumor samples.


Asunto(s)
Análisis Mutacional de ADN/métodos , ADN de Neoplasias/análisis , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Melanoma/genética , Mutación/genética , Reacción en Cadena de la Polimerasa/métodos , Proteínas Proto-Oncogénicas B-raf/genética , Biopsia , ADN de Neoplasias/genética , Humanos , Melanoma/diagnóstico , Melanoma/cirugía , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugía , Melanoma Cutáneo Maligno
5.
Ann Biol Clin (Paris) ; 71(5): 537-44, 2013.
Artículo en Francés | MEDLINE | ID: mdl-24113439

RESUMEN

The analytical and clinical validation of new biomarkers for the early detection of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to calculate a standardized PHI index linked to a higher probability of a positive biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for prostate cancer diagnosis. The purpose of this study is to validate the analytical performance of the (-2)proPSA and to determine the predictive value of PHI for the early detection of prostate cancer. Analytical performances are correct. It is not necessary to dilute samples before analysis. The stability of (-2)proPSA is good until at least 3 hours at room temperature before centrifugation. The study of the PSAT, PSAL, (-2)proPSA and PHI values in a population of patients consulting for an early prostate cancer diagnosis shows that the index PHI is the most powerful predictive marker of cancer with an area under ROC curve of 0.70, whereas it is only 0.56 for total PSA.


Asunto(s)
Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Precursores de Proteínas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Análisis Químico de la Sangre/métodos , Análisis Químico de la Sangre/normas , Conservación de la Sangre/métodos , Conservación de la Sangre/normas , Detección Precoz del Cáncer/normas , Indicadores de Salud , Humanos , Límite de Detección , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/química , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Estabilidad Proteica , Reproducibilidad de los Resultados
6.
Ann Biol Clin (Paris) ; 70(4): 387-96, 2012.
Artículo en Francés | MEDLINE | ID: mdl-22796610

RESUMEN

Iron plays a fundamental role in biology and its concentration in living organisms is regulated very precisely. Many molecules of storage and transportation are used to maintain the intracellular homeostasis. Cancer cells have alterations in this balance. Recent studies have shown that breast cancer cells present abnormal expression of several proteins such as hepcidin and ferroportin. A prognostic impact of these alterations has been reported in patients with breast cancer. Regulatory molecules of iron metabolism could become therapeutic targets. This is an innovative approach that has emerged for treating a cancer which, despite advances in treatment and the emergence of targeted therapies, remains the leading cause of cancer death in women.


Asunto(s)
Neoplasias de la Mama/metabolismo , Hierro/metabolismo , Anemia/diagnóstico , Anemia/etiología , Péptidos Catiónicos Antimicrobianos/metabolismo , Biomarcadores , Citocinas/metabolismo , Daño del ADN , Estradiol/fisiología , Femenino , Hepcidinas , Humanos , Inflamación/metabolismo , Estrés Oxidativo
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