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1.
Ann Biol Clin (Paris) ; 74(2): 196-202, 2016.
Artigo em Francês | MEDLINE | ID: mdl-27029725

RESUMO

Since January 16(th) 2010, the French legislation requires that the medical laboratories must be accredited according to ISO 15189 standards. This concerned all the biological medical technics, including molecular biology technics. In this work, we described the validation steps by real time quantitative PCR of L858R mutation in EGFR gene, frequently detected in non-small lung cancers (NSCLC). Epidermal growth factor - tyrosine kinase inhibitors (EGFR-TKIs) are authorized in Europe for the treatment of metastatic NSCLC after failure of, at least one, prior chemotherapy. Thus, in view of accreditation of this analysis, we have used the recommendation of the COFRAC (Comité français d'accréditation) and INCa (Institut national du cancer). Several parameters have been tested, such as the primers, the limit of detection, and the sensitivity and specificity of the method. In addition, a risk study has been evaluated. Although long and fastidious, the method of validation is required to perform analysis in optimal conditions to guaranty optimal results for the patients.


Assuntos
Análise Mutacional de DNA/métodos , Receptores ErbB/genética , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase em Tempo Real/métodos , Substituição de Aminoácidos/genética , Arginina/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Células Cultivadas , Análise Mutacional de DNA/normas , Humanos , Leucina/genética , Limite de Detecção , Neoplasias Pulmonares/genética , Células MCF-7 , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
BMC Cancer ; 15: 169, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25879949

RESUMO

BACKGROUND: Overexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration. METHODS: In this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained. RESULTS: We identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%. CONCLUSIONS: Our results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Taxoides/administração & dosagem , Trastuzumab/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Docetaxel , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Receptor ErbB-2/biossíntese
3.
PLoS One ; 8(1): e55103, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23359294

RESUMO

The presence of a TP53 gene mutation can influence tumour response to some treatments, especially in breast cancer. In this study, we analysed p53 mRNA expression, LOH at 17p13 and TP53 mutations from exons 2 to 11 in 206 patients with breast carcinoma and correlated the results with disease-free and overall survival. The observed mutations were classified according to their type and location in the three protein domains (transactivation domain, DNA binding domain, oligomerization domain) and correlated with disease-free and overall survival. In our population, neither p53 mRNA expression nor LOH correlated with outcome. Concerning TP53 mutations, 27% of tumours were mutated (53/197) and the presence of a mutation in the TP53 gene was associated with worse overall survival (p = 0.0026) but not with disease-free survival (p = 0.0697), with median survival of 80 months and 78 months, respectively. When alterations were segregated into mutation categories and locations, and related to survival, tumours harbouring mutations other than missense mutations in the DNA binding domain of P53 had the same survival profiles as wild-type tumours. Concerning missense mutations in the DNA binding domain, median disease-free and overall survival was 23 months and 35 months, respectively (p = 0.0021 and p<0.0001, respectively), compared with 78 and 80 months in mutated tumours overall. This work shows that disease-free and overall survival in patients with a frameshift mutation of TP53 or missense mutation in the oligomerization domain are the same as those in wild-type TP53 patients.


Assuntos
Neoplasias da Mama/genética , Proteínas de Ligação a DNA/metabolismo , Mutação de Sentido Incorreto , Proteína Supressora de Tumor p53/metabolismo , Sítios de Ligação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Cromossomos Humanos Par 17 , Feminino , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
4.
Endocr Relat Cancer ; 18(6): 783-92, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21878572

RESUMO

Survivin, an anti-apoptotic protein, was described as strongly expressed in human cancers including breast cancer. However, little is known about the association between Survivin variants (Survivin-2B, Survivin-ΔEx3, Survivin-3B, and Survivin-2α) and the other apoptotic-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Human Apoptosis Gene Arrays were used to screen genes that could be associated with Survivin variants. Expression of the five transcripts was measured by RT-PCR in 135 breast carcinomas and Cox survival analysis was analyzed according to the patient outcome. Significant associations between Survivin transcripts and apoptotic genes were found. Interestingly, Survivin-3B variant showed major inverse correlations with pro-apoptotic genes. In addition, in vitro results indicated that overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/cyclophosphamide-induced apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of Survivin-3B expression had a shorter overall (P=0.030 and P=0.042 respectively), and disease-free (P=0.024 and P=0.009) survival. Our data suggest that Survivin-3B contributes to cell survival through the anti-apoptotic pathway and that its expression level could be an important factor in determining therapeutic strategies for breast carcinoma.


Assuntos
Apoptose/genética , Neoplasias da Mama/genética , Carcinoma/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Mutação , Isoformas de Proteínas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Survivina , Proteína Supressora de Tumor p53/genética
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