排序方式: 共有11条查询结果,搜索用时 13 毫秒
1.
Gelsi-Boyer V Trouplin V Roquain J Adélaïde J Carbuccia N Esterni B Finetti P Murati A Arnoulet C Zerazhi H Fezoui H Tadrist Z Nezri M Chaffanet M Mozziconacci MJ Vey N Birnbaum D 《British journal of haematology》2010,151(4):365-375
Chronic myelomonocytic leukaemia (CMML) is a haematological disease currently classified in the category of myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) because of its dual clinical and biological presentation. The molecular biology of CMML is poorly characterized. We studied a series of 53 CMML samples including 31 cases of myeloproliferative form (MP-CMML) and 22 cases of myelodysplastic forms (MD-CMML) using array-comparative genomic hybridisation (aCGH) and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1. Mutations in ASXL1 and in the genes associated with proliferation (CBL, FLT3, PTPN11, NRAS) were mainly found in MP-CMML cases. Mutations of ASXL1 correlated with an evolution toward an acutely transformed state: all CMMLs that progressed to acute phase were mutated and none of the unmutated patients had evolved to acute leukaemia. The overall survival of ASXL1 mutated patients was lower than that of unmutated patients. 相似文献
2.
Erlich RB Kherrouche Z Rickwood D Endo-Munoz L Cameron S Dahler A Hazar-Rethinam M de Long LM Wooley K Guminski A Saunders NA 《British journal of cancer》2012,106(1):107-115
Background:
We examine the potential value of a series of clinically relevant PI3K-mTOR inhibitors alone, or in combination with histone deacetylase inhibitors, in a model of head and neck squamous cell carcinoma (HNSCC).Methods:
Head and neck squamous cell carcinoma cell lines, human keratinocyte and HNSCC xenograft models were treated with histone deacetylase inhibitors (HDACIs) and new generation PI3K and dual PI3K-mTOR inhibitors either alone or in combination. Cell and tumour tissue viability and proliferation were then determined in vitro and in vivo.Results:
Phosphatidylinositol-3-phosphate kinase, AKT and dual PI3K-mTOR inhibitors caused marked in vitro enhancement of cytotoxicity induced by HDACIs in HNSCC cancer cells. This effect correlates with AKT inhibition and is attenuated by expression of constitutively active AKT. Histone deacetylase inhibitor and phosphatidylinositol-3-phosphate kinase inhibitors (PI3KIs) inhibited tumour growth in xenograft models of HNSCC. Importantly, we observed intratumoural HDAC inhibition and PI3K inhibition as assessed by histone H3 acetylation status and phospho-AKT staining, respectively. However, we saw no evidence of improved efficacy with an HDACI/PI3KI combination.Interpretation:
That PI3K and dual PI3K-mTOR inhibitors possess antitumour effect against HNSCC in vivo. 相似文献3.
Mouriaux F Kherrouche Z Maurage CA Demailly FX Labalette P Saule S 《Melanoma research》2003,13(2):161-166
The KIT gene encodes c-kit, a transmembrane receptor that has tyrosine kinase activity and plays a role in haematopoiesis, gametogenesis and melanogenesis. The c-kit protein is found in normal cutaneous and choroidal melanocytes, and there is evidence that expression is lost in melanoma. Expression of c-kit was analysed in 57 paraffin-embedded sections of choroidal melanoma specimens and three choroidal melanoma cell lines using immunochemistry and Western blotting. Of the tumour specimens, 75% stained positively for c-kit with a membrane pattern of reactivity. Of the six patients who underwent proton beam therapy before enucleation, five tumours exhibited no c-kit immunoreactivity and the other tumour demonstrated weak staining. Of the three melanoma cell lines used, c-kit expression was observed in only one. No correlations between c-kit positivity and parameters such as cell type, largest macroscopic tumour dimension, scleral invasion or pigmentation were observed. In contrast, a significant positive association was found between c-kit staining and mitotic activity (P = 0.02). However, c-kit expression did not significantly influence survival when evaluated by univariate analysis. In conclusion, c-kit is expressed in most choroidal melanoma tumours. Further analysis should provide new insights into the mechanisms underlying the molecular and cellular changes in choroidal melanomas. 相似文献
4.
Sophy Laibe Zoulika Tadrist Christine Arnoulet Danielle Sainty Marie-Joëlle Mozziconacci 《Leukemia research》2009,33(8):1133-1136
Chronic myeloproliferative disorders (MPDs) are divided into Philadelphia-positive chronic myeloid leukemia (CML) and Philadelphia-negative disorders including polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis (IMF). Concomitance of a CML and another MPD is a rare event. We report here the case of a patient presenting initially with IMF who developed a Philadelphia-positive CML 7 years later. At the time of CML diagnosis, two distinct clones were present, one with a 13q deletion and one with a t(9;22). We raise the problem of a CML developing on an initial IMF, or two MPDs occurring from a common or two different stem cells. 相似文献
5.
6.
7.
8.
9.
Clotilde Descarpentries Frédéric Leprêtre Fabienne Escande Zoulika Kherrouche Martin Figeac Shéhérazade Sebda Simon Baldacci Valérie Grégoire Philippe Jamme Marie-Christine Copin David Tulasne Alexis B. Cortot 《Journal of thoracic oncology》2018,13(12):1873-1883
Introduction
Genomic alterations affecting splice sites of MNNG HOS transforming gene (MET) exon 14 were recently identified in NSCLC patients. Objective responses to MET tyrosine kinase inhibitors have been reported in these patients. Thus, detection of MET exon 14 splice site mutations represents a major challenge. So far, most of these alterations were found by full-exome sequencing or large capture-based next-generation sequencing (NGS) panels, which are not suitable for routine diagnosis.Methods
Aiming to provide a molecular testing method applicable in routine practice, we first developed a fragment-length analysis for detecting deletions in introns flanking MET exon 14. Second, we designed an optimized targeted NGS panel called CLAPv1, covering the MET exon 14 and flanking regions in addition to the main molecular targets usually covered in genomic testing. In patients with MET exon 14 mutations, MET gene amplification, gene copy number and MET receptor expression were also determined.Results
Among 1514 formalin-fixed paraffin-embedded NSCLC samples, nonoptimized NGS allowed detection of MET exon 14 mutations in only 0.3% of the patients, and fragment length analysis detected deletions in 1.1% of the patients. Combined, the optimized CLAPv1 panel and fragment-length analysis implemented for routine molecular testing revealed MET exon 14 alterations in 2.2% of 365 additional NSCLC patients. MET gene amplification or high gene copy number was observed in 6 of 30 patients (20%) harboring MET exon 14 mutations.Conclusions
These results show that optimized targeted NGS and fragment-length analysis improve detection of MET alterations in routine practice. 相似文献10.
Zak Z Gautier T Dumont L Masson D Deckert V Duverneuil L Pais De Barros JP Le Guern N Schneider M Moulin P Bataillard A Lagrost L 《Atherosclerosis》2005,178(2):279-286
OBJECTIVE: In order to determine the influence of the lipid status on the ability of cholesteryl ester transfer protein (CETP) to modify the plasma lipoprotein profile, the effect of hypercholesterolemia versus hypertriglyceridemia were compared in wild-type and CETP-transgenic (CETPTg) rats expressing CETP at a constant level. METHODS AND RESULTS: Wild-type and CETPTg rats were fed either a chow diet, a high fat/high cholesterol (HF/HC) diet, or a sucrose diet. As compared to wild-type rats, CETPTg rats fed the standard chow exhibited lower high-density lipoproteins (HDL)-cholesterol concentration (-65%, p<0.01), but similar non-HDL-cholesterol concentrations. Both wild-type and CETPTg rats fed the HF/HC diet displayed pronounced increases in total and non-HDL-cholesterol levels, with no influence of CETP expression in this case. In contrast, the sucrose diet produced significant changes only in CETPTg rats which then exhibited a 82% increase in non-HDL-cholesterol in addition to a 80% reduction in HDL cholesterol when compared to sucrose-fed, wild-type rats (p<0.01 in both cases). The triglyceride to cholesterol ratio in very low-density lipoprotein (VLDL) was 10-fold lower in 'HF/HC' rats than in 'chow' and 'sucrose' rats (p<0.005 and p<0.01, respectively), and VLDL from 'HF/HC' animals were proven to constitute poor cholesteryl ester acceptors. CONCLUSIONS: CETP expression modified dramatically the lipoprotein phenotype in 'sucrose' rats but not in 'HF/HC' rats. These observations suggest that a CETP inhibitor treatment is susceptible to produce profound changes in hypertriglyceridemia or combined hyperlipidemia. 相似文献