References of "DELVENNE, Philippe"
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See detailAberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.
Guenin, Samuel; Mouallif, Mustapha ULg; Deplus, Rachel et al

in PLoS ONE (2012), 7(8), 42704

Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern ... [more ▼]

Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC) markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1) promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression. [less ▲]

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See detailHuman papillomavirus, lichen sclerosus and penile cancer: A study in Belgium.
D'Hauwers, K. W. M.; Depuydt, C. E.; Bogers, J. J. et al

in Vaccine (2012), 30(46), 6573-7

PURPOSE: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma ... [more ▼]

PURPOSE: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma (SCC). Human papillomavirus (HPV) is found in 40-46% of cases: penile cancer is considered to behave as vulvar cancer. Non HPV related risk factors are lack of circumcision, phimosis, chronic inflammation, and smoking. The role of lichen sclerosus (LS) is unclear. Clinical diagnosis is difficult and treatment often mutilating. Preventive measures can be taken since the risk factors are known: the use of the prophylactic HPV vaccines may contribute. We measured the prevalence of HPV and LS in penile cancer in Belgium. MATERIALS AND METHODS: We found 76 samples of penile lesions in the archives of the departments of Histology of four university hospitals in Belgium. Real-time PCR of type-specific HPV DNA was performed targeting 18 HPV types. PRINCIPAL RESULTS: Patients with penile intraepithelial neoplasia (PeIN) were 56.1 years of age: patients with invasive penile cancer (IPC) 68.5 (p=0.009). Fifty-five samples (55/76) were adequate for HPV targeting. Overall HPV DNA was 70.9%: 89.5% in samples of PeIN (n=19) and 61.1% in samples of IPC (n=36). Invasive penile cancer samples were less likely to be HPV infected (p=0.028). HPV 16 was most prevalent: 48.3%: 20% PeIN, and 28.3% IPC. HPV DNA of the types, included in the prophylactic vaccines, was found in 33% of PeIN and 31.7% of IPC samples. Thrice, low risk HPV (lrHPV) types 6 (1 IPC) and 11 (1 PeIN, 1 IPC) were solely present. There was no difference in the presence of LS between HPV positive and HPV negative samples (p=0.944). CONCLUSIONS: Prevalence of HPV DNA in penile lesions in Belgium is high. However, the prophylactic vaccines may contribute to primary prevention of only a subset of cases. The role of LS remains unclear. [less ▲]

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See detailDetection and quantification of human papillomavirus in benign and malignant parotid lesions.
Descamps, Geraldine; Duray, Anaelle; Rodriguez, Alexandra et al

in Anticancer Research (2012), 32(9), 3929-32

Background/Aim: Human papillomavirus (HPV) is implicated in head and neck squamous cell carcinomas. However, the causal role of HPV in carcinomas of the parotid gland remains uncertain and less documented ... [more ▼]

Background/Aim: Human papillomavirus (HPV) is implicated in head and neck squamous cell carcinomas. However, the causal role of HPV in carcinomas of the parotid gland remains uncertain and less documented. This study aimed to determine the potential implication of HPV in the development of benign and malignant lesions of the parotid gland. MATERIALS AND METHODS: Paraffin-embedded biopsies were obtained from 40 patients with benign parotid gland tumors and from 39 patients with parotid gland carcinomas. The 79 samples were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus Polymerase Chain Reaction (PCR) and type-specific E6/E7 PCR to detect 18 HPV types. RESULTS: Our results showed a low prevalence of HPV, with only three HPV-positive cases among the 40 benign tumors and one infected carcinoma in the malignant population. CONCLUSION: No association between the presence of HPV DNA and the development of parotid gland tumors was found in our study. [less ▲]

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See detailLes cancers viro-induits: interrelations genetique-environnement
Delvenne, Philippe ULg; Renoux, V. M.; Arafa, M. et al

in Revue Médicale de Liège (2012), 67(5-6), 381-9

Among cancers diagnosed worldwide on a yearly basis, 20% are thought to be associated with a viral infection. The viruses involved are, by order of decreasing incidence, the hepatitis viruses, the ... [more ▼]

Among cancers diagnosed worldwide on a yearly basis, 20% are thought to be associated with a viral infection. The viruses involved are, by order of decreasing incidence, the hepatitis viruses, the papillomaviruses and the Epstein-Barr virus. These virus-induced cancers generate a high level of interest not only for the study of mechanisms involved in the neoplastic transformation, but also for the set-up of specific immunotherapies including prophylactic and therapeutic antitumor vaccination. [less ▲]

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See detailIs an alcoholic fixative fluid used for manual liquid-based cytology accurate to perform HPV tests?
Garbar, Christian; Mascaux, Corinne; De Graeve, Philippe et al

in Pathology and Laboratory Medicine International (2012), 4

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See detailThérapie du mésothéliome pleural : compréhension des mécanismes de résistance à la chimiothérapie
Costa, Chrisostome ULg; Vandermeers, Fabian ULg; Reddy, NS Sathyanarayana ULg et al

Diverse speeche and writing (2011)

Thérapie du mésothéliome pleural : compréhension des mécanismes de résistance à la chimiothérapie. Chrisostome Costa 1, Fabian Vandermeers 2, Sathyanarayana Reddy 2, Céline Mascaux 3, Pascale Hubert 2 ... [more ▼]

Thérapie du mésothéliome pleural : compréhension des mécanismes de résistance à la chimiothérapie. Chrisostome Costa 1, Fabian Vandermeers 2, Sathyanarayana Reddy 2, Céline Mascaux 3, Pascale Hubert 2, Philippe Delvenne 2, Luc Willems 1,2 1 Laboratoire de biologie cellulaire et moléculaire, ULg, Gemboux Agro Bio-Tech, 13 av. Maréchal Juin, 5030 Gembloux ; Tél. : 32-(0)-81-622157 ; Fax : 32-(0)-81-6138 88 ; Courriel: ccosta@doct.ulg.ac.be 2 GIGA, ULg, Liège 3 Institut Bordet, ULB, Bruxelles - Introduction : Le mésothéliome pleural malin (MPM) est un cancer de la plèvre causé principalement par l’inhalation de fibres d’amiante. Nous avons montré précédemment que les inhibiteurs d’histones deacetylases (tel que le valproate, VPA) augmentent significativement l’efficacité des composés utilisés en chimiothérapie (pemetrexed et cisplatin) et prolonge la survie des patients atteints de MPM. Malheureusement, une proportion importante des patients développe une résistance au traitement de seconde ligne avec la doxorubicine et le VPA. - But du projet : L’objectif du travail est de disséquer les mécanismes qui régissent la réponse au traitement de seconde ligne du MPM. - Méthodes et résultats : Nous avons tout d’abord comparé deux types de lignées cellulaires présentant soit une sensibilité (cellules M14K) soit une résistance (cellules H28) au traitement combiné VPA+doxorubicine. En utilisant des microdamiers (Agilent), nous avons analysé le profil d’expression génique de cellules M14K et H28 traitées avec le VPA et la doxorubicine. Après quantification des fluorescences, une analyse statistique (Genespring GX) et une modélisation bioinformatique (Ingenuity) ont permis d’identifier les gènes candidats les plus relevants. En fonction de la p-value et du fold change, un nombre limité de gènes ont été sélectionnés et validés par la technique de qRT-PCR. Parmi ceux-ci, nous avons identifié le gène TGFA dont l’expression corrèle avec la résistance au traitement. En effet, nous avons observé que le niveau d’expression basale du gène TGFA est beaucoup plus important dans la lignée résistante H28 que dans la lignée sensible M14K. Dans le but de valider son implication dans la réponse à la thérapie, nous avons diminué (par interférence ARN) ou augmenté (par transfection d’un vecteur d’expression) l’expression de TGFA respectivement dans les lignées H28 ou M14K. Nous avons ensuite déterminé les taux d’apoptose en évaluant la fragmentation de l’ADN en présence de doxorubicine et de VPA. Les résultats montrent que la diminution de l’expression de TGFA permet une augmentation sensible de l’apoptose induite par le traitement combiné doxorubicine et VPA dans la lignée résistante H28 (de 9% à 36%). A l’inverse, la surexpression de TGFA est associée avec une diminution d’apoptose dans la lignée sensible M14K (de 28% à 18%). Ces observations ont été confirmées par une analyse de l’activité des caspases 3 et 7. En accord avec la propriété de la protéine TGFAd’induire la prolifération cellulaire via le récepteur à l’EGF, des inhibiteurs de l’activité tyrosine kinase (l’Iressa et le Tarceva) augmentent l’apoptose induite par la doxorubicine et le VPA dans la lignée résistante H28 (de 16% à 40%). L’efficacité du traitement combiné VPA+doxorubicine+Iressa/Tarceva est actuellement évaluée en modèle murin (souris SCID). - Conclusions : Nous avons identifié un gène, le TGFA, dont l’expression corrèle avec la résistance à l’apoptose induite par la doxorubicine et le VPA. L’utilisation d’inhibiteurs du récepteur EGF pourrait donc améliorer le traitement de seconde ligne du MPM. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.
Renoux, Virginie ULg; Bisig, Bettina ULg; Langers, Inge ULg et al

in European journal of immunology (2011), 41(11), 3240-3252

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK cell infiltration in HPV-associated pre-neoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-alpha and IFN-gamma) in the presence of HPV-VLPs. Using flow cytometry and microscopy we observed that NK cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailIdentification of novel accessible proteins bearing diagnostic and therapeutic potential in human pancreatic ductal adenocarcinoma
Turtoi, Andrei ULg; Musmeci, Davide; Wang, Yinghong et al

in Journal of Proteome Research (2011), 10(9), 4302-13

Pancreas ductal adenocarcinoma (PDAC) remains a deadly malignancy with poor early diagnostic and no effective therapy. Although several proteomic studies have performed comparative analysis between normal ... [more ▼]

Pancreas ductal adenocarcinoma (PDAC) remains a deadly malignancy with poor early diagnostic and no effective therapy. Although several proteomic studies have performed comparative analysis between normal and malignant tissues, there is a lack of clear characterization of proteins that could be of clinical value. Systemically reachable ("potentially accessible") proteins, suitable for imaging technologies and targeted therapies represent a major group of interest. The current study explores potentially accessible proteins overexpressed in PDAC, employing innovative proteomics technologies. In the discovery phase, potentially accessible proteins from fresh human normal and PDAC tissues were ex vivo biotinylated, isolated and identified using 2D-nano-HPLC-MS/MS method. The analysis revealed 422 up-regulated proteins in the tumor, of which 83 (including protein isoforms) were evaluated as potentially accessible. Eleven selected candidates were further confirmed as up-regulated using Western blot and multiple reaction monitoring protein quantification. Of these, transforming growth factor beta-induced (TGFBI), latent transforming growth factor beta binding 2 (LTBP2), and asporin (ASPN) were further investigated by employing large scale immunohistochemistry-based validations. They were found to be significantly expressed in a large group of clinical PDAC samples compared to corresponding normal and inflammatory tissues. In conclusion, TGFBI, LTBP2, and ASPN are novel, overexpressed, and potentially accessible proteins in human PDAC. They bear the potential to be of clinical value for diagnostic and therapeutic applications and merit further studies using in vivo models. [less ▲]

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See detailNovel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues
Turtoi, Andrei ULg; Dumont, Bruno ULg; Greffe, Yannick et al

in Journal of Proteome Research (2011), 10(7), 3160-82

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a ... [more ▼]

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer lesions. Due to the fact that our technology is applicable to any type of tissue biopsy, it bears the ability to accelerate the discovery of new relevant biomarkers in a broad spectrum of pathologies. [less ▲]

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See detailFrom the Clinics to the Bench and back to the Clinics: design of a medical treatment for Cervical Intraepithelial Neoplasia (CIN)
Jost, Maud; Frankenne, Francis; Maillard, Catherine ULg et al

Conference (2011, May 20)

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See detailCancer du sein: importance de la nomenclature anatomo-pathologique
BLETARD, Noëlla ULg; DETREMBLEUR, Nancy ULg; SCAGNOL, Irène ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 261-4

The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign ... [more ▼]

The breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign or malignant tumours and therefore provides the clinicians with essential information for the therapeutic strategy. In the Pathology laboratory, immunohistochemistry and molecular biology have improved the specificity of the diagnosis and have introduced new prognostic and predictive markers for tumour management. The last edition of the WHO classification, released in 2003, distinguishes 21 varieties of invasive carcinoma and 2 categories of intraepithelial neoplasia based on the morphology and immunohistochemical profile. Other diseases can affect the breast, although much less frequently, such as Paget’s disease of the nipple, phyllode tumours, sarcomas, lymphomas... These diseases will not be reviewed here. [less ▲]

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See detailTechniques de prélèvements cytologiques en pathologie mammaire
LAMBERT, Chantal ULg; Colin; Delvenne, Philippe ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 261-4

Mammary cytology is part of the breast cancer test. Its accuracy depends on both the sample quality and the cyto-pathologist’s competence. Extracting cells in a liquid environment allows obtaining smears ... [more ▼]

Mammary cytology is part of the breast cancer test. Its accuracy depends on both the sample quality and the cyto-pathologist’s competence. Extracting cells in a liquid environment allows obtaining smears in less hemorrhagic thin layers, containing more cells and with less interference with the fixation artefact. This technique keeps materiel for further immunocytochemistry and cell biology studies if needed. It will be especially useful in automated analysis. [less ▲]

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See detailMucosal junctions: open doors to HPV and HIV infections?
Herfs, Michael ULg; Hubert, Pascale ULg; Moutschen, Michel ULg et al

in Trends in microbiology (2011), 19(3), 114-120

Throughout adult life, new developmental commitment of adult stem cells causes reversible epithelial replacements in various mucosal surfaces, including the uterine cervix and the anal canal. Located at ... [more ▼]

Throughout adult life, new developmental commitment of adult stem cells causes reversible epithelial replacements in various mucosal surfaces, including the uterine cervix and the anal canal. Located at the squamocolumnar junctions, these metaplastic conversions are associated with chronic inflammation and deregulated expression of soluble and cell-membrane factors important for antiviral immune response. In this paper, we propose that these histological and immunological features increase the susceptibility of these metaplastic microenvironments to human papillomavirus and human immunodeficiency virus infections. Identification of the anatomical sites and cell populations within the anogenital tract, which is the site primary infected by these viruses, is crucial for the understanding of the pathogenesis of viral disease and development of antiviral strategies. [less ▲]

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See detailCombined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma.
Ernoux-Neufcoeur, P.; Arafa, M.; Decaestecker, C. et al

in Journal of Cancer Research & Clinical Oncology (2011), 137(1), 173-81

PURPOSE: We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal ... [more ▼]

PURPOSE: We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC). METHODS: Paraffin-embedded tumours from HSCC patients (n = 75) were evaluated for p16, p21 and p53 expression by immunohistochemistry. HPV DNA was detected by GP5+/6+ consensus PCR and subsequent genotyping by E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. RESULTS: Among the 61 specimens that tested positive for the beta-globin, HPV typing identified 50 patients with high-risk (hr) HPV types. HPV 16E7 DNA was detected in 74% (37 cases) of these specimens. Twelve patients were found to be infected with multiple HPV types. However, the presence of hrHPV DNA was not found to correlate with the proportion of disease-free patients. The 5-year disease-free survival rate was 73% in p53- tumours versus 48% in p53+ tumours (P = 0.008). CONCLUSION: In our series of patients with stage IV HSCC, the hrHPV+ subgroup had a similar prognosis (in terms of recurrence risk) as the HPV- subgroup. p53 overexpression was associated with a worse prognosis. [less ▲]

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See detailIFN-gamma and TNF-alpha potentiate prostaglandin D2-induced human eosinophil chemotaxis through up-regulation of CRTH2 surface receptor.
EL SHAZLY, Amr ULg; MOONEN, Vincent ULg; MAWET, Marie et al

in International immunopharmacology (2011), 11(11), 1864-70

Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic ... [more ▼]

Prostaglandin D2 (PGD2) receptor CRTH2, is a pro-inflammatory molecule involved in eosinophil recruitment to the allergic airway. We investigated the expression of CRTH2 in eosinophil from allergic rhinitis patients (AR) and tested the modulatory role of several TH1 and TH2 cytokines closely related to the allergic immunological response, on the expression of CRTH2 receptor, utilizing human eosinophil cell line (Eol-1).The expression of CRTH2 was tested by immunohistochemistry and flow cytometry (FACS). Chemotaxis was performed in micro-chemotaxis chambers. It is shown that the expression of CRTH2 by eosinophils was significantly higher in the nasal tissue and peripheral blood of AR patients, when compared to control subjects. PGD2 exhibited a typical bell shape dose response in attracting eosinophil from AR patients with optimal activity at 10(-7)M. Eol-1 cell surface expression of CRTH2 was significantly up-regulated by 10ng/ml IFN-gamma and TNF-alpha. The percentage of Eol-1 cells expressing the receptor increased by IFN-gamma and TNF-alpha from 12.74%+/-2.66 to 55%+/-8 and 33.8%+/-9.4, respectively. PGD2-induced Eol-1 chemotaxis was not blocked by SB203580, H-89 Dihydrochloride, Bisindo-lylmaleimide, or Genistein. PGD2-induced Eol-1 chemotaxis was potentiated by IFN-gamma and TNF-alpha without changing the signal transduction pathway. Correlation of our results to peripheral blood eosinophils from allergic rhinitis patients confirmed that 3hour pretreatment of eosinophils by 10ng/ml IFN-gamma and TNF-alpha, increased the mean fluorescence intensity (MFI) of CRTH2 from 8.23 to 9.68 and 9.38, respectively, and potentiated PGD2-induced eosinophil chemotaxis. Our results demonstrate a novel synergism between PGD2, IFN-gamma and TNF-alpha, in eosinophil chemotaxis. [less ▲]

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See detailThe human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain.
Metzger, B.; Chambeau, L.; Begon, Dominique ULg et al

in BMC medical genetics (2011), 12(1), 144

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of ... [more ▼]

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC). METHODS: We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. RESULTS: EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. CONCLUSIONS: These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC. [less ▲]

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