Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer
Fahmy, Karim ; ; et al
in International Journal of Cancer = Journal International du Cancer (in press)
Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas ... [more ▼]
Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density. [less ▲]Detailed reference viewed: 65 (17 ULg)
Expression of the helicase-like transcription factor and its variants during carcinogenesis of the uterine cervix: implications for tumour progression.
; ; et al
in Histopathology (2011), 58(6), 984-8Detailed reference viewed: 13 (3 ULg)
High incidence of high-risk HPV in benign and malignant lesions of the larynx.
; ; et al
in International Journal of Oncology (2011), 39(1), 51-9
The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 ... [more ▼]
The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and 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. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup. [less ▲]Detailed reference viewed: 17 (4 ULg)
Progression model tissue microarray (TMA) for the study of uterine carcinomas.
; Boniver, Jacques ; Delvenne, Philippe
in Disease Markers (2010), 28(5), 267-72
Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers ... [more ▼]
Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers which may be relevant for the diagnosis, prediction of disease progression and therapeutic response.High throughput technologies for testing and validating molecular targets in cancer lesions and in their precursors are presently available. Among them, the tissue microarray (TMA) presents the advantage of a morphological control of the analyzed tissue fragment. In this article, we review the different aspects of the TMA technology with a special consideration to a uterine carcinogenesis model. [less ▲]Detailed reference viewed: 12 (3 ULg)
Current concepts in the pathology and epigenetics of endometrial carcinoma.
; Somja, Joan ; Dehan, Pierre et al
in Pathology (2010), 42(7), 613-7
In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and is the fourth most common cancer in women. Two different clinicopathological subtypes are ... [more ▼]
In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and is the fourth most common cancer in women. Two different clinicopathological subtypes are recognised: the oestrogen-related (type I, endometrioid) and the non-oestrogen related (type II, non-endometrioid). This article reviews the epidemiology, risk factors, genetic alterations during endometrial carcinogenesis, features of tumours and precursors and early detection of the disease. Insights into the epigenetic alterations, with emphasis on DNA methylation during endometrial carcinogenesis, and their diagnostic value are also provided. [less ▲]Detailed reference viewed: 65 (13 ULg)
Characterization of hepatitis C virus-induced nasal mucosa remodelling.
El Shazly, Amr ; ; Roncarati, Patrick et al
in Histopathology (2010), 57(3), 488-92Detailed reference viewed: 30 (5 ULg)
Cervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR.
Henkens, Rachel ; Delvenne, Philippe ; et al
in BMC Cancer (2008), 8
BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the ... [more ▼]
BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the cell cycle. We have previously demonstrated using RNA interference that cells lacking VHR arrest in the G1 and G2 phases of the cell cycle and show signs of beginning of cell senescence. METHODS: In this report, we evaluated successfully the expression levels of VHR protein in 62 hysterectomy or conization specimens showing the various (pre) neoplastic cervical epithelial lesions and 35 additional cases of hysterectomy performed for non-cervical pathologies, from patients under 50 years of age. We used a tissue microarray and IHC technique to evaluate the expression of the VHR phosphatase. Immunofluorescence staining under confocal microscopy, Western blotting and RT-PCR methods were used to investigate the localization and expression levels of VHR. RESULTS: We report that VHR is upregulated in (pre) neoplastic lesions (squamous intraepithelial lesions; SILs) of the uterine cervix mainly in high grade SIL (H-SIL) compared to normal exocervix. In the invasive cancer, VHR is also highly expressed with nuclear localization in the majority of cells compared to normal tissue where VHR is always in the cytoplasm. We also report that this phosphatase is highly expressed in several cervix cancer cell lines such as HeLa, SiHa, CaSki, C33 and HT3 compared to primary keratinocytes. The immunofluorescence technique under confocal microscopy shows that VHR has a cytoplasmic localization in primary keratinocytes, while it localizes in both cytoplasm and nucleus of the cancer cell lines investigated. We report that the up-regulation of this phosphatase is mainly due to its post-translational stabilization in the cancer cell lines compared to primary keratinocytes rather than increases in the transcription of DUSP3 locus. CONCLUSION: These results together suggest that VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy. [less ▲]Detailed reference viewed: 86 (16 ULg)
NK CELLS AND NKG2D LIGANDS IN HPV-ASSOCIATED CERVICAL CANCER
Jacobs, Nathalie ; Renoux, Virginie ; Dortu, Estelle et al
Poster (2007, April 12)Detailed reference viewed: 32 (3 ULg)
Le cancer du col de l'utérus: du virus au traitement
Delvenne, Philippe ; Goffin, Frédéric ; Kridelka, Frédéric et al
in Revue Médicale de Liège (2007), 62(S1)
Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this ... [more ▼]
Squamous cell cancer of the uterine cervix is associated with a high morbidity and mortality worldwide and in Belgium. New therapeutic approaches have been recently proposed. The development of this cancer is related to the infection by oncogenic human papillomavirus (HPV) types. The link between cervical cancer and HPV has, in recent years, generated, a great interest for studies aiming to better understand the role of the immune system in the control of these infections and for the development of prophylactic anti-HPV vaccines. [less ▲]Detailed reference viewed: 183 (25 ULg)