References of "Roncarati, Patrick"
     in
Bookmark and Share    
Full Text
See detailOsteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ULg; Nokin, Marie-Julie; Leroi, Natacha ULg et al

Conference (2016, March 22)

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These ... [more ▼]

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model. [less ▲]

Detailed reference viewed: 40 (18 ULg)
Full Text
Peer Reviewed
See detailHMGB1 secretion during cervical carcinogenesis promotes the acquisition of a tolerogenic functionality by plasmacytoid dendritic cells
Demoulin, Stéphanie ULg; Herfs, Michael ULg; SOMJA, Joan ULg et al

in International Journal of Cancer = Journal International du Cancer (2015), 137

Detailed reference viewed: 41 (13 ULg)
Full Text
Peer Reviewed
See detailThe importance of the tumor microenvironment in the therapeutic management of cancer
Pottier, Charles ULg; Wheatherspoon, Alodie; RONCARATI, Patrick ULg et al

in Expert Review of Anticancer Therapy (2015), 15

Detailed reference viewed: 37 (8 ULg)
Full Text
Peer Reviewed
See detailCarcinogenic HPV infection in the cervical squamo-columnar junction
Mirkovic, Jelena; Howitt, Brooke; RONCARATI, Patrick ULg et al

in Journal of Pathology (The) (2015), 236

Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and ... [more ▼]

Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to 1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and 2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analyzed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16ink4, Ki67 and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from 8 of 10 with visible SCJ cells, 6 of which were HPV16/18 DNA positive. In 5 of these latter cases, the SCJ cells were positive for p16ink4 and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in micro-dissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16ink4 immunoreactivity, elevated proliferative index and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16ink4 expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ. [less ▲]

Detailed reference viewed: 42 (4 ULg)
Full Text
Peer Reviewed
See detailDeltaNp63 isoform-mediated beta-defensin family up-regulation is associated with (lymph)angiogenesis and poor prognosis in patients with squamous cell carcinoma.
Suarez-Carmona, Meggy ULg; Hubert, Pascale ULg; Gonzalez, Arnaud ULg et al

in Oncotarget (2014), 5(7), 1856-1868

Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype ... [more ▼]

Beside a role in normal development/differentiation, high p63 immunoreactivity is also frequently observed in squamous cell carcinoma (SCC). Due to the complexity of the gene, the role of each p63 isotype in tumorigenesis is still confusing. Constitutively produced or induced in inflammatory conditions, human beta-defensins (HbetaDs) are cationic peptides involved in host defenses against bacteria, viruses and fungi. Here, we investigated both the role of p63 proteins in the regulation of HbetaDs and the implication of these antimicrobial peptides in tumor (lymph)angiogenesis. Thus, in contrast to TAp63 isotypes, we observed that DeltaNp63 proteins (alpha, beta, gamma) induce HbetaD1, 2 and 4 expression. Similar results were observed in cancer tissues and cell lines. We next demonstrated that DeltaNp63-overexpressing SCC are associated with both a poor prognosis and a high tumor vascularisation and lymphangiogenesis. Moreover, we showed that HbetaDs exert a chemotactic activity for (lymphatic) endothelial cells in a CCR6-dependent manner. The ability of HbetaDs to enhance (lymph)angiogenesis in vivo was also evaluated. We observed that HbetaDs increase the vessel number and induce a significant increase in relative vascular area compared to negative control. Taken together, the results of this study suggest that DeltaNp63-regulated HbetaD could promote tumor (lymph)angiogenesis in SCC microenvironment. [less ▲]

Detailed reference viewed: 135 (13 ULg)
Full Text
Peer Reviewed
See detailAltered alpha-defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour-permissive microenvironment.
Hubert, Pascale ULg; Herman, Ludivine; RONCARATI, Patrick ULg et al

in Journal of Pathology (The) (2014), 234(4), 464-77

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical ... [more ▼]

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human alpha-defensin 5 (HD-5) and its possible role in these processes. We showed that HD-5 was able to prevent HPV virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a CCR2/CCR6-dependent manner and stimulated the infiltration of these professional antigen-presenting cells in a (pre)neoplastic epithelium transplanted in vivo in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of HD-5 were also assessed in vitro and in vivo. However there was a striking regional disparity in expression of HD-5, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical SC junction. Taken together, these results suggest one possible explanation for why the SC junction is uniquely vulnerable to both high-risk HPV infection (via reduced HD-5 expression and viral entry) and progression of neoplasia (via altered cell-mediated immune responses and altered microenvironment). Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [less ▲]

Detailed reference viewed: 46 (14 ULg)
See detailImplication of plasmacytoid dendritic cells in the malignant transformation of cervical epithelial metaplasia
Demoulin, Stéphanie ULg; Herfs, Michael ULg; Somja, Joan ULg et al

Poster (2010, September)

The cervical transformation zone is a dynamic area of a few millimeters in which a glandular epithelium has been replaced by a squamous epithelium through a metaplastic process. Interestingly, a ... [more ▼]

The cervical transformation zone is a dynamic area of a few millimeters in which a glandular epithelium has been replaced by a squamous epithelium through a metaplastic process. Interestingly, a substantial majority (87%) of cervical (pre)cancerous lesions develops within this peculiar microenvironment. Our previous studies reported that intrinsic immune features altered in the metaplastic epithelium could contribute to cancer development by preventing efficient antitumor/antiviral immune response. Plasmacytoid dendritic cells (pDC) are key effectors in host innate immunity and orchestrate adaptive immune responses. Recently, infiltration by these subtypes of dendritic cells has been shown in different cancers. However their implication in antitumor response is largely debated. The present study was performed to determine the implication of pDC in the cervical “metaplasia-dysplasia-cancer” sequence. We demonstrated that the density of pDC increases in the epithelium of metaplastic and (pre)cancerous cervical tissues as well as in underlying stroma as compared with normal exocervical epithelium. This could be partially explained by the increased expression of chemerin, their chemotactic peptide, observed in those areas. We developed a method to efficiently generate pDC cells exhibiting morphological and immunohistochemical features of blood pDC from a limited number of CD34+ cord blood progenitors. Using these in vitro generated pDC, we demonstrated that medium conditioned by transformed keratinocytes modified the activation status of pDC, by inducing a decreased expression of costimulatory molecules such as CD86 and HLA-DR. Moreover, malignant keratinocytes diminished the ability of pDC to produce IFNα in response to an oligonucleotide containing CpG motifs, a defined microbial stimulus for pDC. These results suggest that pDC could be educated within the metaplastic and/or (pre)cancerous microenvironment to acquire a tolerogenic phenotype that could promote carcinogenesis. In agreement with those results, we observed that both metaplastic areas and (pre)cancerous lesions of the cervix are infiltrated by T regulatory cells. [less ▲]

Detailed reference viewed: 41 (7 ULg)
Full Text
Peer Reviewed
See detailCharacterization of hepatitis C virus-induced nasal mucosa remodelling.
El Shazly, Amr ULg; Arafa, Mohammad; Roncarati, Patrick ULg et al

in Histopathology (2010), 57(3), 488-92

Detailed reference viewed: 34 (5 ULg)
Full Text
Peer Reviewed
See detailSurface Mucin-1 does not play a role in dendritic cell migration
Cloosen, Silvie; Caberg, Jean-Hubert ULg; Huls, Mariska B. et al

in Molecular Immunology (2009), 46(4), 738-742

Detailed reference viewed: 33 (4 ULg)
Full Text
Peer Reviewed
See detailIncreased migration of Langerhans cells in response to HPV16 E6 and E7 oncogene silencing: role of CCL20
Caberg, Jean-Hubert ULg; Hubert, Pascale ULg; Herman, Ludivine ULg et al

in Cancer Immunology, Immunotherapy (2009), 58(1), 39-47

Detailed reference viewed: 72 (7 ULg)