References of "RONCARATI, Patrick"
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See detailMethylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer
Nokin, Marie-Julie ULiege; Bellier, Justine ULiege; Durieux, Florence et al

in Breast Cancer Research (2019), 21(1

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See detailDeciphering the radiosensitivity of HPV-positive tumors
Bruyère, Diane ULiege; Lebeau, Alizée ULiege; RONCARATI, Patrick ULiege et al

Poster (2018, May 30)

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be ... [more ▼]

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be elucidated. A few hypotheses have been suggested regarding this differential radiosensitivity like, for example, an altered microtumoral environment or virus-host protein interactions. In this study, we focused on interactions between DNA repair proteins and virus oncoproteins. A large panel of 147 proteins implicated in DNA repair pathways was tested for potential interaction with HPV16 E6 and/or E7 oncoproteins using the GPCA method (Gaussia Princeps Complementation Assay). The proteins highlighted by the screening were validated by co-IP. The functional experiments, realized on HPV negative head and neck cancer (UPCI-SCC-111, FaDu, UPCI-SCC-40), vulva cancer (C33a) and control keratinocytes (HaCaT) stably transduced with E6 and/or E7, are in progress. [less ▲]

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See detailDeciphering the radiosensitivity of HPV-positive tumors
Bruyère, Diane ULiege; Lebeau, Alizée ULiege; RONCARATI, Patrick ULiege et al

Poster (2018, May 28)

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be ... [more ▼]

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be elucidated. A few hypotheses have been suggested regarding this differential radiosensitivity like, for example, an altered microtumoral environment or virus-host protein interactions. In this study, we focused on interactions between DNA repair proteins and virus oncoproteins. A large panel of 147 proteins implicated in DNA repair pathways was tested for potential interaction with HPV16 E6 and/or E7 oncoproteins using the GPCA method (Gaussia Princeps Complementation Assay). The proteins highlighted by the screening were validated by co-IP. The functional experiments, realized on HPV negative head and neck cancer (UPCI-SCC-111, FaDu, UPCI-SCC-40), vulva cancer (C33a) and control keratinocytes (HaCaT) stably transduced with E6 and/or E7, are in progress. [less ▲]

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See detailProteomic signatures reveal a dualistic and clinically relevant classification of anal canal carcinoma
Herfs, Michael ULiege; Longuespée, Rémi ULiege; Quick, Charles et al

in Journal of Pathology (2017), 241

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See detailTyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.
El-Shazly, A. E.; Roncarati, Patrick ULiege; Lejeune, Margaux ULiege et al

in International Immunopharmacology (2017), 45(45), 180-186

We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However ... [more ▼]

We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR. [less ▲]

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See detailNew role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
Henry, Aurélie ULiege; Nokin, Marie-Julie ULiege; Leroi, Natacha ULiege et al

in Oncotarget (2016)

Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness ... [more ▼]

Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines. Clonogenic experiments showed that OPN-depleted GBM cells were sensitized to irradiation. In comet assays, these cells displayed higher amounts of unrepaired DNA fragments post-irradiation when compared to control. We next evaluated the phosphorylation of key markers of DNA double-strand break repair pathway. Activating phosphorylation of H2AX, ATM and 53BP1 was signi cantly decreased in OPN-de cient cells. The addition of recombinant OPN prior to irradiation rescued phospho-H2AX foci formation thus establishing a new link between DNA repair and OPN expression in GBM cells. Finally, OPN knockdown improved mice survival and induced a signi cant reduction of heterotopic human GBM xenograft when combined with radiotherapy. This study reveals a new function of OPN in DNA damage repair process post-irradiation thus further con rming its major role in GBM aggressive disease. [less ▲]

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See detailOsteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ULiege; Nokin, Marie-Julie; Leroi, Natacha ULiege 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 ▲]

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See detailHuman cytomegalovirus and primary intracranial tumours: Frequency of tumour infection and lack of correlation with systemic immune anti-viral responses
BIANCHI, Elettra ULiege; RONCARATI, Patrick ULiege; HOUGRAND, Olivier ULiege et al

in Neuropathology and Applied Neurobiology (2015), 41(2), 29-40

Aims: Human cytomegalovirus (HCMV) is a ubiquitous beta human herpesvirus able to influence infected cell survival and proliferation and to modulate the host immune response. As there is accumulating ... [more ▼]

Aims: Human cytomegalovirus (HCMV) is a ubiquitous beta human herpesvirus able to influence infected cell survival and proliferation and to modulate the host immune response. As there is accumulating evidence that HCMV is detected in primary intracranial astrocytic tumours, in this study we looked for the presence of HCMV in intracranial tumours and tried to correlate this eventual presence with the anti-HCMV systemic immunoreactivity and with the detection of HCMV in peripheral blood. Methods: In this study, we analysed 43 glioblastomas (GBM), 14 oligodendrogliomas (OL) and 20 meningiomas (MG) by immunofluorescence (IF) targeting HCMV immediate early antigen (IE1) and by nested PCR (nPCR) amplifying HCMV glycoprotein B (gB). Results: Detection of IE1 by IF showed the presence of HCMV in 70% of GBM, 57% of OL and 85% of MG, in contrast to gB nPCR, which detected HCMV in only 50% of GBM, 38% of OL and 46% of MG. Unexpectedly, HCMV DNA and antigens were detected within GBM, OL and MG of patients that exhibit negative viral serology. More surprisingly, PCR on the peripheral blood did not detect HCMV in patients with a HCMV-positive tumour. Conclusions: Our results are in agreement with previous observations demonstrating HCMV in glial tumours and highlight the presence of HCMV in meningiomas. We also showed that anti-HCMV specific systemic immunoreactivity and detection of HCMV in peripheral blood are not predictive of HCMV presence in primary intracranial tumours. © 2014 British Neuropathological Society. [less ▲]

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See detailThe importance of the tumor microenvironment in the therapeutic management of cancer
Pottier, Charles ULiege; Wheatherspoon, Alodie; RONCARATI, Patrick ULiege et al

in Expert Review of Anticancer Therapy (2015), 15

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