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  • American Association for Cancer Research (AACR)  (4)
  • 1
    Online Resource
    Online Resource
    Abstract 3889: RPL28 promoter polymorphism rs4806668 is associated with reduced survival in FOLFIRI-treated metastatic colorectal cancer patients
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3889-3889
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3889-3889
    Abstract: Fluorouracil (5-FU), folinic acid, and irinotecan (FOLFIRI) is a standard treatment of metastatic colorectal cancer (mCRC). Our study aimed to investigate genetic variability in candidate genes in relation to patients' outcomes using two independent cohorts of 417 FOLFIRI-treated mCRC cases recruited in Canada and Italy. We used a haplotype-tagging polymorphism (htSNP) approach to maximize the coverage of genetic variability of the selected genes and genotyping was performed using time-of-flight mass spectrometry iPLEX Sequenom Technology. Associations between polymorphisms and clinical outcomes were tested using Cox proportional hazards model adjusted for covariates. Of the genes tested, RPL28 encodes a ribosomal protein and its silencing was shown to enhance sensitivity to 5-FU and irinotecan in vitro.1 RPL28 rs4806668G & gt;T was associated with a shorter progression-free survival (PFS) in the Canadian (hazard ratio (HR) 3.23, P = 0.013), Italian (HR 3.28, P = 0.021) and combined (HR 3.36, P & lt; 0.001) cohorts. This marker was also associated with a reduced overall survival (OS) in the Canadian (HR 3.09, P = 0.032), Italian (HR 3.05, P = 0.030) and combined (HR 3.07, P = 0.002) cohorts. These carriers of the rs4806668 TT genotype associated with reduced survival represent less than 5% of the population of European ancestry and its frequency varies greatly among ethnic groups. This htSNP, located in the promoter region of RPL28, is in strong linkage disequilibrium with six other polymorphisms and may affect RPL28 gene expression. In support, the rs4806668T allele was associated with increased RPL28 expression in colon tissues of healthy individuals of the GTEx cohort, compared to rs4806668G carriers. Functional investigations are required to elucidate the underlying molecular mechanism. These results suggest a role for the ribosomal RPL28 protein in cancer cell response to FOLFIRI treatment. This work is supported by the Canadian Institutes of Health Research. 1Allen et al. Mol Cancer Ther. 2012 Jan;11(1):119-31 Citation Format: Adrien Labriet, Éric Lévesque, Elena De Mattia, Erika Cecchin, Derek Jonker, Félix Couture, David Simonyan, Angela Buonadonna, Mario D'Andrea, Lyne Villeneuve, Giuseppe Toffoli, Chantal Guillemette. RPL28 promoter polymorphism rs4806668 is associated with reduced survival in FOLFIRI-treated metastatic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3889.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-3889
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    Resveratrol Inhibits Proliferation and Survival of Epstein Barr Virus–Infected Burkitt's Lymphoma Cells Depending on Viral Latency Program
    American Association for Cancer Research (AACR) ; 2011
    In:  Molecular Cancer Research Vol. 9, No. 10 ( 2011-10-01), p. 1346-1355
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 9, No. 10 ( 2011-10-01), p. 1346-1355
    Abstract: Resveratrol (3,4′,5-trihydroxy-trans-stilbene), a polyphenolic natural product, shows chemopreventive properties against several cancers, heart diseases, inflammation, and viral infections. Epstein Barr virus (EBV), a γ-herpesvirus, contributes to the development of several human cancers including Burkitt's lymphoma (BL). In this study, we asked whether treatment with resveratrol would affect the viability of EBV-positive BL cells displaying different forms of latency. We report here that resveratrol, regardless of EBV status, induces caspase-dependent apoptosis by arresting cell-cycle progression in G1 phase. However, resveratrol strongly induced apoptosis in EBV(−) and latency I EBV(+) cells, whereas latency II and latency III EBV(+) BL cells showed a survival advantage that increased with the extent of the pattern of viral gene expression. Resveratrol-induced cell-cycle arrest and apoptosis occurred in association with induction of p38 MAPK phosphorylation and suppression of ERK1/2 signaling pathway. Moreover, NF-κB DNA-binding activity was inhibited in all BL lines except EBV(+) latency III cells. LMP1 oncogene, which is expressed in latency III phenotype, is involved with the higher resistance to the antiproliferative effect of resveratrol because siRNA-mediated inhibition of LMP1 greatly increased the sensitivity of latency III BL cells as well as that of lymphoblastoid cell lines to the polyphenol. We propose that a combined resveratrol/siRNA strategy may be a novel approach for the treatment of EBV-associated B-cell malignancies in which the viral pattern of gene expression has been defined. Mol Cancer Res; 9(10); 1346–55. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1541-7786.MCR-11-0145
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2097884-4
    SSG: 12
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  • 3
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    Abstract 4568: Inhibition of autophagy in EBV-positive Burkitt's lymphoma cells enhances EBV lytic genes expression and replication
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4568-4568
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4568-4568
    Abstract: Autophagy, an important degradation system involved in maintaining cellular homeostasis, serves also to eliminate pathogens and process their fragments for presentation to the immune system. Several viruses have been shown to interact with the host autophagic machinery to suppress or make use of this cellular catabolic pathway to enhance their survival and replication. Epstein Barr virus (EBV) is a γ-herpes virus associated with a number of malignancies of epithelial and lymphoid origin in which establishes a predominantly latent infection. EBV lytic cycle characterized by the sequential expression of immediate early (IE), early and late antigens results in the production of infectious particles which allow the virus to spread. In this study we analyzed the relationship between EBV and autophagy after inducing the virus productive cycle in Burkitt's lymphoma (BL) cells. By monitoring autophagy markers and EBV lytic genes expression, we demonstrate that autophagy is enhanced in the early phases of EBV lytic activation but decreases thereafter concomitantly with increased levels of EBV lytic proteins. In a cell line defective for late antigens expression, we found an inverse correlation between EBV early antigens expression and autophagosomes formation indicating that early after activation, the virus is able to suppress autophagy. We report that inhibition of autophagy by Bafilomycin A1 or shRNA knockdown of beclin1 gene, enhance EBV lytic genes expression as well as intracellular viral DNA and viral progeny yield. Taken together, these findings indicate that viral replication induces an autophagic response which can inhibit the further expression of EBV early lytic products. Moreover, our findings open the possibility to utilize pharmacological modulators of autophagy to control EBV infection and treat EBV-related lymphomas. Citation Format: Alessandra De Leo, Francesca Colavita, Fabiola Ciccosanti, Gian Maria Fimia, Paul Lieberman, Elena Mattia. Inhibition of autophagy in EBV-positive Burkitt's lymphoma cells enhances EBV lytic genes expression and replication. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4568. doi:10.1158/1538-7445.AM2015-4568
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-4568
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Effect of TP53 Arg72Pro and MDM2 SNP309 Polymorphisms on the Risk of High-Grade Osteosarcoma Development and Survival
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 10 ( 2009-05-15), p. 3550-3556
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 10 ( 2009-05-15), p. 3550-3556
    Abstract: Purpose: The germ-line polymorphisms TP53 Arg72Pro and MDM2 SNP309 T & gt;G are risk factors for tumor development and affect response to chemotherapy and survival in several cancers, but their prognostic and predictive value in patients with high-grade osteosarcomas is not yet defined. The purpose of this study was to investigate the effect of the TP53 Arg72Pro and the MDM2 SNP309 on the risk of osteosarcoma development and survival. Experimental Design: The relative risk to develop osteosarcomas and the overall survival associated to TP53 Arg72Pro and MDM2 SNP309 polymorphisms were investigated in 201 patients. Correlations with event-free survival (EFS) were analyzed in a homogeneous subgroup of 130 patients with high-grade osteosarcomas of the limbs, nonmetastatic at diagnosis, which underwent neoadjuvant chemotherapy. Results: Multivariate analysis showed that the MDM2 polymorphism T309G was associated with an increased risk of developing osteosarcomas [GG versus TT; odds ratio, 2.09; 95% confidence interval (95% CI), 1.15-3.78]. A case/control gender approach evidenced a significant increased risk only for female osteosarcoma patients (GG versus TT; odds ratio, 4.26; 95% CI, 1.61-11.25). Subjects carrying the TP53 Arg72Pro polymorphism were found to have a significantly increased death risk (Pro/Pro versus Arg/Arg; hazard ratio, 2.90; 95% CI, 1.28-6.66). In the subgroup of 130 high-grade osteosarcomas, the TP53 Arg72Pro was an independent marker of EFS (Pro/Pro versus Arg/Arg; hazard ratio, 2.67; 95% CI, 1.17-6.11). Conclusion: The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53 Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-2249
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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