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  • 1
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    Online Resource
    Abstract 4412: Prognostic significance of NF-κB in Middle Eastern diffuse large B cell lymphoma and efficacy of NF-κB inhibition as a viable therapeutic target
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4412-4412
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4412-4412
    Abstract: NF-kB is frequently over expressed in variety of NHL and has been implicated in lymphomagenesis; however, its role in diffuse large B-cell lymphoma (DLBCL) as a prognostic biomarker has not been fully elucidated. Therefore, we investigated the role of NF-kB and its association with clinico-pathological features in a tissue microarray cohort of 230 DLBCL patient samples. We then elucidated the role of NF-kB inhibition on cell viability and apoptosis in-vitro using DLBCL cell lines. Using immunohistochemistry, NF-kB was detected in 25.6% (52/203) DLBCL tumors, was associated with activated B cell (ABC) phenotype (p=0.0054) and overexpression of anti apoptotic marker, XIAP (p=0.0013). DLBCL with nuclear expression of NF-kB showed a significantly poor overall survival as compared to those with no NF-kB expression (p=0.0236). In the multivariate analysis using Cox Proportional Hazard model for IPI and NF-kB expression, the relative risk was 2.97 for high NF-kB expression (95% CI 1.27-6.94; p=0.0113) and 7.55 for high IPI group (95% CI 3.34-18.35; p & lt;0.0001). In-vitro, Bay11-7085 inhibited constitutively active NF-kB expression in a dose dependent manner. Inhibition of NF-kB also down-regulated expression of down-stream target gene products, such as Bcl-2, Bcl-Xl, XIAP and Survivin leading to apoptosis via the mitochondrial apoptotic pathway. NF-kB overexpression was found to be an independent prognostic marker for poor survival in DLBCL. Inhibition of NF-kB caused apoptosis via activation of the mitochondrial apoptotic pathway. Altogether, these results suggest that NF-kB may be a useful prognostic biomarker and a potential target for therapeutic intervention in DLBCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4412. doi:10.1158/1538-7445.AM2011-4412
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-4412
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 2
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    Online Resource
    Abstract 2711: JC virus T-Antigen (SV40) is an independent prognostic marker for poor disease free survival in epithelial ovarian carcinoma
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2711-2711
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2711-2711
    Abstract: Epithelial ovarian cancer is the leading cause of death from gynecologic cancers and because of the pelvic location of the ovaries, the patients present at an advanced stage that is generally incurable. SV40 is a type of polyoma virus has been shown to induce tumors in rodents, transform cells in tissue culture and promote tumor transformation in transgenic mice. Many studies have reported the presence of simian virus 40 (SV40) deoxyribonucleic acid (DNA) or protein in human brain tumors, bone cancers, non-Hodgkin's lymphomas, malignant mesothelioma and other solid epithelial tumors including epithelial ovarian carcinomas. We studied the expression of SV40 in a tissue microarray cohort of 156 epithelial ovarian cancers by immunohistochemistry. The incidence of SV40 expression was 44.3% (58/131) and poorly differentiated carcinomas showed a trend towards higher expression of SV40 as compared to moderately and well differentiated tumors (p=0.0898). Validation of SV40 IHC expression was done by polymerase chain reaction (PCR) assay in selected clinical samples and ovarian cancer cell lines. A good concordance was observed between immunohistochemical expression of SV40 and amplification by PCR. Earlier studies have reported various molecular targets of SV40: up-regulation of c-MET oncogene and IGF-1; inhibition of tumor suppressor genes like p53, RASS1FA and protein phosphotase PP2A. To elucidate the link between these targets and SV40 we assessed the immunohistochemical expression of p53, RASS1FA, PP2A, c-MET and IGF-1 the cohort of epithelial ovarian carcinomas. In addition we also analyzed the association of SV40 with known oncogenic mutations in p53, KRAS and PIK3CA genes. SV40 expression showed a significant association with presence of p53 mutation (p & lt;0.0001.) as well as p53 overexpression (p & lt;0.0001). In addition, SV40 expression was associated with overexpression of c-MET (p=0.0111) and IGF-1(p=0.0334). EOC patients with SV40 expression had a poor progression free survival (PFS) of 13.2 months as compared to 20 months with absent SV40 expression (p=0.0980). In the multivariate analysis using Cox Proportional Hazard model for multiple factors like age, FIGO stage, grade, the relative risk was 1.70 for high SV40 expression (95% CI 1.10 – 2.69; p=0.0227) and 2.32 for high stage group III-IV (95% CI 1.33 – 3.90; p=0.0038). Thus, SV40 over expression was an independent prognostic marker in EOC. Altogether, our data highlights the prognostic utility of SV40 as a prognostic biomarker and confirms the well-known effect of SV40 on down-regulation or inactivation of p53, and activation of c-MET/IGF-1 in the epithelial ovarian carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2711. doi:10.1158/1538-7445.AM2011-2711
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2711
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    Abstract 3546: Prevalence of Lynch Syndrome among Middle Eastern endometrial cancer using targeted next generation sequencing
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3546-3546
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3546-3546
    Abstract: Endometrial carcinoma (EC) is the second most common gynecologic cancer worldwide. Although most ECs are sporadic, 2%-5% tend to be familial, with Lynch syndrome (LS) being the most commonly associated. The purpose of this study was to identify the incidence of LS in a large cohort of Middle eastern ECs and determine the feasibility of microsatellite instability (MSI) screening by immunohistochemistry (IHC) followed by molecular screening in deficient cases. We performed screening of 436 unselected EC for MSI status using IHC, followed by Target Capture sequencing of MSI deficient cases. MLH1 methylation analysis was performed by Real-time PCR, for cases showing deficient MLH1 by IHC. Complete loss of tumor nuclear protein expression in at least one of the four MMR genes was noted in 12.2% (53/436) of EC cases with 32 cases being MLH1 deficient, 10 MSH2 deficient, five MSH6 deficient and six PMS2 deficient. Of the 53 EC cases showing loss of expression in MMR genes, germline MMR mutations were found in four cases (0.9%). Promoter methylation analysis of 32 MLH1 deficient cases showed four cases to be unmethylated (12.5%). Our current study highlights the incidence of LS among patients with EC in Saudi Arabia. Screening of all EC patients using immunohistochemistry and reflex MLH1 promoter methylation testing followed by gene sequencing is feasible and desirable. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Rong Bu, Tariq Masoodi, Saud Azam, Wael Haqawi, Khadija Alobaisi, Maha Alrasheed, Valorie Balde, Nabil Siraj, Mark R. Diaz, Laila Ghazwani, Felisa DeVera, Hassan AlDossari, Khawla S. Al-Kuraya. Prevalence of Lynch Syndrome among Middle Eastern endometrial cancer using targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3546.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-3546
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    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
    The biological and clinical impact of inhibition of NF-κB-initiated apoptosis in diffuse large B cell lymphoma (DLBCL) : NF-κB predicts poor prognosis in DLBCL
    Wiley ; 2011
    In:  The Journal of Pathology Vol. 224, No. 3 ( 2011-07), p. 355-366
    Details
    In: The Journal of Pathology, Wiley, Vol. 224, No. 3 ( 2011-07), p. 355-366
    Type of Medium: Online Resource
    ISSN: 0022-3417
    URL: Article
    DOI: 10.1002/path.2864
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 1475280-3
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  • 5
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    Online Resource
    Abstract 2104: Frequent inactivation of A20 and its prognostic significance in Middle Eastern colorectal carcinoma
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2104-2104
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2104-2104
    Abstract: A20, also known as TNF alpha induced protein3 (TNFAIP3), is a tumor suppressor gene and a well-known negative regulator of the NF-kB pathway in hematolymphoid neoplasms. In colorectal carcinoma (CRC), aberrant NF-kB regulation has been associated with poor prognosis and resistance to therapy. However, role of A20 gene in CRC is unknown. Therefore, we sought to elucidate the biological role of A20, mechanism of its inactivation and its prognostic role in colorectal carcinoma. We investigated the genetic and epigenetic abnormalities of A20 gene in CRC. In a tissue microarray cohort of 434 CRC, we studied loss of A20 protein expression by immunohistochemistry and A20 deletions by FISH. We also screened 116 random CRC and 14 CRC cell lines for mutations in A20 gene and A20 promoter methylation. Of the 116 CRC samples, A20 deletions were seen in 15.3% and incidence of A20 mutation was 2.5%; most of the mutations (4/5) were missense mutations. A20 promoter hyper-methylation was seen in 50.8% and was correlated with loss of protein expression (p=0.0079). A20 inactivation, defined as loss or reduced expression of protein was observed in 63% of CRC and A20 inactivation was an independent prognostic marker for poor survival in all CRC. In addition A20 expression retained its prognostic value in the following subgroups: Stage III; Stage II and III; and Stage III and IV. A20 was inactivated in majority of the CRC due to promoter methylation and can be targeted to modulate NF-κb expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2104. doi:10.1158/1538-7445.AM2011-2104
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2104
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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