GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Al-Kuraya, Khawla S.  (7)
  • Bu, Rong  (7)
  • Siraj, Abdul K.  (7)
  • 1
    Online Resource
    Online Resource
    Abstract 1492: FoxM1 expression and its association with matrix metalloproteinases in diffuse large B-cell lymphoma
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1492-1492
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1492-1492
    Abstract: Forkhead Box M1 (FoxM1) has been shown to play a critical role in pathogenesis of various malignancies however its role in lymphoid malignancies is not fully elucidated. Therefore, in this study, we first investigated the role of FoxM1 in a large series of DLBCL tissues in a tissue micro array (TMA) format by Immunohistochemistry (IHC). We then followed this with in vitro studies on DLBCL cell lines using either pharmacological inhibitors of FoxM1 or siRNA knock down strategy. Using IHC, FoxM1 was detected in 84.6% of DLBCL tumors. FoxM1 expression was found to be significantly associated with early stage (p=0.0149), germinal centre phenotype (p=0.0126) and high proliferative tumor marker Ki67 (p & lt;0.0001). In addition, FoxM1 expression was also significantly associated with expression of SKP2 (p & lt;0.0001) and inversely associated with p27 expression (0.0215). Metalloproteinases, such as MMP-2 and MMP-9 play an important role in invasion and migration of cancer cells were also found to be significantly associated with expression of FoxM1 (p=0.0008 and p=0.0002) respectively. Our in vitro studies showed that treatment of DLBCL cell lines with thiostrepton, a specific inhibitor of FoxM1 inhibited cell proliferation, invasion and migration of DLBCL cells and induced apoptosis in a dose dependent manner. Inhibition of FoxM1 led to down-regulation of MMP-2, MMP-9 and SKP2 expression while the expression of p27 was up-regulated in DLBCL cells. Similar results were obtained using siRNA targeted against FoxM1. Furthermore, treatment of DLBCL cells with thiostrepton caused a dose dependent apoptosis in all DLBCL cell lines used in the study. On dissecting the apoptotic pathway, we found that thiostrepton induced its apoptotic effect via the mitochondrial pathway and activation of caspases. Finally, treatment of DLBCL cells with thiostrepton down-regulated the expression of XIAP, cIAP1 and Survivin. Altogether, these results suggest that FoxM1 signaling contribute in pathogenesis of germinal centre subtype of DLBCL and may serve as useful molecular biomarker and potential therapeutic target. 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 1492. doi:10.1158/1538-7445.AM2011-1492
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-1492
    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
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract 4312: Targeting FoxM1 in inducing anticancer effects in triple-negative breast cancer cells
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4312-4312
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4312-4312
    Abstract: Triple-negative breast cancer (TNBC) is highly aggressive and a major threat to survival due to absence of molecular targets. Invasion, metastasis and chemoresistance are the greatest obstacles to the successful tumor treatment in breast cancer patients. In this study, over-expression of Forkhead box transcription factor M1 (FoxM1) was observed in 79% (770/975) of breast cancers from Saudi Arabia. FoxM1 over-expression was found to be an independent prognostic marker in multivariate analysis in late stage (Stage 3 and 4) breast cancer (p=0.0110). Our in vitro results show that treatment with thiostrepton, a dual FoxM1 and proteasome inhibitor caused cell viability loss and induce apoptosis in a dose dependent manner in triple-negative breast cancer cell lines. Thiostrepton treatment also inhibited colony formation and invasion/migration capabilities of triple-negative breast cancer cells. In vivo, thiostrepton treatment regressed TNBC cells; MDA-MB-231 generated xenografts via down-regulation of FoxM1 and its downstream targets. Altogether, our results suggest that FoxM1 and its associated signaling pathway may be a potential target for therapeutic intervention in the treatment of aggressive breast cancer. Key words: Triple-negative breast cancer, FoxM1, Apoptosis and Invasion Citation Format: Rong Bu, Abdul K. Siraj, Maqbool Ahmed, Fouad Al-Dayel, Khawla S. Al-Kuraya. Targeting FoxM1 in inducing anticancer effects in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4312. doi:10.1158/1538-7445.AM2017-4312
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-4312
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Role of X-Linked Inhibitor of Apoptosis as a Prognostic Marker and Therapeutic Target in Papillary Thyroid Carcinoma
    The Endocrine Society ; 2015
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 100, No. 7 ( 2015-07), p. E974-E985
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 100, No. 7 ( 2015-07), p. E974-E985
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2014-4356
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
    detail.hit.zdb_id: 2026217-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 3117: Pleiotrophin is a marker of poor prognosis in Middle Eastern papillary thyroid carcinoma
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3117-3117
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3117-3117
    Abstract: Pleiotrophin (PTN) is a heparin binding growth factor known to have role in neuronal development. It is highly expressed in embryo but has a very limited expression in adult tissues. PTN is considered a proto-oncogene and has been hypothesized to play role in oncogenesis as its expression is found to be increased in many different cancer subtypes. Its role in cell transformation, cell growth, survival, migration and angiogenesis has also been shown in various different types of cancers. The function of PTN is hypothesized to be carried out by its interaction with cell surface proteoglycans or binding to its selective cell surface receptor, protein tyrosine phosphatase receptor Z1 (PTPRZ1). The significance of role of PTN in pathogenesis of thyroid cancer has not been explored especially with the fact that papillary thyroid carcinoma (PTC) originating in this ethnic population is the second most common female malignancy, after breast. So in search for novel druggable molecular target we sought for PTN expression in a large cohort of Saudi PTC. We analysed PTN alteration in more than 1000 primary papillary thyroid carcinoma in a tissue microarray format with clinical follow up data. We found that PTN was overexpressed in 65.5% (658/1006) of PTC and was significantly associated with aggressive clinical parameters such as tall cell variant histological subtype (p = 0.0333), extrathyroidal extension (p = 0.0292), lymphovascular invasion (p = 0.0182) and large tumour size (p = 0.0160). Important significant molecular association was seen with PTPRZ-1 (p = 0.0316), Midkine (p = 0.0008) and pSTAT-3 (p & lt;0.0001). Finally patients showing PTN overexpression have worse disease free survival compared to patients showing low or absent PTN expression (p = 0.0218). On multivariate analysis PTN is found to be an independent marker of poor prognosis taking into consideration parameters such as Age, Stage, Lymph node status and Extrathyroidal extension (p = 0.0430). This study highlights the importance of PTN as druggable molecular target which can be therapeutically exploited by its inhibitors in treatment of PTC. Keywords: Papillary Thyroid Cancer; Pleiotrophin; Pleiotrophin Receptor Citation Format: Shaham Beg, Maqbool Ahmed, Azhar Hussein, Rong Bu, Zeeshan Qadri, Saif AlSobhi, Fouad Al Dayel, Abdul K. Siraj, Khawla S. Al-Kuraya. Pleiotrophin is a marker of poor prognosis in Middle Eastern papillary thyroid carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3117.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-3117
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 4323: ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4323-4323
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4323-4323
    Abstract: Aberrant activation of anaplastic lymphoma kinase (ALK) gene caused by mutation, rearrangement or overexpression plays a fundamental role in tumorigenesis in several tumors and represents an important therapeutic target. Currently, only limited data is available on thyroid cancer with respect to the genetic alteration of ALK. Therefore we investigate the ALK overexpression and amplification, and its correlation with various clinicopathological features and molecular biomarkers in a large cohort of 1040 Middle Eastern PTC. In our study, ALK protein expression was determined by immunohistochemistry. ALK gene amplification and rearrangement were analyzed by in situ hybridization (FISH). We also correlated the data with clinicopathological characteristics and other molecular markers. Our data showed that ALK is overexpressed in 136 of the 997 (13.6%) PTC samples. ALK amplification and rearrangement were not observed by FISH. ALK overexpression was significantly associated with surgical margin, but had no effect on the survival of PTC patients. Interestingly, ALK overexpression was found to be significantly correlated with the higher expression of pAKT and PIK3CA in PTC samples, suggesting that ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC. In addition, ALK overexpression is also correlated with overexpression of anti-apopototic marker XIAP and BCL-XL and cell cycle regulatory marker SKP2. Altogether, our results suggest that ALK overexpression presents in a small subset of samples and is not associated with survival in PTC. However ALK overexpression is significantly correlated with PI3K/AKT signaling pathway and might provide a potential therapeutic target for PTC patients with ALK overexpression. Citation Format: Rong Bu, Sarita Prabhakaran, Shaham Beg, Zeenath Jehan, Abdul K. Siraj, Maqbool Ahmed, Azhar Hussain, Saif A. Alsobhi, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya. ALK overexpression is associated with activation of PI3K/AKT signaling pathway in PTC. [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 4323. doi:10.1158/1538-7445.AM2015-4323
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-4323
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract 2255: SMAD4 loss is associated with poor prognosis in Middle Eastern colorectal cancer
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2255-2255
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2255-2255
    Abstract: Background: Colorectal cancer (CRC) is major cause of morbidity and mortality in cancer patients worldwide and it ranks as the most common cancer in males and the third most common among females in Saudi Arabia. Alteration in TGF-β pathway has been reported in many cancers. So In search for new molecular targets we analyzed the role of SMAD4, critical TGF-β pathway mediator, in Saudi colorectal cancers Methods: 426 CRC cases were analyzed for SMAD4 mutations by targeted capture sequencing and protein expression status by immunohistochemistry in a tissue microarray format. Results were analyzed for association with any clinico-pathological parameters and for prognostic significance. Results: SMAD4 mutations were detected in 11.9 %( 50/418) cases of Saudi colorectal cancers. CRC with SMAD4 mutations were significantly associated with NRAS mutations (p=0.0481). SMAD4 complete loss of expression by immunohistochemistry was seen in 12.8% (52/404) cases and this loss was associated with young age (p=0.0236) and inversely with MSI-high tumors (p=0.0005). SMAD4 expression loss by immunohistochemistry and mutation were significantly associated with each other (p=0.0028). In the multivariate analysis using the Cox proportional hazard model SMAD4 expression loss was an independent marker of poor prognosis (p=0.0119) Conclusion: SMAD4 alteration was found to be associated with a poor overall survival in the Saudi colorectal cancer patients. With the advent of targeted anticancer therapy, this study confirms the findings of other investigators and highlights a potential target which can be exploited to improve the survival of CRC patients in the Kingdom of Saudi Arabia Citation Format: Maqbool Ahmed, Abdul K. Siraj, Tariq Masoodi, Rong Bu, Fouad Al-Dayel, Khawla S. Al-Kuraya. SMAD4 loss is associated with poor prognosis in Middle Eastern colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2255. doi:10.1158/1538-7445.AM2017-2255
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-2255
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Fatty Acid Synthase and AKT Pathway Signaling in a Subset of Papillary Thyroid Cancers
    The Endocrine Society ; 2008
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 10 ( 2008-10), p. 4088-4097
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 93, No. 10 ( 2008-10), p. 4088-4097
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2008-0503
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2026217-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...