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
  • American Association for Cancer Research (AACR)  (2)
  • 1
    Online Resource
    Online Resource
    Abstract 5087: Thromboxane synthase and thromboxane receptor targeting have anti-angiogenic efficacy in-vivo and reduce angiogenic secretions from human colorectal tumor explants ex-vivo .
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5087-5087
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5087-5087
    Abstract: Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. The VEGF inhibitor avastin is commonly used to treat metastatic CRC. However, a poor overall response rate of approximately 40% suggests further anti-angiogenic strategies are warranted. While COX-2 inhibitors are promising, chronic use is associated with increased cardiovascular risk. Downstream of COX-2, the thromboxane (TX) signalling pathway promotes tumour development, and is thought to promote cancer growth via increased tumour-associated angiogenesis. This study aimed to examine the TX signalling pathway as a novel anti-angiogenic target for the treatment of CRC. Methods: We examined the effect of TX-pathway inhibition (using thromboxane synthase (TXS) inhibitors, thromboxane receptor (TP) antagonists and dual inhibitors; n=15) on blood vessel formation in-vivo using a transgenic zebrafish model (TgEGFP fli-1). Zebrafish larvae were treated with increasing concentrations of these inhibitors 4-6 h post-fertilization (hpf). Fish were fixed at 48hpf and vascular formation assessed under the flouresence microscope by counting of intersegmental vessels (ISV). The most promising TX-pathway inhibitors (ozagrel, seratrodast, AH-23848) were brought forward for further analysis using ex-vivo 3D-explant culturing. Angiogenic protein secretions from CRC tumour explants were assessed following 72 h treatment with these inhibitors using Meso-Scale Discovery multi-spot arrays (7-spot immunoassay system against human VEGF, Ang-1, Ang-2, bFGF, PAI-1, VCAM-1, ICAM-1) and compared with the known anti-angiogenic agent, avastin. Results: In-vivo vascular screening revealed significant effects on ISV formation for a number of TX-pathway inhibitors. The 3 inhibitors with the greatest effect on vessel formation were ozagrel (TXS inhibitor), seratrodast (TP antagonist) and AH-23848 (TXS/EP4 inhibitor). Treatment with 100uM of these inhibitors reduced vessel formation to 70% (p & lt;0.0001), 40% (p & lt;0.0001) and 35% (p & lt;0.0001) of untreated control for ozagrel, seratrodast and AH-23848 respectively. Human explant culturing revealed that the secretion of a number of angiogenic metabolites from CRC tumour explants was significantly reduced following thromboxane pathway targeting, including VEGF, bFGF, Ang-1, PAI-1 and ICAM. Conclusion: Thromboxane pathway targeting demonstrates anti-angiogenic effects in-vivo. In CRC patients, these effects may be mediated in part through a reduction in angiogenic protein secretions. Targeting this pathway may be a novel anti-angiogenic approach for the treatment of metastatic CRC alone, or in combination with traditional agents. Citation Format: Mary-Clare Cathcart, Jacintha O’ Sullivan, Breandan N. Kennedy, John V. Reynolds, Graham P. Pidgeon. Thromboxane synthase and thromboxane receptor targeting have anti-angiogenic efficacy in-vivo and reduce angiogenic secretions from human colorectal tumor explants ex-vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5087. doi:10.1158/1538-7445.AM2013-5087
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-5087
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    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
    Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 23 ( 2010-12-01), p. 9742-9754
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 23 ( 2010-12-01), p. 9742-9754
    Abstract: The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03–1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01–1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10−11 − 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers. Cancer Res; 70(23); 9742–54. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-10-1907
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    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
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...