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17 results on '"Lo, Dominic"'

10. Investigation of an unusual landslide at Sai Kung SaiWan Road, Sai Kung, Hong Kong.

Author

Lo, Dominic O. K., Law, Rachel H. C., Wai, Roland C. T., Ng, Axel K. L., Williamson, Steven J., Lee, Jason K. S., and Cheng, Y. M.

Subjects
*LANDSLIDES, *DEBRIS avalanches, *ROAD embankments, *ROCKSLIDES, *RAINSTORMS
Abstract

An intense rainstorm on 21 May 2016 resulted a total of 34 natural terrain landslides in the vicinity of Sai Kung Sai Wan Road in the Sai Kung East Country Park, Hong Kong. One of these landslides was a large-scale failure with a source volume of about 2100m3. It was almost an order of magnitude larger than all the others. The debris severely eroded a road embankment, undermining the road and resulting in road closure. The nature of the landslide was unusual in that it was a structurally controlled rockslide, with a basal failure surface formed from a persistent, planar sheeting joint within columnar jointed tuff rock with a maximum depth of about 12 m, while the other landslides that occurred in the country park during the same rainstorm involved only shallow failures within the regolith. An investigation of this unusual landslide was undertaken to diagnose the probable mechanism and causes of the failure. As there was concern about further large-scale instability occurring in the adjacent hillside where the sheeting joint was inferred to extend into, the potential for further large-scale instability was assessed as part of the investigation. The key components of the investigation included detailed engineering geological mapping, ground investigation and engineering analyses. This paper presents the findings of the investigation. [ABSTRACT FROM AUTHOR]

Published
2018
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16. Pharmacological manipulation of LSF suppresses Wnt signaling and inhibits growth of allogeneic and syngeneic colon cancer xenografts

Author

Lotfollahzadeh, Saran, Lo, Dominic, York, Emily A., Napoleon, Marc Arthur, Yin, Wenqing, Elzinad, Nagla, Le, John, Zhang, Mengwei, Yang, Xiaosheng, Morrissey, Austin, Elsadawi, Murad, Zhao, Qing, Schaus, Scott E., Hansen, Ulla, and Chitalia, Vipul C.

Abstract

Aberrant hyperactivation of Wnt signaling driven by nuclear β-catenin in the colonic epithelium represents the seminal event in the initiation and progression of colorectal cancer (CRC). Despite its established role in CRC tumorigenesis, clinical translation of Wnt inhibitors remains unsuccessful. LSF (encoded by TFCP2) is a transcription factor and a potent oncogene. We identified a chemotype named Factor Quinolinone Inhibitors (FQIs) that specifically inhibits LSF DNA-binding, partner protein-binding, and transactivation activities. We examined the role of LSF and FQIs in CRC tumor growth. Here, we show that LSF and β-catenin interacted in several CRC cell lines irrespective of their mutational profile, which were disrupted by FQI2-34. FQI2-34 suppressed Wnt activity in CRC cells in a dose-dependent manner. Leveraging both allogeneic and syngeneic xenograft models, we show that FQI2-34 suppressed CRC tumor growth, significantly reduced nuclear β-catenin, and downregulated Wnt targets such as AXIN-2 and SOX-9 in the xenograft cells. FQI2-34 suppressed the proliferation of xenograft cells. Adenocarcinomas from a series of stage IV CRC patients revealed a positive correlation between LSF expression and Wnt targets (AXIN-2 and SOX-9) within the CRC cells. Collectively, this study uncovers the Wnt inhibitory and CRC growth-suppressive effects of these LSF inhibitors in CRC cells, revealing a novel target in CRC therapeutics.

Published
2022
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17. The role of transcription factors in the pathogenesis of colorectal cancer

Author

Lo, Dominic

Subjects
Oncology
Abstract

Colorectal cancer (CRC) is one of the most diagnosed malignancies and third most leading causes of death in the world. In the pathogenesis of CRC, a benign adenomatous polyp can develop into an invasive cancer through multiple routes of gene inactivation. One of the most common mutations found in CRC is a loss of function mutation of APC. Wild-type APC forms a destruction complex with Axin2 and GSK-3β to degrade β-catenin in the cytosol. If β-catenin is not degraded, it can be translocated into the nucleus, wherewith the help of LSF it binds to the DNA and initiates Wnt signaling. The Wnt pathway is responsible for the upregulation of pro-oncogenic genes. The components of this pathway have become a prime target for CRC drug therapies. In this study, we examined the effectiveness of a newly developed drug named FQI-234. FQI-234 is designed to target LSF and hinder its ability to modulate the binding of β-catenin to DNA. An animal model was developed and 20 nude mice were subcutaneously injected with HT-29 cells. Following approximately one week, 10 mice were randomly selected to be in the experimental group and given 15 administrations of FQI-234 at 5 mg/kg over three weeks. Volumes of the tumors from each mouse were calculated throughout the experiment and at its conclusion. These calculations revealed a slower growth rate and smaller volume in those tumors treated with FQI-234. Tumors were then harvested and divided. Half of the tumors halves were used for RT-PCR and the other halves were fixed in formalin, embedded in paraffin, and then stained for histological examination. IHC staining exhibited a downregulation in levels of β-catenin, LSF, Axin2, and Sox9. Suppression of cell proliferation and upregulation of cell apoptosis was also evident. RT PCR confirmed these results with a decrease in levels of Axin2, Sox9, and Cyclin D1 shown in the xenografts treated with FQI-234. Overall this study showed for the first time in an animal model the tumor-suppressive effects of the LSF targeted compound, FQI-234.

Published
2021

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