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- Chen, Wei Sheng, et al.
(author)
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Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in Lgals8 -/- mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the Lgals8 -/- and Pdpn -/- mice; likewise, galectin-8-induced lymphangiogenesis is reduced in Pdpn -/- mice. Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic endothelial cell (LEC) sprouting. Instead, inhibiting integrins α1β1 and α5β1 curtails both galectin-8- and VEGF-C-mediated LEC sprouting. Together, this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role.
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| 3. |
- Kristan, Matej, et al.
(author)
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The Visual Object Tracking VOT2013 challenge results
- 2013
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In: 2013 IEEE INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE. - 9781479930227 ; , s. 98-111
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Conference paper (peer-reviewed)abstract
- Visual tracking has attracted a significant attention in the last few decades. The recent surge in the number of publications on tracking-related problems have made it almost impossible to follow the developments in the field. One of the reasons is that there is a lack of commonly accepted annotated data-sets and standardized evaluation protocols that would allow objective comparison of different tracking methods. To address this issue, the Visual Object Tracking (VOT) workshop was organized in conjunction with ICCV2013. Researchers from academia as well as industry were invited to participate in the first VOT2013 challenge which aimed at single-object visual trackers that do not apply pre-learned models of object appearance (model-free). Presented here is the VOT2013 benchmark dataset for evaluation of single-object visual trackers as well as the results obtained by the trackers competing in the challenge. In contrast to related attempts in tracker benchmarking, the dataset is labeled per-frame by visual attributes that indicate occlusion, illumination change, motion change, size change and camera motion, offering a more systematic comparison of the trackers. Furthermore, we have designed an automated system for performing and evaluating the experiments. We present the evaluation protocol of the VOT2013 challenge and the results of a comparison of 27 trackers on the benchmark dataset. The dataset, the evaluation tools and the tracker rankings are publicly available from the challenge website(1).
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| 4. |
- Liu, Anbu, et al.
(author)
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DDR1/2 enhance KIT activation and imatinib resistance of primary and secondary KIT mutants in gastrointestinal stromal tumors
- 2024
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In: Molecular Carcinogenesis. - 0899-1987. ; 63:1, s. 75-93
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Journal article (peer-reviewed)abstract
- Gastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. In this study, we observed that discoidin domain receptors 1 and 2 (DDR1 and DDR2) exhibited high expression in GISTs, were associated with KIT, and enhanced the activation of both wild-type KIT and primary KIT mutants. Inhibition of DDR1/2 led to a reduction in the activation of KIT and its downstream signaling molecules, ultimately impairing GIST cell survival and proliferation in vitro. Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first-line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. In addition, DDR1/2 inhibition resulted in decreased KIT expression, while KIT inhibition led to upregulation of DDR1/2 expression in GISTs. The presence of DDR1/2 also decreased the sensitivity of wild-type KIT or primary KIT mutants to imatinib, indicating a possible role for DDR1/2 in promoting GIST survival during KIT-targeted therapy. The development of drug-resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. Similar to primary KIT mutants, DDR1/2 can associate with and enhance the activation of secondary KIT mutants, further diminishing their sensitivity to imatinib. In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
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