Publications by authors named "Julie Gormley"
The development, maintenance and metastasis of solid tumors are highly dependent on the formation of blood and lymphatic vessels from pre-existing ones through a series of processes that are respectively known as angiogenesis and lymphangiogenesis. Both are mediated by specific growth-stimulating molecules, such as the vascular endothelial growth factor (VEGF) and adrenomedullin (AM), secreted by diverse cell types which involve not only the cancerogenic ones, but also those constituting the tumor stroma (i.e.
View Article and Find Full Text PDFDegradation of extracellular matrix components is a key step in tumor progression, facilitating invasion, angiogenesis, and metastasis. The lysosomal cysteine protease cathepsin S (Cat-S) is a prominent player in this process. We evaluated the antitumor activity of Fsn0503h, the first Cat-S-antagonistic humanized monoclonal antibody, in a panel of cancer cell lines and in human colon carcinoma xenografts.
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- Meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer used in photodynamic therapy (PDT) to kill tumor cells by generating reactive oxygen species, but its hydrophilicity limits its cellular uptake.
- A study focused on improving TMP delivery by encapsulating it in chitosan/alginate nanoparticles, which showed better uptake and photocytotoxic effects in human colorectal carcinoma cells compared to free TMP.
- Additionally, the nanoparticles were conjugated with antibodies targeting death receptor 5 (DR5), enhancing their efficacy and providing a targeted delivery method for TMP in treating colorectal tumors with PDT.
Background: Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression.
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- Cathepsin S is a cysteine protease linked to tumor growth and blood vessel formation, and its inhibition with the monoclonal antibody Fsn0503 has been shown to reduce colorectal cancer growth and angiogenesis.
- In studies, it was found that chemotherapy with CPT-11 increased Cathepsin S levels in specific cancer cell lines, suggesting a potential counterproductive effect.
- Combining Fsn0503 with CPT-11 not only decreased tumor growth more effectively than CPT-11 alone but also significantly disrupted tumor blood vessel development, indicating a promising approach for enhancing colorectal cancer treatment.
Article Synopsis
- Angiogenesis is crucial for tumor growth, and targeting it can lead to new cancer treatments; this study focuses on the role of cathepsin S and VEGF in this process.
- Fsn0503, a cathepsin S inhibitory antibody, was found to stop endothelial cell invasion and tube formation in lab tests, and it slowed down blood vessel development in human tumor models.
- When combined with anti-VEGF treatments, Fsn0503 shows promise in significantly improving the effectiveness of current anti-angiogenic therapies, which could also benefit conditions linked to abnormal blood vessel formation.
Article Synopsis
- Cathepsin S is a cysteine protease that aids tumor and endothelial cell invasion in cancer, and researchers aimed to inhibit its effects using an antibody called Fsn0503.
- Experiments showed that Fsn0503 effectively blocked the invasion of various tumor cell lines, particularly colorectal cancer cells, and inhibited processes like endothelial cell tube formation and tumor growth in animal models.
- The findings suggest that targeting cathepsin S with antibody inhibitors like Fsn0503 could offer a potential therapeutic strategy for cancer treatment, pending further studies.
Article Synopsis
- The study focuses on death receptor family-induced apoptosis, specifically targeting DR4 and DR5 with therapeutic antibodies, which have shown success in clinical trials.
- The search for effective antibodies targeting the Fas receptor has been challenging due to the differences in behavior of antibodies in lab settings compared to living organisms.
- A new high-throughput screening method has been developed to identify potential therapeutic antibodies that can effectively induce apoptosis by artificially cross-linking those bound to the Fas receptor.