https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37909 Wed 23 Jun 2021 11:11:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37859 P = 0.04). The surrounding or invasion of nerves by cancer cells (perineural invasion) was detected in 12% of esophageal cancers and was associated with reduced survival (P = 0.04). Nerves were found to express the following receptors for nerve growth factor (NGF): neurotrophic receptor tyrosine kinase 1 and nerve growth factor receptor. An association was suggested between high production of NGF by cancer cells and the presence of nerves (P = 0.02). In vitro, NGF production in esophageal cancer cells was shown by Western blot, and esophageal cancer cells were able to induce neurite outgrowth in the PC12 neuronal cells. The neurotrophic activity of esophageal cancer cells was inhibited by anti-NGF blocking antibodies. Together, these data suggest that innervation is a feature in esophageal cancers that may be driven by cancer cell-released NGF.]]> Wed 17 Nov 2021 16:31:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47072 Wed 13 Mar 2024 09:25:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46031 NTR), are increasingly implicated in cancer progression, but their clinicopathological significance in oesophageal cancer is unclear. In this study, the expression of NGF, NTRK1 and NGFR were analysed by immunohistochemistry in a cohort of 303 oesophageal cancers versus 137 normal adjacent oesophageal tissues. Immunostaining was digitally quantified and compared to clinicopathological parameters. NGF and NGFR staining were found in epithelial cells and at similar levels between oesophageal cancers and normal oesophageal tissue. NGFR staining was slightly increased with grade (p=0.0389). Interestingly, NTRK1 staining was markedly higher in oesophageal squamous cell carcinoma (OR 2.31, 95%CI 1.13–4.38, p<0.0001) and significantly lower in adenocarcinoma (OR 0.50, 95%CI 0.44–0.63, p<0.0001) compared to normal oesophageal tissue. In addition, NTRK1 staining was decreased in grade 2 and grade 3 (OR 0.51, 95%CI 0.21–1.40, p<0.0001) compared to grade 1, suggesting a preferential involvement of this receptor in the more differentiated forms of oesophageal carcinomas. Together, these data point to NTRK1 as a biomarker and a candidate therapeutic target in oesophageal squamous cell carcinoma.]]> Wed 09 Nov 2022 15:59:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37505 Wed 02 Mar 2022 14:28:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43873 Tue 04 Oct 2022 12:29:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37622 NTR and the proneurotrophin co-receptor sortilin, remains unclear. In the present study, analysis of these proteins was conducted by immunohistochemistry and digital quantification in a series of 204 lung cancers of different histological subtypes versus 121 normal lung tissues. TrkA immunoreactivity was increased in squamous cell carcinoma compared with benign and other malignant lung cancer histological subtypes (p < 0.0001). NGF and proNGF were also increased in squamous cell carcinoma, as well as in adenocarcinoma (p < 0.0001). In contrast, p75^NTR was increased across all lung cancer histological subtypes compared to normal lung (p < 0.0001). Sortilin was higher in adenocarcinoma and small cell carcinoma (p < 0.0001). Nerves in the tumor microenvironment were negative for TrkA, NGF, proNGF, p75^NTR and sortilin. In conclusion, these data suggest a preferential therapeutic value of targeting the NGF-TrkA axis in squamous cell carcinomas of the lung.]]> Thu 24 Mar 2022 11:36:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37858 P = 0.0014). Sortilin inhibition by siRNA and the pharmacologic inhibitor AF38469 strongly reduced the adhesion and invasion of pancreatic cancer cells without affecting cell survival and viability. Sortilin inhibition also decreased the phosphorylation of the focal adhesion kinase in Tyr925. Together, these data show that sortilin contributes to pancreatic cancer invasion and could eventually be targeted in therapy.]]> Thu 24 Mar 2022 11:34:45 AEDT ]]>