Senior Research FellowBSc(N Territory), PhD(Cant)
My research interests are focusing on the activity of tyrosine kinases, targeted inhibitors, effects of ascitic fluid ,and anti-tumour properties of natural food compounds in the progression of advanced ovarian cancer.
To understand these factors, I am using three dimensional (3D) cell cultures, chicken embryos and a syngeneic mouse model to investigate the biological activity in ovarian cancer.
Tyrosine kinases and targeted blockers in ascitic ovarian cancer cells
Receptor tyrosine kinases including EGFR, HER-2 and c-Met and non receptor tyrosine kinase including Jaks are selectively expressed in primary tissue and metastatic tumour of advanced ovarian cancer cells.
Their over expression is positively correlated with a poor prognosis in the advanced disease. Despite wealth information of these tyrosine kinase expressions and activation, little is known about the biological activity of tyrosine kinases in ovarian cancer cells are present in ascitic fluid.
This project is investigating the expression and activation of tyrosine kinases in ovarian cancer cells isolated from ascitic fluid. The proteomic profiles of each tyrosine kinases are explored in order to identify drugable targeted blockers.
Effects of ascitic fluid on ovarian cancer cells
Women with advanced disease often have with the accumulation of ascites in the abdominal cavity.
The ascitic fluid contains a mixture of cytokines, growth factors, chemokines and bioactive lipid molecules.
In addition, the ascitic fluid contains various of cell types including white blood cells, mesenchymal cells, red blood cells and ovarian cancer cells (single cells and clusters).
In recent years, a few studies have started to investigate the biological activity of ascitic fluid,which is believed to influence behavior of ovarian cancer cells.
Even though the exact insight mechanisms of how ascitic fluid exert to ovarian cancer cells is poorly defined, my research suggests that ascitic fluid can increase expression of oncogenic proteins in ovarian cancer cells and reduce the cellular uptake of targeted drugs.
Anti-tumour properties of naturally occurring compounds
Naturally occurring compounds have been an integral part of modern cancer research for many years.
These compounds are cheap and easily accessible for general public.
Toxicity profile of natural compounds are favourable. Therefore, anti-tumour properties of natural compounds are intensively investigated.
I am interested in the biological activity of resveratrol and its derivatives. Resveratrol shows anti-tumour activities in an in vitro in various tumour types including ovarian cancer.
However, there is big cap of knowledge whether resveratrol is really active in an in vivo model and human.
Furthermore, due to the rapid metabolism of resveratrol in vivo and human, the derivatives of resveratrol could provide a better natural compound that could have potential anti-tumour in vivo condition.
Majid, M. A., Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2023). The effects of the obesity-related hormones leptin, insulin, IGF-I and adiponectin on Ishikawa and HEC-1A, MCF-7 and SKOV-3 cancer cell lines. EC Gynaecology, 12(8). Retrieved from https://ecronicon.net/ec_gynaecology
Chitcholtan, K., Dyer, A., & Sykes, P. (2023). Predicting tumour progression of ID-8 syngeneic mouse ovarian cancer with blood biomarkers fo CA-125, IL-6 and VEGF: A prospective laboratory-based study. Clinical & Experimental Obstetrics & Gynaecology, 50(10), 212. doi: 10.31083/j.ceog5010212
Yunianto, I., Currie, M., Chitcholtan, K., & Sykes, P. (2023). Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer. Journal of Obstetrics & Gynaecology Research, 49, 2563-2574. doi: 10.1111/jog.15761
Kumar, D., Moghiseh, M., Chitcholtan, K., Mutreja, I., Lowe, C., Kaushik, A., Butler, A., Sykes, P., Anderson, N., & Raja, A. (2023). LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: A proof-of-concept research. Journal of Materials Chemistry B. Advance online publication. doi: 10.1039/d2tb02416k
Mekhileri, N. V., Major, G., Lim, K., Mutreja, I., Chitcholtan, K., Phillips, E., Hooper, G., & Woodfield, T. (2023). Biofabrication of modular spheroids as tumour-scale microenvironments for drug screening. Advanced Healthcare Materials, 12, 2201581. doi: 10.1002/adhm.202201581