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.
Publications
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
Journal - Research Article
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
Journal - Research Article
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
Journal - Research Other
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
Journal - Research Article
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
Journal - Research Article
Dunn, E., Chitcholtan, K., Sykes, P., & Garrill, A. (2022). The anti-proliferative effect of PI3K/mTOR and ERK inhibition in monolayer and three-dimensional ovarian cancer cell models. Cancers, 14, 395. doi: 10.3390/cancers14020395
Journal - Research Article
Sarwar, M., Sykes, P. H., Chitcholtan, K., & Evans, J. J. (2022). Collagen I dysregulation is pivotal for ovarian cancer progression. Tissue & Cell, 74, 101704. doi: 10.1016/j.tice.2021.101704
Journal - Research Article
McGregor, R. A., Chitcholtan, K., & Ware, A. W. (2022, August-September). The role of the epithelial sodium channel in breast and ovarian cancer. Verbal presentation at the 16th New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Verbal presentation and other Conference outputs
Sarwar, M., Sykes, P. H., Chitcholtan, K., & Evans, J. J. (2021). Deciphering biophysical modulation in ovarian cancer cells. Cell Biochemistry & Biophysics, 79, 375-386. doi: 10.1007/s12013-020-00964-9
Journal - Research Article
Chitcholtan, K., Harker, D., Simcock, B., & Sykes, P. (2020). Sensitivity of EGFR/HER-2 positive cells isolated from ascitic fluid of advanced ovarian cancer patients to EGFR/HER-2 inhibitors. Applied Sciences, 10(7), 2343. doi: 10.3390/app10072343
Journal - Research Article
Sarwar, M., Sykes, P. H., Chitcholtan, K., & Evans, J. J. (2020). Extracellular biophysical environment: Guilty of being a modulator of drug sensitivity in ovarian cancer cells [Short communication]. Biochemical & Biophysical Research Communications, 527(1), 180-186. doi: 10.1016/j.bbrc.2020.04.107
Journal - Research Other
Sarwar, M., Sykes, P. H., Chitcholtan, K., Alkaisi, M. M., & Evans, J. J. (2019). The extracellular topographical environment influences ovarian cancer cell behaviour. Biochemical & Biophysical Research Communications, 508, 1188-1194. doi: 10.1016/j.bbrc.2018.12.067
Journal - Research Article
Hassan, W., Chitcholtan, K., Sykes, P., & Garrill, A. (2018). Ascitic fluid from advanced ovarian cancer patients compromises the activity of receptor tyrosine kinase inhibitors in 3D cell clusters of ovarian cancer cells. Cancer Letters, 420, 168-181. doi: 10.1016/j.canlet.2018.02.013
Journal - Research Article
Sarwar, M., Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2018). Microenvironment biophysics: It is vital to tumour cell behaviour including resistance to chemotherapy. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/
Conference Contribution - Published proceedings: Abstract
Tino, A., Dachs, G., Sykes, P., Evans, J., & Chitcholtan, K. (2018). Ovarian cancer cell lines grown in a three dimensional collagen model respond differentially to lysophosphatidic acid and tumour necrosis factor-alpha. Proceedings of the New Zealand Society for Oncology (NZSO) Conference. Retrieved from http://www.nzsoncology.org.nz/
Conference Contribution - Published proceedings: Abstract
Chitcholtan, K., Harker, D., Simcock, B., & Sykes, P. (2018, August). Inhibition of EGFR/HER-2 affects growth of ascitic ovarian cancer cells in vitro study. Poster session presented at the Queenstown Molecular Biology (QMB) Meetings, Queenstown, New Zealand.
Conference Contribution - Poster Presentation (not in published proceedings)
Sarwar, M., Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2018, August). Unseen to be seen: A hidden microenvironment regulates ovarian cancer cell behaviour. Poster session presented at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Poster Presentation (not in published proceedings)
Kumar, D., Mutreja, I., Chitcholtan, K., & Sykes, P. (2017). Cytotoxicity and cellular uptake of different sized gold nanoparticles in ovarian cancer cells. Nanotechnology, 28, 475101. doi: 10.1088/1361-6528/aa935e
Journal - Research Article
Yunianto, I., Chitcholtan, K., Currie, M., & Sykes, P. (2017). JAK/STAT pathway inhibition for the treatment of ovarian cancer. Proceedings of the University of Otago Student Research Symposium: Te Wānaka Rakahau: Ākoka. (pp. 98). Retrieved from http://www.otago.ac.nz/graduate-research/scholarships/otago643219.html
Conference Contribution - Published proceedings: Abstract
Sarwar, M., Chitcholtan, K., Alkaisi, M. M., Sykes, P. H., & Evans, J. J. (2017, September). The cell-environment handshake: An interaction that regulates gene expression. Verbal presentation at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Verbal presentation and other Conference outputs
Hassan, W., Chitcholtan, K., Sykes, P., & Garrill, A. (2016). A combination of two receptor tyrosine kinase inhibitors, canertinib and PHA665752 comprises ovarian cancer cell growth in 3D cell models. Oncology & Therapy, 4(2), 257-274. doi: 10.1007/s40487-016-0031-1
Journal - Research Article
Lassé, M., Ulluwishewa, D., Healy, J., Thompson, D., Miller, A., Roy, N., Chitcholtan, K., & Gerrard, J. A. (2016). Evaluation of protease resistance and toxicity of amyloid-like food fibrils from whey, soy, kidney bean, and egg white. Food Chemistry, 192, 491-498. doi: 10.1016/j.foodchem.2015.07.044
Journal - Research Article
Tino, A. B., Chitcholtan, K., Sykes, P. H., & Garrill, A. (2016). Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein. Journal of Ovarian Research, 9, 84. doi: 10.1186/s13048-016-0293-0
Journal - Research Article
Chitcholtan, K. (2016). Do we have enough knowledge to win the fight against ovarian cancer? Edorium Journal of Gynecology & Obstetrics, 2, 1-7. doi: 10.5348/G06-2016-7-ED-1
Journal - Research Other
Chitcholtan, K. (2016, April). Three dimensional (3D) cell cultures and ovarian cancer research. Verbal presentation at the Australia New Zealand Gynaecological Oncology Group (ANZGOG) Annual Scientific Meeting, Sydney, Australia.
Conference Contribution - Verbal presentation and other Conference outputs
Hogg, S. J., Chitcholtan, K., Hassan, W., Sykes, P. H., & Garrill, A. (2015). Resveratrol, acetyl-resveratrol, and polydatin exhibit antigrowth activity against 3D cell aggregates of the SKOV-3 and OVCAR-8 ovarian cancer cell lines. Obstetrics & Gynecology International, 2015, 279591. doi: 10.1155/2015/279591
Journal - Research Article
Hogg, S. J., Evans, J. J., Sykes, P. H., & Chitcholtan, K. (2015). A method to investigate the anti-metabolic activity of anti-cancer agents on ovarian cancer cells cultured in a 96-well high throughput format. Journal of Ovarian Research, 8, 43. doi: 10.1186/s13048-015-0172-0
Journal - Research Article
Orcheston-Findlay, L., Nock, V., & Chitcholtan, K. (2015, February). Controlling the oxygen microenvironment in 2D cancer cell monolayers on-chip. Poster session presented at the Seventh International Conference on Advanced Materials & Nanotechnology (AMN-7), Nelson, New Zealand.
Conference Contribution - Poster Presentation (not in published proceedings)
Yoshida, A., Chitcholtan, K., Evans, J. J., Uemura, S., & Beasley, S. W. (2014). Provision of optimal conditions for in vitro differentiation into peristaltic smooth muscle from a murine induced pluripotent stem cell line. JSM Regenerative Medicine & Bioengineering, 2(1), 1011.
Journal - Research Article
Evans, J. J., Majid, M., Chitcholtan, K., & Sykes, P. H. (2014). Responses of proliferation and VEGF secretion by Ishikawa cells are not parallel when exposed to leptin and adiponectin. Endocrine Reviews, 35(3, Suppl.), MON-0306. Retrieved from http://press.endocrine.org/series/endo-meetings
Conference Contribution - Published proceedings: Abstract
Chitcholtan, K., Evans, J., & Sykes, P. (2014, November). Inhibition of EGFR/HER-2 affects growth of ascitic ovarian cancer cells in vitro study. Poster session presented at the 15th Biennial Meeting of the International Gynecologic Cancer Society (IGCS), Melbourne, Australia.
Conference Contribution - Poster Presentation (not in published proceedings)
Majid, M. A., Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2014, November). Growth factors modulate endometrium cancer cells' proliferation and VEGF secretion. Poster session presented at the 15th Biennial Meeting of the International Gynecologic Cancer Society (IGCS), Melbourne, Australia.
Conference Contribution - Poster Presentation (not in published proceedings)
Chitcholtan, K., Asselin, E., Parent, S., Sykes, P. H., & Evans, J. J. (2013). Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Experimental Cell Research, 319(1), 75-87. doi: 10.1016/j.yexcr.2012.09.012
Journal - Research Article
Donoeva, B., Chitcholtan, K., Evans, J., Reeves, R., & Golovko, V. (2013). Targeting cancer cells with gold-nanoparticles. Proceedings of the Sixth International Conference on Advanced Materials and Nanotechnology (AMN6). [USB Memory Stick] [Abstract]
Conference Contribution - Published proceedings: Abstract
Hassan, W., Garrill, A., & Chitcholtan, K. (2013, August). Targeting growth factor receptors in advanced ovarian cancer. Poster session presented at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Poster Presentation (not in published proceedings)
Majid, M., Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2013, August). Adipokines alter behaviour of endometrial cancer cells. Verbal presentation at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Verbal presentation and other Conference outputs
Chitcholtan, K., Harris, E., Yu, Y., Harland, C., & Garrill, A. (2012). An investigation into plasmolysis in the oomycete Achlya bisexualis reveals that membrane-wall attachment points are sensitive to peptides containing the sequence RGD and that cell wall deposition can occur despite retraction of the protoplast. Canadian Journal of Microbiology, 58(10), 1212-1220. doi: 10.1139/w2012-099
Journal - Research Article
Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2012). The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer. Journal of Translational Medicine, 10(1), 38-53. doi: 10.1186/1479-5876-10-38
Journal - Research Article
Evans, J. J., Chitcholtan, K., Dann, J. M., Guilford, P., Harris, G., Lewis, L. K., Nagase, J., … Sykes, P. H. (2012). Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades. Gynecologic Oncology, 125(1), 214-219. doi: 10.1016/j.ygyno.2011.12.429
Journal - Research Article
Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2012). Three-dimensional (3D) micro-environments may provide cell templates for drugs that are different from those of two dimensions (2D). Endocrine Reviews, 33(3, Suppl.), SAT-271. Retrieved from http://press.endocrine.org/series/endo-meetings
Conference Contribution - Published proceedings: Abstract
Evans, J. J., & Chitcholtan, K. (2011). Extracellular matrix proteins in the anterior pituitary gland. Open Neuroendocrinology Journal, 4, 111-119. doi: 10.2174/1876528901104010111
Journal - Research Article
Samsuri, F., Alkaisi, M. M., Evans, J. J., Chitcholtan, K., & Mitchell, J. S. (2011). Detection of changes in cell membrane structures using the Bioimprint technique. Microelectronic Engineering, 88(8), 1871-1874. doi: 10.1016/j.mee.2010.12.069
Journal - Research Article
Yoshida, A., Beasley, S., Chitcholtan, K., & Evans, J. (2011). iPSCell differentiation into gut as precursor to in vitro bowel reconstitution may obviate need for bowel transplantation. ANZ Journal of Surgery, 81(Suppl. 1), (pp. A40). doi: 10.1111/j.1445-2197.2011.05733.x
Conference Contribution - Published proceedings: Abstract
Chitcholtan, K. (2011, May). Inhibitory activity of doxorubicin, cisplatin and a green tea compound on microtumours of epithelial endometrial ca. Verbal presentation at the New Zealand Society for Oncology (NZSO) Conference, Auckland, New Zealand.
Conference Contribution - Verbal presentation and other Conference outputs
Chitcholtan, K., Sykes, P. H., & Evans, J. J. (2011, August). Responses of cancer cells, to doxorubicon and cisplatin, are different in 3D and 2D environments. Verbal presentation at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.
Conference Contribution - Verbal presentation and other Conference outputs
Parker, H., Chitcholtan, K., Hampton, M. B., & Keenan, J. I. (2010). Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells. Infection & Immunity, 78(12), 5054-5061. doi: 10.1128/IAI.00299-10
Journal - Research Article
Chitcholtan, K., Evans, J., & Sykes, P. H. (2010). Multicellular spheroids of epithelial endometrial cancer: Characterisation and application for anti-cancer drug screening. Proceedings of the International Gynecologic Cancer Society (IGCS) 13th Biennial Meeting. Retrieved from http://www.igcs.org/index.html
Conference Contribution - Published proceedings: Abstract
Chitcholtan, K., Hampton, M. B., & Keenan, J. I. (2008). Outer membrane vesicles enhance the carcinogenic potential of Helicobacter pylori. Carcinogenesis, 29(12), 2400-2405. doi: 10.1093/carcin/bgn218
Journal - Research Article
Chitcholtan, K., Hampton, M., & Keenan, J. (2008). Outer membrane vesicles (OMVs) of Helicobacter pylori alter cellular signalling pathways in human gastric epithelial cells. New Zealand Medical Journal, 121(1271). Retrieved from http://journal.nzma.org.nz/journal/121-1271/2990/content.pdf
Conference Contribution - Published proceedings: Abstract
Chitcholtan, K., Hampton, M., & Keenan, J. (2007). H. pylori outer membrane vesicles induce DNA damage in gastric epithelial cells. Zoonoses and Public Health.54(Suppl. 1), (pp. 155). [Abstract]
Conference Contribution - Published proceedings: Abstract
Davis, K. A., Chitcholtan, K., Hampton, M., & Keenan, J. I. (2007). Helicobacter pylori outer membrane vesicles induce cytoskeletal rearrangements and cell signaling events in gastric epithelial cells. Zoonoses and Public Health.54(Suppl. 1), (pp. 151). [Abstract]
Conference Contribution - Published proceedings: Abstract
Walker, S. K., Chitcholtan, K., Yu, Y., Christenhusz, G. M., & Garrill, A. (2006). Invasive hyphal growth: An F-actin depleted zone is associated with invasive hyphae of the oomycetes Achlya bisexualis and Phytophthora cinnamomi. Fungal Genetics & Biology, 43(5), 357-365. doi: 10.1016/j.fgb.2006.01.004
Journal - Research Article
Senior Research Fellow