Saving Lives
in your Community
Through Screening
and Research.

 

Saving Lives
in your Community
Through Screening
and Research.

Research

The Lions Cancer Institute has for many years supported by way of a Postgraduate Scholarship, “top up” financial support for a selected student studying with the University of Western Australia to undertake further study over three years to attain either a Honours or PhD degree, specializing in the study of cancer causes and towards a cure.
Tracey Seymour is the ninth student assisted by the Lions Cancer Institute over the past 22 years through the Karen and Joshua Chinnery Memorial Scholarship, managed by the Institute.

The Scholarship, instigated and supported by the Lions Club of Armadale Kelmscott and assisted by other Lions Clubs in 1995, was set up in memory of the late wife and son of current Chairman, Lion Phil Chinnery. Karen and Joshua both died from a brain tumour in 1992 and 1995 respectively.
The Lions Cancer Institute is determined to continue the support of students such as Tracey in the search for better treatments and hopefully a cure for cancer. Up to now only one student has been able to be supported over the three year course of study, but we are very hopeful of increasing this to two students studying concurrently. Of course, this costs money and we appeal to all to consider donating to the scholarship to help keep this essential study going.

2018 PhD Student Report

Tracey Seymour

PhD student from The University of Western Australia and Telethon Kids Institute

My PhD research focuses on finding new therapies for the most common brain tumour, glioblastoma. Glioblastoma is a fatal type of human brain tumour. Current treatment includes maximal safe surgical resection, followed by radiotherapy and chemotherapy such as temozolomide. But these treatments are not curative and an average survival of 15 months is very dismal. Poor patient outcomes are mainly due to glioblastoma cells having the ability to resist radiotherapy and temozolomide.
My PhD research involves pre-clinical studies that is currently testing new therapies, in hope to find therapies that will augment current treatments and improve patient outcomes.

Research aims

  1. Determine whether new treatments will interact together with radiotherapy and/or chemotherapies such as temozolomide and gemcitabine.
  2. Explore the mechanism in which these new therapies help to improve tumour cell death.
  3. Examine whether combining new therapies to radiation therapy or chemotherapies such as temozolomide and gemcitabine will provide a survival benefit.

Aim 1: Determine whether new treatments will interact together with radiation therapy and/or chemotherapies such as temozolomide and gemcitabine.

Current Findings
We have tested three new drug therapies. The most promising therapy tested was an inhibitor of a protein called cell cycle checkpoint kinase 1/2 (inhibitor of Chk1/2). Using several different glioblastoma cell lines, we have shown that the inhibitor of Chk1/2 causes a reduction in tumour cell growth. More importantly, this Chk1/2 inhibitor works together with radiotherapy and chemotherapies such as temozolomide and gemcitabine.

Significance
This study has helped us determine a potential new therapy for patients with glioblastoma.

Aim 2: Explore the mechanism in which these new therapies help to improve tumour cell death.

Current Findings
Using protein analysis, we confirmed that the Chk1/2 inhibitor was stopping the protein called cell cycle checkpoint kinase 1/2. We also determined that this prevented tumour cells from repairing damage caused by radiotherapy or chemotherapy such as temozolomide or gemcitabine. Therefore, tumour cells remain damaged and further studies will determine if these damaged tumour cells are undergoing the process of dying.

Significance
These experiments help us understand how the Chk1/2 inhibitor is working to improve tumour cell death.

Aim 3: Examine whether combining new therapies to radiation therapy or chemotherapies such as temozolomide and gemcitabine will provide a survival benefit.

Current Findings
Using three of our glioblastoma cell lines, we have implanted these cells into the brains of mice. Firstly, the immediate effects of the inhibitor of Chk1/2 with/without radiotherapy, temozolomide or gemcitabine was examined. Combination therapy reduced tumour cell growth and increased tumour cell DNA damage. Excitedly, in two out of three cell lines, the combination of Chk1/2 inhibitor with radiotherapy, temozolomide or gemcitabine significantly extended survival.

Significance
These studies show the potential of combining the Chk1/2 inhibitor with radiotherapy or chemotherapy in improving patient outcomes.
All of these experiments will provide robust data that will inform future clinical trials for glioblastoma patients.

Conference attendance

  1. Seymour T, Kuchibhotla M, Nowak A, Gottardo N & Endersby R. Exploring cell cycle checkpoint inhibition and gemcitabine treatment for glioblastoma, Australian Society for Medical Research, Perth June 2018. Oral Presentation
  2. Seymour T, Kuchibhotla M, Nowak A, Gottardo N & Endersby R. Cell cycle checkpoint inhibition enhances conventional glioblastoma treatments. Lorne Cancer Conference, Victoria. February 2018. Poster Presentation
  3. Seymour T, Kuchibhotla M, Nowak A, Gottardo N & Endersby R. Cell cycle checkpoint inhibition enhances conventional glioblastoma treatments. Telethon Kids Institute Scientific Retreat, Perth November 2017. Oral presentation.
  4. Seymour T, Kuchibhotla M, Nowak A, Gottardo N & Endersby R. Cell cycle checkpoint inhibition enhances conventional glioblastoma treatments. Child and Adolescent Health Services Symposium, Perth October 2017. Poster presentation.
  5. Seymour T, Nowak A, Gottardo N & Endersby R. Sensitising glioblastoma to enhance cancer therapy, Combined Biological Sciences Meeting, Perth August 2017. Oral Presentation
  6. Seymour T, Nowak A, Gottardo N & Endersby R. Sensitising glioblastoma to enhance cancer therapy, Australian Society for Medical Research, Perth June 2017. Oral Presentation

2017 PhD Student Report

Tracey Seymour

PhD student from The University of Western Australia

Currently I am researching the most common human brain tumour glioblastoma at the Telethon Kids Institute within the Brain Tumour Research Group. Glioblastoma is the most common and aggressive type of human brain tumour. Current treatment includes maximal safe surgical resection, followed by radiotherapy and chemotherapy. Despite intensive treatment, this tumour remains incurable with patients surviving only 15 months from diagnosis. Radiotherapy and chemotherapy fail to efficiently kill these tumour cells and this is partly due to the ability to repair treatment-induced damage.

The research involved in my PhD includes pre-clinical studies that focus on testing new drugs to improve the clinical outcomes and survival of those diagnosed with glioblastoma.

Current research aims
  1. Determine whether novel therapies will interact synergistically with radiation therapy and/or chemotherapies such as temozolomide and gemcitabine.
  2. Examine the survival benefits of novel therapies in addition to radiation therapy and/or chemotherapies such as temozolomide and gemcitabine using animal models.
  3. Determine the mechanism in which these novel therapies help to enhance tumour cell death.
Aim 1: Determine whether novel therapies will interact synergistically with radiation therapy and/or chemotherapies such as temozolomide and gemcitabine.

Current Findings
We have tested three new drug therapies; they are inhibitors of the DNA damage repair pathway and inhibit kinases ATR, Chk1/2 and Wee1. Using several different glioblastoma cell lines, we have shown that these new drugs would cause a reduction in tumour cell growth. Additionally, we have also combined these new drugs with radiation therapy, temozolomide or gemcitabine. From these combination treatments, we have shown that the inhibitor of kinase Chk1/2 interacts synergistically with radiation therapy, temozolomide and gemcitabine.

Significance
This study has helped us determine which treatment combinations will act synergistically (act together), antagonistically (act against each other) and additively (work separately). For these treatment combinations, we want synergistic interaction and not antagonistic and additive interaction as these predict potential toxicity issues. Finding synergistic interactions will set the basis for which treatment combinations will be testing in our animal models (see Aim 2).

Aim 2: Examine the survival benefits of novel therapies in addition to radiation therapy and/or chemotherapies such as temozolomide and gemcitabine using animal models.

Current Findings
Using one of our glioblastoma cell lines, we implanted these cells into the brains of mice. Once tumour was established, we examined the acute effects of radiation, temozolomide or gemcitabine with/without the inhibitor of Chk1/2. The addition of inhibitor of Chk1/2 to radiation therapy significantly reduced tumour cell growth. Furthermore, the combination of inhibitor of Chk1/2 and gemcitabine significantly increased tumour cell damage and concomitantly reduced growth. Animal studies are still ongoing, and current experiments are establishing the survival benefit of the inhibitor of Chk1/2.

Significance
These studies will establish whether the addition of these new drugs to current treatments of glioblastoma will enhance tumour cell death and most importantly improve survival. The data collected from these studies will help to inform future clinical trials with patients.

Aim 3: Determine the mechanism in which these novel therapies help to enhance tumour cell death.

Current Findings
Current studies are still ongoing and are in early optimisation stages.

Significance
These experiments will help us understand how these new drug treatments are working to enhance glioblastoma tumour cells.

 

Conference attendance

Cooperative Trials Group for Neuro-Oncology (COGNO), Sydney, September 2016. Poster presentation
Seymour T, Jackson M, Tat-Lai C, Nowak A, Kakulas F. Gene expression profiling reveals stem cell signatures and therapeutic targets for glioblastoma and gliosarcoma.

Telethon Kids Scientific Retreat, Perth, November 2016. Oral presentation
Seymour T, Nowak A, Gottardo N, Endersby E. Sensitising glioblastoma to enhance cancer therapy.

Australian Society of Medicial Research (ASMR), Perth, June 2017. Oral presentation
Seymour T, Nowak A, Gottardo N, Endersby E. Sensitising glioblastoma to enhance cancer therapy.

Combined Biological Science Meeting (CBSM), Perth August 2017. Oral presentation
Seymour T, Nowak A, Gottardo N, Endersby E. Sensitising glioblastoma to enhance cancer therapy.

2016 PhD Student Report

Tracey Seymour

PhD student from The University of Western Australia

Firstly, as the recipient of the Lions Cancer Institute Top-up scholarship, I would like to sincerely thank the Lions Cancer Institute for their generosity and interest in my research project.

The financial support provided by the Lions Cancer Institute has allowed me to concentrate on my research project and allowed me to attend the Australasian Society for Stem Cell Research 2015 annual meeting held in Hunters Valley, New South Wales where I presented preliminary data showing abnormal gene expression found in adult brain tumours.

The continuous financial aid from the Lions Cancer Institute will also allow me to attend the COGNO annual scientific meeting in Sydney during September of this year where I have been given the opportunity to present a scientific poster.

My PhD research project investigates cancer stem cells and abnormal gene expression in the most common adult brain tumour, glioblastoma. Working with research groups at The University of Western and Telethon Kids Institute, I have identified several genes that are abnormal in this brain tumour. One abnormal gene identified is SOX2, a gene normally expressed by normal stem cells which suggest that this brain tumour may harbour cancer stem cells.

As there is no cure for this particular brain tumour, the need for new effective treatment is urgent. However, it is still unknown why the current clinically used therapies are not a cure. Therefore, I am currently treating brain tumour cells with clinically used chemotherapy drugs to determine if cancer stem cells and the abnormally expressed genes are the mechanisms behind tumour reoccurrence after treatment.

Publications

  1. Seymour T, Twigger A-J & Kakulas F (2015). Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain. International Journal of Molecular Sciences 16, 27288-27301.
  2. Seymour T, Nowak A, Kakulas F (2015). Targeting aggressive cancer stem cells in glioblastoma. Review. Frontiers of Oncology, 29015; 5, Article 159. DOI:10.3389/fonc.2015.00159

Scholarship for PhD students

Information about Scholarship coming soon.

Skin Damage

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