The Sussex Cancer Fund recently announced funding for an exciting new project researching The Effects Of Stress on Tumour Recurrence. The project is essentially concerned with the understanding of the underlying molecular mechanisms of how stress hormones act on the cells in the body. This vital information will enable cancer clinicians to create bespoke treatments for all cancer patients moving forward; impacting the efficacy of cancer treatment.
Dr Melanie Flint “Our goal is to highlight the importance of reducing stress during cancer treatments to improve patient outcomes.”
Under the guidance of Dr Melanie Flint and Ms. Sonali Kaushik, Ms Sarah Baron, ST7 registrar in Obstetrics & Gynaecology, upcoming sub-speciality trainee in Gynae-Oncology, has been appointed to the project. Although Sarah has been working on the project for a relatively short time, good progress has already been made.
The project can be divided into two parts.
1. Create viable mini-tumours (spheroids and more complex organoids) and test their behaviour and interaction with the immune system with and without the presence of cortisol (a stress hormone)
2: A feasibility study where we will monitor the stress levels of patients from diagnosis and through treatment and follow up, using cortisol levels and questionnaires – correlating these with their disease outcomes.
Learning and Project Protocol
With all cancer research projects, there are several levels of approval needed before projects can progress, Projects have to be scrutinized to ensure the project is viable and making the most efficient use of the money available, methodology and theories must be sound and any ethical considerations studied.
Sarah and the team have written the application for ethical approval for the study in patients with ovarian cancer. This has been approved by the pre-sponsorship research panel at the University of Brighton and is in the final stages of University of Brighton completion now. The University of Brighton is the Sponsor and Sussex Cancer Fund is the funder. Following the all-clear from the University of Brighton, it will then go to IRAS (Integrated Research Application System) for approval.
In addition to the project creation and approval process, Sarah has undergone specialist training in cell and tissue culture, which will allow her to grow identical tumour cells in the lab, viable mini-tumours (spheroids). These ‘immortal’ tumour cells will then be tested on to observe their behaviour and interaction with the immune system with and without the presence of cortisol the stress hormone. As these cells have been ‘grown in a lab’ rather than collected from patients, the study can commence without the ethical approval levels needed for real patient tissue studies and also means there is potential for more tissue material to work on.
To aid the observation of these cells Sarah is using a confocal microscope, a specialist microscope that uses lasers through a pinhole, which allows the viewer to see the specimen in much better detail, allowing you to section very thin layers through samples using lasers, which would not be possible with a conventional widefield optical epi-fluorescence microscope. This has allowed Sarah to prove the effect of the stress hormone on the cells.
The Results So Far:
Sarah has generated the first data sets—see photos, which means we have the first lots of results helping to prove stress has a physiological effect on cells. Sarah has successfully grown ovarian cancer cells in 2D and 3D (spheroids) and proven that they are viable i.e. alive and behaving how natural human tissue would.
Sarah has also successfully proven that these cells express the stress hormone receptor in the cytoplasm and when the stress hormone is added the receptor moves to the nucleus. She has also shown that this can be blocked with a stress hormone blocker.
So essentially Sarah has proven that there is an actual physiological change in the cells when subjected to stress and this change can be stopped or ‘blocked’. This could eventually lead to patients being routinely given stress prevention treatments either through drugs or other traditional stress reduction methods to lower the risk of these physiological changes that may be negatively affecting the efficacy of their cancer treatments.
Photos showing Immunofluorescence of cells in their different states.
Immunofluorescence showing that ovarian cancer cells express the glucocorticoid (stress hormone) receptor (green) in their cytoplasm.
Photo 2 Immunofluorescence showing that ovarian cancer cells & cortisol the glucocorticoid (stress hormone) receptor is more widespread in the nucleus (blue).
Photo 3 Immunofluorescence showing ovarian cancer cells, Cortisol and blocker. The cocorticoid (stress hormone) receptor remains in the cytoplasm.
Plan for the next 3 months:
The next stage is to get the ethics approved by the NHS and start recruiting patients for the study. Patients will be recruited for monitoring their stress levels from diagnosis and through treatment and follow up, using cortisol levels and questionnaires then correlating these with their disease outcomes. These findings will then contribute to the laboratory work on cells and cortisol to give a clearer picture of the effects of stress.
The patient recruitment part will also allow for the collection of patient tissue to develop the organoids for study. The spheroids created for the first part of this study are from immortal cell lines, not from patients, so easier to handle and don’t need ethical approval but the next stage involves different types of tissue and will need to come from patients. Sarah will then undergo training in developing the patient tissues to be able to form organoids to undergo the next part of the project.
Sarah will then start looking at creating a coculture. Essentially growing two types of cells together in this case immune cells and cancer cells together with stress hormones and blockers. Making sure they are viable, i.e. alive and behaving as expected if natural cells and then examining the cytokines. Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. With aim of understanding how stress affects immunity and how stress treatments can stop any negative effects.
We wish the team the best of luck with their studies and look forward to hearing the results of the next stage. It is only through the generosity of our supporters that we are able to continue our research work. If you would like to contribute to this or any of our other cancer research projects you can do so via the donate button below.