Expression of Components of the Renin-Angiotensin System by the Embryonic Stem Cell-Like Population within Keloid Lesions

Authors: Hugo Humphries, Helen D. Brasch, Bede van Schaijik, Swee T. Tan, Tinte Itinteang

Plastic and Reconstructive Surgery (2019). Volume 144(2)  pp 372 – 384. Doi:10.1097/PRS.0000000000005867.

https://journals.lww.com/plasreconsurg/Abstract/2019/08000/Expression_of_Components_of_the_Renin_Angiotensin.22.aspx

Keloid disorders are characterised by abundant scar tissue resulting from excessive collagen deposition in the skin, being 15 times more common in dark-skinned people. They appear to be genetically inherited and are associated with wound repair but, unlike hypertrophic scars, which are confined to the area around the wound, keloid lesions extend beyond it.

The Gillies McIndoe Research Institute has now demonstrated that the renin-angiotensin system is present in keloid lesions and in the stem cells of the lesion. This raises the possibility of inhibitors of the renin-angiotensin system, classically associated with cardiovascular homeostasis and electrolyte balance, being potential treatments.

These results provides support and a possible mechanism for the recent observation that enalapril, an ACE inhibitor, and so connected to the renin-angiotensin system, is efficacious in treating keloid disorder.

Characterization of Cancer Stem Cells in Renal Clear Cell Carcinoma

Authors: Reuben Cane, Andrew Kennedy-Smith, Helen D. Brasch, Stephanie Savage, Reginald W. Marsh, Tinte Itinteang, Swee T. Tan 

Journal of Stem Cell and Regenerative Biology (2019) Volume 5, pp6 – 17. https://www.ommegaonline.org/articles/publishimages/16710-JSRB-19-RA-2462.pdf

Renal cell carcinoma is the ninth most common cancer, with renal clear cell carcinoma comprising up to 85% of renal cell carcinomas. Obesity, smoking and high blood pressure are well-established risk factors for these cancers.

Surgery is the conventional treatment although there is still a 40% recurrence rate. 30% eventually develop metastases. Advanced disease can be treated with drugs. The five-year survival rate is only 10%.

The GMRI and collaborators have proposed that tumour development and proliferation is driven by cancer stem cells that possess self-renewal and pluripotent properties and are responsible for metastasis and recurrence. Our research has demonstrated that many types of cancer express cancer stem cells.

This study concludes that there are at least two types of cancer stem cells in renal clear cell carcinoma, each expressing several common constituents with some constituents that are unique to a specific population. There is evidence that one of these populations is more mature than the other.

Therefore it has now been demonstrated that this most common type of kidney cancer has cancer stem cells similarly to many other cancers. The implication is that the GMRI’s novel cancer treatment approach may be efficacious.

Therapeutic Targeting of Cancer Stem-Like Cells – The Current State of the Art

The GMRI has just published a review article in Frontiers in Oncology following an invitation to submit an article to the special issue on ‘Therapeutic Targeting of Cancer Stem-Like Cells – The Current State of the Art

https://www.frontiersin.org/research-topics/8187

The article describes the links between cancer stem cells and the renin-angiotensin system, which controls blood pressure and fluid balance, and outlines the evidence that suggests targeting this system might target cancer stem cells.

Lead author Dr Imogen Roth explains in the article, titled ‘Therapeutic Targeting of Cancer Stem Cells via Modulation of the Renin-Angiotensin System’, how the renin-angiotensin system also appears to have a role in stem cell differentiation, and suggests that the renin-angiotensin system might also have a role in cancer stem cell maintenance.

To support this, Dr Roth outlines numerous studies which have shown that the renin-angiotensin system is elevated in cancer, and how common anti-hypertensive medications which target the renin-angiotensin system have been shown to prevent or reduce the development of cancer.

As such, it appears that the roles of the renin-angiotensin system in both stem cell maintenance and tumour development may converge on cancer stem cells, making targeting the renin-angiotensin system a potential cancer therapy.

The article can be viewed at https://doi.org/10.3389/fonc.2019.00745

Our research on the international stage at the Royal Australasian College of Surgeons’ Annual Scientific Congress, May 2019

Dr Swee Tan with the plaques for being the ‘Distinguished Invited Lecturer’ in the plenary session (on the left) and for presenting the ‘Tom Reeve Lecture’ (on the right).

In May, we were honoured to deliver presentations at the 88th Annual Scientific Congress of the Royal Australasian College of Surgeons, held in Bangkok. Over 1750 delegates attended the Congress from Australia, New Zealand, and around the world. Many of our colleagues inspired us with the discoveries they shared.

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We’ve won an international award for our work in Dupuytren’s Disease

Dr Kirin Tan is the co-author of our winning paper.

We’re honoured to receive further recognition of our work in Dupuytren’s Disease — a debilitating condition affecting the hands. Dr Kirin Tan co-authored the winning paper with our team when he was a medical student at Auckland University doing an elective at the GMRI. The paper, titled The Role of Stem Cells in Dupuytren’s Disease: A Review, won the Best Oceanic Paper Award from Plastic and Reconstructive Surgery Global Open, a prestigious international journal.

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Matthew Munro: improving patient management

PhD student Matt Munro has identified new markers that could help the management of colon cancer patients.

For a former research technician, Matt Munro says the GMRI has been the perfect place to undertake his PhD. Matt is investigating the role of cancer stem cells (CSCs) and the renin-angiotensin system in colon cancer.

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Erin Paterson: creating a powerful resource

Erin Paterson: ‘Everything I do is working towards the ultimate goal of a better understanding of cancer’.

Erin Paterson coordinates the vital cell culture and tissue banking programme for the GMRI’s primary cell lines. After taking tissues donated by patients to the GMRI and growing cells from them, these cells are used for the GMRI’s research.

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Our interns: specialists in the making

Tessa Pilkington, Claire Luke-Krishnan and Jazmean Williams.

We love working with our interns and fostering the next generation of scientists and medical experts. They contribute to our wide range of research on cancers and other conditions. This year we have had three interns outside of our usual summer studentship programme, with Tessa Pilkington, Claire Luke-Krishnan, and Jazmean Williams joining us for four months. We’ve asked them questions about their internship experience.

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Private donor pledging: your opportunity to make a real difference

By supporting our research, you’ll play a part in making a real difference in the lives of people suffering from cancer.

Image by Lina Trochez. Unsplash licence.

 

Our goals as a charity are not small — the Gillies McIndoe Research Institute exists to reduce human suffering and improve lives. You can help us to achieve our aspirations.

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In our five years we’ve launched two clinical trials

Since the GMRI opened its state-of-the art laboratory facility in Newtown, Wellington, we’ve gained approval for four clinical trials to test our novel cancer treatment based on our discoveries in the lab. We didn’t expect to be here in just five years — we thought it would take much longer. At the recent Royal Australasian College of Surgeons’ Annual Scientific Congress in Bangkok we heard many comments from colleagues who are excited about our work. They see our approach to cancer treatment as unique and radical.

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