Publication Summaries

Gillies McIndoe Wins Business Excellence Award

 

Clint Gray and Margie Beattie at the awards. Photo courtesy of 2degrees Wellington Regional Business Excellence Awards.

It was a real thrill to be named the winner in the ‘Not for Profit’ category of the 2degrees Wellington Regional Business Excellence Awards at a gala awards function in Lower Hutt on 18 November.

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Agreement to Progress Topical Strawberry Birthmarks Treatment

Heather Jenkinson in the lab.

Our work in understanding and treating strawberry birthmarks in children has moved a step closer to further development through an agreement we have reached with AFT Pharmaceuticals and Massey University.

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Scholarships Support Emerging Talent

We have been fortunate to receive funding for two new scholarships that will support our research efforts, as well as our efforts to develop emerging talent in our research field.

It’s important to us that we play a role in developing the next generation of research scientists and Dr Clint Gray, our Chief Scientist, has been instrumental in attracting the funding to support and attract PhD students to our laboratory. We are working to develop a centre of excellence and an attractive pathway for promising scientists to broaden their skills, knowledge, and practice, and contribute towards valuable scientific research.

 

Melody Collins Memorial Scholarship

Melody Collins and family

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Glioblastoma Phase II Clinical Trial Expected to Begin in 2023

Our fundraising has been progressing, and early next year we hope to begin our phase II clinical trial on glioblastoma, the most common and most aggressive brain cancer.

We are very grateful for the significant and generous donation of $1 million from the Hugo Charitable Trust received earlier this year towards the trial. Hugo backs our work and we have been working with other trusts and philanthropists since to help make the clinical trial happen.

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Malaysian Fundraiser Contributes $11k Towards Research into use of Repurposed Drugs

Malaysian High Commissioner Nur Izzah Wong Mee Choo, Margie Beattie and Carol Law

We are grateful to the Malaysian High Commission for hosting a fundraising lunch raising $11,000 in support of our research into the use of repurposed drugs.

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Summer Students Bolster our Efforts

Dr Sam Siljee, Georgia Hoggarth, Freya Weth and Anya Weth.

This summer we will have two university students join our team as part of our summer student programme.

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Open Days Prove Rewarding

Dr Clint Gray and Gillies McIndoe Ambassador Andrea Skews.

This spring we have hosted a series of Open Days in our Wellington-based laboratories, to enable some supporters to enjoy a tour of our facilities.

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Women’s Golf Classic Chips In

We are grateful to have received $2000 towards our research efforts through a recent raffle fundraiser held during a golf tournament at the Royal Wellington Golf Club.

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A $1 million gift brings our glioblastoma clinical trial closer

Members of Living Options and the Hugo Charitable Trust visiting the GMRI.

Members of Living Options and the Hugo Charitable Trust visiting the GMRI. From left to right: Alison Wildey, Lorenzo Chambers, Maryanne Green, Aiobheann Monaghan, Dr Swee Tan, and Mark Owens.

We’re very grateful to the Hugo Charitable Trust for their generous donation of $1 million towards our phase II clinical trial on our new treatment for glioblastoma. Glioblastoma is a severe, usually fatal, brain cancer. The Trust’s donation brings us significantly closer to starting the trial.

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Organoids provide a promising way for testing cancer treatments

Doctor Matt Munro in a lab, holding a pipette and smiling at the camera.

Dr Matt Munro is creating colon organoids from colon tissue samples to test how effective different cancer treatments are.

Dr Matt Munro is developing colon organoids to test the effectiveness of possible treatments for colon cancers. The human organoids are miniature ‘organs in a dish’, created from human tissue samples. Organoids could one day be used routinely to test new treatments and customise treatment for individual patients to improve their outcomes.

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Iron women, a mountain challenge, and butterflies —three of our amazing supporters’ stories

Two women, Emma Treadwell and Sarah Hogan, run cross the finish line holding hands high in triumph and grinning.

Sarah Hogan (right) and Emma Treadwell (left) finishing the 2022 Ironman in Port Macquarie, Australia, raising funds for our glioblastoma clinical trial.

Our ambassadors go up mountains, around countries, and push themselves really hard — for our cause, and for New Zealanders who may face brain cancer. These three stories show how wonderful people selflessly raise awareness of our research and the funding it needs. We cherish these three supporters, their amazing stories, and the many other special people who support and inspire us.

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Erin Paterson promoted to Laboratory Manager/Senior Laboratory Technician

Erin Paterson in the lab wearing a white lab coat, while using a microtome machine.

Erin Paterson cuts tissue sections using a microtome.

We congratulate Erin Paterson, who has been promoted to her new role as Laboratory Manager/Senior Laboratory Technician. Erin’s been at the GMRI since 2017. Over the years she’s been responsible for coordinating the cell culture programme for the GMRI tissue bank, which is vital to our research.

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Meet Freya Weth, our new PhD student

Freya Weth wears a white lab coat and smiles at the camera with an image of a glioblastoma organoid on her computer.

Freya Weth, looking at a glioblastoma organoid grown in the GMRI lab.

We welcome Freya Weth, who’s joining us for the next three years to complete her PhD in biomedical science. She’s received the Graham Langridge Scholarship and was ‘in complete disbelief’ when she heard the news.

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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

Expression of Components of the Renin-Angiotensin System in Pyogenic Granuloma

Authors: Jessica C. Papali’i-Curtin, Helen D. Brasch, Bede van Schaijik, Jennifer de Jongh, Reginald W. Marsh, Swee T. Tan and Tinte Itinteang

Frontiers in Surgery (2019). doi:10.3389/fsurg.2019.00013 
https://www.frontiersin.org/articles/10.3389/fsurg.2019.00013/full

Pyogenic granuloma is a relatively common benign vascular tumour affecting the skin. Most commonly it occurs as a small red nodule, primarily in the head and neck region, and bleeds repeatedly. Current treatments include surgery, prescription drugs and in some circumstances laser therapy.

Although the pathogenesis of pyogenic granuloma is uncertain, the small blood vessels are immature. We have previously shown that two sub-populations of embryonic stem cell markers are expressed in them.

We have now demonstrated that the renin-angiotensin system is present in these stem cells. This system, which has long been associated with the regulation of blood pressure and fluid balance, can be modulated and controlled with a range of drugs.

The consequence of these findings is that it may be possible to treat pyogenic granuloma by inhibiting the renin-angiotensin system at the origin of the condition.

Expression of Cathepsins B, D and G in WHO Grade I Meningioma

Authors: Rosanna M. A. Rahman, Bede van Schaijik, Helen D. Brasch, Reginald W. Marsh, Agadha C. Wickremesekera, Reuben Johnson, Kelvin Woon, Swee T. Tan and Tinte Itinteang

Frontiers in Surgery (2019). doi:10.3389/fsurg.2019.00006 https://www.frontiersin.org/articles/10.3389/fsurg.2019.00006/full

One of the most common primary tumours of the central nervous system is meningioma. While surgery is the standard approach for treatment, it is not achievable in 50% of the cases. A better method of management is therefore required.

The Gillies McIndoe Research Institute and collaborators have characterised stem cells in meningioma and demonstrated the renin-angiotensin system (RAS)  within these cells. This system is known to promote tumour growth as well as regulate blood pressure.

The RAS can be activated by classical methods involving renin and the prorenin receptor or by an alternative process involving a group of protease enzymes called cathepsins. This paper establishes that two of these cathepsins (cathepsins B and D) are localised to the stem cells in meningioma while cathepsin G is present in cells in the matrix.

We conclude that, if the RAS is to be the basis of a therapy for meningioma, inhibition of these enzymes will need to be part of the treatment.

Expression of Embryonic Stem Cell Markers in Microcystic Lymphatic Malformation

Authors: Elizabeth K. Eady, Helen D. Brasch, Jennifer de Jongh, Reginald W. Marsh, Swee T. Tan and Tinte Itinteang
Lymphatic Research and Biology (2019) Doi: 10.1089/lrb.2018.0046
https://www.liebertpub.com/doi/10.1089/lrb.2018.0046

Malformations of the lymph vessels occurs in about 1 in 5,000 infants. It is characterised by slowly increased swelling, frequently in the head and neck area. They are classified as either macrocystic (involving larger lymph vessels) or microcystic (small vessels). These vessels are thin and so prone to leakage. Treatment of the microcystic form is unsatisfactory while sclerotherapy is the preferred treatment for the macrocystic ones.

Some have suggested that these malformations may originate from gene mutations. Others have described progenitor-like cells in them and, as embryonic stem cells have been described in venous malformations, GMRI researchers have proposed that similar stem cells may be present in lymphatic malformations.

Using several techniques, the GMRI team has confirmed the presence of progenitor cells and identified a small population of stem cells in microcystic lymphatic malformations. The implication of this finding is that the possible origin of the condition has been identified and consequently a novel potential approach to treating the condition identified.

Cancer Stem Cells in Liver Metastasis from Colon Adenocarcinoma Express Components of the Renin-Angiotensin System

Authors: Ananatha Narayanan, Susurutha K. Wickremesekera, Bede van Schaijik, Reginald W. Marsh, Helen D. Brasch, Swee T. Tan and Tinte Itinteang

Journal of Cancer Metastasis and Treatment (2019).5: 36 – 46. Doi:10.20517/2394-4722.2018.77

https://jcmtjournal.com/article/view/3054

Colorectal (colon) cancer accounts for about 10% of all cancers. It is the second most common cause of cancer death in New Zealand.

Colorectal cancer may spread in the body. The liver is the most common site for secondary tumours, with up to 50% of patients developing consequent liver tumours.

The concept of cancer stem cells, the focus of much of the GMRI’s research,  proposes that there is a sub-population of cells within a cancer that have properties similar to embryonic stem cells which are the driving force of the development of the cancer. The paper identifies three sub-populations of these cells, through their distinctive markers, which are shown to be present in liver metastases arising from colon adenocarcinoma.

The GMRI and collaborators have shown that the renin-angiotensin system, which is well-known as a regulator of blood pressure and fluid balance, is associated with stem cells in a range of cancers. There are a number of modulators of this system which are prescribed when it is malfunctioning. The paper demonstrates that this hormonal system is present within the stem cells of metastatic liver cancer.

Our findings suggest that these properties could be used as a novel therapeutic target for treating these liver cancers.