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.

Embryonic Stem Cell-like Population Within Venous Malformation Expresses the Renin-Angiotensin System

Authors: Elysia M.S. Tan, Helen D. Brasch, Paul F. Davis, Tinte Itinteang and Swee T. Tan

PRS Global Open (2019).10.1097/GOX.0000000000002170. https://journals.lww.com/prsgo/Abstract/latest/Embryonic_Stem_Cell_like_Population_within_Venous.98030.aspx

Venous (vein) malformation is the most common type of vascular abnormality. These defective veins affect about 1% of the population and, although present a birth, may not be noticed until later. They frequently involve the skin and occasionally muscle. About 40% occur in the head and neck, with another 40% found in the extremities and 20% on the trunk.

Generally management of venous malformations is unsatisfactory. The basis of them is poorly understood but mutations of several different genes have been proposed.

GMRI researchers have recently demonstrated the activity of the renin-angiotensin system in these lesions. This system is well-known as a regulator of blood pressure. As a result of this finding there is the prospect of being able to control the development of this condition by means of inhibition of the renin-angiotensin system. This paper establishes that this system is located in the stem cells of the venous malformations. The finding provides a basis for proposing that the use of renin-angiotensin inhibitors may be beneficial for the treatment of venous malformations.

Chalkley Counting in Oral Tongue Squamous Cell Carcinoma: Does It Have a Prognostic Value?

Authors: Paul Campbell, Reuben Bennet, Louise Joyce Lim, Helen D. Brasch, Reginald Marsh, Tinte Itinteang and Swee T. Tan

Journal of Biotechnology and Biomedical Science (2019). doi:10.14302/issn.2576-6694.jbbs-19-2625 https://openaccesspub.org/jbbs/article/1014

Oral cavity squamous cell carcinoma is the 15th most common cancer worldwide with substantial geographical differences and greater incidence in developing countries. It affects males most commonly, in their fifth and sixth decades of life, although the incidence is increasing in women and those under the age of 45. Risk factors include alcohol abuse, tobacco smoking and betel quid chewing.

The prognosis depends on several factors, including the development of new blood vessels. Quantification of this development has led to its use for determining tumour-related prognosis. One method is Chalkley counting, which has been shown to be appropriate for predicting the survival of patients with gastrointestinal tumours. However its applicability for quantifying blood vessel development in breast cancer has been questioned.

The GMRI team and collaborators have investigated the effectiveness of Chalkley counting for quantifying blood vessel development in oral tongue squamous cell carcinoma and its relation to cancer progression and metastasis. Only one of the four markers for the vessel development showed any correlation with the prognosis. We conclude that Chalkley counting is not a reliable prognostic method for oral tongue squamous cell carcinoma. 

Clinical study on new cancer treatment for glioblastoma (brain cancer) shows promising early results

The GMRI uses the analogy of a beehive as an explanation for cancer.

Photo by Maxime Gilbert / CC0 1.0

Early results of our clinical trial testing the GMRI’s new cancer treatment for patients with glioblastoma, a devastating brain cancer, were reviewed at a recent independent Data Monitoring Board meeting. The Board concluded that these early results show promise in treating the disease.

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Meet Dr Imogen Roth, our new cancer biologist

Dr Imogen Roth started in February and is already working on research for the GMRI.

Imogen returned to New Zealand after a postdoctoral research fellowship at the Ludwig Institute for Cancer Research at the University of Oxford, supported by a prestigious Nuffield Medical Fellowship. She’s happy to be back, and contributing to research science in New Zealand. Imogen wants to use her background in cancer biology and tumour suppressor genes to look closely at cancer stem cells. She already has ideas on what she can develop into experiments and projects. She loves looking closely at things to understand how they work.

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Mourning the loss of an extraordinary patron

To our great loss, one of our patrons, Sir John Jeffries, passed away in January. Sir John had long been a supporter of our work. He was generous and compassionate, and we’ll miss his guidance and encouragement.

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Nurturing the next generation of scientists

Returning summer students. From top left, these students include: Claudia Paterson, Therese Featherston, Hugo Humphries, and Sabrina Koh.

Our summer student programme is an integral part of the GMRI’s activities. Every year we welcome up to 6 exceptional students to take part in a 3-month research placement. They impress and amaze us with their ability and capacity. Some of them return for a second and sometimes third summer.

Let us introduce you to four of our returning students. And just before we do, we’d like to extend a heartfelt thank you to Lady Gillian and Sir Roderick Deane, who have supported the summer studentship programme since it began in 2013.

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