As 2018 is coming to an end, on behalf of the GMRI I’d like to thank you all for your ongoing interest and support of our work. We rely on the dedication and generosity of donors and many other people and organisations to be able to keep pushing the boundaries, seeking to bypass what has been done to treat cancer for the last 100 years. We’re excited about what we’ve accomplished this year as we focus on our goal to treat cancer without surgery, radiotherapy, and chemotherapy. We couldn’t have achieved as much without the support of so many.
Authors: Agadha C. Wickremesekera, Helen D. Brasch, Valerie M Lee, Paul F. Davis, Kelvin Woon, Reuben Johnson, Swee T. Tan and Tinte Itinteang
Journal of Clinical Neuroscience. (in press 2018). doi.org/10.1016 /j.jocn.2018.10.068
Up to 30% of melanoma tumours metastasise to the brain and between 5%-8% of all brain tumours have originated from melanomas. For many years the median survival period of patients with metastatic melanoma to the brain has remained at 6-9 months following conventional treatments. The short period of remission has been attributed to the initiation, propagation and differentiation of cancer stem cells that possess the ability to undergo uncontrolled growth and propagation.
The cancer stem cell concept proposes that a small population of cancer stem cells are the driving force of cancer growth. The presence of cancer stem cells has been demonstrated in a number of cancers, including melanomas. In collaboration with the Department of Neurosurgery at the Wellington Regional Hospital, the GMRI team has discovered three cancer stem cell subpopulations in metastatic melanoma to the brain, suggesting the presence of a hierarchy amongst the cancer stem cells, similar to what we have found in glioblastoma. The characterisation of these cells raises the possibility of providing a therapeutic target for these metastatic tumours.
Authors: Shreeja Mehrotra, Susrutha K. Wickremesekera, Helen D. Brasch, Bede Van Schaijik, Reginald W. Marsh, Swee T. Tan and Tinte Itinteang
Colorectal cancer is the third most common cancer worldwide with an approximately 50% mortality rate. It metastasises with the liver being the most common secondary site. Up to 70% of the deaths associated with colorectal cancer manifest liver metastasis. Although surgery of the liver has the best outcome for these patients, a procedure following diagnosis is possible in only about 20% of cases.
Three sub-populations of cancer stem cells have been characterised in liver metastasis. These stem cells are thought to be responsible for generating the tumour, tumour differentiation, maintenance, spread and relapse. Components of the renin-angiotensin system are expressed in cancer stem cells. The cathepsin enzymes (B, D and G) digest proteins and so can facilitate the invasion and metastasis of colorectal cancer to the liver. The paper reports the detection of these three enzymes in the stem cells found in liver cancer.
The research team has established the presence of stem cells in strawberry birthmarks (haemangiomas) that are proliferating. This has been determined by confirming the presence of proteins characteristic of these cells. However there is a family of three proteins called STATs that are associated with stem cells which are also known to have a role in the development of red blood cells – an activity known to occur in strawberry birthmarks. These STATs can be modified by the binding of phosphate groups. These phosphorylated proteins can promote the expansion and regulate the development of stem cells.
The role of these modified STAT proteins in strawberry birthmark development has been investigated. All three phosphorylated STATs studied were demonstrated in proliferating strawberry birthmarks but their expressions were reduced in the involuting (shrinking) haemangiomas. The STAT3 variant was the most abundant form. These reductions as the strawberry birthmark involutes reflect a depletion of the stem cells.
Professor Andrew H Kaye is the Head of the Department of Surgery at the University of Melbourne. He is a neurosurgeon, and was Director of the Department of Neurosurgery at The Royal Melbourne Hospital 1992-2017. He graduated from The University of Melbourne in 1973, and subsequently trained in Neurosurgery at The Royal Melbourne Hospital and The Royal Children’s Hospital in Melbourne. He undertook further neurosurgery training in Oxford, London and at The Cleveland Clinic. On returning to Australia in 1983 he was appointed Neurosurgeon at The Royal Melbourne Hospital, and commenced research into neuro-oncology at the Ludwig Institute for Cancer Research. He was appointed Professor of Neurosurgery at The University of Melbourne in 1992, and the James Stewart Professor of Surgery and Head of the Department of Surgery at The University of Melbourne, Royal Melbourne Hospital in 1997.
Prof Kaye’s lecture will be held at:
5.00 pm Thursday 13 September
Rutherford House Lecture Theatre 2 (RHLT2)
Pipitea Campus, Victoria University of Wellington, Bunny Street, Wellington
The lecture is open to the public. Seats are limited so if you would like to attend please click here.
Authors: Kirin Tan, Helen D. Brasch, Bede van Schaijik, James R. Armstrong, Reginald W. Marsh, Paul F. Davis, Swee T. Tan and Tinte Itinteang
Plastic Reconstructive Surgery Global Open 2018. Volume 6,
Dupuytren’s disease is a slowly developing condition involving the palm of the hand. Knots of tissue (nodules) form, which eventually grow into cords that pull one or more fingers into a bent position. These affected fingers cannot be straightened, restricting a person performing a number of activities.
The current management of the disease involves either injections of steroids or collagenase or surgery but, nonetheless, recurrence is up to 70%. While the cause of the condition is uncertain, we have identified embryo stem cell-like cells in it. These cells have been shown to express constituents of the renin-angiotensin system. Our findings suggest that these stem cells might give rise to the condition and that regulating the renin-angiotensin system may have a role in its treatment.
The production of the angiotensin II component of the renin-angiotensin system may be promoted by the proteases cathepsins B, D and G. This paper establishes the presence of these three proteases in Dupuytren’s disease tissues and demonstrates that the B and D forms are localised to the stem cells which are known to express the renin-angiotensin system.