Expression and Localization of Cathepsins B, D and G in Cancer Stem cells in Liver Metastasis from Colon Adenocarcinoma

Authors: Shreeja Mehrotra, Susrutha K. Wickremesekera, Helen D. Brasch, Bede Van Schaijik, Reginald W. Marsh, Swee T. Tan and Tinte Itinteang

Frontiers in Surgery April 2018. Volume 5, doi.org/10.3389/fsurg.2018.00031 https://doi.org/10.3389/fsurg.2018.00040

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.

$300,000 from Hugo keeps our research rolling

Philanthropist Hugh Green first started donating to worthy causes over 50 years ago.

We rely on the dedication and kindness of donors to keep our work going. So we were thrilled to recently receive a very large and generous donation of $300,000 from the Hugo Charitable Trust. We’ll put this money towards our cancer clinical study programme.

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Collecting for the tissue bank — the work of two research nurses

Our labs at the GMRI rely on human tissue samples for our research projects. These samples are stored in the GMRI tissue bank, which forms a valuable and unique resource for our work. To collect the types of samples we need requires the knowledge of two research nurses. With many years of nursing experience between them, Carolyn Croasdale and Merie Claridge make up this experienced team.

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Meet the team testing well-known medications for brain cancer treatment trial

Clinical Study Co-ordinator, Frances FitzJohn, and Clinical Study Doctor, Dr David Young.

In the Hutt Hospital outpatients clinic, Dr David Young and Frances FitzJohn are the face of the GMRI team treating patients with devastating brain cancer, glioblastoma. They are trialling the novel cancer treatment developed by the GMRI, consisting of a blend of commonly used medications. The 3-year clinical trial started earlier this year. If successful, this approach could transform the way cancer is treated, potentially prolonging life and improving life quality.

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The GMRI shines at international conferences

Sabrina Koh presents on the presence of stem cells in head and neck squamous cell cancer.

We’re proud to share the experiences of our students and trainees who have recently presented at international conferences.

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Phosphorylated Forms of STAT1, STAT3 and STAT5 Are Expressed in Proliferating But Not Involuted Infantile Hemangioma

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

Frontiers in Surgery April 2018. Volume 5, doi.org/10.3389/fsurg.2018.00031 https://doi.org/10.3389/fsurg.2018.00031

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.

GMRI and CCDHB to jointly host public lecture by distinguished neurosurgeon and neuroscientist

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.

Expression and Localization of Cathepsin B, D, and G in Dupuytren’s Disease

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,

doi:10.1097/GOX.0000000000001686

https://journals.lww.com/prsgo/Fulltext/2018/02000/Expression_and_Localization_of_Cathepsins_B,_D,.9.aspx

 

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.

 

New cancer treatment for glioblastoma — a devastating brain cancer

A new cancer treatment developed by the Gillies McIndoe Research Institute is being trialled for glioblastoma, a devastating brain cancer, which could revolutionise how the cancer is treated.

If proven effective, the cancer could be treated at home — without chemotherapy, radiotherapy, or surgery. Patients would instead take commonly used, inexpensive medications. The treatment would cost a fraction of current treatments.

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Mentoring the next generation of scientists

Dr Itinteang with our recent summer students. Left to right: Sabrina Koh, Hugo Humphries, Therese Featherston, Dr Tinte Itinteang, Claudia Paterson, Shanella Nallaiah, Min Yi Lee.

Running a laboratory isn’t just about pioneering new research. It’s also an opportunity to foster the talents and enthusiasm of future scientists.

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