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Laboratory Research
The department has a well equipped laboratory, constructed and equipped with funds
donated to the Orthopaedic Foundation in 1996. Facilities are available for cell
culture and moelcular biology studies including Northern / Southern Blot hybridisations,
Immunohistochemistry, P.C.R., In-situ hybridisation and more. A "nude"
animal facility allows the study of orthopically transplanted tumours in mice populations.
Each year sees additional staff in the laboratory in paid and postgraduate degree
studies and the department will host 2 international research positions in 1999.
Primary bone tumours
Secondary bone tumours
Hydroxyapatite
incorporation using a vascular pedicle
A
possible role for bisphosphonates in the management of osteosarcoma
Cell ongrowth on implant substrates
 Jane Fisher, Hong Zhou, Peter Choong, Scott Mackie
Osteosarcoma is the commonest primary tumour of bone in adolescent and young adults. With
increasing sophistication of imaging techniques and chemotherapy, survival has improved
tremendously and more patients are potential candidates for limb sparing surgery. Our
studies examine the way in which osteosarcoma may spread to other sites in the body as
well as the way the tumour may enlarge locally. We use a variety of techniques including
cell culture, immunohistochemistry, histology and in-situ hybridisation to analyse tissue
from patients with osteosarcoma. We have developed an in-vivo model of osteosarcoma which
spontaneously metastasizes to lung, thus allowing us to closely examine the development of
osteosarcoma and to identify crucial steps in the metastatic cascade. We are also
attempting to manipulate the behaviour of osteosarcoma by altering the genetic make-up of
the tumour in order to test various hypotheses about the regulation of tumour growth and
spread. A further area of our interest is in the role of osteoclast activity in the local
growth of osteosarcoma. To date, there is an assumption that bone destruction which
accompanies osteosarcoma development is solely due to malignant bone forming cells. We are
investigating the role of osteoclasts in the process of bone destruction and the expansion
of tumour, and if osteoclasts can be implicated in tumour growth, a variety of therapeutic
measures may be opened to osteosarcoma treatment.
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Jane Fisher, Hong Zhou, Peter Choong, Scott Mackie
Bone is a common site for spread of tumours that arise from a variety of organs. Breast,
prostate and lung are the commonest tumours that target bone during the process of
metastasis. Each year 1 in 8 women are affected by breast cancer and up to two thirds of
these will develop bone metastases. 1 in 10 men will develop prostatic carcinoma and many
of these will have spread to the pelvic and vertebral bones. The problems of pain,
fracture and loss of function are the challenges facing current treatment. We are studying
the role of proteolytic enzymes in the development and spread of metastases. We have
examined the expression of this system in primary breast tumours and bone secondaries and
have observed a high expression of the receptor and inhibitor of urokinase plasminogen
activator in aggressive tumours and also those that metastasize. Prostatic carcinoma
differs from breast carcinoma in that the former tumour is mainly osteoblastic while
breast carcinoma metastases are either lytic or mixed. We are currently studying samples
obtained from pathologic specimens to answer the question as to why some metastases
stimulate bone formation while others are lytic. We are also examining the development of
prostatic carcinomas in bone in an in-vivo model.
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Peter Scougall, Wayne Morrison, Peter Choong, Jane Fisher, Tim Bennett
Bone grafts are frequently required in reconstructive surgery. The limited supply of
bone from each patient and the morbidity associated with its harvest make alternate and
artificial sources attractive. Coralline hydroxyapatite is an artificial structure that
has chemical similarities with bone and can be incorporated into human bone. It is
possible to augment the local blood supply of conventional bone graft blocks by placing a
vascular pedicle into the bone. It may be possible to establish a blood supply in
hydroxyapatite in the same way. Our study examines the incorporation of
hydroxyapatite blocks into normal bone and the effect of introducing a vascular pedicle
into the structure.
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Scott Mackie, Jane Fisher, Peter Choong
The role of bisphosphonates in the management of hypercalcaemia of malignancy,
osteoporosis, Paget's disease, Myeloma and metastatic tumour are well established.
The mechansisms of the bisphosphonates in reducing the activity of osteoclasts (bone
resorbing cells) are central to their effects in these conditions. Osteosarcoma is
generally considered to be an osteogenic (bone forming) primary bone tumour but a lytic
(bone destroying) front is seen at the advancing edge of the tumour.
Osteoclast-mediated lysis may be targeted by bisphosphonates and in-vitro assessment of
possible direct effects are being investigated, as well as the role of bisphosphonates in
an in-vivo model of osteosarcoma growth.
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Bruce Love, Jane Fisher
Prosthetic implants capitalise on surface design and geometry to improve fixation. What
may be important is the manner in which bone cells react to such surfaces. This experiment
investigates the gene expression of bone cells after in-vitro culture growth on various
synthetic surfaces.
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ŠJuly 2000 St. Vincent's Hospital, Melbourne |
