The 3rd Sino-Australian Symposium 2010
SYMPOSIUM PROGRAM
The 3rd Sino-Australian Symposium
Translational Medicine
A Joint Symposium between
Shanghai Jiao Tong University and
The University of Sydney
10-11 September, 2010
Friday, September 10, 2010
Venue: Conference Room 203
Science & Teaching Building
227 Chongqing South Road, Shanghai
08.30
Tea and Coffee
09.00
Symposium Opening
Professor Guoqiang Chen, Executive Dean - Shanghai Jiao Tong
University School of Medicine
09.10
Speech from Professor Nicholas King
The University of Sydney
09.20
Exchange of official gifts and taking photos
Each of the speakers has 15 minutes’ talk and 5 minutes’ discussion
Basic Research Part
Chair: Associate Professor Stephen Twigg
09.30
Dr. Beric Henderson
Regulation of BRCA1 and BARD1 intracellular targeting to centrosome
and nuclear sites of DNA repair
09.50
Associate Professor Qian Zhao
Pathologically Decreased MiR-26a Directly Increases AEG-1 and EZH2
Expression: An Oncogenic Symphony Which Facilitates Breast
Tumorigenesis by Antagonizing Apoptosis
10.10
Dr. Dinny Graham
Progesterone action in normal and malignant human breast
10.20
Professor Xuemei Tong
Warburg effect revisited: the role of ChREBP in cancer metabolism and
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The 3rd Sino-Australian Symposium 2010
tumorigenesis
10.40
Morning Tea
11.00
Associate Professor Stephen Twigg
The role of connective tissue growth factor in regulation of fat cell
differentiation: dependence on transforming growth factor beta signalling
pathways
11.20
Professor Xiaoying Li
GPR48 Regulates Adipogenesis and Energy Expenditure
11.45
Lunch
Sheng Le Restaurant
Pre-clinical Animal Model Research Part
Chair: Professor Honglin Wang
13.00
Professor Tingting Tang
Enhancement of Bone Regeneration with Stem Cell based Therapy
13.20
Dr. Aaron Schindeler
The cellular contribution of muscle progenitors to bone repair
13.40
Professor Honglin Wang
Plasmin is involved in the pathogenesis of psoriasis by inducing IL-23 and
CCL20 expression
14.00
14.30
Afternoon Tea
Dr. Scott Byrne
Sunlight-induced modulation of skin immunity via the induction of
inflammatory cytokines and chemokines
14.40
Associate Professor Shangang Li
Rabbit cloning and trasgenic medical model rabbits
15.00
Lab Tour
17.30
Dinner at Chuan Guo Yan Yi, 555 Xujiahui Road, Shanghai
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The 3rd Sino-Australian Symposium 2010
Saturday, September 11, 2010
Venue: Conference Room 203
Science & Teaching Building
227 Chongqing South Road, Shanghai
08.30
Tea and Coffee
Clinical Trials Part
Chair: Professor Albert Lam
09.00
Professor Albert Lam
Value of sonography in the management of vascular birthmark in children
09.20
Professor Yuemin Xu
Urethral Reconstruction Using Free Mucosal Grafts
09.40
Associate Professor Lyndal Trevena
Clinical trials of complex interventions in the community
10.00
Professor Ming Zhu
Prenatal and postnatal MR diagnosis of congenital heart disease
10.20
Professor Kate White
Nursing Professional Pathways in Clinical Trials Research
10.40
Professor Xiaodong Sun
Efficacy and safety of intravitreal injection of KH902 compared with
Bevacizumab (Avastin) in subjects with neovascular age-related macular
degeneration (AMD)
11.00
Dr. Phan Viet Hong
Pharmacokinetic differences and ethnic variability in tolerance of cytotoxic
drugs
11.30
13.00
Lunch (KAKADU Australian Restaurant, tel: 54680118)
Group One: Wrap Up Meeting
Nick King, Lyndal Trevena, Louise Freckelton, Guoqiang Chen, Yong
Zhang, Rong Huang, Jiaying Dai
Group Two: Lab Tour
Sunday, September 12, 2010
One-day-trip to Suzhou Tongli Town for Sydney delegation (Lyndal Trevena,
Scott Byrne, Viet Phan, Christopher Rosewarne, Beric Henderson, Dinny Graham,
Albert Lam, Cathy Lam, Nick King, Louise Freckelton, Aaron Schindeler, Stephen
Twigg, Rong Huang, Jiaying Dai)
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The 3rd Sino-Australian Symposium 2010
ABSTRACT
Dr Beric Henderson
Head, Gene Expression Laboratory
Westmead Millennium Institute (University of Sydney)
Westmead, NSW 2145
Australia
beric.henderson@sydney.edu.au
Topic: Regulation of BRCA1 and BARD1 intracellular targeting to centrosome
and nuclear sites of DNA repair
Abstract: The breast cancer tumour suppressor, BRCA1, is mutated in many
familial breast cancers and functions in the cell nucleus and at the centrosome
to regulate DNA repair and mitosis, respectively. BRCA1 usually functions in
the cell as a heterodimer with the related protein, BARD1. In recent years we
have studied regulation of BRCA1 and BARD1 protein intracellular transport to
different locations including the nucleus, mitochondria and centrosome. The
heterodimerisation of BRCA1/BARD1 inhibits their nuclear export and causes
nuclear retention of the dimer complex. Cancer mutations in the C-terminus of
BRCA1 reduce its nuclear localisation and movement into DNA
damage-induced repair foci and also recruitment to centrosomes. We mapped
the BRCA1 sequences which target it to DNA damage foci in response to
ionizing radiation, and showed that the extreme amino and carboxy-termini
were critical for this response. This reflected binding of BARD1 to the
amino-terminus and interaction of the C-terminal BRCT domain with other
upstream factors. We have used systematic 3-D confocal analyses to compare
the localization patterns of BRCA1 and 14 other DNA damage proteins or
domains at DNA repair foci and identified differences in localization and
retention of several factors at these structures. More recently we have
investigated the targeting and dynamics of BRCA1/BARD1 assembly at the
centrosome and nuclear DNA repair sites in living cells using confocal
photobleaching assays (FRAP/FLIP). BRCA1 is a critical initiator of inherited
breast/ovarian cancers, and cell biology studies can directly address its role in
the DNA damage response and in DNA repair.
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The 3rd Sino-Australian Symposium 2010
Associate Professor Qian Zhao
Head , Dept. of Pathophysiology
Shanghai Jiao Tong University School of Medicine
qzhao@shsmu.edu.cn
Topic: Pathologically Decreased MiR-26a Directly Increases AEG-1 and EZH2
Expression: An Oncogenic Symphony Which Facilitates Breast Tumorigenesis
by Antagonizing Apoptosis
Abstract: MiR-26a has been reported as oncogene in glioblastoma or tumor
suppressor gene in hepatocellular carcinoma and B-cell lymphoma, however,
its role in breast tumor is unclear. Here, we report that miR-26a is
downregulated in breast cancer patients as well as MCF-7 and Bcap-37 cell
lines. Transient overexpression of miR-26a impairs viability and initiates
apoptosis of MCF-7 and Bcap-37 cells. AEG-1 and EZH2 are identified as two
direct targets of miR-26a and significantly upregulated in breast cancer.
Furthermore, retrovirus delivered miR-26a impairs the ability of MCF-7 cells to
form colonies in vitro and to develop tumor in vivo. MCF-7 xenografts with
enhanced expression of miR-26a show that a decrease in expression of both
AEG-1 and EZH2 is companied by an increase in apoptosis. Moreover,
knockdown of AEG-1 or EZH2 leads to apoptosis while re-expression of
AEG-1 partially reverses the proapoptotic effect of miR-26a in MCF-7 cells.
Our findings suggest that miR-26a functionally antagonizes human breast
tumorigenesis by targeting AEG-1 and EZH2.
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The 3rd Sino-Australian Symposium 2010
Dr Dinny Graham
Senior postdoctoral researcher, Breast Cancer Research Group
Westmead Institute for Cancer Research
Westmead Millennium Institute (University of Sydney)
dinny.graham@sydney.edu.au
Topic: Progesterone action in normal and malignant human breast.
Abstract: The female hormone progesterone is critical for normal reproductive
function, and has diverse roles in the breast, endometrium, ovaries, brain and
bone. The basis for the diversity of progesterone action in target tissues is
unknown, but new knowledge on the higher order structure of the genome
emphasises that nuclear structure is critical in regulating specificity of gene
expression. The well documented disruptions in nuclear structure in cancers
are known to contribute to different gene expression between normal and
cancer cells. Progesterone effects are mediated by the nuclear progesterone
receptor (PR). Ligand activation of PR results in receptor dimerization,
recruitment of transcriptional cofactors and binding to specific response
elements in target genes to regulate transcription. We have previously shown
that in response to hormone PR moves into subnuclear foci, representing sites
of active transcription. We have evidence that normal foci formation is
important for the fidelity of PR transcriptional response and that disruptions in
chromatin architecture, as seen in malignancy, alter PR foci formation and
influence transcriptional outcome. PR foci are significantly larger in cancer
cells than normal breast cells and form in the absence of hormone.
Genome-wide transcriptional profiling of progesterone effects in normal breast
and breast cancer cells revealed remarkably distinct patterns of gene
expression regulation in normal and malignant cells, supporting the view that
altered chromatin organization is responsible for aberrant PR function in
cancer. Using global PR chromatin immunoprecipitation and high throughput
sequencing coupled with gene expression profiling in progesterone responsive
normal and malignant breast models we are linking the altered transcriptional
response to progesterone with altered patterns of PR genomic interaction.
These studies are providing insights into the role of higher order chromatin
organization in regulating transcriptional response to progesterone in normal
and malignant target tissues.
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The 3rd Sino-Australian Symposium 2010
Professor Xuemei Tong
Department of Biochemistry, Molecular and Cell biology,
Institute of Medical Science,
Shanghai Jiao Tong University School of Medicine
xuemeitong@gmail.com
Topic: Warburg effect revisited: the role of ChREBP in cancer metabolism and
tumorigenesis
Abstract: Altered metabolism has been considered as one of the hallmarks of
proliferating cells especially cancer cells. Many human tumors display a high
rate of aerobic glycolysis (Warburg effect), de novo fatty acid synthesis and
nucleotide biosynthesis. Aerobic glycolysis along with increased lipid and
nucleotide biosynthesis promotes tumor cell growth and proliferation by
providing essential synthetic and bioenergetic requirements. Recent success in
blocking tumorigenesis by targeting tumor energy pathways suggests the
importance of bioenergetics in sustaining tumor growth. Thus, understanding
the regulation of glucose, lipid and nucleotide metabolism in normal and tumor
cells will provide us with new strategies for cancer therapy and prevention.
The transcription factor carbohydrate responsive element binding protein
(ChREBP) was previously shown to play important roles in redirecting glucose
metabolism in support of lipogenesis in non-proliferating hepatocytes. However,
whether it plays a more generalized role in reprogramming metabolism during
cell proliferation and tumorigenesis remains to be elucidated. We have
demonstrated that ChREBP is required for cell proliferation in HCT116 human
colorectal cancer cells and HepG2 human hepatocellular carcinoma cells.
Suppression of ChREBP results in diminished aerobic glycolysis, de novo lipid
and nucleotide biosynthesis, and is accompanied by stimulation of
mitochondrial respiration. Therefore, ChREBP is required to maintain high
levels of aerobic glycolysis in these cancer cells. Attenuation of ChREBP
activates p53 and induces cell cycle arrest. In vivo, ChREBP inhibition reduces
tumor growth via a p53-dependent mechanism. Our findings not only
demonstrate that ChREBP plays a key role in glucose-dependent metabolism,
cell proliferation and tumor maintenance, but also suggest that
ChREBP-dependent regulation of glucose, lipid and nucleotide metabolism
may provide us with new avenues to explore more effective cancer therapies
and prevention.
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The 3rd Sino-Australian Symposium 2010
Associate Professor Stephen Twigg
A/Prof. in Medicine (Central), Sydney Medical School,
and Director of the Endocrinology and Diabetes Research Foundation
The University of Sydney,
Medical Head of Endocrinology Research Laboratories,
Senior Endocrinologist, Royal Prince Alfred Hospital,
Sydney, AUSTRALIA
stephen.twigg@sydney.edu.au
Topic: The role of connective tissue growth factor in regulation of fat cell
differentiation: dependence on transforming growth factor beta signalling
pathways
Abstract: Adipocyte differentiation is a key process implicated in the
pathogenesis of obesity and insulin resistance. Its regulation is triggered by a
cascade of transcription factors, including the CCAAT/enhancer binding
proteins (C/EBPs) and peroxisome proliferator-activated receptor-gamma
(PPARgamma). Growth factors such as transforming growth factor-beta1
(TGF-beta1) are known to inhibit adipocyte differentiation in vitro, via the
C/EBP pathway, but whether a related mediator of TGF-beta1 effects,
connective tissue growth factor (CTGF), also known as CCN2, has a similar
role has not previously been defined unknown. Our recently published data in
mouse 3T3-L1 cells and primary cultures of murine preadipocytes showed that
CTGF caused an inhibition in the development of the adipocyte phenotype,
according to the gene expression of the differentiation markers adiponectin
and PPARgamma, as well as suppression of lipid accumulation and
expression of the lipogenic enzyme glycerol-3-phosphate dehydrogenase.
Subsequent studies have shown that CTGF applied to cells early in the course
of differentiation inhibits mRNA, total cell protein levels and nuclear localisation
of the beta- and delta-isoforms of C/EBP and, subsequently, total cell
C/EBP-alpha levels. CTGF cell effects require TGFbeta type-II receptor and
also LRP-1 signaling. In vivo, expression of CTGF mRNA was twofold higher in
the central fat depots of mice compared with subcutaneous fat, further
suggesting a potential adipose tissue role for CTGF. In summary, these data
show that CTGF inhibits the adipocyte differentiation program through TGF
beta dependent mechanisms, which has implications for human metabolic
disease.
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The 3rd Sino-Australian Symposium 2010
Professor Xiaoying Li
Deputy Director Shanghai Institute of Endocrinology and Metabolism,
Chief physician Department of Endocrinology and Metabolism,
Ruijijn Hospital,
Shanghai Jiao Tong University School of Medicine
xiaoying_li@hotmail.com
Topic: GPR48 Regulates Adipogenesis and Energy Expenditure
Abstract: Adipogenesis is regulated by intracellular signaling cascades. The
substantial transcriptional factors in concert with some critical cofactors have
been identified, however, whether membrane proteins are involved in this
process is largely unexplored. In the present study, we characterize a pivotal
role of newly identified G-protein-coupled receptor 48 (Gpr48) in adipogenesis.
Gpr48 knockout mice showed a marked reduction of body weight and white
adipose tissues (WAT). PPAR-γ, aP2 and FAS etc are down-regulated in WAT.
However, C/EBPβ and C/EBPα expressions were not changed. Moreover,
mice embryonic fibroblasts (MEFs) lack of Gpr48 also showed a deficiency in
adipogenesis, suggesting that Gpr48 is essential for this process.
Adipogenesis was also impaired in 3T3-L1 cells when Gpr48 expression was
knocked down using specific small interfering RNA (siRNA), whereas
overexpression of a constitutively active Gpr48 promoted adipocyte
differentiation. At the molecular level, we demonstrate that Gpr48 activates
cAMP-PKA-CREB signaling pathway in adipocyte and uppromoter activity. Furthermore, in Gpr48 null mice, we found that the food
intake and energy expenditure were increased by CLAMS. These data for the
first time supports Gpr48 as a key regulator of adipogenesis and suggests a
potential therapeutic target for obesity and related diseases.
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The 3rd Sino-Australian Symposium 2010
Professor Tingting Tang
Director, Shanghai Key Laboratory of Orthoapedic Implant,
Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital,
Shanghai Jiaotong University School of Medicine
tingtingtang@hotmail.com
Topic: Enhancement of Bone Regeneration with Stem Cell based Therapy
Introduction: Recently, the use of bone marrow derived mesenchymal stem
cells (MSCs) for bone repair has gained much focus while the osteoinductive
capacity of bone morphogenetic proteins (BMPs) had been well demonstrated
by many researchers. It is believed that the BMP gene modified stem cells lead
to an enhanced osteogenic ability in vivo.
Methods: In the present study, the bone marrow derived mesenchymal stem
cells (MSCs) were transfected with BMP2 gene in vitro, loaded on the
scaffolds and implanted into the local areas in vivo to enhance the bone repair.
Different animal models including the critical-size segmental bone defects in
weight bearing animals or aged animals, periprosthetic bone defects, and
experimental necrosis of femoral head were used to investigate the effects of
BMP2 gene therapy technique on the treatment of various clinical problems.
The study also evaluate the safety of stem cell based BMP-2 gene medicine.
Results: The results showed that the the stem cell based BMP2 gene
medicine had successfully repaired the segmental bone defects in large
weight bearing animals (goat model), osteoporotic bone defects (aged rat
model), periprosthetic bone defects (dog model), and experimental necrosis of
femoral head (goat model). The study also showed that the cellular and
humoral immune reaction were activated against adenovirus in vivo.
Conclusion: The stem cell based BMP2 gene therapy combined the seed
cells (MSCs), growth factors (BMP2) and osteoconductive materials and
effectively meet the requirements to deal with variety of orthopaedic problems
associated with bone loss and bone formation deficit.
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The 3rd Sino-Australian Symposium 2010
Dr Aaron Schindeler
Research Scientist
Orthopaedic Research & Biotechnology
Kids Research Institute at The Children's Hospital at Westmead (University of
Sydney)
AaronS@chw.edu.au
Topic: The cellular contribution of muscle progenitors to bone repair
Abstract: Orthopaedic bone repair is dependent on the presence of
osteocompetent progenitors that are able to differentiate and generate new
bone. Muscle is found in close association with orthopaedic injury, however its
capacity to make a cellular contribution to bone repair remains ambiguous. We
hypothesized that myogenic cells of the MyoD-lineage are able to contribute to
bone repair. We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in
which all cells of the MyoD-lineage are permanently labelled with a human
alkaline phosphatase (hAP) reporter. In the absence of orthopaedic injury,
MyoD-lineage contribution is limited to skeletal muscle and the presence of
reporter-positive cells in non-muscle tissues is negligible. We tracked the
contribution of MyoD-lineage cells in mouse models of tibial bone healing. In a
closed tibial fracture model, there was no significant contribution of hAP+ cells.
In contrast, open tibial fractures featuring periosteal stripping and muscle
fenestration had up to 50% of hAP+ cells in the open fracture callus. Serial
sections stained for hAP and for type I and type II collagen showed that
MyoD-lineage cells were surrounded by bony or cartilaginous matrix, indicating
a functional role in the repair process. To resolve whether these MyoD-lineage
cells originated from the adjacent muscle, a tibial drill hole defect model was
developed with an optional muscle flap that could be laid over the bone defect.
Only when the muscle flap was present were MyoD-lineage cells found to
contribute to defect repair. These data document for the first time that muscle
cells play an important secondary role in traumatic ectopic ossification and
bone repair and will lead to important translational applications.
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The 3rd Sino-Australian Symposium 2010
Professor Honglin Wang
Principal Investigator, Shanghai Institute of Immunology
Institute of Medicine Science
Shanghai Jiao Tong University School of Medicine
honglin.wang@sjtu.edu.cn
Topic: Plasmin is involved in the pathogenesis of psoriasis by inducing IL-23
and CCL20 expression
Abstract: Skin-homing pathogenic T cells play a key role in the
immunopathogenesis of psoriasis. However, mechanisms underlying
recruitment of pathogenic T cells to skin lesions are poorly understood.
Plasmin is a serine protease that is released as plasminogen from the liver into
the circulation, and activated by tissue plasminogen activator, urokinase
plasminogen activator, and factor XII. Recently, accumulating evidence
demonstrates that plasmin is also recognized as a potent signaling molecule in
particular monocytes/macrophages by inducing a pro-inflammatory response.
Here, we show that expression of the CC chemokine, CCL20, is partially
confined to dermal macrophages, and both skin-homing CLA+ memory T cells
and TH17 cells display high levels of CCR6, the receptor of CCL20 in psoriatic
lesions. Importantly, we find that the expression levels of plasminogen
activators are highly elevated in psoriatic skin. As a consequence,
plasminogen is significantly decreased in psoriatic skin compared with normal
skin. In vitro, plasmin triggers CCL20 induction in human monocyte-derived
macrophages, and its release requires activation of NF-kappa B, and p38
MAPK, but not of JAK1 and ERK1/2 MAPK signaling pathway. Finally, we
demonstrate that simultaneous injection of plasmin together with recombinant
murine MCP-1 resulted in the induction of psoriasiform skin inflammation
around the injection sites with recruitment and activation of macrophages and
TH17 cells. Taken together, our data reveal that plasmin at sites of
inflammation in psoriasis stimulate CCL20 production mediated by NF-kappa
B or p38 MAPK signaling pathway that plays an essential role in the
recruitment of pathogenic T cells, and thus provide a potential mechanism of
how skin-homing pathogenic T cells maintain their continual presence in
psoriasis through a positive chemotactic feedback loop.
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The 3rd Sino-Australian Symposium 2010
Dr Scott Byrne
Head, Cellular Immunology Research Group
Infectious Diseases and Immunology
Dermatology Research Laboratories
Sydney Medical School
University of Sydney (Camperdown Campus)
scott.byrne@sydney.edu.au
Topic: Sunlight-induced modulation of skin immunity via the induction of
inflammatory cytokines and chemokines.
Abstract: The ultraviolet (UV) radiation contained in sunlight has wide-ranging
immunosuppressive capabilities spanning both the induction and effector
phases of an immune response. This property of UV is a key event in skin
carcinogenesis but it may also have beneficial effects including protection from
multiple sclerosis, enhancing allograft tolerance, as well as treating psoriasis
and graft versus host disease. Other health benefits of UV exposure include
vitamin D synthesis and the production of antimicrobial peptides. Dermal mast
cells play a critical role in UV-modulation of skin immunity and our group is
interested in identifying novel UV-induced factors that could recruit and
activate dermal mast cells. To that end, we have discovered that the mast cell
chemoattractant CCL5 (RANTES) is significantly upregulated in UV-irradiated
skin. This was important because mast cells expressed the receptor for CCL5
and were attracted to the skin following intradermal CCL5 injection. We have
also discovered that the mast cell activating cytokine; interleukin-33 (IL-33) is
significantly upregulated in UV-exposed skin. This is important because
IL-33-stimulated
mast
cells
produced
significant
amounts
of
immuno-regulatory cytokines. Our studies have identified two important
UV-induced factors that coordinate the recruitment and activation of mast cells
that ultimately lead to systemic immune suppression and regulation. This will
facilitate the design and implementation of novel therapeutic strategies.
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The 3rd Sino-Australian Symposium 2010
Associate Professor Shangang Li
Laboratory Animal Science Department,
Shanghai Jiao Tong University, School of Medicine
lis101@163.com
Topic: Rabbit cloning and transgenic medical model rabbits
Abstract: In the last decade, rapid progress has been made to improve the
somatic cell nuclear transfer (SCNT) technology which induced people to get
animals from single cells. It has been demonstrated that in bovines, pigs and
ferret cultured cells could be genetically modified and used as nuclear donors
to produce genetic disease model animals with specific genetic traits.
Theoretically, it should then also be feasible to produce gene modified t rabbit
for special use. The development of SCNT technology in rabbits was slowly.
Only after the female rabbits were successfully cloned from freshly isolated
cumulus cells using modified oocyte activation and embryo transfer protocols,
new progress were got gradually in the sequenced studies and the transgenic
cloned rabbit were reported recently by different protocols.
There are many factors effecting on the development of the cloned embryos
from SCNT, such as activation protocols, donor cells prepare, cytoplasm status,
embryo activation, and embryo transfer. Here we reviewed the progress and
status of the cloned rabbit with cumulus cells, fibroblast cells, Mesenhcymal
stem cells and ES like cells; the cytoplasm and different enucleation method;
the mechanism of activation in reconstructed embryos; and the details of
embryo culture and embryo transfer of cloned embryos. we reported the our
new results of the cloned transgenic GFP rabbit and HGPRT RNAi rabbits.
Finally, The future usage of this technique was elaborated in production animal
models, reprogramming research, and genome preservation and so on.
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The 3rd Sino-Australian Symposium 2010
Clinical Professor Albert Lam
MBBS, MD, FRANZCR, DDU
Head, Diagnostic Ultrasound, Department of Medical Imaging, Royal
Alexandra Hospital for Children, Sydney, Australia
Clinical Professor, Disciplines of Medical Imaging and Paediatrics, Sydney
Medical School, University of Sydney, Australia
albertl@chw.edu.au
Topic: Value of sonography in the management of vascular birthmark in
children
Abstract: Haemangiomas are the most common benign tumours in infancy
and occur in up to 2.6% of newborns, with a prevalence at 1 year of
10–12%.They follow a typical evolution characterized by their appearance
within days or weeks after birth, a rapidly growth phase, stabilization and
gradual spontaneous partial or total resolution. Congenital haemangioma is a
distinctive form that proliferate fully in utero, so are fully developed at birth.
Although the clinical presentation at birth is usually an alarming violaceous
mass with a telangiectatic surface, the prognosis is excellent in most cases,
with rapid spontaneous involution during the first year of life. This entity has to
be differentiated from the rare malignant sarcoma which urgent intervention is
mandatory for a good response. Vascular malformations are structural
abnormalities and as such are present at birth, grow in proportion to the
patient's growth and have no tendency at all to resolution. They can be further
divided according to their vessel or vessels of origin into capillary, venous,
lymphatic, arteriovenous and other mixed malformations. Retrospective review
of all the sonography performed in patients attending the Vascular Birthmark
Clinic in the Children’s Hospital at Westmead, Sydney, Australia from 1995 to
2009 were undertaken with the aim is to evaluate the diagnostic value of
high–resolution sonography and Doppler in the vascular birthmarks in young
infants. The images were correlated with other forms of imaging studies (MRI,
CT and angiography), pathology and clinical outcome.
Our result shows high-resolution sonography with Doppler study is useful in
the diagnosis of haemangioma; including the congenital types but limited in the
delineation of full extend of vascular malformation. MRI and MR angiography
are required for further evaluation.
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The 3rd Sino-Australian Symposium 2010
Professor Yuemin Xu
Department of Urology, Shanghai No 6 People’s Hospital
Shanghai Jiao Tong University School of Medicine
xuyuemin@263.net
Topic: Urethral Reconstruction Using Free Mucosal Grafts
Abstract:
Introduction
Longer urethral strictures are not easily corrected by excision with primary
anastomosis. They are best treated with substitution urethroplasty using free
grafts or penile skin flaps. Neourethra created by free mucosa may be
necessary for patients who have had complications from previous penile
surgery resulting in a shortage of local skin.
There are more than 200 patients with urethral strictures in our hospital ever
year; of then 35% patients are treated with substitution urethroplasty.
Materials and Methods
Between Jan 2000 and Dec 2009, free mucosal grafts are adopted for in 258
patients with urethral strictures in our hospital. Of then colonic mucosa was
adopted in 44 cases; lingual mucosa 120 cases; buccal mucosa 94 cases.
Distance of urethral stricture was from 2.5 to 20 cm.
Results
The patients were followed up 6 to 98 months (mean 35.4 months). Urethral
restricture recurred or complications were found in 17 patients. The other
patients were voiding well，The peak flow rate ranged between 14 and 51 ml/s.
Conclusions
Lingual and buccal mucosas have an advantage of easy to harvest, a little
trauma to patient and a strong antiinfection, especially for the treatment of
urethral stricture < 6 cm in length. Colonic mucosa provides rich material for
urethroplasty, the technique may be considered in patients failed other
conventional procedures or complicated urethral strictures involving the entire
or multiple portions of the urethra.
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The 3rd Sino-Australian Symposium 2010
Associate Professor Lyndal Trevena
Associate Professor, School of Public health
Associate Dean (International)
Director, Office for Global Health
Sydney Medical School
University of Sydney
lyndal.trevena@sydney.edu.au
Topic: Clinical trials of complex interventions in the community
Abstract: Over the past decade, definitions of ‘translational research’ have
expanded beyond bringing laboratory results to trials in human populations.
Recent definitions have also recognised that new discoveries will not improve
the health of populations if they are unable to be implemented in ‘real world’
settings. Translational research now not only includes ‘bench to bedside’ T1
and T2 research but also recognises implementation in clinical practice
systems as T3 and even T4 research. Conducting clinical trials in the
community and ‘real world’ clinical practice poses a number of methodological
challenges. In particular T3 & T4 studies need to consider ‘how’ evidence from
clinical trials can be implemented in different healthcare settings. As such, they
become ‘complex interventions’ because of the numerous new components
and interactions that need to be considered when implementing evidence
within healthcare systems. These studies require a new cycle of Phase 1-IV
development, evaluation and implementation. This paper will provide
examples of T3 and T4 research using the MRC framework for clinical trials of
complex interventions. These phases require consideration of methods such
as modelling, cost-effectiveness and trial designs such as individual or
cluster-randomised trials, stepped wedge designs, preference trials and N-of-1
designs.
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The 3rd Sino-Australian Symposium 2010
Professor Ming Zhu
Professor, Department of Radiology
Shanghai Children’s Medical Center
Shanghai Jiao Tong University School of Medicine
dongsuzhen@126.com
Topic: Prenatal and postnatal MR diagnosis of congenital heart disease
Abstract: Congenital heart disease is a relatively common problem with an
incidence of approximately 6 to 7 per 1,000 live births. Echocardiography is
currently the main initial imaging modality for diagnosis of prenatal and
postnatal congenital heart diseases. Cardiac magnetic resonance imaging
(MRI) has become an important alternative to echocardiography in the
evaluation for prenatal and postnatal patients with congenital heart disease.
Cardiac MRI is a tool for answering questions regarding specific individual
morphology and hemodynamic function of known anatomy. Cardiac MRI is
now increasingly being used in infants and fetus for investigation of congenital
heart disease. However, little information is available on its clinical role,
accuracy, and technical aspects. We retrospectively identified all neonates and
fetus who underwent a cardiac MRI examination for the evaluation of
congenital heart disease at our institution over a 4-year period and reviewed
their surgical records. The data in this study were a relatively large group data
and acquired from one medical center. For fetus with heart disease, fast
imaging employing steady-state acquisition (FIESTA) sequence is most useful
and unlike ultrasound imaging, MRI is not affected by maternal and fetal
conditions such as obesity and oligohydramnios, which particularly impair
ultrasound visualization of the fetal cardiac diseases. For neonates,
contrast-enhanced magnetic resonance angiography (CE-MRA) is very helpful
and neonatal cardiac diseases can be diagnosed by magnetic resonance
imaging safely and reliably.
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The 3rd Sino-Australian Symposium 2010
Professor Kate White
Professor of Cancer Nursing
Cancer Institute of NSW Chair in Cancer Nursing
Sydney Nursing School
University of Sydney
kate.white@sydney.edu.au
Topic: Nursing Professional Pathways in Clinical Trials Research
Abstract: The number of clinical trials undertaken globally has increased in
recent years, with more than 70,000 trials currently registered in 169 countries*
led by pharmaceutical companies, research organisations and clinical trial
investigators. Clinical trials are conducted within an intensely regulated
environment to ensure safe and effective treatments are approved for use. The
conduct of clinical trials is complex and requires staff to be both
knowledgeable and multi-skilled to meet the demands of the clinical trial
protocol and its requirements. In recent years the role of the clinical trial
nurses has evolved, with wide recognition that they played a critical role in
ensuring safe and successful completion of the trial.
The role of the clinical trials nurse has evolved in recent years, moving
beyond as initial recruitment and consent of trial participants, to include the
conduct of trial assessments and observations, the administration of treatment
interventions, the measurement of outcomes and the monitoring of patient
safety. This paper will provide an overview of a national investigation of the
Clinical Research Nurse role, the contribution to clinical trial research and the
development of career pathways in this field.
On Behalf of research team: Dr Kathleen Scott , Cath Johnson
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The 3rd Sino-Australian Symposium 2010
Professor Xiaodong Sun
Professor, Shanghai First People’ s Hospital
Shanghai Jiao Tong University School of Medicine
xdsun@sjtu.edu.cn
Topic: Efficacy and safety of intravitreal injection of KH902 compared with
Bevacizumab (Avastin) in subjects with neovascular age-related macular
degeneration (AMD)
Abstract:
Purpose
Evaluate the efficacy of KH902 compared with Avastin in improving best
corrected-visual acuity and evaluate the mean change from baseline in BCVA
over time up to 3 months and 12 months. Evaluate the safety and tolerability.
Methods and Materials
A multicenter, randomized, double-masked, active treatment controlled study.
This study includes screening phase, fixed-dosing phase (3 months), extended
PRN treatment phase (9 months). The subjects will be divided into 2 groups.
One group will be treated with KH902 0.5 mg/eye/0.05ml/time, at the same
time, the other group will be treated with Avastin 1.25 mg/eye/0.05ml/time.
Results
Trials are under way.
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The 3rd Sino-Australian Symposium 2010
Dr Phan Viet Hong
PhD student – Sydney Medical School, University of Sydney
Oncology Fellow - Sydney Cancer Centre
vietph74@yahoo.com
Topic: Pharmacokinetic differences and ethnic variability in tolerance of
cytotoxic drugs.
Abstract:
Recent evidence shows an ethnic variability in tolerance of anticancer drugs
among lung and breast cancer (LC and BC) patients. Pharmacogenetic
differences in drug metabolizing enzymes have been proposed as the cause of
these differences; however, they have not been associated with altered
cytotoxic drug pharmacokinetics (PK). Other possible explanations include
differences in diet, use of concomitant medication, and inflammatory status. To
explore these issues we established a collaboration between Sydney
University, Sydney Cancer Centre and Jiao Tong University (Renji Hospital) to
investigate interethnic differences in cytotoxic drug metabolism,
inflammatory/nutritional status, genotype, and outcomes between Asian and
Caucasian LC and BC patients. Here we present the preliminary PK data.
Methods: Early BC patients receiving standard adjuvant anthracycline-based
chemotherapy regimens and metastatic LC patients receiving palliative
treatment with paclitaxel and carboplatin were recruited. Plasma samples were
collected using a limited sampling strategy and concentrations were measured
using HPLC for epirubicin and LC-MS for paclitaxel. Empiric Bayes estimates
of clearance (CL) were obtained using a population PK analysis implemented
in the NONMEM software. The toxicity profile after cycle 1 of chemotherapy
was graded and correlated with the pharmacokinetics of anthracyclines (BC)
and paclitaxel (LC).
Results: Forty-two BC patients (30 Caucasians, 12 Asians) and 44 LC
patients (33 Caucasian, 11 Asians) have been recruited. In BC, 11/12 (92%)
Asians had grade IV neutropenia compared to 19/29 (66%) Caucasians
(p=0.066). Asians had more severe anaemia and thrombocytopenia. In LC,
there were no statistically significant ethnic differences in toxicity. PK analyses
showed that paclitaxel CL in Asian LC patients (n=8, mean=11.0 L/h) was
lower than in Caucasian patients (n=24, mean=13.4 L/h) (p=0.045). There was
a trend for epirubicin CL to be lower in Asian patients (n=10, mean=78.0 L/h)
compared to Caucasians (n=26, mean= 84.2 L/h).
Conclusions: Preliminary data indicate Asian LC and BC patients have lower
clearance of anthracyclines and paclitaxel, respectively, than Caucasians,
which is likely to explain ethnic differences in toxicity. However, larger patient
numbers are required to provide more conclusive results.
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