Day 1 :
Australian National University
Time : 09:00-09:30
Veronica J James completed her PhD in Physics from the University of NSW in 1971. Working in crystallography, she published 40 papers on the molecular structures of small organic crystals, before moving into the fi bre diffraction studies of collagen and keratin. In this area she has carried out the diffraction study that produced the successful structure for hard keratin and also pioneered the fi bre diffraction diagnostic tests for breast, colon, prostate cancers and for Alzheimer’s Disease. She was awarded an OAM for her Phones for the Deaf Program and her Advanced Physics Programs in 1996
Such tests have been established using low angle X-ray diffraction of hair, nails or skin for a number of cancers and other diseases. In all such tests a change, specific to the cancer or disease is superimposed on the pattern for control samples. The results for all such tests is a sensitivity of 100%, since there have been no false negatives and a specificity >99% since there are less than 1% false positives. These results are much higher than for any other test to date.\\\\r\\\\n Since tests using transgenic mice have revealed that these tests can diagnose the relevant cancers and diseases much earlier than any other test, these false positives may not be false. Further to this should the cancer or disease be cured, the change disappears showing immediately whether the medical treatment has been successful. This talk will cover tests for prostate cancer and breast cancer. The results for prostate cancer indicate that this test can accurately determine whether the cancer is high or low grade and establish whether the cancer has invaded and by what method. The test for breast cancer accurately diagnoses all cancers but has different changes if the patient has a BRAC gene or not. Such tests can save lives.
Deakin University, Australia
Time : 09:30-10:00
Jagat R Kanwar is group leader and head of the Nanomedicine and Laboratory of Immunology and Molecular Biomedical Research has an international reputation in investigating fundamental and applied molecular aspects of cancer and chronic inflammation. Our nanomedicine laboratory of immunology and molecular biomedical research (NLIMBR) is discovering the novel and safe targeted nanomedicine based nano-nutraceuticals for cancers, autoimmune disorders and inflammatory diseases. We also vested the molecular diagnosis including role of a non-invasive exosomes in blood, inflammatory sites and cancer tissues. Our research focused on cancer and inflammatory autoimmune diseases aims to investigate the underlying mechanisms involved in apoptosis, autophagy and inflammation by targeting the production of cytokines, chemokines, oxygen radicals and matrix metalloproteinase. Our research also aims to investigate the nanotherapeutics encapsulating peptides, LNA modified aptamers/miRNAs/siRNA in vivo models. We have made significant progress in field of ocular drug delivery and microfluidic and Lab-on-a-Chip devices techniques for cancer cells as well as stem cell capture, disease specific biomarkers and exosomes. His publications more than 150 research papers and have added to the body of knowledge in the fields of nanobiotechnology, cancer gene therapy, cell biology and immunology. Kanwar research work has generated a total of 12 patent/PCTs. He is the member of various scientific committees and societies.
Drug resistance is a common drawback for most chemotherapeutic drugs and it promotes cancer survival and recurrence. The major protein that help a cell acquire MDR is P-glycoprotein (P-gp) and studies have showed that P-gp expression has been directly related to the degree of drug resistance in cells. P-gp also known as ABCB1 acts as a membranous molecular pump that effectively effluxes the chemotherapeutic drugs from within the cells. Overexpression of survivin in cancer cells has also been related to cause resistance to various chemotherapeutic compounds and therapies inhibiting survivin expression have shown sensitization of human cancer cells to various chemotherapeutic drugs such as docetaxel, paclitaxel and bortezomib. Studies have also shown that CD133 positive cancer stem cells resist chemotherapy which is mainly due higher expression of inhibitors of apoptosis protein (IAP) families and it has been also observed that the colony formation of CD133 positive cells is quite higher when compared to CD133 negative cells mainly due to overexpression of survivin. A major area of interest has come up using biomolecules which focusses on specifically target the diseased tissues. In our previous studies we have shown chimeric form of Fe-bLf (LNA-Nucleolin+EpCAM aptamer)-spions showed high specificity towards the tumour both in vitro and in vivo. In another study using ceramic polymer nanocarriers (ACSC NCs) we have shown that Fe-bLF(LNA-EpCAM aptamer+LNAsiRNA(survivin))-ACSC NCs were highly specific to tumour when compared to any other parts of the mice and the nanocarriers led to significant cytotoxicity specifically in tumour cells without harming the primary cells. We have also used novel oligo LNA siRNA (survivin) to target the nanocarriers and inhibit survivin expression in drug resistant cancer stem cells. Nanoparticles loaded with SR9 and LNAsiRNA-5-FU have been used in this study to target cellular survivin in colon cancer cells. Our results show that inhibition of survivin has a direct inhibitory effect on p-gp and CD133. The mechanism for explaining this phenomenon has also been investigated and a pathway has been proposed through which inhibition of survivin significantly lowers both p-gp and CD133 expression in colon cancer cells.
Bar Ilan University, Israel
Time : 10:00-10:30
Izhak Haviv has completed his PhD at the age of 32 years from Weizmann Institute of Science and Postdoctoral studies from University of California, Berkeley (c/o Tjian lab, Head, HHMI). He is the Director of cancer research center of excellence in the Faculty of Medicine in the Galilee of Bar Ilan University, an academic clinical and translational research organization. He has an Affiliate Position in the University of Melbourne for 11 years and at Peter MacCallum Cancer Centre, Australia for 16 years. He has published more than 59 papers in reputed journals.
Recent successes of targeted drugs on end stage cancer patients highlight the value of mutation-based biomarkers for drug response. However, the impact of these drugs is often temporary and the patients progress to acquired resistance. A common mechanism of drug evasion involves feedback mechanisms that increase expression or phosphorylation-driven activation of an alternative oncogenic pathway. The objective of this work was to set up a streamlined methodology (kinome profiling, shRNA negative RNAi screens, evolution tracking etc.) for rational drug combination designs. It includes pre-clinical assessment of the novel drugs focused on cancer cases, refractory to biomarker predicted targeting and seeking combination therapies that would block the spontaneous drug evasion. We explored the efficacy of the combination approach on a panel of cancer patient derived xenografts in mice using tumor size or metabolic imaging as an end point. Each cancer case was subject to target somatic mutation screening which resulted in a targeted drug recommendation and then mouse groups were treated either with sequeincing-based therapy or with combination of these therapies with blockers of the suspected evasion mechanisms. As a blocker of the evasion mechanism and epithelial to mesenchymal transition, we characterized the utility of a molecule that leads to the destruction of IRS1/2 of the IGF1R pathway. Use targeted drugs such as Erlotinib, Zelboraf, Afinitorand Gleevec, all increase the attenuation of the cancer growth temporarily, followed by acquired resistance while inclusion of the IRS1/2 destruction lead to sustained efficacy and even lead to regression of the recurrent tumor mass.