Day 1 :
University of Bradford, UK
Time : 10:00-10:30
Diana Anderson holds the Established Chair in Biomedical Sciences at the University of Bradford. She has obtained her first degree in the University of Wales and second degree in the Faculty of Medicine, University of Manchester. She has 450+ peer-reviewed papers, 9 books, has successfully supervised 29 PhDs, and been a Member of Editorial Boards of 10 international journals. She has been or is Editor in Chief of a book series on Toxicology for J Wiley and Sons and the Royal Society of Chemistry respectively. She gives key note addresses at various international meetings. She is a consultant for many international organizations, such as the WHO, NATO, TWAS, UNIDO and the OECD. Her h index = 54.
Detection tests have been developed for many cancers, but there is no single test to identify cancer in general. We have developed such an assay. In this modified patented Comet assay, we investigated peripheral lymphocytes of 208 individuals: 20 melanomas, 34 colon cancers, 4 lung cancer patients, 18 suspect melanomas, 28 polyposis, 10 COPD patients and 94 healthy volunteers. The natural logarithm of the olive tail moment was plotted for exposure to UVA through different agar depths for each of the above groups and analyzed using a repeated measures regression model. Response patterns for cancer patients formed a plateau after treating with UVA where intensity varied with different agar depths. In comparison, response patterns for healthy individuals returned towards control values and for pre/suspected cancers, were intermediate with less of a plateau. All cancers tested exhibited comparable responses. Analyses of receiver operating characteristic curves, of mean log olive tail moments, for all cancers plus pre/suspected-cancer versus controls gave a value for the area under the curve of 0.87; for cancer versus pre/suspected-cancer plus controls the value was 0.89; and for cancer alone versus controls alone (excluding pre/suspected-cancer), the value was 0.93. By varying the threshold for test positivity, its sensitivity or specificity can approach 100% whilst maintaining acceptable complementary measures. Evidence presented indicates that this modified assay shows promise as both a stand-alone test and as a possible adjunct to other investigative procedures, as part of detection programs for a range of cancers.
- Diana Anderson et al, (2014) Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics. The FASEB Journal article. 28 (10): 4563-4570.
Harvard TH Chan School of Public Health, USA
Keynote: Perioperative use of NSAID might prevent early relapses in breast and other cancers: an upstream approach
Time : 10:30-11:00
Michael Retsky is working as Staff at Harvard TH Chan School of Public Health and Faculty at University College London. He was on Judah Folkman’s Staff at Harvard Medical School for 12 years. He is the Editor of a Nature/Springer Book on the Breast Cancer Project to be published in 2017. He was the first person to use what is now called Metronomic Adjuvant Chemotherapy and is a Founder and on the Board of Directors of the Colon Cancer Alliance. He has published more than 60 papers in Physics and Cancer.
A bimodal pattern of hazard due to relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. We are studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high quality database from Milan for patients treated with mastectomy only, we proposed that relapses within three years of surgery are stimulated somehow by the surgical procedure. Most relapses in breast cancer fall in this early category. Retrospective data from a Brussels Anesthesiology Group suggests a plausible mechanism. Use of ketorolac, a common NSAID analgesic, used in surgery was associated with far superior disease-free survival in the first five years after surgery. The expected prominent early relapse events in months 9-18 are reduced five-fold. Transient systemic inflammation, accompanying surgery (identified by IL-6 in serum) could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. We suggest this would be most effective for triple negative breast cancer and be especially valuable in low and middle income countries. Similar bimodal patterns have been identified in other cancers suggesting a general effect.
Jianhua Luo has been studying Molecular Pathology related to human malignancies from the last 25 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 17 years, he has been largely focusing on the genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. His group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless tissue origin. Recently, his group discovered several novel fusion transcripts and their association with aggressive prostate cancer. One of the fusion genes called MAN2A1-FER, was found present in 6 different types of human cancers. He later defined a critical MAN2A1-FER/EGFR signaling pathway that is essential for MAN2A1-FER mediated transformation activity. In addition, his group developed a genome intervention approach to treat human cancers that are positive for fusion gene.
Mutations and chromosome rearrangement are some of the key features of human malignancies. Recently, we discovered a panel of cancer-specific fusion genes that play key roles in human cancer development. One of these fusion genes called MAN2A1-FER generated a constitutively activated tyrosine protein kinase. The fusion translocates FER kinase from the cytoplasm to Golgi apparatus. The fusion protein ectopically phosphorylates the N-terminal domain of EGFR, and activates the EGFR signaling pathway in the absence of a ligand. MAN2A1-FER has been found in a variety of human malignancies. It transforms immortalized cell lines into highly aggressive cancer cells. Expression of MAN2A1-FER produces spontaneous liver cancer in animals. Cancer cells positive for MAN2A1-FER are highly sensitive to several tyrosine kinase inhibitors, and can be targeted by genome therapy intervention. Thus, targeting at MAN2A1-FER or other oncogenic fusion genes may hold promise to treat human cancer effectively.
Andrei L Gartel is working as an Associate Professor in the Department of Medicine at the University of Illinois at Chicago, and is the Academic Editor of PLoS ONE. He is the Author of 88 peer-review publications that include more than 25 reviews. He has more than 11,000 citations and his h-index is 38. His scientific interests include cancer, regulation of oncogenic transcription factors FOXM1, protein-protein interactions; cell cycle and regulation of CDK inhibitor p21. Specifically, his lab is interested in identification of new FOXM1 inhibitors. He received his funding from NIH, DOD and private companies/foundations.
FOXM1 is an oncogenic transcription factor that is overexpressed in majority of human cancers and it is a potential target for anticancer drugs. We identified proteasome inhibitors as the first type of drugs that target FOXM1 in cancer cells. Chaperone HSP70 is induced after treatment with proteasome inhibitors and we identified this chaperone as a novel negative regulator of FOXM1 after proteotoxic stress. We showed that FOXM1 and HSP70 interact in cancer cells following proteotoxic stress and FOXM1/HSP70 interaction led to inhibition of FOXM1. Honokiol is a natural product that inhibits FOXM1-mediated transcription and FOXM1 protein expression. We found that honokiol’s inhibitory effect on FOXM1 is a result of direct binding of honokiol to FOXM1. This binding is specific to honokiol, a dimerized allylphenol, and was not observed in compounds that either were monomeric allylphenols or un-substituted dihydroxy phenols. We have previously shown that FOXM1 interacts with nucleophosmin (NPM) in cancer cells and NPM determines cellular localization of FOXM1. Mutations in NPM1 result in cytoplasmic re-localization of NPM (NPM1mut) and favorable outcome for the AML patients. We found the evidence that improved outcomes in the subset of NPM1mut AML may be partially explained by the cytoplasmic re-localization and consequent functional inactivation of FOXM1. We also showed an important role of FOXM1 in chemo-resistance in AML with nuclear, but not cytoplasmic FOXM1. These data imply that suppressing of FOXM1 in AML could increase sensitivity to standard chemotherapy, while overexpression of FOXM1 would increase chemo-resistance of AML cells.