Day 1 :
Keynote Forum
Christopher S Lange
SUNY Downstate Medical Center, Brooklyn, NY, USA
Keynote: Cancer stem cells in breast and gynecological cancers: How to individualize treatment based on the sensitivity of patient’s CSCs
Time : 09:40-10:40
Biography:
Christopher S Lange is the Associate Chair, Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn (2010–Present), Professor of Molecular and Cell Biology, School of Graduate Studies, SUNY Downstate Medical Center (1992–Present), Professor, Director, Radiobiological Division, Department of Radiation Oncology, SUNY Downstate Medical Center (1980–Present), Associate Director, Residency Program, SUNY Downstate Medical Center (2009), Assistant Professor of Radiology, Radiation Biology and Biophysics, University of Rochester School of Medicine and Dentistry, New York (1969–1980), NHS Senior Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1968–1969), NHS Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1962–1968), MRC Research Assistant, Radiobiology Laboratory, Churchill Hospital, Headington, England (1961–1962).
Abstract:
A necessary and appropriate condition for cancer cure is the elimination of all of a patient’s cancer stem cells (CSCs). However, CSC identification has been problematic. Cell surface biomarkers have been claimed to select SCs and CSCs. But, only a tiny fraction of the selected cells are functionally SCs or CSCs. Hill, Kern and Shibata, show that, if based on such markers, the numbers are internally inconsistent, throwing the CSC hypothesis in doubt. Functional assays do not have this problem. Agar colonies from individual patient cervical cancers showed that inherent radiosensitivity (SF2) of the cells that formed colonies was the single most important factor correlating with clinical outcomes, but large error bars prevented accurate outcome predictions for individual patients. Our Hybrid Spheroid (HS) Assay (HSA) [US Patent No.: 8,936,938] solves this problem. HSs are composed of an initial known mixture of fibroblasts and tumor cells, forming an in vivo-like ex vivo system that provides a CSC niche. HS growth curves provide the CSC fraction, the SF for each tested agent, and clinical outcome predictions for solid tumors. The impact of our HSA is 3-fold: (1) In the cancer clinic, patients predicted to fail on the standard treatment and could be offered alternatives which are also based on the assay. (2) The selection and testing of potential new therapeutic agents in the pharmaceutical industry could use the HSA to determine which agents are valuable for further clinical testing, avoiding the considerable expenses of a negative clinical trial and considerably reducing the cost and time to bring successful agents into the clinic. (3) The HSA could also be used to determine if there is a subset of patients whose tumors are susceptible to the new modality, and hence these patients could be identified by the HSA to develop a battery of agents likely to be useful on select tumors in select patients. Each of these impacts is not currently available in the clinic or in the pharmaceutical industry. The clinical impact (1) alone should lead to major increases in cancer cure rates and the second and third impacts would magnify these increases.
Keynote Forum
Shinji Osada
Gifu Municipal Hospital, Japan
Keynote: Strategy for colorectal cancer liver metastases
Time : 10:40-11:25
Biography:
Shinji Osada is a Professor at the Department of Surgical Oncology, Gifu University School of Medicine, Japan. He has published several articles in the field of Ophthalmology. He is a recipient of many awards and grants for his valuable contributions and discoveries in major area of research. His international experience includes various programs, contributions and participation in different countries for diverse fields of study. His main research areas are Anti-Cancer Drug, Eye Cancer, Eye diseases, Cancer Immunobiology and Cancer Immunobiology.
Abstract:
In this presentation, the surgical indications for liver metastasis from colorectal cancer (CRC) and its optimal timing will be discussed. Clinically, our treatment policy has been to perform hepatectomy first, if the resection can be done with no limit on size and number of tumors. However, if curative resection is not, chemotherapy is begun first and timing for the possibility of a radical operation is planned immediately. Recurrence was detected after hepatectomy, similar between simultaneous and staged resection, but early detection was higher in simultaneous cases, indicating the staged operation to be better. As a research target focused on hepatocyte growth factor (HGF) and its receptor (c-Met), the signaling pathway might induce cancer progression in the process of liver regeneration after hepatectomy. Actually, c-Met overexpression was closely associated with liver metastases, but its expression was detected to reduce in the metastatic site compared with primary lesions. In addition, pre-treatment of CRC cells with HGF enhanced 5-FU-induced cell death by 63% compared with the control during the expression of signaling pathway by HGF/c-Met activation. E2F is a transcriptional factor of thymidylate synthase (TS), which is important to metabolite 5FU, and the D-type cyclins, which play a critical role in the cell cycle and correlate the activation of E2F. The expression of E2F1 was decreased significantly to 50.5% by HGF with a reduction of cyclin D1 to 52.1%. TS were also decreased in a time-dependent manner to 80.6±2.0% after 24 hours and to 52.7±1.5% after 96 hours. In conclusion, the presence of HGF was found to increase the 5FU-induced death signal, the best procedure for favorable patient prognosis will be a hepatectomy after chemotherapy. The present study also lead to a novel concept in which the hepatectomy-induced high serum level of HGF for liver regeneration allows drug-resistant cancer cells to become sensitive again.
Keynote Forum
Antonio Gómez-Muñoz
University of the Basque Country, Spain
Keynote: Regulation of pancreatic cancer cell migration by the axis ceramide kinase/ceramide 1 phosphate
Time : 11:45-12:30
Biography:
Antonio Gomez-Muñoz received his PhD in Biochemistry and Molecular Biology from the University of the Basque Country (Bilbao, Spain) in 1988. Part of his thesis was developed at the Medical School of the University of Nottingham in the UK during 1987. He achieved postdoctoral training at the University of Alberta (Edmonton, Alberta, Canada) from 1988 to 1994. He then accepted a Research position at the Spanish Research Council (CSIC) from 1995 to 1996. From 1997 to 1998 he worked as Researcher in the Faculty of Medicine, University of British Columbia (Vancouver, British Columbia, Canada). He then returned to the University of the Basque Country where he is currently Professor of Biochemistry and Molecular Biology. His major research interest is on the targeting of sphingolipid metabolism with the aim of developing new strategies for prevention of inflammatory diseases, obesity, and cancer. He has produced over 100 publications in the field.
Abstract:
Pancreatic cancer is an aggressive disease characterized by invasiveness, rapid progression and profound resistance to treatment. It is the fourth leading cause of cancer mortality with a 5-year survival rate of only 6%. Accumulating evidence indicates that sphingolipids play critical roles in cancer growth and dissemination. In particular, ceramide 1- phosphate (C1P), which is formed by the action of ceramide kinase on ceramide, stimulates cell proliferation (1), and promotes cell survival (2, 3). The mechanisms by which C1P stimulates cell growth involves activation of extracellularly regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K), c-Jun N-terminal kinase (JNK), or mammalian target of rapamycin (mTOR), whereas C1P-enhanced cell survival implicates inhibition of serine palmitoyl transferase (SPT) and acid sphingomylinase (ASMase) (4). More recently, we found that C1P enhances human pancreatic cancer cell migration and invasion potently and that this effect is completely abolished by pertussis toxin (PTX), suggesting the participation of a Gi protein-coupled receptor in this process. We also observed that human pancreatic cancer cells migrate spontaneously. However, contrary to the effect of C1P, spontaneous cell migration was insensitive to treatment with PTX (5). Investigation into the mechanisms responsible for spontaneous migration of the pancreatic cancer cells revealed that ceramide kinase (CerK) is a key enzyme in the regulation of this process. In fact, inhibition of CerK activity, or treatment with specific CerK siRNA to silence the gene encoding this kinase, potently reduced migration of the pancreatic cancer cells. By contrast, overexpression of CerK stimulated cell migration, an action that was concomitant with prolonged phosphorylation of ERK1-2 and Akt, in a PTX independent manner. It can be concluded that the axis CerK/C1P plays a critical role in pancreatic cancer cell migration/invasion, and that targeting CerK expression or activity may be a relevant factor for controlling pancreatic cancer cell dissemination.
Keynote Forum
Guilin Tang
University of Texas MD Anderson Cancer Center, USA
Keynote: Clonal cytogenetic abnormalities of undetermined significance
Time : 12:30-13:10
Biography:
Guilin Tang is a Hematopathologist and Cytogeneticist, Section Chief of Clinical Cytogenetic Laboratory in the Department of Hematopathology, and Adjunct Medical Director of the Department of School of Health Professions. Her clinical interests include diagnosis of hematologic neoplasms (both leukemia and lymphomas) and cancer cytogenetics. Her major research interest is the characterization and risk stratification of cytogenetic abnormalities in various types of hematological malignancies, to better understand the pathogenesis, identify new clinicopathologic entities and predict patient prognosis. She is also very interested in characterization of clinically indolent cytogenetic clones (clonal cytogenetic abnormalities of undetermined significance), especially those emerged following cytotoxic therapies.
Abstract:
Myelodysplastic syndromes are a group of hematopoietic stem cell diseases characterized by cytopenia(s), morphological dysplasia, and clonal hematopoiesis. In some patients, the cause of cytopenia(s) is uncertain, even after thorough clinical and laboratory evaluation. Evidence of clonal hematopoiesis has been used to support a diagnosis of myelodysplastic syndrome in this setting. In patients with cytopenia(s), the presence of clonal cytogenetic abnormalities, except for +8, del (20q) and –Y, can serve as presumptive evidence of myelodysplastic syndrome. Recent advances in next generation sequencing have detected myeloid neoplasm-related mutations in patients who do not meet the diagnostic criteria for myelodysplastic syndrome. Various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance. Similarly, studies have shown that certain chromosomal abnormalities, including ones commonly detected in myelodysplastic syndrome, may not be associated necessarily with an underlying myelodysplastic syndrome. These clonal cytogenetic abnormalities of undetermined significance (CCAUS) are similar to clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance. Here, we review the features of CCAUS, distinguishing CCAUS from clonal cytogenetic abnormalities associated with myelodysplastic syndrome, and the potential impact of CCAUS on patient management.