Day 2 :
Keynote Forum
Adhip P N Majumdar
Wayne State University, USA
Keynote: Cancer stem cells: Implications for recurrence of colorectal cancer and development of preventive strategies with natural agents
Time : 10:10-10:45
Biography:
Adhip P N Majumdar received his MS and PhD degrees from the University of London, England, and DSc (Doctor of Science) degree in Gastroenterology from the University of Aarhus, Denmark. He has been a Professor at Wayne State University since 1992. He also holds the post of Senior Research Career Scientist at the Detroit VA Medical Center. Over the past several years his work has been streamlined to uncover the biochemical and physiological pathways governing the growth of gastrointestinal (GI) tract. He has published 200 original scientific articles in peer-reviewed journals and a multitude of book chapters and review articles. He is particularly interested in elucidating the patho-physiology of age-related changes in the GI mucosa, specifically those that lead to malignancy. To this end, he has begun to investigate the role of pluripotent, self-renewing CSCs in the development and progression of GI malignancies. He has been continually funded by the VA and NIH and is considered one of the nation’s leading investigators in gastrointestinal aging and cancer.
Abstract:
Recent evidence supports the contention that epithelial cancers, including sporadic colorectal cancer (CRC), the incidence of which increases with aging, are diseases driven by self-renewing cancer stem cells (CSCs). One of the characteristics of CSCs is their resistance to 5-FU based chemotherapy, the mainstay of colon cancer therapeutic with significant toxicities, resulting in high disease recurrence underscoring the need for improved CSC-targeted non-toxic preventive or therapeutics for recurrent CRC Investigations were carried out to examine the role of CSCs in the development of CRC and also to develop preventive and/or therapeutic strategies using natural agents to combat this malignancy. Initially we found that curcumin, the major active ingredient of turmeric (Curcuma longa), used in South Asian cuisine, with no discernible toxicity synergizes with FOLFOX (5-FU + Oxaliplatin) and this combination which attenuates EGFR signaling causes a marked inhibition in inhibition of colon cancer cell growth. However, use of curcumin as a chemotherapeutic agent has come under intense scrutiny because of its poor bioavailability. Recently, it has been reported that curcumin complexed with essential turmeric oils (ETOcurcumin) exhibit 7-10 fold higher bioavailability than standard curcumin. We found ETO-curcumin to synergize with palm oil (Trocotrinol) and together they were found to be highly effective in inhibiting the growth FOLFOX-resistant colon cancer cells that are highly enriched in CSCs. The results suggest that the combination of ETO-curcimin and palm oil could be an effective preventive/therapeutic strategy for recurrent colon tumor that are highly enriched in CSCs. Likewise, we found eicosapentaenoic acid (EPA), one of the components of omega-3 polyunsaturated fatty acids to also synergize with FOLFOX and that the combination of EPA and FOLFOX to be highly effective in inhibiting the growth of FOLFOX-resistant colon cancer cells in vitro and in vivo in SCID mice xenograft model. PTEN–Akt axis and Wnt signaling pathway were found to play a pivotal role in regulating the growth inhibitory process. In conclusion, our results suggest that certain natural agents by themselves or together with the conventional 5-FU based chemotherapy could be effective in eliminating or inhibiting the proliferation of CSCs and thus could be utilized to prevent the recurrence of colorectal cancer.
Keynote Forum
Alexander Herzog
Herzog’s Special Hospital, Germany
Keynote: The role of hyperthermia as complementary treatment in metastatic breast cancer
Time : 11:00-11:35
Biography:
Abstract:
Keynote Forum
Myron R Szewczuk
Queen’s University, Canada
Keynote: Novel therapeutic target in multistage tumorigenesis
Time : 09:35-10:10
Biography:
Myron R Szewczuk, PhD is Professor of Immunology, Department of Biomedical and Molecular Sciences and Medicine, Queen’s University, Kingston, Ontario Canada since 36 years. He received his BSc in Chemistry (U. of Guelph), MSc in Biochemistry (Guelph), PhD in Immunochemistry (U. of Windsor) and Post doctoral Training with Gregory Siskind, MD in Cellular Immunology at Cornell University Medical College, NYC. His recent research focuses on the role of glycosylation in receptor activation with a focus on TOLL-like, nerve growth factor Trk, EGFR and insulin receptors. He has discovered a novel receptor signaling platform and its targeted translation in multistage tumorigenesis.
Abstract:
A novel organizational signaling platform linked to glycosylated receptor tyrosine kinases (RTK) (e.g., EGFR, TrkA, insulin) and TOLL-like (TLR) receptors is identified to regulate receptor activation process, all of which are known to play major roles in tumorigenesis. This signaling paradigm proposes that ligand binding to its receptor on the cell surface induces a conformational change of the receptor to initiate matrix metalloproteinase-9 (MMP-9) activation to induce neuraminidase-1 (Neu1). Activated Neu1 hydrolyzes α-2,3-sialyl residues linked to β-galactosides, which are distant from the ligand binding sites. These findings predict a prerequisite desialylation process by activated Neu1 enabling the removal of steric hindrance to receptor association. In addition, the relative levels of specific sialoglycan structures on the cell surface correlate with the ability of cancer cells to form avascular 3D multicellular tumor spheroids and in vivo xenograft tumors. Here, we have identified an innovative and promising entirely new targeted therapy for cancer. Mammalian neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G-protein coupled receptor tethered to RTKs and TLRs is identified as a major target in the multistage tumorigenesis. Preclinical studies support an entirely new cancer targeted therapy unaffected by mutations of growth factor receptors, involved in tumor neovascularization, chemo resistance of tumors, immune-mediated tumorigenesis, and tissue invasion and metastasis.
- Cancer Therapies | Oncology | Radiation Oncology | Cancer Diagnostics Types | Cancer Innovations | Approaches in Cancer Therapy
Location: Diplomat
Chair
Jaime Tisnado
Virginia Commonwealth University, USA
Co-Chair
Adhip P N Majumdar
Wayne State University, USA
Session Introduction
Jaime Tisnado
Virginia Commonwealth University, USA
Title: Carotid blow out syndrome: Interventional radiologic management
Biography:
Jaime Tisnado graduated from Leoncio Prado Military Academy. He received his BM degree from San Marcos National University, College of Sciences. He received his MD degree summa cum laude from the same San Marcos National University Medical School. He was an Intern at GBMC, a division of John's Hopkins University Hospital in Baltimore, MD, 1965, and then an Intern and Resident in Surgery at The State University of New York, Upstate Medical Center in Syracuse NY, 1966-67. He was a Resident in Radiology for 4 years at Thomas Jefferson University Medical Center in Philadelphia, 1967-71. Then he took 2 years fellowships in Vascular and Interventional Radiology and Neuroradiology both at the same institution, Thomas Jefferson University in Philadelphia, PA, 1971-73. He then became an Assistant Professor of Radiology and Director of Interventional Radiology at Albany Medical College, Albany, NY, 1974-77. Thereafter he moved to Virginia Commonwealth University, in Richmond, VA, where he became Associate Professor of Radiology and Director of Interventional Radiology and eventually became Professor of Radiology and Professor of Surgery, at the same university from 1985 till 2010. Thereafter, he was named one of the few Professor Emeritus of Radiology and Surgery, all at the same Virginia Commonwealth University in 2010 till now. He has published more than 100 articles in peer reviewed journals, about 400 scientific posters and electronic exhibits all over the country and the world, and about 200 abstracts, 4 books, many chapters in books, and about 200 papers presented at meetings, at the local, national, and worldwide level. He has been selected many times to Who is Who in America, the Best Radiologists in America, the Best Physicians in USA, etc. Moreover, he is the only person in the country and in the world who has, at the same time and forever, more than 5 fellowships in the most prestigious professional organizations of USA.
Abstract:
Carotid blow out syndrome (CBOS) is a catastrophic neurovascular emergency associated with a high morbidity and mortality (M&M). The etiology of CBOS is: head and neck malignancies with tumor invasion, postoperative complications, inflammation, trauma, vasculitides, collagen diseases, and post radiation therapy for malignancies, among others. The conventional surgical management has been and is carotid artery and/or branch ligation or bypass, and is rather difficult and associated with significant M&M and could be ineffective in controlling the situation. At this time, the ideal management of this serious problem is the IR and INR endovascular: insertion of stents of ndifferent kinds (covered or uncovered, selfexpanding or balloon-expandable) and/or embolization of the carotid or vertebral arteries or branches, with temporary or permanent agents and/or devices. A permanent or temporary success is expected with stent insertion and/or embolization, or both procedures combined. We have managed many patients, not considered ideal candidates for surgery, at least during the acute phase, with stents from different manufacturers, mostly covered. In addition, we have embolized some patients as well and some other patients have had both methods. The procedures have been done in the IR suite by the IR, INR and surgeons as well, working in team, in a collaborative rather than in an adversarial manner. No major complications related to the procedures have been found. The patients have had a long-term or a temporary improvement in their condition. The emergent management of CBOS by stenting and/or embolization or both is a safe, effective and relatively easy procedure to temporarily manage these seriously ill patients. A longer follow up and many more patients studied are necessary to establish the definitive role of stenting and/or embolization in CBOS. In conclusion, the conventional surgical management of CBOS may be difficult and/or ineffective, therefore, the endovascular management is considered the first choice of therapy, at least for now, especially in clinically desperate situations.
Adhip P N Majumdar
Wayne State University, USA
Title: Gut microbiome regulation of cancer stem cells and colon carcinogenesis
Biography:
Adhip P N Majumdar received his MS and PhD degrees from the University of London, England, and DSc (Doctor of Science) degree in Gastroenterology from the University of Aarhus, Denmark. He has been a Professor at Wayne State University since 1992. He also holds the post of Senior Research Career Scientist at the Detroit VA Medical Center. Over the past several years his work has been streamlined to uncover the biochemical and physiological pathways governing the growth of gastrointestinal (GI) tract. He has published 200 original scientific articles in peer-reviewed journals and a multitude of book chapters and review articles. He is particularly interested in elucidating the patho-physiology of age-related changes in the GI mucosa, specifically those that lead to malignancy. To this end, he has begun to investigate the role of pluripotent, self-renewing CSCs in the development and progression of GI malignancies. He has been continually funded by the VA and NIH and is considered one of the nation’s leading investigators in gastrointestinal aging and cancer.
Abstract:
Colorectal cancer (CRC), whose incidence increases markedly after the age of 50 years, is a multi-step process resulting from accumulation of mutations during progression from normal epithelium to carcinoma. Loss or inactivation of the tumor suppressor gene in adenomatous polyposis coli (Apc) initiates genomic instability that is thought to produce the phenotypic appearance of an adenoma. Increasing evidence suggests that pluripotent cancer stem cells (CSCs) are involved in the development and progression of many types of malignancies, including CRC. Earlier, we reported that patients with ≥3 adenomas (High-risk for CRC) exhibit a marked increase in CSCs in the colon than those without adenomas. Although the regulatory mechanisms for this increase in CCSs are poorly understood, we have suggested a role for secondary bile acids in the intestine, specifically deoxycholic (DCA) and lithocholic (LCA) acids, bio-transformed by gut microbiota, in regulating this process. Indeed, we observed a marked rise in Fusobacterium nucleatum and Enterobacterium (in High-risk CRC patients. An opposite phenomenon was noted both are associated with CRC) for the anti-inflammatory Bifidobacteria and for probiotic Lactobacillus acidophilus. Among the secondary bile acids, DCA and LCA are thought to be the most significant with respect to the development of CRC. Interestingly, we found the levels of DCA and LCA in the colon of High-risk (HR) CRC patients to be markedly higher than those at lower risk (LR) for CRC. Interestingly, we found DCA and/or LCA to induce not only mutations of CRC initiating genes such as β-catenin but also CSCs in normal human colonic epithelial cells, as evidenced by increased colon sphere formation and elevated expression of several CSC markers as well as MMP-2, accompanied by an induction in drug exclusion and increased expression of multiple drug resistance (MDR) transporters ABCB1 and ABCG2. Our observations suggest that alterations in specific gut micro-organisms resulting in increase in DCA and LCA that induce stemness in colonic mucosal cells where CRC-initiating genes are mutated are responsible for the development of sporadic
CRC.
Junliang Liu
University of Manitoba, Canada
Title: Brain metastases: Post-whole brain radiotherapy systemic treatment increases survival
Biography:
Junliang Liu underwent his Radiation Oncology Residency in University of Manitoba, Canada from 2000 to 2005. Since July 2005, he has been an attending Radiation Oncologist working at CancerCare Manitoba, Canada. He was the Radiation Oncology Residency Program Director from 2006 to 2012. He graduated from West China University of Medical Sciences (now is the Medical School Sichuan University), China in 1983 and pursued a Master’s Degree in Pediatrics from 1983 to 1986 in the same medical school. He was a Pediatrician working at Sichuan Provincial People’s Hospital, China from 1986 to 1991. He was a Guest Researcher supervised by Professor Hans Wigzell at the Department of Immunology, Karolinska Institute, Sweden, from 1991 to 1994. He earned a PhD in Immunology from La Trobe University, Melbourne, Australia in 1997, and conducted Post-Doctoral Research in Immunology at University of Alberta, Canada, from 1997 to 2000, before his residency training in Radiation Oncology. His publications included the ones in the prestigious journals of Nature Medicine and Proceedings of the National Academy of Sciences of the United States of America (PNAS). His current research interest is the treatment outcomes of gastrointestinal malignancies, breast cancer, and metastatic cancer.
Abstract:
Purpose/Objective: The prognosis of cancer patients with brain metastases has been dismal even with availability of stereotactic radiosurgery. This study is to explore the impact of post-whole brain radiotherapy (WBRT) systemic treatment.
Material & Methods: A consecutive cohort of patients with brain metastases were treated with WBRT with a dose-fractionation of mostly 30 Gy in 12 fractions, daily treatment, five days per week. Data was analyzed by dividing patients into group 1 patients who received post-WBRT systemic treatment and group 2 patients who did not have post-WBRT systemic treatment.
Results: Between July 1, 2005 to May 1, 2016, 65 patients’ male 31, female 34, aged 25 to 92 years old were identified. Eleven out of 65 patients received post-WBRT systemic treatment including chemotherapy (for 10 out of 11 patients) and target therapy (for 1 out of 11 patients). The median post-WBRT survival for patients who received post-WBRT systemic treatment was 14 months, compared to a much short median survival of only 3 months for patients who did not receive post-WBRT systemic treatment.
Conclusion: Post-WBRT systemic treatment increases the overall survival of patients with brain metastases.
Biography:
Fikri Selcuk Simsek graduated from EskiÅŸehir Osmangazi University Medicine faculty. He completed his Master’s from EskiÅŸehir Osmangazi University Medicine faculty (2005) and Doctorate from Eskisehir Osmangazi University Medicine faculty (2011). Presently, he is working as Assistant Professor in Nuclear Medicine Department at the Firat University.
Abstract:
Introduction: DTC (Differentiated Thyroid Cancer) is most frequent endocrine malignancy, and after the surgery RA (Radioiodine Ablation) is the second step. But up to 20% of patients don’t have sufficient response to first dose. These cases mostly receive more than one doses. This increased patients and medical staff’s radiation exposure. In addition RA requires discontinuation of levotiroxin and this is really hard period psychologically and physically for patients. TSH>30 uIu/ml is a criteria for RA and some studies reported, if TSH is increased, TR (Theraphy Response) can be higher. In addition, tumor size
and TR rate have negative correlation in most of cancers. In this preliminary study, we assessed different TSH levels and sizes
relation between TR. Our hypothesis is, these findings can give us opportunity to individualised radioiodine theraphy and
more successful patient management.
Methods: We retrospectively reviewed DTC patients who received RA after surgery in 2011. Total 66 patients can be found. They assessed 6-12 months with I-131 (Iodine131) WBI (Whole Body Imaging) and stimulated Tg (Thyroglobulin) for TR. If Tg<0.2 and I-131WBI negative; 0.2
Findings: NR rate for TSH<30; 30-50 uIu/ml; >50 uIu/ml are 25%; 14.3%; 10.8% respectively. ER and HLR rate for TSH>50 uIu/ml and <50 uIu/ml are 75.6% and 83.4%. Tumor size have <10 mm; 1040 mm have 4.0%; 13.0% and 42.9% NR rate.
Conclusion: TSH<30 uIu/ml isn’t sufficient for RA. But there is no significant differencies between 30-50 uIu/ml and >50 uIu/ml. If tumor size>40 mm NR rate is very high. In these patients radioiodine doses maybe increased. But these preliminary findings needs to be supported by high scale studies.
Oleg V. Gerasimenko
Cardiff University, UK
Title: Potential protection from the side effects of antileukemic drug asparaginase
Biography:
Oleg V Gerasimenko completed his PhD in 1991 at BogomoletzInst, Kiev, Ukraine before moving to Liverpool, UK in 1993 to join research group lead by Prof. Ole H Petersen. He became Lecturer in 2000 and Reader in 2005 before moving to Cardiff School of Biosciences in 2010. Since then he is a Team Leader of wellequipped MRC funded research group together with Prof. Ole H Petersen (Head of School of Biosciences) and Dr. Julia Gerasimenko.
Abstract:
Asparaginase is an essential element in the successful treatment of childhood acute lymphoblastic leukemia, the most common type of cancer affecting children. However, in about 5–10% of cases this treatment causes acute pancreatitis (AP) as a side-effect. In AP, a potentially fatal human disease, the inactive pancreatic pro-enzymes become active enzymes inside the pancreatic acinar cells, digesting the pancreas and its surroundings. Under physiological conditions intracellular calcium signalling and Mg-ATP level are the key elements needed for stimulant-evoked exocytotic enzyme secretion from pancreatic acinar cells. Physiological Ca2+ signals stimulate ATP production, whereas sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis leading to AP. Alcohol and gallstones are the major causes of the disease. Recently we have investigated in vitro the mechanism by which L-Asparaginase evokes AP.For the first time, we have shown that like other
pancreatitis-inducing agents, L-Asparaginase evoked excessive intracellular Ca2+ release followed by Ca2+ entry, decreased the intracellular ATP levels and reduced Ca2+ extrusion. The toxic Ca2+ signals induced by L Asparaginase caused extensive cell necrosis. Our data suggest that the L Asparaginase-induced pathology depends on protease activated receptor 2. The inhibition of PAR2 receptor prevented the toxic L-Asparaginase-elicited Ca2+ signals and cell necrosis. Inhibition of Ca2+ entry with GSK-7975A markedly reduced L-Asparaginase-induced cellular pathology. We have demonstrated a decreased rate of Ca2+ extrusion due to the reduction in the intracellular ATP level limiting the energy supply to the Ca2+ ATPase in the plasma membrane. Supplementation of the medium with sodium pyruvate provided a similar degree of protection against pancreatic necrosis as PAR2 inhibition or GSK-7579A. The established mechanism of action of L-Asparaginase has been confirmed for several sources of asparaginase, including drug Elspar, PEG-asparaginase and asparaginase from both and Erwinia. We have now developed model of asparaginase-induced AP that allows us to fully test our previous findings and develop protection from the side effects of Asparaginase. Both Ca2+ overload and ATP loss play key roles in Asparaginase-induced AP and therapeutic strategies must take both target points into account. We suggest that a combined pharmacological control of intracellular calcium and ATP levels will prevent or alleviate AP and improve childhood cancer treatments.
Omnia Abd El-Fattah
Tanta University Hospital, Egypt
Title: Quality-of-life scores in locally advanced laryngeal carcinoma patients as a predictive value and impact on survival
Biography:
Omnia Abd El-Fattah is an Assistant Professor of Clinical Oncology, Faculty of Medicine Tanta University Hospital, Egypt, member of the Egyptian Association for Cancer-based National Cancer Institute, Cairo, Egypt and Patients' Friends Society tumors in Gharbia based Department for Clinical Oncology, Tanta University Hospital, Egypt. She has Master’s and MD degrees in Clinical Oncology in 2002 and 2009 respectively from Faculty of Medicine Tanta University Hospital, Egypt. Her Master’s and MD theses focused on non-Hodgkin's lymphomas. She is teaching postgraduate students and is interested in participating in a therapeutic service in university hospitals. She attended many courses in the capabilities of faculty development and supervised multiple Master’s and MD theses. She has attended multiple national and local conferences of Clinical Oncology and has multiple international published papers in Clinical Oncology.
Abstract:
Purpose: The purpose is to analyse the factors that determine quality-of-life (QOL) scores among successfully treated locally advanced laryngeal squamous cell carcinoma patients and clarify their impact on survival.
Patients & Methods: A study was conducted to determine the relationship between QOL scores (Physical and mental component of short form SF-36 questionnaire and the pain, eating, speech, and mood domains from University of Washington Quality of Life (UW-QOL) questionnaire and all-cause survival among 62 locally advanced laryngeal cancer patients.
Results: The physical and mental component of short form SF-36 score and the pain, eating and mood domains from UWQOL score were significant survival predictors. The speech domain of UW-QOL score was not associated with survival.
Conclusion: QOL scores were valuable in predicting and detecting those patients with poor survival who had low score to improve survival by close follow up, early treatment of recurrence and any detected deterioration in one or more of QOL domain in those patients.
- Clinical Oncology | Chemotherapy | Cancer Screening Tests
Location: Diplomat
Chair
Myron R Szewczuk
Queen’s University, Canada
Co-Chair
Hanso Lee
Kanwon National University, South Korea
Session Introduction
Omnia Abd El-Fattah
Tanta University Hospital, Egypt
Title: Predictive value of PKM2 expression in advanced Non-Small Cell Lung Cancer patients (NSCLC) treated with front-line platinum-based chemotherapy
Biography:
Omnia Abd El-Fattah is an Assistant Professor of Clinical Oncology, Faculty of Medicine Tanta University Hospital, Egypt, member of the Egyptian Association for Cancer-based National Cancer Institute, Cairo, Egypt and Patients' Friends Society tumors in Gharbia based Department for Clinical Oncology, Tanta University Hospital, Egypt. She has Master’s and MD degrees in Clinical Oncology in 2002 and 2009 respectively from Faculty of Medicine Tanta University Hospital, Egypt. Her Master’s and MD theses focused on non-Hodgkin's lymphomas. She is teaching postgraduate students and is interested in participating in a therapeutic service in university hospitals. She attended many courses in the capabilities of faculty development and supervised multiple Master’s and MD theses. She has attended multiple national and local conferences of Clinical Oncology and has multiple international published papers in Clinical Oncology.
Abstract:
Background: The aim of the study was, to assess the expression of pyruvate kinase isozymes M2 (PKM2) in advanced NSCLC patients treated with front-line platinum-based chemotherapy and analyze its predictive value on both progression free and overall survival.
Methods: 72 cases with histologically confirmed stage IIIB and IV NSCLC who were treated with front-line platinum-based chemotherapy. 32 NSCLC patients were treated with front-line non-platinum-based doublets were enrolled in this study (as control), immunohistochemical staining for PKM2 was evaluated.
Results: In Platinum group, the median OS (overall survival) was 7 vs. 19 months; PË‚0.001 for those patients with high compared to those with low expression respectively and the median PFS was 5 vs. 9 months; PË‚0.001 for those patients with high PKM2 expression compared to those with low expression respectively. In control group, there was no significant difference between high and low PKM2 expression as regard median OS (9 vs 10 months; P≤0.451) and median PFS progression-free survival (7 vs. 8 months; P=0.638). Conclusions: Our study proved that PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.
Adhip P N Majumdar
Wayne State University, USA
Title: micoRNAs in regulation of cancer stem cells and colon carcinogenesis
Biography:
Adhip P N Majumdar received his MS and PhD degrees from the University of London, England, and DSc (Doctor of Science) degree in Gastroenterology from the University of Aarhus, Denmark. He has been a Professor at Wayne State University since 1992. He also holds the post of Senior Research Career Scientist at the Detroit VA Medical Center. Over the past several years his work has been streamlined to uncover the biochemical and physiological pathways governing the growth of gastrointestinal (GI) tract. He has published 200 original scientific articles in peer-reviewed journals and a multitude of book chapters and review articles. He is particularly interested in elucidating the patho-physiology of age-related changes in the GI mucosa, specifically those that lead to malignancy. To this end, he has begun to investigate the role of pluripotent, self-renewing CSCs in the development and progression of GI malignancies. He has been continually funded by the VA and NIH and is considered one of the nation’s leading investigators in gastrointestinal aging and cancer.
Abstract:
Accumulating evidence supports the contention that many malignancies, including sporadic colorectal cancer (CRC), the incidence of which increases with aging, are diseases driven by self-renewing cancer stem cells (CSCs). We have reported that CSC population in the colonic mucosa increases with advancing age, accompanied by a concomitant rise in microRNA-21 (miR-21) and reduction in miR-145 in the colon. Likewise, similar changes in miR-21 and miR-145 were also noted in the colonic mucosa of patients with CRC. These observations prompted us to speculate a role for miR-21 and miR-145 in regulating CSCs. Indeed, we found overexpression of miR-21 in colon cancer cells greatly increases CSCs and induces tumor growth. An opposite phenomenon was noted in colon cancer cells where miR-145 was upregulated. In addition, administration of either antagomir-21 (anti-sense miR-21) or excess miR-145 greatly decreases the growth of xenograft of colon cancer cells in SCID mice. Cell culture studies have further demonstrated miR-21 to regulate miR-145 and vice versa. Although the precise mechanism(s) by which miR-21 or miR-145 regulates CSCs in the colonic mucosa during the progression of CRC is unknown, our studies suggest that they induce differentiation of colon CSCs, as evidenced by the increased expression of CK-20 in colon cancer cells following downregulation of miR-21 and upregulation of miR-145. In contrast, Sox-2 expression is decreased following overexpression of miR-145. Our recent studies further suggest that both miR-21 and miR-145 are regulated by the long non-coding RNA (lncRNA) CCAT2 (Colon Cancer Associated Transcript 2), which is known to be upregulated in CRC. This inference comes from the observation that down regulation of CCAT2 in colon cancer cells, which produces a marked 50% reduction in miR-21 expression, causes a 7-fold increase in miR-145 expression. In conclusion, our current observations suggest that miR-21 and miR-145, that are upregulated and downregulated, respectively, in the colonic mucosa during aging and CRC, play critical roles in regulating stemness in colon cancer cells. Both miR-21 and miR-145 are regulated by CCAT2.
Fikri Selcuk Simsek
Firat University, Turkey
Title: Can we use more accurate parameters than SUVmax in mediastinal nodal staging in NSCLC
Biography:
Fikri Selcuk Simsek graduated from EskiÅŸehir Osmangazi University Medicine faculty. He completed his Master’s from EskiÅŸehir Osmangazi University Medicine faculty (2005) and Doctorate from Eskisehir Osmangazi University Medicine faculty (2011). Presently, he is working as Assistant Professor in Nuclear Medicine Department at the Firat University.
Abstract:
Purpose: Mediastinal nodal staging (MNS) in NSCLC with FDG-PET/CT has been really problematic. For nodal staging, mostly SUVmax>2.5 or visual interpretation were used (in the past and now). But these parameters are insufficient and many patients go to invasive staging methods. We aimed determining 2 new parameters for MNS with FDG-PET/CT and targeted to reduce invasive methods.
Methods: Between 01/2013 to 12/2016, 27 patients underwent FDG-PET/CT before LN excision and histopathological examination. Total 113 LN were included in the study. Detailed reports of operation and pathology carefully examined, equivalent LN was found by re-examining PET/CT images with two nuclear medicine specialists. Decision was made with concensus.
Results: When cut-off LN SUVmax>2.5; SE, SP, PPV, NPV were 100%, %81.25, %68.8, %100 respectively; when cut-off >2.01 was taken for SUVmax LN/SUVmean Mediastinal Blood Pool (MBP) SE, SP, PPV, NPV and accuracy were 100%, 96.25%, 91.7%, 100% and 97.35%; when cut-off value was taken as >1.69 for SUVmax LN/SUVmean liver SE, SP, PPV, NPV and accuracy were found as 96.97%, 93.75%, 86.5%, 98.7% and 94.69%.
Conclusion: When 2.01 was used as a cut-off for SUVmax LN/SUVmean MBP and 1.69 for SUVmax LN/SUVmean liver were more useful than classic evaluation of MNS in PET/CT. These two parameters are compared first and are more useful. We think that if these parameters used for the evaluation of mediastinal lymph nodes in NSCLC, invasive procedures and morbidity maybe reduced, time and cost consumption maybe decreased; more accurate patient management can be achieved.
Rui Hou
Chinese Acadamy of Medical Science, China
Title: Animal and cellular models of hepatocellular carcinoma bone metastasis: Establishment and characterisation
Biography:
Rui Hou completed MD from Tongji Medical College, Huazhong University of Science of Technology. He is now an Attending Surgeon at Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences. He has published more than 10 papers in reputed journals and expertised in the field of General Surgery
and the Fundamental Research of Cancer Progression/Metastasis.
Abstract:
Background: An increasingly high occurrence of bone metastases in hepatocellular carcinoma (HCC) patients highlights the importance of fundamental research on HCC bone metastasis, which has been limited in its success due to the lack of a model system.
Purpose: The purpose of the study is the establishment of animal and cellular models of HCC bone metastasis and discovery of HCC bone metastasis-related ngenes.
Methods: Luciferase-transfected HCC cell lines HCCLM3, MHCC97H and SMMC-7721 were used to inoculate nude mice intracardially. Formation of bone metastases was examined by bioluminescence imaging, SPECT and pathology study. Metastatic cells in bone were isolated and subcultured. Differences between bone metastatic cells and their parental cells were studied by in vitro/in vivo assays.
Results: Mouse model of HCC bone metastasis was successfully established. Injected tumour cells formed metastases in the skull, the spine, the hind limbs, and the sternum, causing osteolytic lesions via act of MMP-1 and recruitment of osteoclasts. Four bone metastatic cell lines were extracted from HCCLM3-inoculated mice and were demonstrated to exhibit a much stronger ability to form bone metastases as well as other phenotypes, including enhanced in vitro migration/invasion and colony formation. Moreover, the expression of PTHrP, MMP-1, and CTGF was significantly elevated in bone metastatic cells compared to parental HCC cells.
Conclusion: The nude mouse model and bone metastatic cell lines together provide an effective simulation of HCC bone metastasis. This model system will become powerful tool with which to explore the mechanisms and therapies of HCC bone metastasis. Additionally, PTHrP, MMP-1, and CTGF are candidate genes related to HCC bone metastasis.
Manar Atoum
Hashemite university, Jordan
Title: Polymorphisms of leptin (-2548 G/A) and leptin receptor (Q223R) genes among jordanian breast cancer females
Biography:
Manar Atoum is a Professor in Molecular Genetics and is interested in Oncology and Gene Polymorphism. She has completed her Master’s from Yarmouk
University, Jordan in 1992 and Bachelor’s degree from Jordan University of Science and Technology.
Abstract:
Background: Breast cancer is the most common cancer among females. Breast cancer is curable during its early stages and is lethal during its late stages.
Aims: This study is aimed to assess the possible association of leptin levels with breast cancer risk, in addition to investigate the relationship between LEP (-2548 G/A) and LEPR (Q223R) polymorphism and breast cancer risk among Jordanian females.
Methods: A total of 60 blood samples collected from breast cancer patients were analyzed to identify; the serum level of leptin and leptin receptor related polymorphism. A total of 40 healthy females were enrolled as control group. Serum level of leptin was detected by enzyme-linked immunosorbent assay (ELISA), DNA from patients and control were amplified and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
Results: The distribution of the two polymorphisms in the studied population was consistent with the Hardy-Weinberg equilibrium. Leptin level was significantly lower in breast cancer patients compared to the controls (p=0.05).
Conclusion: Our results showed a significant association between low leptin levels in serum and Q223R polymorphism(in leptin receptor gene) with an increase of breast cancer risk. Moreover, no association was found between -2548 G/A polymorphism (in leptin gene) with breast cancer risk. Further studies with larger sample size are suggested.