Day 2 :
Keynote Forum
Syed Azizur Rahman
University of Sharjah, UAE
Keynote: Childhood cancer - A silent killer of children in low and middle-income countries
Time : 10:00-10:40
Biography:
Syed Azizur Rahman is currently working at University of Sharjah, UAE as a Chairman of the Health Services Administration Department. He had completed his PhD in 2001 from the London School of Hygiene and Tropical Medicine, University of London. He Prior to that, he worked for the London School of Hygiene and Tropical Medicine, Research Scientist at British Columbia Cancer agency, Canada and as Clinical Assistant Professor at University of British Columbia. He has published good number of papers in reputed journals and has been serving as an editorial board member of the Journal of Public Health Issues and Practice.
Abstract:
Childhood cancer is an emerging health challenge in many developing countries. Globally, an estimated 215,000 children of < 15 years and 85,000 adolescents of 15-19 develop cancer each year, and 80% of them live in developing countries. This population will exceed 90% in the next two decades due to an increasing size of the young population in favor of developing countries. Over 100,000 children die needlessly every year, most without any basic effective pain relief, undiagnosed, misdiagnosed, diagnosed too late or not treatment at all. If diagnosed at an early stage, and if treatment is available, most childhood cancers are highly curable. At least 50% of childhood cancer can be cured by simple treatments. The survival gap between rich and poor countries is widening. The reason is mainly due to the success of pediatric cancer therapy in developed countries. Diagnostic and treatment protocols, and high adherence rates in these countries improve childhood cancer survival by 75-80%. However, in low and middle-income countries (LMIC), children are not benefitting from these improvements. Largely, because of abandonment rates are high and there are limited supportive care services to prevent treatment related morbidity or mortality. High treatment cost is preventing families from receiving care, contributing low adherence rates. Due to non-availability of universal health coverage, over 20% of families had to stop treatment because they could not afford it. Where families are living on $2 a day, drugs costing $1 a day are not affordable. Forty-four percent of cancer-affected children in a LMIC die prematurely as their parents cannot afford the cost of treatment. Access to relatively low -cost oncology medicine, quality of drugs are also major issue. In parts of Africa and Asia, between 50-70% percent of imported medicines are declared to be ineffective, fake or counterfeit. Lack of awareness in low-income countries is an issue for the children’s cancer. Children who are diagnosed with cancer in LMIC countries are virtually given a death sentence. Social stigma, perception of
incurability- refusal, traditional healers, lack of trained staff, palliative, curative care are some major constraints to address childhood cancer in developing countries. There is an urgent need to establish diagnosis and treatment protocols, set-up registration mechanisms, create awareness, improve access to effective and affordable (cost-effective) medications, staff training, social infrastructure and most importantly to engage international communities to come and support the few/meagre efforts taking places in LMIC. Children have long been the focus of global health efforts, but childhood cancer has fallen through the cracks - even in WHO and UNICEF.
Break: Networking and Refreshments Break 10:40 -11:00 @ Foyer
- Organ Specific Cancers | Cancer Treatment & Therapies | Cancer Vaccines | Cancer Diagnosis & Diagnostics
Location: Olimpica 3+4
Chair
Oliver Micke
Franziskus Hospital Bielefeld, Germany
Co-Chair
Syed Azizur Rahman
University of Sharjah, UAE
Session Introduction
Karen A Beningo
Karen A Beningo
Title: The mechanical enhancement of cancer cell invasion
Biography:
Karen A Beningo received her PhD in Cell, Development and Neural Biology from the University of Michigan Medical School, Ann Arbor, MI USA. She completed her Post-doctoral studies with Dr. Yuli Wang at University of Massachusetts Medical School in Worcester, MA. She is currently an Associate Professor in the Department of Biological Sciences at Wayne State University and a Member of the Tumor Biology and Microenvironment subgroup of the Karmanos Cancer Institute. She has reviewed for numerous national cancer institute study sections, has authored 25 manuscripts and has received over 2800 citations.
Abstract:
The ability of a cell to invade surrounding tissues is an abnormal cellular process for most cells and is only acquired during the stages of tumor progression and metastasis. What initiates this dramatic change is not fully understood nor is the signals that guide the invasion process. This study has focused on the influence of mechanical cues from the environment that guide the invasive process. We have discovered number mechanical parameters, aside from environmental stiffness that can direct this cellular process. One surprising mechanical signal was the enhancement of invasion of fibrosarcoma cells 2-4 fold above normal levels by simply tugging on the extracellular matrix at magnitudes that mimic those of cellular movements made by fibroblasts within the ECM (Extra Cellular Matrix). We further identified genes that were differentially expressed upon receiving the mechanical cue. Of particular interest was the down-regulation of the beta3-integrin. We have further discovered that this mechanical signal results in the inactivation of PAK1 and the subsequent activation of cofilin, a key protein in the formationmof the invasive structures known as invadopodia. Through confocal microscopy we have determined that tugging on the ECM results in a maturation of invadopodia, as determined by elongation and proteolytic degradation of fluorescent ECM surrounding the invadopodia. In summary, we have identified that tugging on ECM fibers at magnitudes equivalent to a cell migrating or remodeling the microenvironment can elevate effective invasive behavior of highly invasive cancer cells.
Oliver Micke
Franziskus Hospital Bielefeld, Germany
Title: Re-irradiation in cancer - Can amifostine help us?
Biography:
Oliver Micke has completed his PhD from Muenster University Hospital in 2006. He is Head of the Department for Radiotherapy and Radiation Oncology at Franziskus Hospital Bielefeld since 2006. In addition, he is the Medical Director of Franziskus Hospital Bielefeld, a premier teaching hospital of the Medical University of Hanover (MHH). He has published more than 200 papers in reputed national and international journals and has been serving as Reviewer as well as an Editorial Board Member of repute.
Abstract:
A second irradiation course has been established for the treatment of recurrent head and neck cancer since more than 5 decades. 24-month survival rates are limited to 30-40%. Severe acute and late toxicities are observed in up to 50% of all treated patients. Does selective cytoprotection with amifostine offer a way to reduce the high toxicity profile? We reanalyzed the data of three earlier published mono-centric studies which had combined re-irradiation of a solid tumor with the application of 500 mg amifostine IV before daily radiotherapy. 42/53 patients received re-irradiation because of head and neck cancer disease. 11 have had other solid tumors (rectal cancer 5, cervical cancer 2, endometrial cancer 2, uterus sarcoma 1, and prostate cancer 1). All head and neck cancer patients received additional chemotherapy for radio-sensitizing. The therapy was possible in all patients without serious adverse events due to amifostine. The combination of chemo- and radiotherapy was possible in all treated patients. The total irradiation doses were >110 Gy for both courses. Acute mucosal and skin toxicities (mucositis, stomatitis, diarrhea, dermatitis, cystitits and proctitis) were reduced to grade 1 / 2 level in 49/53 patients. Grade 3
/4 toxicities were seen in only <10% (n=4). No objective data were available for late toxicities and survival. In conclusion, we suggest initiating new research on the combination of amifostine and re-irradiation of solid tumors. We await the reduction of acute toxicity and positive impact on late toxicity profile as well as effect of irradiation in this situation.
Biography:
Syed Azizur Rahman has completed his PhD in 2001 from the London School of Hygiene and Tropical Medicine, University of London. He is currently working at University of Sharjah, UAE as a Chairman of the Health Services Administration Department. Prior to that, he worked for the London School of Hygiene and Tropical Medicine, Research Scientist at British Columbia Cancer agency, Canada and as Clinical Assistant Professor at University of British Columbia. He has published good number of papers in reputed journals and has been serving as an editorial board member of the Journal of Public Health Issues and Practice.
Abstract:
Background: According to the World Health Organization, breast cancer is the most common cancer among women worldwide, claiming the lives of hundreds of thousands of women each year and affecting countries at all levels of modernization. Breast cancer is considered the most common cancer in the UAE. The average age of women who get breast cancer in the UAE is about 10 years younger than women in Europe and USA. Breast self-examination (BSE) is a screening technique that can be done at home which allows the woman to examine her breast tissue for any physical or visual changes.
Aim: This study aimed to assess the awareness of breast cancer and breast self-examination and practice among the female students at the University of Sharjah.
Method: A cross sectional study was conducted to explore the awareness level of breast cancer and breast self-examination and practice among the female students at the University of Sharjah. Data were organized and analyzed using Statistical Package for Social Sciences.
Results: The majority of the student has heard about breast cancer and breast self-examination. Social media is the main sources of information. Less than half of the participants have knowledge about the risk factor of breast cancer. Difference of knowledge on both the breast cancer and BSF were found among the student of three campuses. Only 28% of the participants perform breast self-examination. This finding suggests organizing comprehensive awareness program among the female student to reduce cancer episode in UAE.
Break: Lunch Break 13:15- 14:15@Hotel Restaurants
Mohammed Y Almaghrabi
King Abdullah Medical City, Saudi Arabia
Title: Holism and stereotactic body radiation therapy
Biography:
Mohammed Y Almaghrabi is a currently working as Radiation Oncologist at King Abdullah Medical City, Saudi Arabia. He is leading stereotactic radiosurgery/ stereotactic body radiation therapy task groups at the same hospital. He was Head of Radiation Oncology department at Prince Faisal Cancer Centre, Saudi Arabia. He has his research experience from University of Ottawa Canada and Nantes University, France. He has been a recipient of many awards and grants. He was selected as a Sectional Editor (Radiation Oncology, Biomarkers) for Journal of Cancer Treatment and Diagnosis, Reviewer for British Journal of Radiology and CARO annual scientific meeting. His research experience includes various programs, contributions and participation in different countries for diverse fields of study.
Abstract:
Holism is a new concept dealing with Stereotactic Body Radiation Therapy (SBRT) settings. SBRT experts concern with lessening organ toxicity. Use of DVH (dose-volume histogram) solely in SBRT treatment care plan/ protocols might cause grave consequences if other factors ignored. Correlation between specific injury and radiation dose is still uncertain. Sometimes there are discrepancies between studies in defining the injury. There is little known about most of the toxicity mechanisms. Use of biologically equivalent dose model is still controversial. It seems inevitable that SBRT delivery, patient factors (including comorbidities, patient's BMI, gender, habits, age, and ECOG PS score), tumor factors and treatment factors should carefully be examined.
Song Han
University of Florida, USA
Title: Stroma-derived extracellular vesicles deliver tumor-suppressive mi-RNAs to pancreatic cancer cells
Biography:
Song Han completed her MD in 1987 and PhD in 1996, both from Shanghai Jiao Tong University School of Medicine, China. She received Postdoctoral training (1996-2008) at Cardiff University, UK. She is currently a Research Faculty at the University of Florida. Her research interest includes the understanding and translational application of extracellular vesicle transporting microRNAs in the cross-talk between tumor-associated stroma (TAS) and cancer cells in pancreatic cancer tumor microenvironment. She has published more than 45 papers in reputed journals and has been serving as reviewer of several high-impact journals.
Abstract:
The biology of tumor-associated stroma (TAS) in pancreatic ductal adenocarcinoma (PDAC) is not well understood. The paradoxical observation that stroma-depletion strategies lead to progression of PDAC reinforced the need to critically evaluate the functional contribution of TAS in the initiation and progression of PDAC. PDAC and TAS cells are unique in their expression of specific miRNAs, and this specific miRNA expression pattern alters host to tumor microenvironment interactions. Using primary human pancreatic TAS cells and primary xenograft PDAC cells co-culture, we provided evidence of miRNA trafficking and exchanging between TAS and PDAC cells, in a two way, cell-contact independent fashion, via extracellular vesicles (EVs) transportation. Selective packaging of miRNAs into EVs led to enrichment of stromal specific miR-145 in EVs secreted by TAS cells. Highly-concentrated exosomes, but not micro-vesicles, derived from human TAS cells demonstrated a tumor suppressive role by inducing PDAC cell apoptosis. This effect was mitigated by anti-miR-145 sequences. Our data suggest that TAS-derived miRNAs are delivered to adjacent PDAC cells via exosomes and suppress tumor cell growth. These data highlight that TAS cells secrete exosomes carrying tumor suppressive genetic materials, a possible anti-tumor capacity. Future work of the development of patient-derived exosomes could have therapeutic implications for unresectable PDAC.
- Young Researchers Forum
Location: Olimpica 3+4
Session Introduction
Claudio Luchini
University and Hospital Trust of Verona, Italy
Title: New molecular insights of pancreatic ductal adenocarcinoma
Biography:
Claudio Luchini is a Surgical Pathologist with expertise in the field of next-generation sequencing and of systematic review with meta-analysis. He has studied at Verona University, Italy and then Indiana University, USA and Johns Hopkins University as Research Fellow. He has published his important works in Journal of Clinical Oncology and Cancer Cell. With the tool of meta-analysis, he has highlighted the prognostic role of important morphological and molecular alterations in cancer. The main goal of his research is to find morphological and molecular markers for early diagnosis of tumors or to better stratify cancer prognosis.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a high malignant neoplasm that will represent the second cause for cancer death in the next 20 years. Recent molecular studies have better clarified its complex genetic landscape. However, many mechanisms of tumorigenesis of such tumor remain still unclear and of difficult comprehension. The study of peculiar variants of this tumor type may help in the comprehension of the biology of PDAC. To this aim, we have studied with immunohistochemistry, FISH (Fluorescent in situ hybridization) analysis and whole-exome sequencing the rare PDAC variant named undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC). Firstly, we observed some clinical and prognostic peculiarities in this PDAC variant. Then we report strikingly molecular similarities of UCOGC to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS, and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. Lastly, we describe a new potential PDAC driver gene which we found in 25% of UCOGC studied with whole-exome sequencing: the SERPINA3 gene.
Carla Lettieri
University Federal Fluminense, Brazil
Title: Is universal and quality cancer treatment a human right?
Biography:
Carla Lettieri is a PhD student of Law and Sociology at University Federal Fluminense and completed her Master’s degree in International Relations at Pontifícia Universidade Católica do Rio de Janeiro- PUC-Rio. She works as Program Coordinator at Instituto Ronald McDonald which, among other actions, advocates for the right of children with cancer to have access to free, universal treatment with the highest quality as possible.
Abstract:
This paper aims at discussing the access to cancer treatment through the less of the International Covenant on Human Rights and answering to the question: Is free, universal and quality treatment considered a human right? And if so, how it could be implemented? The Universal Declaration of Human Rights states in the article 25 that everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control. Cancer can affect any person indistinctly, but obviously, not every person has the same capability to pursue the cure and quality of life. The global epidemiology of cancer demonstrates that not every human being have access to cancer treatment. In fact, according to the World Health Organization, even though Cancer is the second leading cause of death globally and was responsible for 8.8 million deaths in 2015, 70% of them occurred in low- and middle-income countries. Many factors contribute to the number of deaths: late diagnosis, unavailability of hospitals, the quality of the hospitals available, presence of behavioral or environmental risks, among others. The consequences of the disease are severe not only for the patients, but also for their families and society. According to the World Cancer Report 2014, the economic impact of cancer is significant and increasing. The economic losses of the cancer were estimated in U$ 1.6 billion in 2010. In this scenario, is there any space for an International Covenant on the Rights of Persons with Cancer?
Break: Networking and Refreshments Break 15:55-16:15 @ Foyer
M N Vidanapathirana
University of Colombo, Sri Lanka
Title: Documentation in palliative care: Audit on completeness of medical records at a palliative care setting in Sri Lanka
Biography:
M N Vidanapathirana is a final year medical student currently studying at Faculty of Medicine, University of Colombo. She has completed internships at World Bank Sri Lanka(Health Sector) and Doctors of the World(Médecins du Monde), a French NGO. Her research interests include palliative care, oncology and endocrinology.
Abstract:
Introduction & Aim: Medical documentation in palliative care is important for information dissemination within the multidisciplinary team and for medico-legal purposes. This study aimed to assess the completeness of the ‘Patient Assessment Form’ (PAF) within two timeframes at the Palliative Care Clinic, Maharagama and compare them for differences in completeness. Methods: This study was a retrospective internal desk research. All PAFs stored in the clinic were reviewed for two timeframes, which were the first four months since starting the clinic (September-December 2015) and the last four months prior to data collection (October 2016 -January 2017). Data analysis was done with SPSS 23 using descriptive statistics.
Results: There were 56 and 42 PAFs for the two timeframes, respectively. In both timeframes, only clinic number showed 100% documentation. In the first timeframe, age (94.6%) was the best documented and psychosocial section was the most poorly documented (48.2%). Reason for referral (55.4%), presenting conditions (60.7%) and problems (73.2%) were inadequately documented. For the second-time frame, primary diagnosis was the best recorded (97.6%) while site of metastases was the worst (59.5%). Documentation of presenting conditions (73.8%) and treatment plan (69%) were insufficient. There was no improvement in overall documentation of PAF with time (p=0.061). However, significant improvements were noted in the documentation of religion (p=0.007) and caregiver information (p=0.002). No difference in documentation between medical and nursing officers was seen for either timeframe (p=0.243, p=0.082).
Conclusions: Documentation in the PAF is incomplete. Training health personnel in this regard would improve documentation and care provision.
Perla Pérez Treviño
Tecnologico de Monterrey (ITESM), Mexico
Title: 3D imaging detection method of HER2: Application of dual conjugated affibody-quantum dots probes and ratiometric analysis
Biography:
Perla Pérez-Treviño is a PhD student in Biotechnology from the Tecnologico de Monterrey (ITESM), Mexico. Since 2012 to the present, she has been working as Research Assistant at Institute of Cardiology and Vascular Medicine, Zambrano-Hellion Hospital, School of Medicine, ITESM. She has published two papers as first author in important peer reviewed journals and two more that are in revision. Her work is focused in the study of molecular and microstructural cell alterations during various chronic pathologies, and currently, she is working in assessing the expression of biomarkers in 3D models of cancer cells growth and tumors.
Abstract:
HER2 overexpression is associated with Breast Cancer (BC) poor prognosis, due to increased metastases and angiogenesis, and decreased apoptosis. HER2 is commonly assessed by immunohistochemistry. Technique that requires extensive sample processing to get thin fixed samples (3-5 ïm) that are analyzed using standard HER2 detection probes, and subjective algorithms for HER2 interpretation. Consequently, lacks accuracy and reproducibility, and could lead to misdiagnosis. Therefore, we developed a 3D imaging detection method of HER2 using affibody molecules conjugated with quantum dots (Aff QDs) and ratiometric analysis (RMA). Affibody anti-HER2 and affibody negative control were conjugated by the maleimide reaction with QD605 and QD545, respectively. Fixed HER2+ and HER2-BC spheroids were incubated with a mixture (1:1) of both Aff- QDs, and confocal image stacks were recorded in the z-axis. Images were processed by RMA (AffantiHER2 QD605/Affneg- D545 fluorescence), to assess the specific HER2 signal. We found that the non-specific accumulation for both Aff-QDs was the same within HER2-spheroids. However, the AffantiHER2-QD605 signal in HER2+ spheroids, was significantly higher (5.910.81 F/F0) than that of Affneg-QD545 (2.670.56 F/F0, p<0.05) and was optimally resolved up to 50 depth. After RMA, non-specific signals were removed in HER2+ and HER2- spheroids, and no false HER2 signal was found. Therefore, Aff-QDs can efficiently penetrate in spheroids, used as 3D BC models, with minimal sample manipulation; after RMA, specific and objective 3D HER2 result can be obtained. The method proposed here, could reduce the typical problems associated with traditional immunohistochemistry and improves HER2 detection by 3D analysis.
D M Gomez
University of Colombo , Sri Lanka
Title: Temporal trends in patient characteristics and treatment at a palliative care setting, Sri Lanka
Biography:
D M Gomez is a final year undergraduate at the Faculty of Medicine, University of Colombo, Sri Lanka’s most elite medical school. He has so far performed excellently, being awarded first class honors in the basic and applied sciences streams. A six week elective he did on palliative care, along with his internship at
‘Medecins du Monde’(Doctors of the World) inspired him and has sparked a flame for research on the topic.
Abstract:
Introduction & Aim: Palliative needs of cancer patients in Sri Lanka remain unclear. Aim of this study is to identify the temporal trends in patient characteristics and treatment at a main palliative care setting in Sri Lanka.
Methodology: This was a retrospective study conducted at the Palliative Care Clinic, National Cancer Institute Maharagama. All Patient Assessment Forms (PAFs) in the clinic were reviewed for two timeframes i.e. the first four months since starting the clinic (September-December 2015) and the last four months prior to data collection (October 2016 -January 2017). An expertdeveloped audit tool was used and trends evaluated under four thematic areas: socio demographic characteristics, disease characteristics, palliative-care problems and treatment.
Results: There were 56 and 42 PAFs for the two timeframes, respectively. The median age of patients seeking palliative care increased from 55 to 58.5 years. Presentation of unmarried individuals (p=0.044) without caregivers (p=0.002) for care decreased significantly with time. The most common cancers in the first timeframe were upper gastrointestinal (17.9%) and oro-pharyngeal carcinoma (12.5%) and those in the second timeframe were oro-pharyngeal (33.3%) and lung carcinoma (14.3%). Most patients at presentation for palliative care had metastasis in both timelines. Over time, pain increased as a presenting complaint (p=0.039). Other physical problems (p=0.039) and social problems (p=0.011) were also more frequently identified. Treatment-wise, symptom control was the most frequent problem addressed in both timeframes, however, there was a temporal improvement in the address of financial problems (p=0.008).
Conclusions: In patients presenting for palliative care, significant time trends were identified in all four thematic areas. These trends require consideration when refining palliative care services..
- Surgical Oncology | Cancer Treatment & Therapies | Organ Specific Cancers
Location: Olimpica 3+4
Session Introduction
Monica Rizzo
Emory University School of Medicine, USA
Title: Single incision for early stage breast cancer: A minimally invasive approach
Biography:
Monica Rizzo is an Associate Professor of Surgery at Emory University School of Medicine. She is Board Certified by the American College of Surgeons. She did her Surgical Oncology Fellowship at Emory University. She is an academic surgeon and her clinical expertise includes the surgical treatment of breast cancer, melanoma, and soft tissue sarcoma. As a researcher, she has published more than 50 research articles in peer reviewed journals. She is currently serving at many international committees. She is the Chair of the Society of Surgical Oncology Disparity Committee.
Abstract:
Breast conserving surgery (BCS) with sentinel lymph node (SLN) biopsy is standard of care for the treatment of early stage breast cancers. The use of a minimally-invasive single incision has not been rigorously compared to multi-incision traditional approach. A tertiary surgical oncology database was retrospectively reviewed over two years study period. The single incision approach used one incision to resect the tumor and the Lymphazurin-tagged axillary SLNs. The multi-incision group used a breast and a separate axillary incision. Patient satisfaction was collected in the first postoperative visit and documented as excellent, good and poor. BCS-SLN accounted for 110 patients with median age 63 years, with 64 (58%) cancers occurring in the upper outer quadrant (UOQ). There were 48 patients in the single incision group. A single incision approach was used in 41 (64%) of UOQ cancers (p<0.001), with a median of two SLNs. The single-incision approach showed no difference in percentage of biopsy clip removal or frequency of tumor-free margins and did not prolong operative time. Overall, eight patients (7.2%) had positive margins; seven underwent to re-excision and no residual disease was found, one patient refused additional surgery. Patient satisfaction was excellent in all patients treated with a single incision. There were no differences in complications or reoperations in the two groups. This study demonstrates that the single incision approach for BCS-SLN is safe and effective. This technique should be considered for upper outer quadrant breast cancers, and has the potential to improve patient satisfaction and cosmetic results.
Break: Networking and Refreshments Break 10:30 -10:50 @ Foyer
Javier Camacho
CINVESTAV, Mexico
Title: Calcium-activated potassium channels as potential early markers of cervical cancer
Biography:
Javier Camacho has studied ion channels involved in cancer for almost 20 years. Several patents have been filed based on the findings of his group. He focuses his research in finding early tumor markers and novel therapeutic targets for cervical, liver and lung cancer. He studies ion channel gene and protein expression in human cell lines, in vivo cancer models and human biopsies. His group also investigates the effect of ion channel blockers on the proliferation of human cell lines and primary cultures from human biopsies, and the preventive and therapeutic effect of such blockers on tumor development in vivo.
Abstract:
Cervical cancer is a major cause of cancer death in women in developing countries. Thus, novel early markers and therapeutic targets are urgently needed. Ion channels have gained great interest as tumor markers for different malignancies including cervical cancer. Actually, some years ago, we suggested Kv10.1 channels as cervical cancer early markers. Here, we studied the expression of another potassium channel, namely, the calcium-activated potassium channel KCa1.1 (KCNMA1) in cervical cancer models. Transgenic mice expressing the E7 oncogene of human papilloma virus and non-transgenic mice were treated with estradiol pellets during three or six months to induce cervical lesions. Human biopsies from patients with either noncancerous, low- or high-grade intra-epithelium lesions or cervical cancer were also studied. mRNA and protein expression were studied by real-time RT-PCR and immunochemistry, respectively. Cervical dysplasia and cervical cancer were observed only in the transgenic mice treated with estradiol for three and six months, respectively. Estradiol treatment increased KCa1.1 mRNA and protein expression in both transgenic and non-transgenic mice. However, the highest levels were observed in the transgenic mice with cervical cancer. Human biopsies form non-cancerous cervix did not display KCa1.1 protein expression. However, increased KCa1.1 protein expression was observed in the rest of the human biopsies, we observed that the higher the grade of the lesion, the stronger the KCa1.1 immuno staining. These results suggest KCa1.1 channels as potential early cervical cancer markers.
Kamran Mansouri
Kermanshah University of Medical Sciences, Iran
Title: L-arginine/5-FU combination treatment discriminates for a good cause: Rescuing the normal cells while killing cancerous ones
Biography:
Kamran Mansouri completed his PhD at Tehran University of Medical Sciences, Iran. He is the Head of Department of Molecular Medicine at Kermanshah University of Medical Sciences, Iran. He has published more than 50 papers in reputed journals.
Abstract:
In breast cancer therapy, where reducing the adverse effects of chemotherapy is a determinant factor of success especially during pregnancy, modulatory effect of L-arginine on various cancers is still a controversial issue. Therefore, the present study aims to determine the effect of L-arginine combination with 5 fluorouracil (5-FU) on normal and cancer cells. The primary human umbilical vein endothelial cells (HUVECs) and human breast cancer cell line (BT-20) were treated with L-arginine/5- FU to study their effect on cell survival, NO concentration, and glycolytic activity. Moreover, using molecular docking study, L-arginine effect on glycolysis enzymes activity was evaluated. L arginine/5-FU effect on angiogenesis was also assessed in vitro and in vivo. Furthermore, L-arginine effect on 5-FU toxicity was assessed by measuring embryo weight. Real-time PCR and zymography were used to evaluate VEGF and MMP2, 9 expression and enzyme activities, respectively. L-arginine/5-FU combination treatment carried out on the primary human umbilical vein endothelial cells (HUVECs) increased cells survival while induced cell death in BT-20. Nitric oxide (NO) concentration assays in both cell lines was showed to be increased. An inhibitory effect of L-arginine on glycolysis enzyme, human glucokinase (HG) was affirmed through molecular docking study and further supported by glycolysis experiment showing glucose and lactate levels decrease in cancer cells but not in normal cells. Angiogenesis induction in HUVECs was confirmed through VEGF and MMP-2, 9 up-regulated gene expressions and increased MMP-2, 9 activities. However, a down-regulation of the above mentioned genes expression was observed in BT- 20 treated with each drug alone and in combination. Furthermore, an in vivo increased angiogenesis and decreased embryo toxicity was observed under the treatment with the combination of the drugs. Altogether, findings speculate that L arginine inhibits cell death induced by 5-FU in normal cells by attenuating the adverse effects of 5-FU, while it doesn’t do so in cancer cells (BT-20).
Elie Hadchity
Lebanese University, Lebanon
Title: Kruppel like factor 4 and Heat Shock Protein 27: Potential biomarkers for lung and larynx cancers
Biography:
Elie Hadchity has completed his PhD from Claude Bernard University Lyon, France. He is a Professor at Faculty of Sciences and the Faculty of Medicine of the Lebanese University. He leads a Research team Antitumor Therapeutic Targeting, and his research work focused on the identification of novel therapeutic targets and novel biomarkers. He has several papers in reputed journals and an International Patent.
Abstract:
Lung and larynx cancers are among the prevalent human cancers worldwide and no molecular markers are presently used for predicting prognosis in these cancers. Late detection and lack of standard treatment strategies result in high levels of mortality and poor prognosis. Prognostic stratification of larynx cancer patients based on molecular prognostic tumor biomarkers may lead to more efficient clinical management. Krüppel like factor 4 (KLF4) and Heat Shock Protein 27 (HSP27) are implied in tumorigenesis and are considered promising candidate biomarkers for various cancers. However, their role in larynx and lung carcinomas remains to be elucidated. Immunohistochemical and reverse transcription-polymerase chain reaction analyses in larynx and lung cancer tissue samples and normal tissue samples revealed a differential expression of KLF4 and HSP27 between normal and tumor tissues. KLF4 was significantly decreased in larynx carcinoma compared with normal tissue, whereas HSP27 was significantly overexpressed in tumor tissues compared with normal tissues, at the protein and mRNA levels. The KLF4 expression decreased gradually with tumor progression whereas HSP27 expression increased. In lung cancer, a significant decrease of KLF4 expression was observed in the Non-Small-Cell Lung-Carcinoma (NSCLC) when compared to normal tissue, while a significant over-expression was detected in the Small Cell-Lung-Carcinoma (SCLC). KLF4 and HSP27 exhibit opposite functions and roles in the carcinogenic process. Their role in larynx or lung cancer initiation and progression highlights their use as potential future targets for prognosis and treatment. KLF4 and HSP27 expression levels may act as potential biomarkers in patients with larynx and lung cancers.
Hana Tomaskova
University of Ostrava, Czech Republic
Title: Cancer incidence in Czech black coal miners in association with coalworkers´ pneumoconiosis in the period 1992-2013
Biography:
Hana Tomášková graduated Technical University and she has completed her PhD at Medical Faculty, University of Plucky, Czech Republic in the Hygiene, preventive medicine and epidemiology. She is working as a biostatistician and epidemiologist at the Institute of Public Health in Ostrava, and as a lecturer at Department of Epidemiology and Public Health, Medical Faculty, Ostrava University. She is involved in occupational and environmental epidemiology. She has published more than 20 papers in ISI journals. She has served as a Research Team Member in two International Projects and 15 National Projects.
Abstract:
The aim of the study was comparison of cancer incidence risk of lungs, stomach, colon, bladder and kidney in ex-miners of black-coal mines and the general male population of the Czech Republic. Two cohorts of ex-miners according presence of coal workers´ pneumoconiosis (CWP) were analyzed. The first cohort included the miners without CWP (N=6,687) and the second cohort included the miners who were compensated for CWP (N=3,476). Personal and occupational data was merged with the data in the National Population Register and the National Oncological Register for the period from 1992 to 2013. Cancer risk in miners in comparison with the general male population of the Czech Republic was evaluated by SIR (Standardized Incidence Ratio) and 95% confidence interval (CI). About twice as high risk of lung cancer was found in miners with CWP (SIR=2.01; 95% CI 1.70–2.36). Lung cancer risk correlated with the severity of CWP (simple CWP SIR=1.99; 95% CI 1.64–2.38, progressive massive fibrosis SIR=3.18; 95% CI 1.79–5.09). No increased risk of lung cancer was found in the exminers without CWP. The risk of malignant neoplasm at the other selected sites was comparable with the risk in general male population of the Czech Republic. This study found increased lung cancer risk in coal miners with CWP, but not without CWP, comparing with the general population. These results confirmed previous analysis that was a basis for the inclusion of lung cancer in association with CWP into a new Czech list of occupational diseases.
Break: Networking & Lunch 12:50-13:50 @ Hotel Restaurant
- Poster Presentation Slot I
Location: Meeting Halls
Session Introduction
Sarah Konrad
German Cancer Consortium(DKTK), Germany
Title: A specific neuronal calcium sensor protein as potential predictive biomarker for ovarian cancer therapy
Biography:
Sarah Konrad has completed her MSc in Chemistry from the Technical University of Munich (TUM) in 2014. She is now a PhD student of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and is conducting her PhD in the Department of Gynecological Tumor Genetics (Prof. Alfons Meindl/ Dr. Juliane Ramser) at the Technische Universität München (TUM). Her project focuses on identifying and functionally characterizing new prognostic and therapyrelevant biomarkers for personalized ovarian cancer therapy.
Abstract:
Sporadic ovarian cancer has the highest relative mortality among gynecological cancers as approximately 75% of patients are diagnosed at an advanced stage, resulting in poor overall survival. To improve patient’s outcome targeted therapy strategies are required urgently. In search of new biomarkers for personalized therapies, we recently identified a gene encoding a specific neuronal calcium sensor (NCS). The NCS-family is known to be involved in calcium-signaling on membranes and functions as a calcium dependent molecular switch. We demonstrated that its expression, analyzed on mRNA as well as on protein level, was significantly associated with patient survival. Moreover, the putative biomarker persisted also as a significant factor for OS (p=0.008) and RFS (p=0.014) in multivariable analyses. As little is known about the involvement of the protein in cancer, we established stable knock-downs in ovarian cancer cell lines to explore the effect of its expression on cancer cell viability and migration. Most strikingly, the knock-down cells reacted significantly less sensitive to cisplatin treatment as compared to the control cells. This effect was further investigated using different cisplatin concentrations and treatment durations. The differences were reproducible and remained significant. Since platinum-based therapy represents the “gold standard” in ovarian cancer treatment, we postulate a predictive potential of our candidate to select patients that most probably benefit from platinum-based treatment from patients which will likely not have a benefit.
Hongyu Han
Sun Yat-sen University Cancer Center, China
Title: Regulation of TP63α/sonic hedgehog axis in n-dimethylnitrosamine-induced liver cancer stem cells
Biography:
Hongyu Han has completed her PhD from Sun Yat-sen University Cancer Center in 2010. She was a research scientist in University of Pennsylvania and Fox
Chase Cancer Center during 2014-2016. Currently, she is a Scientist in the Department of Nutrition in Sun Yat-sen University Cancer Center. Her research interests focus on the effects and mechanisms of dietary factors and cancer development. She has published more than 10 papers in reputed journals.
Abstract:
Nitroso-compounds are critical dietary risk factor of liver cancer. Cancer stem cells (CSCs) play a significant role in the formation and development of cancer. To date, the action of nitroso-compounds on the induction of liver CSCs as well as the underlying mechanisms has not been defined. In the present study, we revealed that chronic N-nitroso dimethylamine (NDMA) exposure induced malignant transformation of human normal liver cells. We further showed that NDMA-induced malignant transformed liver cells exhibited CSCs properties, as evidenced by increased sphere formation capacity in serumfree- medium culture, dramatically elevated expression of liver CSCs markers and increased number of CD133+ cells, along with upregulation of TAp63α, downregulation of ΔNp63α, and activation of Sonic Hedgehog pathway. Moreover, we illustrated that suppression of Sonic Hedgehog activity inhibited NDMA-induced liver CSCs properties; over expression of TAp63α activated Sonic Hedgehog pathway and promoted liver CSCs activity, whereas down expression of TAp63α inhibited Sonic Hedgehog and suppressed liver CSCs; an opposite action of ΔNp63α on Sonic Hedgehog pathway and liver CSCs was demonstrated. Taken together, our data suggested for the first time the vital role of TP63α/Sonic Hedgehog axis in regulating NDMA-induced liver CSCs, and thus could provide new insights into the molecular mechanisms of liver carcinogenesis as well as its target intervention.
Caiyun Zhong
Nanjing Medical University, China
Title: Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/β-catenin pathway
Biography:
Caiyun Zhong has completed his PhD from University of California, Davis, USA in 2005 and received Diplomate of the American Board of Toxicology (DABT) in
2010. He is the Director and Professor of the Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University. He has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of journals.
Abstract:
Cancer stem cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for adjuvant therapy to prevent the progression of cancer and prolong life. Phenethyl isothiocyanate (PEITC), the major active component from cruciferous vegetables, exhibits inspiring interventional effects in various human cancers. However, the effects of PEITC on colorectal CSCs and the underlying mechanisms remain unclear. The present study examined the inhibitory effects of PEITC on CSC-like properties in colorectal cancer spheroids. We revealed that PEITC inhibited the spheroid formation capacity of colorectal cancer cells as well as the expression of colorectal CSCs markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that PEITC down-regulated the activation of Wnt/β-catenin pathway, whereas up-regulation of Wnt/β-catenin diminished the inhibitory effects of PEITC on colorectal CSCs. Taken together, this study suggests that PEITC can be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.
Denise C Arruda
1Universidades de Mogi das Cruzes, Brazil
Title: HuAL1 peptide from complementarity-determining region 1 (CDR-1) of mAb HuA induces necroptosis in B16F10-Nex2 cells
Biography:
Denise C Arruda is graduated in Pharmacy from the Federal University of Santa Catarina in 2000. She pursued PhD in Biology Sciences from University of São Paulo (ICB-USP) with postdoctoral degree at the Experimental Oncology Unit - Discipline of Cell Biology, Federal University of São Paulo from 2008-2014. Currently, she is a professor and researcher at the Integrated Nucleus of Biotechnology at University of Mogi das Cruzes. She has published 17 papers in reputed journals, some of them in collaboration with international research groups, and received awards for poster presentation in five international meetings.
Abstract:
Treatment of melanoma, mainly on the metastatic stage, is a great clinical challenge because conventional chemotherapy is rather ineffective. Other strategies, including immunotherapy, have been introduced and are very encouraging. We have previously shown that peptides derived from complementarity determining regions of immunoglobulins (CDRs) display antimicrobial and antitumor activities regardless of the specificity of the antibodies they were derived from. In the present study, we show that CDR 1 from the light chain (L1) of a human IgM, mAb (HuA), specific for difucosyl human blood group A (HuA) induces necroptotic cell death in the murine melanoma cell line B16F10-Nex2 and in other murine and human tumor cell lines. HuAL1 did not exert cytotoxic effects in non-tumorigenic cell lines. Melanoma cells treated with HuAL1 showed DNA degradation, propidium iodide incorporation and abundant superoxide anion production. Moreover, peptide treatment induced mitochondrial swelling and disruption of mitochondrial cristae. All these effects were caspaseindependent and RIPK1- and MLKL-dependent, since cell death was abolished when cells were co-incubated with necrostatin or necrosulfonamide. Confocal microscopy showed that HuAL1 peptide localizes to the cell nucleus, and ELISA assay showed that it probably binds to H3 histone. We propose that necroptosis is induced after chromatin disorganization upon peptide binding to histone. Our results show, for the first time, that a peptide derived from an Ig-CDR can induce necroptotic cell death on tumor cells.
Adriana Camargo Ferrasi
São Paulo State University, Brazil
Title: Genetic variations of interleukin 28B (IL28B) in meningioma
Biography:
Adriana Camargo Ferrasi has completed her PhD from São Paulo State University - Institute of Biosciences and Post-doctoral studies from São Paulo State University - Botucatu Medical School. She is a Permanent Professor of the Post-Graduation Program (Stricto sensu) in Medical Biotechnology of São Paulo State University (UNESP) and Titular Professor in Paulista University (UNIP). She works in the area of molecular biology applied to cancer studies.
Abstract:
Meningioma is the most common tumor of the central nervous system and despite of their benign characteristic and slow growth, they frequently recur after surgical removal. Interleukin 28B seems to be involved in antiviral and antitumor immune response. Recently, IL28B rs12979860 C/T polymorphism was associated with outcome of treatment with IFNα and ribavirin in patients with Hepatitis C virus. Also, patients with CC genotype have higher chances of viral depuration than those with other genotypes. However, there are few data on this polymorphism in tumors, especially in meningioma. Thus, the aim of this study was to analyze allele and genotype frequencies of this polymorphism in patients affected by meningioma and healthy individuals (control) and to sequencing IL28b gene, searching for novel genetic variations. Sixty patients treated by UNESP Neurosurgery Service were included in this study. The Research Ethics Committee approved this study and each subject signed an informed consent form before tissue was obtained. Analysis of rs12979860 C/T polymorphism was performed by PCR-RFLP (PCR - Restriction Fragment Length Polymorphism) and the complete sequencing of the IL28B gene was performed by Sanger Sequencing Capillary Electrophoresis (Applied Biosystems™). The present study showed unpublished results that evidenced a greater frequency of TT genotype in the meningioma patients when compared to healthy individuals. Novel genetic variations (missense and silent) were detected in IL28B gene and only three have been reported in the scientific literature, but not in tumor samples. Amino acids exchanged as consequence of the missense variations are located mainly in the binding domains of IL28B protein to its receptor, reinforcing the probable importance of these alterations in protein function. These results suggest that IL28B protein and its geneticvariations may participate in the molecular mechanisms of meningioma.
Vasileios L Tzounakas
National & Kapodistrian University of Athens (NKUA), Greece
Title: The effect of sex in the storage capacity of red blood cell concentrates in CPD/SAGM
Biography:
Vasileios L. Tzounakas is a Post-doctoral researcher at the Department of Biology (Section of Cell Biology & Biophysics) of the National and Kapodistrian University of Athens (NKUA). He has obtained Ph.D. in Cell Biology. He has served as reviewer in international journals while his main research interests include blood transfusion biology (mainly, red blood cell storage lesion in blood products used for transfusion), erythrocyte biology in health and disease and the study of extracellular vesicles. He has expertise in evaluating the key parameters that affect storage lesion and post-transfusion performance of red blood cells and in the management of blood supplies in a way that will lead to the individualization of transfusion therapy. In this context, he has focused on the elucidation of storagelesion’s features that may serve as a donor’s signature, namely ‘the donor variation effect’.
Abstract:
Statement of the Problem: Red blood cells (RBCs) are the most frequently transfused blood labile product. The “Donorvariation effect”, which refers to donor-to-donor differences observed in both blood storage quality and 24h recovery, is probably a key factor in the efficiency of transfusion therapy. Donor variation effect may be associated with genetically determined features of RBCs and plasma. The aim of this study was to examine whether thedonor’s sex may independently affect the storage capacity of donated RBCs.
Methodology & Theoretical Orientation: For this purpose, 14 leukoreduced units of RBC concentrates in CPD/SAGM (7 male–7 female) were stored for 42 days at 4-6oC. Several parameters of storage quality (including hemolysis, redox status etc) were examined before and throughout the storage period. SPSS was used for statistical analysis of the results.
Findings: In-bag hemolysis, as well as osmotic and mechanical hemolysis, and intracellular calcium indexes were equally low in both groups during the whole period of storage. On the contrary, redox status markers such as total and uric acid dependent antioxidant capacity of the supernatant were significantly higher in male donors’ units (p<0.01). In the same group of donors, intracellular ROS accumulation was higher during the first two weeks of storage (p<0.05), while exogenously stimulated ROS production was higher after the middle of the storage period (797±220 vs 504±48 RFU, p<0.05).
Conclusion & Significance: Donor’s sex does not seem to affect the hemolytic parameters of the leukoreduced RBC units under storage in CPD/SAGM. Male sex is rather associated with better extracellular antioxidant activity, but worse intracellular redox status and increased susceptibility to exogenous oxidative stimuli. Sex may represent a genetic variant that affects some aspects
of the RBC storage lesion.
This study was supported by “IKY FELLOWSHIPS OF EXCELLENCE FOR POSTGRADUATESTUDIES IN GREECE – SIEMENS PROGRAM” to Vasileios Tzounakas.
Chiara Ruggirello
Leipzig University, Germany
Title: Shuttle system for hyperthermia tumor treatment
Biography:
Chiara Ruggirello has completed her Master’s Degree in Medical Veterinary and Pharmaceutical Biotechnologies from Parma University. She did her Master´s
thesis at the Technical University of Denmark (DTU) of Copenhagen, in Nanotechnologies. She started her PhD last October at Leipzig University at the Department of Biochemistry.
Abstract:
Nowadays cancer is one of the leading causes of death in Europe. Major challenges in the management of the disease are due to the lack of agents used for early diagnosis and associated with severe and often therapy-limiting side effects. Although chemotherapeutics can kill neoplastic cells, they also will induce toxicity in non-neoplastic tissues. Therefore, new approaches are necessary with the purpose of optimizing anticancer therapy. Among new experimental approaches, the magnetic particle hyperthermia has been suggested. Hyperthermia, as anticancer therapy, has been proposed since the 1970s, but it has still not established in clinical routine owing to the inability in focusing the heat only to the intended region without damaging the surrounding healthy tissue. By contrast, the so-called magnetic particle hyperthermia has the potential to address this shortcoming. Magnetic nanoparticles (NPs) may be made to accumulate exclusively in tumor tissue. Nevertheless, the only use of NPs is not enough for reducing side effects, they could in fact distribute randomly in the body, causing several adverse effects to non-neoplastic tissues. To develop directed particles, the NP have been coated with peptides, known to deliver the NP to cancer cells selectively. These magnetic NPs, when exposed to Alternating Magnetic Fields (AMF), can generate heat due to hysteresis loss. This behavior may be exploited for treating cancer, revolutionizing the existing hyperthermia procedures. Cancer cells when exposed to elevated temperatures are more sensible to chemotherapeutics and radiations, therefore, hyperthermia can also be associated to chemotherapy and radiotherapy boosting their effect.
Biography:
Esma Oguz has completed his/her Bachelor of Nutrition and Dietetic from Yeditepe University and is currently enrolled in the master’s programme at the Departmant of Nutrition and Dietetic, Marmara University. He/She is also Research Assistant at the same university.
Abstract:
Colorectal cancer (CRC) is one of the most common types of cancer and the fourth leading cancer deaths all around the world. Many risk factors such as tobacco and alcohol consumption, over consumption of red and processed meat, age, physical activity, body weight, diet, inflammatory bowel disease, obesity and diabetes are associated with colorectal cancer. Another factor in the development of colorectal cancer is microbiota. Microbiota consist of bacteria, viruses, fungi and parasites that colonize the gastrointestinal tract from the mouth to the colon. Microbiota influences physiological functions from the maintenance of barrier homeostasis locally to metabolism, haematopoiesis, inflammation, immunity and other functions systemically. The composition of microbiota is related to various diseases such as cancer, non alcoholic fatty liver disease, obesity. Studies show that microbiota plays a role in the etiology of various types of cancer by affecting inflammation, DNA damage and apoptosis. Microbiota has a great influence on immune responses and chronic inflammation is a known risk factor for colorectal cancer. Colon mucosa is constantly exposed to intestinal microbiota and its metabolites, it has the potential of continuous low-grade inflammation with bacterial stimulation of immune responses. Gut dysbiosis is largely associated with direct hostility to colonic cancer or metabolic change. Studies show that various bacterial species include the pathogenesis of CRC. Functional different bacterial species are involved in tumor microbiology during tumorigenesis. For example, some potential pro-oncogenic pathogens such as enterotoxigenic B. Fragilis and Escherichia-Shigella may induce tumor formation. The tumor cells are located in the nucleus of the immune cells, which serve both the pro- and antitumor immunity and can be shaped by the resident microbiota even after progression to the CRC. Microbiota, immune system, and CRC are multifactorial associations that should deeply consider.
Denise C Arruda
Universidade de Mogi das Cruzes, Brazil
Title: Peptide R18H from Brn-2 transcription factor POU domain displays anti-melanoma activity in vitro and in vivo
Biography:
Denise C Arruda is graduated in Pharmacy from the Federal University of Santa Catarina in 2000. She pursued PhD in Biology Sciences from University of São Paulo (ICB-USP) with postdoctoral degree at the Experimental Oncology Unit - Discipline of Cell Biology, Federal University of São Paulo from 2008-2014. Currently, she is a professor and researcher at the Integrated Nucleus of Biotechnology at University of Mogi das Cruzes. She has published 17 papers in reputed journals, some of them in collaboration with international research groups, and received awards for poster presentation in five international meetings.
Abstract:
The Brn-2 transcription factor is related to the development of malignant melanoma, inducing cell proliferation and invasion and, consequently, the formation of metastases. The Brn-2 protein is expressed in melanocytes and overexpressed in melanoma cells. Peptides derived from the Brn-2 transcription factor could compete with the DNA binding sites, thus interfering with the development of melanoma, as well as activating the mechanisms of cell death. In the present work, the cytotoxic activities of peptides derived from the Brn-2 transcription factor were determined against murine melanoma B16F10- Nex2. Cells were treated for 24h with the peptides E12F, R18H, L13S and C9K, derived from the POU domain of the Brn-2 transcription factor. Among the peptides tested, only the R18H peptide was cytotoxic in B16F10 Nex2 cells. Moreover, a time curve was taken to evaluate the antitumor activity of R18H for 30 minutes, 1, 2, 4, 6, 12 and 24 hours. It was observed that the peptide displays antitumor activity early in the first hours of treatment, however, the cytotoxic effect increases only after 24 hours. The R18H peptide induced DNA degradation, chromatin condensation, increase of superoxide anions, phosphatidylserine translocation, activation of caspase 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. These effects characterize death by apoptosis and because caspase 8 was activated we suggest that the extrinsic pathway is followed. R18H also induced membrane permeabilization in cells treated for 24 h, however, the same effect was not observed after treatment for 2 h. To determine if the membrane permeabilization effect could be due to late apoptosis or if in addition to apoptosis the R18H peptide also induced necrosis or necroptosis, we tested the peptide in the presence of necroptosis inhibitors and verified the release of LDH in the extracellular environment of treated cells. The peptide kept its cytotoxic effect in the presence of inhibitors of necroptosis and treated cells did not present LDH release in the extracellular medium. These data indicate that
membrane permeability is a late apoptosis event. It was also observed that peptide R18H showed antitumor activity in vivo. It was observed in the metastatic model that C57Bl/6 mice treated with the R18H peptide showed lower numbers of pulmonary nodules than untreated mice. The peptide was not toxic in mice at high doses, as observed in histopathological analysis of the
lung, liver, kidney, heart and spleen. These results suggest that the R18H peptide has potential to be developed as a new drug for the treatment of melanoma.
Biography:
Eun-Min Kim has completed his PhD from Seoul National University College of Medicine and had worked as a Research Professor in Busan National University
College of Medicine. Currently, he is studying the mechanism of cholangiocarcinoma at Yonsei University in South Korea.
Abstract:
Clonorchis sinensis, the most prevalent parasite in Korea, has been reclassified as Group I bio-carcinogen for cholangiocarcinoma (CCA) in humans by IARC in 2009, C. sinensis associated cholangiocarcinoma (CCA) is still unknown. The aim of this study was to identify distinct gene expression associated with carcinogenesis of C. sinensis. In human cholangiocyte line, H69 cells were continuously exposed to N-nitroso dimethylamine (NDMA) and excretory secretory product of C. sinensis (ESP) over one year. H69 cells that were continuously exposed to ESP of C. sinensis and NDMA showed cancer-like characteristics including cell proliferation was more than 5.7 times and the proportion of cells in the G2/M phase increased up to 42% compare to non-treated H69 cells. Moreover, the expression of the cell cycle protein E2F1 and the cell proliferation related proteins, ki67, and cytokeratin 19 were more than 30-fold increased when NDMA and ESP were added together. Based on these results, whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of H69 stimulation with NDMA and/or C. sinensis ESP with non-treated H69. A total of 1301 differentially expressed genes (DEGs) were identified, 521 of which were up-regulated and 780 were down-regulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichments revealed that numerous DEGs belong to cancer-relevant genes, involved in cell cycles, cell proliferation, and cell adherent-relevant pathways. Among them, we focused on the P53 K-ras signaling genes and found that two genes increased and eight genes decreased from a number of their genes. This result was also confirmed by real-time PCR. In conclusion, these data suggest that the P53 and K-ras signal plays a key role in regulation of cell proliferation, which may cause cholangiocarcinoma under stimulation by ESP of C. sinensis and NDMA.
- Cancer Management & Prevention | Cancer Genetics | Cancer Treatment & Therapies | Complementary and Alternative Cancer Treatment
Location: Olimpica 3+4
Chair
Lloyd Jenkins
Budwig Center, Spain
Co-Chair
Rong Shao
Shanghai Jiao Tong University School of Medicine, China
Session Introduction
Lloyd Jenkins
Budwig Center, Spain
Title: Naturopathic doctor in complementary natural treatment and prevention of cancer
Biography:
Lloyd Jenkins is a certified Naturopath and founder of the Budwig Cancer Clinic in Malaga, Southern Spain. He received authorization from Dr. Johanna Budwig in August 2000 to use her protocol for treating people with all types of cancer. He has written seven books and literally hundreds of articles on how to treat cancer and all common diseases using natural therapies. He has also been on radio talk shows and has spoken at Health Care seminars and events.
Abstract:
The Budwig Center approach in treating cancer is based on the research and studies of the famous German Doctor Johanna Budwig using a totally natural treatment protocol. She was a State Expert for Chemical Research on Drugs and Fats at the Dr. Kaufmann's facility in Munster, Germany. Her research has shown the tremendous effects that commercially processed fats and oils have in destroying cell membranes and lowering the voltage in the cells of our bodies, which then result in chronic and terminal disease. The cells of our body fire electrically. We are all aware of how fats clog up our veins and arteries and are the leading cause of heart attacks, but these very dangerous fats and oils are also affecting the overall health of our minds and bodies at the cellular level. Dr. Budwig discovered that when unsaturated fats have been chemically treated, their unsaturated qualities are destroyed and the field of electrons removed. Without the proper metabolism of fats in our bodies, every vital function and every organ is affected. This includes the generation of new life and new cells. Our bodies produce over 500 million new cells daily. Dr. Budwig points out that in growing new cells, there is a polarity between the electrically positive nucleus and the electrically negative cell membrane with its high unsaturated fatty acids. During cell division, the cell, and new daughter
cell must contain enough electron-rich fatty acids in the cell's surface area to divide off completely from the old cell. When this process is interrupted the body begins to die. In essence, these commercially processed fats and oils are shutting down the electrical field of the cells allowing chronic and terminal diseases to take hold of our bodies. Her most famous discovery was the use of a combination of flaxseed oil combined with Quark or Cottage cheese to restore the adequate electron activity. She also used mostly herbal, homeopathic, essential oils, sunbathing, oil massages and enemas, as well as her oil protein diet to treat and prevent cancer. In August 2000, Lloyd Jenkins visited the famous Dr. Johanna Budwig in her Cancer clinic in Stuttgart Germany. It was with deep interest that he listened to Dr. Budwig talk about her incredible health breakthrough of when she discovered the powerfully healing nature of essential fatty acids in treating cancer and all types of degenerative diseases. Lloyd received her permission to use her program in the Budwig Center Cancer clinic in Spain and has been helping people from all over the world since then to overcome cancer.
Rong Shao
Shanghai Jiao Tong University School of Medicine, China
Title: A neutralizing anti-YKL-40 antibody blocks tumor angiogenesis through binding to an arginine (R) and lysine (K)-rich functional domain of YKL-4
Biography:
Rong Shao is currently a Professor in Department of Pharmacology, School of Medicine, Shanghai Jiao Tong University, and an adjunct Professor of Department of Biology, University of Massachusetts, Amherst. He has published more than 40 papers in top-tier journals. He has also served as an editorial board of more than thirteen peer-reviewed journals and a Reviewer of 48 journals. His research work has been supported by several US federal funding agencies including NIH (NCI), DoD, DoE and Chinese National Science Foundation.
Abstract:
YKL-40, also known as chitinase-3-like-1 (CHI3L1), is strikingly elevated in serum levels of patients with a variety of advanced carcinomas, including breast cancer, colorectal cancer, ovarian cancer, leukemia, lymphoma, and glioblastoma. It thus has been suggested that serum levels of YKL-40 may serve as a cancer diagnostic and prognostic biomarker. However, little is known regarding its therapeutic value of whether and how blockade of YKL 40 can inhibit cancer progression. We recently developed a mouse-derived neutralizing antibody (mAY) against YKL-40 and found that mAY targeted to bind a positively charged arginine (R) and lysine (K)-rich domain (RK-domain) proximal to its C terminus and thus interfered its binding to heparin that is essential for YKL-40 angiogenic activity. The ability of mAY to block YKL-40 angiogenesis is identical to the R or K point mutations, where alanine (A) substituted for K or R in the RK-rich domain both in cultured vascular endothelial cells and animal models xenografted with breast cancer cells MDA-MD-231. These data suggest that mAY neutralizes YKL-40 via blockade of heparin binding of the KR-rich motif, the functional domain of YKL-40, revealing the molecular mechanisms underlying neutralization of YKL-40 activity. Our findings may help pave a new avenue to develop therapeutic agents targeting YKL-40 that is highly elevated in varied cancers and chronic inflammatory diseases.
Break: Lunch Break 13:10- 14:10 @ Hotel Restaurants
Kamran Mansouri
Kermanshah University of Medical Sciences, Iran
Title: L-Arginine is an Achilles' heel in tumor growth and therapy
Biography:
Kamran Mansouri completed his PhD at Tehran University of Medical Sciences, Iran. He is the Head of Department of Molecular Medicine at Kermanshah University of Medical Sciences, Iran. He has published more than 50 papers in reputed journals.
Abstract:
In cancer therapy, modulatory effects of L-arginine on various cancers remain a controversial issue. This amino acid is a substrate for different enzymes and plays a crucial role in regulating multiple metabolic and signaling pathways in both normal and cancer cells. L-arginine has a complex metabolism and its impacts on the cells are highly linked to the types and metabolism of them. Previous studies investigating the effects of L-arginine in cancer therapy have provided conflicting results. While some studies confirm that L-arginine enhances tumor growth, the others introduce L-arginine as an appropriate candidate for cancer treatment. Contradictory assertions in the case of L arginine used in cancer therapy suggest that using or depletion of this amino acid can have different result on the normal and cancer cells. So, this study attempts to reconcile these opposite notions and to revisit the thesis that L-arginine role in cancer therapy.
Manuela Boyle
University of New England, Australia
Title: An overview of the use of natural compounds to reduce drug resistance in cancer therapy: The role of polysaccharide krestin
Biography:
Manuela Boyle is an Australian Integrative Oncologist with board certification by the Institute of Integrative Medicine (USA). With over 20 years of clinical experience in Integrative Medical centres in Australia, Italy, United Kingdom and Singapore, she is a leading integrative oncology educator delivering training and mentoring to medical doctors and allied health practitioners. She is a regularly invited guest speaker at key conferences around the globe and is the published author of several peer-reviewed papers. In 2015, she was accepted as an external expert by the European Centre for Disease Prevention and Control in Stockholm, Sweden, an honorary position aimed to provide independent scientific opinions, expert advice, data and information and to maintain scientific excellence at all times through the best expertise available. She is the Director of Vingyana Integrative Oncology Clinic in Sri Lanka, a state of the art technology and residential medical centre, while maintaining her presence at her clinics in Milano, London and the Gold Coast (Australia).
Abstract:
Introduction & Aim: Cancer cells are better able to adapt to stress than normal cells. In cancer treatment, this adaptation results in tumor cells that develop cancer resistance to chemotherapy drugs. This event is usually the primary obstacle to successful treatment. Finding themselves in a state of high alert, cancer cells have the ability to express resistance not only to drugs they have been exposed to, but to any other noxious agent. Multi-drug resistance is a protection mechanism that can lead to failure of the conventional cancer treatment. Research shows that natural compounds can reverse drug resistance by inhibition of P-glycoprotein, inhibition of glutathione S-transferase drug detoxification system and inhibition of heat-shock proteins. There is ample evidence suggesting that selected natural compounds can produce cytotoxic effects in cancer cell through several mechanisms and that, when they are combined with chemotherapy drugs, these effects are often additive or synergistic.
Method: A review of randomized controlled trails of the mechanisms by which cancer cells, exposed to chemotherapy, have the ability to devise strategies for resistance and survival. This study involves the research of EBSCO, MEDLINE, and PubMed from 1992 to 2012 to retrieve suitable articles. Five double blind placebo controlled clinical human and animal studies were
reviewed.
Results: All the control studies conducted in large multi-centre trials, confirmed improvement in patient survival on a dose of 3 grams of PSK per day orally unless noted. 262 postoperative stomach cancer patients were randomized to receive chemotherapy or chemotherapy and PSK. The addition of PSK increased the five-year disease-free rate (from 59% to 71%) and the five year survival rate (from 60% to 73%). 462 patients with curatively resected colon cancer were randomized to receive chemotherapy or chemotherapy plus PSK. The latter combination increased the eight-year disease free rate (from about 7.8% to 28 %) and ten year survival rate (from 19% to 36%). 278 patients with stage II aT2N1 estrogen-dependent breast cancer were randomized to receive chemotherapy or chemotherapy. The administration of PSK increased the five year survival rate (from 81% to 96%). Disease-free survival also increased. 38 patients with nasopharyngeal cancer who were treated with radiotherapy, with or without chemotherapy, were randomized to receive PSK or no PSK. The addition of PSK increased survival rate (from 15 to 35 months). The PSK dose was 1 gram per day orally.
Conclusions: Dose-dependent of Polysaccharide-K (PSK) has shown anti cancer potential in combination with conventional therapies due to a combination of immune stimulation and inhibition of immuno suppressive cytokines.
- Workshop
Location: Olimpica 3+4
Session Introduction
Lloyd Jenkins
Budwig Center, Spain
Title: Your health is in your gut – Megasporebiotics rediscovered
Biography:
Lloyd Jenkins is a certified Naturopath and founder of the Budwig Cancer Clinic in Malaga, Southern Spain. He received authorization from Dr. Johanna Budwig in August 2000 to use her protocol for treating people with all types of cancer. He has written seven books and literally hundreds of articles on how to treat cancer and all common diseases using natural therapies. He has also been on radio talk shows and has spoken at Health Care seminars and events.
Abstract:
Clinics are finding that up to 90% of health problems are resolved when the microbiome of the gut is corrected resorted. The father of medicine Hippocrates said that “Your health is in your gut”. We are more bacteria than human! — 10 trillion human cells vs. 100 trillion bacteria cells. There are over 1,000 different species of commensal organisms in the GIT out of 35,000 possible. In developed parts of the world due to the diet of many processed foods we tend to suffer more from digestive issues and auto-immune diseases. Distinct Distal Gut Microbiome Diversity and Composition in Healthy Children from Bangladesh and the United States found that: The distal gut of Bangladeshi children harbored significantly greater bacterial diversity than that of U.S. children, including novel lineages from several bacterial phyla.Human gut microbiota community structures in urban and rural populations in Russia “the original microbial community structures occurred in hosts from urban populations 2.6-fold less frequently than in the rural hosts, which implies that the rural population’s microbiota community was the healthy original”. Some of the last hunter-gatherer people on earth who live an ancient, ancestral life.
Their environment hasn’t changed for 1000s of years and they have a massive exposure to ancestral microbial community. They have a vastly different microbiota compared to westernized populations. In fact, virtually no common digestive diseases such as Crohn’s, UC, Colon Cancer, Reflux, etc. found in these parts of world that live on life natural foods.A new study by scientists at the University of California has found that contents of many bifidobacterial probiotic products differ from the ingredients listed. After testing 16 probiotic products available in local Californian stores and also online, they found only one of the products exactly matched the bifidobacterial species claims on the label. Some products had pill to pill and lot to lot variation. 35 strains from commercial products were studied. Primarily lactobacillus sp. and Bifidobacterium sp. There were studies done to evaluate the survivability of common probiotics through the GIT. Only 4 of 35 strains would survive to enter the large intestine and the survivors would have less than 50% survival. We are not aware of any other probiotic that has demonstrated the ability to fix dysbiosis. Thus, addressing the root cause of many diseases. We have worked with a lot patient going through chemotherapy, and oncologists often prohibit using probiotics but not sporebiotics. We work closely with the OncANP which is the Association of Naturopathic oncologist and they utilize the product on patients undergoing chemo to reduce the diarrhea and damage to the microbiome. It is used routinely here in the States for that purpose. We have not seen any adverse reactions thus far. We titrate the patients up as we normally do, but have had success with this application.
Break: Networking and Refreshments Break 16:10 -16:30 @ Foyer
- Poster Presentation Slot II
Location: Meeting Halls
Session Introduction
Seong Gyeong Mun
Yonsei University College of Medicine, South Korea
Title: c-Met overexpression of fibroblasts increases angiogenic signal in breast cancer
Biography:
Seong Gyeong Mun has completed her Bachelor’s degree in Molecular Biology from Dankook University. She is currently pursuing Master’s degree in Yonsei University School of Medicine. She had studied about breast tumor microenvironment in her graduate school days.
Abstract:
We found that c-Met overexpression was induced in normal breast fibroblast (NBF) by the conditioned medium (CM) of cancer cells regardless of subtypes, which made us to hypothesize that c-Met overexpression is a property of cancer associated fibroblast (CAF). Therefore, we investigated whether c-Met overexpressing NBFs contribute to tumor progression. To this end, extracellular matrix (ECM) gene expression alteration was analyzed from the NBFs transfected with c-Met overexpression plasmid using cDNA microarray since CAF constructs tumor microenvironment by ECM remodeling. In our microarray data, matrix metalloproteinase 1 (MMP1) was most up-regulated in c-Met overexpressing NBF (approximately 10-fold) compared to the control NBF. According to previous studies, MMP1 induces VEGFR2 (Vascular endothelial growth factor receptor 2) expression in endothelial cells (ECs). So, it was assumed that c-Met overexpressing NBF contributes to breast cancer angiogenesis. In our study, the CM of c-Met overexpressing NBF induced a better tube formation of endothelial cells (Hy926) than that of control. On the other hand, tube formation by c-Met overexpressing NBF CM was reduced in the presence of c-Met inhibitor. Similar results were also observed in the co culture of NBF and breast cancer cell lines (luminal A, B, Her2, and TNBC). The expression of c-Met and MMP1 was increased by the co-culture, whereas was decreased in the presence of c-Met inhibitor. Tube formation of EC was increased by the CM of the co-culture, whereas decreased by c-Met inhibitor-treated co-culture CM. Based on our results, c-Met inhibitor may be able to suppress angiogenesis in breast cancer by decreasing c-Met-induced MMP1 expression of CAFs.
Eun-Beom Lee
Ajou University School of Medicine, South Korea
Title: Potential transcription factor involves NFE2L1 in hepatoma cell invasiveness through ROS induction
Biography:
Eun-Beom Lee is pursuing Master's Degree from Ajou University School of Medicine. Her major Research Interest is in mitonuclear communication in tumorigenesis and retrograde signaling in hepatoma cells.
Abstract:
Mitochondrial dysfunction is an important metabolic feature in human cancer. However, underlying mechanisms how mitochondrial dysfunction affects tumorigenesis remain unclear. To address the role of transcriptomic regulation by mitochondrial defects in liver cancer cells, we performed gene expression profiling for three different cell models of mitochondrial defects: cells with chemical respiratory inhibition, cells with mitochondrial DNA depletion, and liver cancer cells harboring mitochondrial defects. By comparing gene expression in the three models, we identified 10 common mitochondrial defect (CMD)–related genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. Among the CMD genes, we found that NFE2L1 is a key regulator to regulate hepatoma invasiveness. This study aims to elucidate how mitochondrial defect regulates NFE2L1 transcription. Interestingly, SNU354 and SNU423 cells showed high intracellular reactive oxygen species (ROS) levels. Exogenous treatment of H2O2 increased intracellular ROS and NFE2L1 expression in SNU387 cell harboring active mitochondria. We further selected 11 transcription factors (TFs) that could bind to promoter region of NFE2L1 by using TRANSFAC program. By monitoring NFE2L1 mRNA levels after knocking-down of the TFs, 4 TFs (USF2, STAT3, JUN and SREBP1) were identified to regulate NFE2L1 transcription. Further detailed molecular mechanisms of how mitochondrial ROS regulates NFE2L1 transcription are currently under investigation.
Young-Kyoung Lee
Ajou University School of Medicine, South Korea
Title: Decrease in expression of the mitoribosomal subunit, MRPL13, enhances hepatoma cell invasiveness via elevated claudin-1
Biography:
Young-Kyoung Lee received her PhD in Biochemistry from Ajou University School of Medicine, Suwon, Korea. She is working as a Post-Doctoral Research Fellow at Ajou University School of Medicine. For about last ten years, her research has been focused on elucidation of molecular mechanisms of mitochondrial respiratory defects which are often observed in cancer, the retrograde signaling triggered by the respiratory defect and its relevance to cancer activities.
Abstract:
Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal defect. Specific mitoribosomal translation inhibition with doxycycline and chloramphenicol, or siRNA-mediated MRPL13 knockdown decreased mitochondrial protein expression, reduced the oxygen consumption rate (OCR), and increased CLN1- mediated tumor cell invasiveness in SNU387 cells, which have active mitochondria. Interestingly, we also found that exogenous lactate treatment suppressed MRPL13 expression and OCR, and induced CLN1 expression. A bioinformatics analysis of the open RNA-Seq database from The Cancer Genome Atlas Liver Hepatocellular carcinoma (TCGA-LIHC) cohort disclosed a significant negative correlation between MRPL13 and CLN1 expression. Moreover, in LIHC patients with low MRPL13 expression, two oxidative metabolic indicators, pyruvate dehydrogenase B expression and the ratio of lactate dehydrogenase (LDH) type B to LDH type A, significantly and negatively correlated with CLN1 expression. This observation implied that the combination of elevated glycolysis and deficient MRPL13 activity is negatively linked to CLN1-mediated tumor activity in LIHC. These results suggest that OXPHOS defects may be initiated and propagated by lactate-mediated mitoribosomal deficiencies and that these deficiencies are critically involved in LIHC development.
Gül Ögren
Marmara University, Turkey
Title: Place of functional beverages in preventive treatment for cancer
Biography:
Gül ÖÄŸren has completed her Bachelor of Nutrition and Dietetic from Erciyes University and is currently enrolled in the Master programme in Department of Nutrition and Dietetic, Marmara University. She is also a Research Assistant at the same university.
Abstract:
Functional beverages help us to maintain healthy conditions and to provide comfort just for general nutrition. For this reason, functional beverages play a significant role in our daily lives. It has been found that functional beverages have benefits in many areas of health such as cancer prevention, healthy digestive system, immunity defenses, body weight reduction, energy and hydration, improve overall health, show antioxidant activity, improve cardiovascular health. The positive effects of functional beverages on health are explained by different mechanisms. Reduce oxidative stress and help to prevent many chronic diseases, as well as strengthen the immune system of the individual. Besides water, the best known and most commonly used functional beverages are tea, coffee and fruit juices. Functional beverages contain antioxidant bioactive compounds and different nutrient including alkaloids, anthocyanins, carotenoids, flavonoids, glucosinolates, isoflavones, phenolic acids, tannins and terpenes, vitamins (vitamin C, folate and provitamin A), minerals (potassium, calcium, magnesium) and fibers that have been associated with reduced cancer risk. Reactive oxygen species damages many tissues such as lipids, proteins, especially DNA in living organisms. Free radicals mediate oxidative damage in cancer. The biological damage that occurs in this way is called oxidative stress, and the phenolic components involved in functional beverages have a vital role in removing oxidative stress. DNA is highly susceptible to free radical damage. Modification of DNA is the most important consequence of oxidative stress, and it can become permanent via the formation of mutations and other types of genomic instability. Excessive production of reactive oxygen species and lack of adequate antioxidant components (alkaloids, anthocyanins, carotenoids, flavonoids, glucosinolates, isoflavones, phenolic acids, tannins and terpenes) in the body trigger to formation of cancer. It is thought that phytochemicals in beverages and balanced diet can be a natural treatment method to improve the individual's health condition and to prevent the development of the cancer cell with the minimal toxicity. It has been found that functional components taken with beverages contribute approximately 30% to the prevention of cancer formation in industrial countries. Functional beverages (fruit juices, vegetable juices, caffeinated beverages, dairy and soy beverages, some fermented beverages) provide sufficient quantities of antioxidant component that reduces cancer formation by preventing DNA damage and reducing oxidative stress in the body.
Veysel Akduman
Marmara University, Turkey
Title: The importance of exercise in patients with breast cancer
Biography:
Veysel Akduman has completed his Bachelor of Physical Therapy and Rehabilitation from Afyon Kocatepe University and then graduated his Master’s Degree in Department of Physiotherapy and Rehabilitation, Sifa University. He is currently enrolled in the PhD programme in Department of Physical Therapy and
Rehabilitation, Marmara University, in which he is also a Research Assistant.
Abstract:
Breast cancer leads to physical and mental distress which is linked with increased prevalence of malignancy-related mortality among females worldwide. Survival rates for breast cancer have been improving for more than 20 years and this appears likely to continue. Therapeutic exercises as well as adjuvant treatments are important improving the quality of life and increasing survival rates in cancer patients. Exercise is recommended to minimize the side effects of chemotherapy and radiotherapy, to maximize cardio pulmonary status especially early diagnosis. Aerobic and resistance exercise are mostly performed exercises types in this population, either separately or in combination, have been shown to improve physical functioning and manage some side effects in breast cancer patients receiving chemotherapy. It has been showed that exercise program can help manage symptoms and improve physical functioning during radiation therapy. Some studies in the literature have shown that aerobic exercise in cancer patients reduces fatigue as well as increases quality of life. For many cancer patients, fatigue is a severe and limiting problem. The impairment of physical and mental performance prevents from working or carrying out regular daily activities and hence results in a substantial reduction of the quality of life. In response to fatigue, patients are usually advised to rest and down-regulate their level of daily activities. However, since inactivity induces muscular catabolism and cardiopulmonary endurance, extended rest can help perpetuate fatigue. Moreover, exercise has been proposed as a nonpharmacologic intervention for the treatment of cancer-related fatigue. An isometric exercise is one of the resistance training. One study found that three-week isometric-strength exercise program improved physical performance and reduced fatigue. In another study pointed that the effects of all forms of performed aerobic or resistance exercise, or both, with programme duration of at least six weeks should be considered. Although the exercise training is one of the necessary approach in the non-pharmacological treatment of breast cancer to reduce fatigue, there are still not enough studies in the literature. It is necessary to perform more randomized controlled studies investigating the proper exercises type and procedure to improve quality of life in breast cancer survivors.
Biography:
Emel Mete graduated from Istanbul University Physiotherapy and Rehabilitation Department in 2007. She is pursuing her Master Program in Physiotherapy and
Rehabilitation Department at Marmara University. She is also a research assistant at the same department.
Abstract:
Cancer is defined as a class of diseases in which abnormal cells divide without control and can invade other tissues. It is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008. Acupuncture is one of the major treatment methods in Chinese medicine (CM). The value and safety of acupuncture are documented in the growing body of literature on acupuncture treatment for chronic pain, osteoarthritis, migraine, and the relief of procedural anxiety. In addition, acupuncture has been used to treat a range of problems associated with cancer and cancer treatments, such as hot flashes, chronic fatigue, neuropathy, nausea and vomiting, xerostomia, and dysphagia. Needle stimulation causing a typical needle sensation has been claimed to be important for reaching maximum effects on pain. Acupuncture points in the cutaneous nerve can be used to reduce pain, vomiting and nausea and to treat depression. Cancer treatment can also be used to reduce other effects such as xerostomia and sensory impairment. According to a study, acupuncture treatment was found to be effective in pain control in cancer, acupuncture alone was not better than standard drug treatment, but acupuncture
and drug therapy combination was significantly more effective than drug treatment alone. In another study, standard pain treatment with hand-foot acupuncture was compared in terms of side effects and analgesic efficacy in patients with liver cancer. Acupuncture has resulted in a longer analgesic effect without any side effects. Literature reviews indicate that acupuncture is effective in pain management and it has no side effects. On the other hand, inadequate number of randomized controlled trials and the fact that studies are performed on fewer patients and the short follow-up time lead to an inaccurate explanation of the effectiveness of acupuncture. We think that there is not enough research about acupuncture on cancer and that more randomized controlled trials are needed.
Kazunobu Baba
Hokkaido University, Japan
Title: Inhibitory effect of Lactobacillus helveticus SBT2171 on the growth of colon carcinoma cells and the novel action mechanism
Biography:
Kazunobu Baba has completed her PhD from Kwansei Gakuin University. She is a Postdoctoral Fellow of Institute for Genetic Medicine in Hokkaido University.
She has been studying the function and roles of probiotics to apply the study in prevention and treatment of cancer. She has once received Paper of the Week on
Journal of Biological Chemistry.
Abstract:
Lactobacillus helveticus SBT2171 (LH2171: provided by Megmilk Snow Brand Co., Ltd.) is a lactic acid bacterium that inhibits excessive immune responses. We have revealed that LH2171 shows inhibitory effects on the proliferation of BJAB, a B lymphoma cell line, through reduction of phosphorylation level of c-Jun, a critical regulator of cell proliferation. c-Jun is phosphorylated by activation of MAPKs (Mitogen-activated protein kinases) (JNK and ERK) signaling pathway. JNK (Jun N-terminal kinases) and ERK are activated by MEK4/7 or MEK1/2 pathway, respectively. In this study, we investigated the effect of LH2171 on the proliferation of MC38, a mouse colon carcinoma cell line and HT-29, a human colorectal adenocarcinoma cell line. LH2171 inhibited the proliferation of both MC38 cells and HT-29 cells. As a result of assay for the phosphorylation of factors regulating cell growth, LH2171 inhibited phosphorylation of JNK, but not of ERK and MEK4 in MC38 cells. In addition, LH2171 induced the expression of JNK inactivating phosphatase, MKP1 and MKP1 siRNA treatment could suppress the effect of LH2171 to inhibit cell proliferation. These results indicate that the inhibitory effect of LH2171 on the proliferation of MC38 cells depends on the induction of MKP1 to inhibit JNK activity.
Fatemeh Alibeiki
Ardabil University of Medical Sciences, Iran
Title: Anti-cancer effects of less polar Curcumin analogues on gastric adenocarcinoma and esophageal squamous cell carcinoma cells
Biography:
Fatemeh Alibeiki has been studying at Ardabil University of Medical Sciences, Iran. Currently, she is in her final year of education as a medical student. So far, she has published two papers in high-profile journals. Participating in numerous conferences and workshops is one of her interests and has done so, on a regular basis throughout the years as a student which brought her experience, extensive knowledge and so many scientific certificates. She has also associated with different groups in her university that resulted in holding several conferences and meetings.
Abstract:
Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its antiproliferative activity. In this study, we explored benzylidene cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6- bis benzylidene cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR was performed for gene expression analysis. All synthesized analogues were cytotoxic toward gastric and esophageal cancer cells and showed lower IC50 values than curcumin. Treatment with 2,6-Bis-(3-methoxy-4-propoxy-benzylidene)-cyclohexanone (BM2) was 17 times more toxic than curcumin after 48 h incubation. All novel compounds were more effective than curcumin in apoptosis induction and cell cycle arrest at G1 phase. These results suggest that less polar analogues of curcumin have potent cytotoxicity in vitro. However, they need to be investigated further, especially with animal tumor models, to confirm their chemotherapeutic activity in vivo.
Seung-Kye Cho
Kyung Hee University, South Korea
Title: Effect of WNT7B in macrophage-stimulated mesothelial cells on ovarian cancer cell adhesion
Biography:
Seung-Kye Cho is pursuing his Master’s degree in Life and Nano-pharmaceutical Sciences at Kyung Hee University. He graduated in Oriental Pharmaceutical
Science from the Kyung Hee University. He has interests in providing evidence supporting the importance of the interplay between ovarian cancer cells and
mesothelial cells, and discovering novel factors of peritoneal dissemination of ovarian cancer.
Abstract:
Ovarian cancer is a remarkably metastatic disease that is often characterized by widespread peritoneal dissemination. Recently, several studies have suggested that tumor microenvironment plays a significant role in ovarian cancer metastasis. However, the interaction between macrophages and mesothelial cells for ovarian cancer metastasis is unclear. We first investigated the effect of macrophages on gene expression pattern in mesothelial cells. Following treatment of mesothelial cells with conditioned medium (CM) of macrophages, we conducted a comparative analysis of global expression changes in mesothelial cells using mRNA sequencing. When compared to that in unstimulated-macrophages, 945 genes were upregulated and 777 genes were down-regulated more than 2-fold in macrophage-stimulated mesothelial cells (MSM). Among the total 1722 genes, 94 genes including WNT7B were known to be associated with the regulation of cell adhesion. Interestingly, knockdown of WNT7B using siRNA attenuated the adhesion of ovarian cancer cells to mesothelial cells. These results indicate that the enhanced levels of WNT7B in MSM may play a role in the peritoneal dissemination of ovarian cancer.
Jae-il Roh
Yonsei University, South Korea
Title: Hexokinase 2 is a molecular bridge linking telomerase and autophagy
Biography:
Jae-il Roh has completed his PhD from Yonsei University and continuing his research at the same laboratory. He is working in Prof. Han-Woong Lee’s lab and
interested in mouse genetics, generation of mouse models, and cancer.
Abstract:
Autophagy is systematically regulated by upstream factors and nutrients. Recent studies report that telomerase and hexokinase 2 (HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. Here, we show that HK2 is a molecular bridge linking telomerase to autophagy. TERT-induced autophagy activation and its further enhancement by glucose deprivation were suppressed by HK2 inhibition in HepG2 cells. The HK2 downstream factor mTOR was responsible for TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through a HK2-mTOR pathway. TERC played a similar role as TERT, and simultaneous expression of TERT and TERC synergistically enhanced HK2 expression and autophagy. At the gene level, TERT bound to the HK2 promoter at a specific region harboring the telomerase-responsive sequence TTGGG. Mutagenesis of TERC and the TERT-responsive element on the HK2 promoter revealed that TERC is required for the binding of TERT to the HK2 promoter. We demonstrate the existence of a telomerase-HK2-mTOR-autophagy axis and suggest that inhibition of the interaction between telomerase and the HK2 promoter sensitizes cells to metabolic stress, and this pathway could be targeted for anti-cancer therapies.
Young Hwa Kim
Ajou University School of Medicine, South Korea
Title: Senescent tumor cells lead the collective invasion in thyroid cancer
Biography:
Young Hwa Kim has completed all the requirements for the Doctoral Degree in Biomedical Science and expect to obtain the Ph.D. Degree Certificate at the end of February 2016, officially. She has published 8 papers, out of which she is the first author of 4 papers.
Abstract:
Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC.