Biography:

Ishii has completed his postdoctoral studies from Thomas Jefferson University, Philadelphia, PA. He is the professor of cancer profiling discovery, Osaka University, Japan. Specialty and Present Interest: intractable cancer stem cells, epigenome, metabolome, gastrointestinal tumors.

Abstract:

Till date, international pharmaceutical companies have produced numerous anti-cancer reagents, including molecular targeting strategies and immunotherapies, but resistance exists even for these up-to-date medicines. The most important factors that make present therapeutic strategies ineffective are tumor heterogeneities. To visualize and collect cancer stem cell fractions, we transfected cancer cells with a green fluorescent protein-fusion one-carbon metabolism monitoring cassette. The monitoring system allowed visualization of cancer cell populations with therapy-resistant cancer stem cell properties. The present study revealed that polyamine flux plays a critical role in cancer stem cell properties, and polyamine metabolism is linked with epigenetic regulation of downstream gene expression. Epigenetic studies demonstrated the uncharacterized mechanism of transcription cycles and underscored the significance of molecular profiling in the discovery of novel therapeutic targets for retractable cancer cells. These novel approaches are beneficial for cancer research and may open avenues for treating gastrointestinal cancers that present challenges for treatment.

Biography:

Erik Andrade-Jorge is a Doctorate student in the Department of Biochemistry at Instituto Politecnico Nacional. He is a chemist-pharmaceutical-biologist and has a Master degree in Pharmacology and is currently in the seventh semester of the Doctorate in research in medicine. Currently, he has two different lines research one of these is cancer cell proliferation and another one is in Parkinson’s disease. He has been focused on the rational drug design based on the molecular mechanisms of different pathologies and in the physicochemical properties of the ligands.

Abstract:

Conventional cancer therapies have been shown to have many side effects, the main challenge is to find molecules with higher selectivity to tumor cells rather than normal cells. A main differences between cancer and normal cells, are the levels of thiol-containing compounds, a scavenging mechanism of Reactive Oxygen Species. Cancer cells seem to have higher levels of glutathione than normal cells, and this allow them to survive in adverse conditions, even in chemotherapy. Therefore, glutathione has become a target for the new anticancer therapy. The aim of this contribution was to develop a series of α,β-unsaturated compounds derivate of endogenous amines that may deplete the levels of glutathione, as well as, induce cancer cells to death by apoptosis. Pharmacokinetic evaluation (in silico) showed a good score on the the parameters such as human intestinal absorption, plasma protein binding, biotransformation evaluated by cytochrome CYP2C9 affinity and CYP2D6 affinity, P-glycoprotein substrate, LopP, etc. The in vitro assays showed a EC50 of 5 µM for molecule MF01 and a EC50 of 30 µM for molecule MF02 evaluated by MTT method at 24 and 48 h, in vivo experiments include LD₅₀ and survival experiment. It was estimated a LD₅₀ for MF01 of 8 mg/kg and 80 mg/kg for molecule MF02, which means that molecule MF02 is 10 times less toxic that molecule MF01. There wasn't significant difference on the survival experiment at the dose used, but there was a delay on the tumor's development on the treated group. These results allow us to try others candidates which might possess the same properties.

Biography:

Pioneering in Mexico in the field of medicinal chemistry, Dr. Trujillo has focused on rational drug design based on the physicochemical properties of ligands and receptors, by using new technology. His different research lines include cancer, obesity, adrenoceptors, Parkinson’s, diabetes, and many others. Dr. Trujillo has authored more than 125 publications and has more than 876 citations. He has been the advisor for 72 students to obtain a university degree. He is a member of the National System of Researchers, level III, and is currently in charge of the Ministry of Research and Graduate Studies of the Instituto Politecnico Nacional.

Abstract:

Drug discovery and development is a resource-intensive endeavor that does not always end in success. One of the particularly illustrative examples of this challenge is the development of drugs for cancer treatment. Cancer is one of the leading causes of death worldwide and currently used chemotherapy causes several serious side effects. Hence it is advantageous to combine traditional methodology with new computer-assisted technology to increase the success and lower the investment involved in drug research. The aim of the present work was to develop new compounds with an epigenetic approach for treating cancer cells. This means generating a compound that could inhibit HDAC and ODC while depleting the high level of thiol-containing compounds existing in cancer cells. Overall, the objective is to have an extended conformation of DNA because this tends to silence proliferative genes and activate anti-cancer genes. Additionally, the greater oxidative stress has been shown to lead to death by apoptosis in mitochondrial cells. In silico results allow us to predict that α,β-unsaturated compounds will react with thiol-containing compounds in a selective way by a Michael type 1,4-addition reaction. Moreover, molecular docking clearly demonstrates that one moiety of the ligand recognizes the catalytic site of HDAC while the other one recognizes ODC, a theoretical result that has been corroborated by in vitro studies. Cell viability did not decrease in noncancerous cells (epithelial cells, HaCaT, THLE-3), it did indeed do so in human cancer cells (HuH7, HepG2, Hela), it was found an inhibition constant of 1.5µM estimated for ODC and HDAC. Finally, the administration of one or more of these compounds in an in vivo model was able to extend the life of mice in survival experiments, reaching up to double the time found in the control. This is a preliminary contribution to pave the way for clinical testing of this kind of molecule.

Biography:

Abstract:

Immune system based therapies constitute a promising class of treatment for many types of cancers. Whilst T cells can mediate tumor destruction, their effectiveness is limited due to negative thymic selection, down-regulation of HLA expression by cancer cells and an immunosuppressive microenvironment. To overcome the poor immunogenicity of tumors, Immunocore has developed ImmTACs (immune mobilizing monoclonal T cell receptors (mTCR) against cancer). A soluble mTCR, engineered to recognise a given tumor associated peptide-HLA complex with exceptionally high sensitivity and specificity, redirects host polyclonal T cells via an anti-CD3 antibody fragment, facilitating targeted T cell recognition of tumors. Antigens that exist on tumor cells but not on normal cells are rare, thus the selection and validation of appropriate target antigens and the testing of ImmTACs for specificity is critical. Antigen candidates are selected based on their levels of expression in cancer vs healthy tissues by RT-PCR and the presence of the targeted peptide on the cell surface is confirmed by mass spectrometry. As ImmTACs are specific for humans, efficacy, specificity and off target effects are determined through a detailed molecular and cellular testing programme, using antigen positive tumor cells and HLA appropriate primary human cell lines representing a range of tissues. IMCgp100, the lead ImmTAC, is currently in a Phase I/II clinical trial for the treatment of advanced melanoma. The maximum tolerated dose has been established and emerging data demonstrate several durable responses. IMCgp100 is well tolerated and there is evidence of T cell mobilisation in the tumor microenvironment, release of cytokines and tumor shrinkage.

Biography:

Shunsuke Sakuraba has completed his MD from Juntendo University. He works in the Department of Surgery at Juntendo Shizuoka Hospital and specializes in Open Surgery, Laparoscopic Surgery and Endoscopic Surgery. He has published 2 papers about GIST and MALT lymphoma of GI tract.

Abstract:

We have proposed Pfetin as a new, strong prognostic biomarker in resected gastrointestinal stromal tumors (GISTs). Pfetin is a potassium channel protein. It is highly expressed in fetal cochlea and in the brain, consistent with the fact that the origin of GIST is Cajal cells, and neuronal cells in the gut. Pfetin was discovered by using a proteomics approach and its usefulness as a prognostic biomarker has been reported. We examine Pfetin expression immunohistochemically using paraffin-embedded tissues, and when more than 20% of tumor cells are stained with the anti-Pfetin antibody, they are considered to be Pfetin-positive. Pfetin expression and tumor metastasis were inversely related and GIST with Pfetin-negative status has a poorer prognosis than Pfetin-positive GIST. We also have reported the fact that Pfetin is an independent predictor of recurrence/metastasis for completely resected primary, localized GIST. In our study, 13 cases were Pfetin-negative and 5/13 of these cases recurred. Conversely, 32 cases were Pfetin-positive and 2/32 of these cases recurred. (p=0.002) Pfetin is a strong prognostic biomarker and useful in selecting adjuvant therapy. We reviewed literatures and summarized Pfetin in GIST.

Biography:

Tomoaki Ito received the MD in 2000 and the PhD in Medical Science from Juntendo University, Tokyo, Japan. He completed Post-doctoral studies from Stanford University School of Medicine. He is an Assistant Professor of Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, Shizuoka, Japan. His research interests include oncology and cancer biomarker.

Abstract:

Previously, we found that the ERC (Expressed in Renal Carcinoma) gene was preferentially expressed in renal cancers in the Eker rat. Furthermore, we subsequently confirmed that ERC is a homolog of the human mesothelin gene, a gene that is strongly expressed in normal mesothelial cells, mesotheliomas, and non-mucinous ovarian carcinomas. The ERC/mesothelin gene (MSLN) encodes a 71 kDa precursor protein, which is cleaved to yield 31 kDa N-terminal (N-ERC/mesothelin) and 40 kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin (also known as megakaryocyte-potentiating factor; MPF) is a soluble protein and is released into the extracellular space and blood. C-ERC/mesothelin is a glycoprotein that is tethered to the cell surface by a glycosylphosphatidylinositol anchor. C-ERC/mesothelin expression of tumor by immunohistochemistry can be correlated with patient’s survival in several human cancers. Soluble mesothelin-related peptide (SMRP) has proven to be a promising biomarker in the sera of patients with mesothelioma and ovarian cancer. As for secreted N-ERC/mesothelin, we previously devised a novel enzyme-linked immunosorbent assay (ELISA) system for determining its concentration in serum and showed that it is useful for diagnosing human mesothelioma and ovarian cancer. In addition, we demonstrated that C-ERC/mesothelin was expressed in gastric cancer and pancreatic cancer tissues. Meanwhile, increased serum N-ERC/mesothelin concentrations are not specific to these patients with gastric cancer or pancreatic cancer. Although N-ERC/mesothelin is established as a reliable marker for mesothelioma, N-ERC/mesothelin is not useful as a diagnostic marker of gastric cancer and pancreatic cancer.

Biography:

Diddier Prada graduated as Medical Doctor from the Universidad Industrial de Santander, Colombia. Then, he pursued a PhD in Biomedical Science at the Universidad Nacional Autónoma de México (UNAM). He was a Post-doctoral Fellow at Harvard T.H. Chan School of Public Health, from 2013 to 2016; his stay included one-year and a half as Research Associate in the laboratory of Environmental Epigenetics in the Department of Environmental Health. He is currently working as Associate Researcher at the National Cancer Institute of Mexico, and he is also Associate Professor of Biomedical Informatics in the Faculty of Medicine at the UNAM. He has published papers in highly reputed peer-reviewed journals (e.g. Circulation, Environmental Research, and Environmental Health Perspectives). He has also published one book and five chapters in internationally recognized books, plus one that is currently in press.

Abstract:

Breast cancer is a leading cause of cancer death in the world. In developing countries, most patients are still diagnosed in locally advanced stages (LABC), which highlight the importance of identifying prognostic and predictive biomarkers. In this study, we determined the level of 5-hydroxymethylation (5hmC) in the biopsy at diagnosis. Then, we determined its association with clinical and histopathologic characteristics in a prospective cohort of LABC patients (N=84), diagnosed between 2012 and 2015; using a semi-quantitative enzyme-linked immunosorbent assay. We found a statistically significant association between low 5hmC levels with histological grade: Mean %5hmC in low grade tumors 0.17%, (95% CI 0.07-0.26%), intermediate-grade tumors 0.15% (95% CI 0.10-0.19%), high grade tumors 0.066% (95% CI 0.05-0.08%; p<0.001). We also observed an association between 5hmC levels with histological type: Invasive ductal carcinoma 0.10% (95% CI 0.07-0.12%) vs. non-ductal invasive carcinoma 0.22% (95% CI 0.07-0.36; p=0.008). Additionally, we found a negative and significant association with Ki67 (β=-0.012, standard error [SE]=0.0061, p=0.047), a known marker for cellular proliferation. Multivariate analysis confirmed the association between lower levels of 5hmC with age (β=-0.066, SE=0.031, p=0.036) and histological grade (β=-1.197, SE=0.589, p=0.042). No association was observed with therapeutic response or free-relapse survival, probably attributed to only 2-3 years of follow-up, and to few deaths (N=2) and relapse (N=7) that have been observed. This is the first report on the association between levels of 5hmC with the histological type and histopathologic grade in a prospective cohort of LABC. Our findings suggest that 5hmC levels may be a potential biomarker for tumor aggressiveness in LABC.

Biography:

Jianying Zhang received her PhD degree in Statistics from Purdue University in 2008. She has worked at the Center for Biostatistics at the Wexner Medical Center of the Ohio State University, Columbus, OH for about 8 years. She has collaborated extensively with investigators in the Comprehensive Cancer Center on basic science and translational laboratory experiment and clinical trials and has been the Co-investigator of over 10 P01/U01/R01 and industrial grants. She has published over 40 collaborative papers in reputed journals.

Abstract:

Cox regression models have been used for prognostic prediction based on omics data for years. But due to model over-fitting and the improper way of model development and various other factors, very few published prognostic signature has found its clinical success in applications. This study illustrated how an improper model develop or testing procedure could mislead the result and applied the proper cross-validated (CV) Cox model building and testing procedure to identify a prognostic microRNA signature based on 159 triple negative breast cancer (TNBC) patients. In each CV procedure (K-fold), the full data was split into train data and test data first. Then four steps were followed: feature selection, model selection, addition of significant clinical covariates, and model performance assessment. For each of the four steps, various methods were compared. For example, univariate cox model or recurrence vs recurrence-free comparison was applied to feature selection. Stepwise and penalized Cox model were used for model selection for the training data. Model performance was assessed on the test data by AUC of 3-year or 5-year recurrence and ROC calculated using the time-dependent ROC method. The final proposed penalized Cox model contained 6 miRs: miR-146b-5p, miR-363, miR-99a, miR-590-3p, miR-1280, and miR-1294 that attained a mean AUC of 0.736 for the 5-year recurrence of the test data from 100 runs of 5-fold cross-validated penalized Cox model building and testing. When the pathologic binary variable NODES (1 if 1+ positive nodes) were added to the 6-miR model, the mean AUC for test data was increased to 0.752. Permutation method was used to show if the AUC of the final 7-term model was significantly greater than 0.5.  Enrichment analysis and literature further verified the association between most of the proposed miRs and TNBC recurrence or metastasis. Independent validation of the miRs will be discussed.

Biography:

Hajime Orita graduated and took the surgical training from Juntendo University School of medicine in Japan. Now he is the associate professor of dept. of upper GI and especially do laparoscopic surgery. He had been post doctal studies and recived the adjunct associate professor degrer from Johns Hopkins University School of medicine. He has published more than 10 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

The aim of this study is to evaluate FAS as a marker of digestive cancer to measure FAS serum levels in patients with digestive cancer and explore each digestive cancer metabolic features.

Cancer metabolism is a futuristic strategy point for diagnosis and management. Lipid metabolism in particular is a vast uncharted territory for targeting tumor control. It is well known that many cancer cells up-regulate of fatty acid synthesis. Cancer cells require fatty acid for building blocks of new organelles and cells. Fatty acid synthase (FAS) is the enzyme responsible for fatty acid biosynthesis. It is over-expressed in many human cancers, reported to be correlated with cancer growth, contributes to poor prognosis and inhibition of FAS results in decreased cell proliferation, and loss of cell viability.

Previously we have reported high expression not only in tissue, but also in serum in patients with digestive cancers. Although FAS is found to be over-expressed in many solid tumors, its role in digestive cancer has not been extensively evaluated. We have reported that it seems to be up-regulated during the early stages of tumorigenesis.

In Digestive neoplasm, Upper GI (esophageal and gastric) and colorectal ones have different characteristics due to carcinogenesis. Upper GI neoplasm results from the continuous inflammation from Helicobacter pylori and various other factors. Therefore colorectal one arises from adenoma carcinoma sequences. Our results show a different tendency for each other. Compare between premalignant status and malignancy, by using serum and tumor FAS level we can approach the mechanism of reprogramming the regulation of metabolic pathways.

Biography:

Lisa Repsold is a PhD student at the Department of Physiology, University of Pretoria, South Africa. She completed her Masters degree cum laude and is currently conducting her PhD study with a title: ‘Angiogenic, apoptotic and autophagic profiling of chronic myeloid leukaemia patients’ platelets ex vivo before and after treatment with Imatinib’. She has published three papers in internationally accredited peer-reviewed journals and presented her research at national conferences. In her research career she has mastered several scientific techniques including scanning and transmission electron microscopy, flow cytometry, cell culture techniques and western blot.

Abstract:

Platelets are known contributors to vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in the release of angiogenic activators thereby promoting angiogenesis. Angiogenesis-regulating proteins are ideal biomarkers in the study of cancer pathophysiology and represent desirable therapeutic- and diagnostic targets.

The in silico-designed analogue of 2-methoxyestradiol, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16), binds to carbonic anhydrase II delaying early metabolism and is thus carried into the circulation. The effect it potentiates on blood components, especially on platelets, is of significance in cancer progression. This study thus investigated the possible ex vivo apoptotic, autophagic and angiogenic effects of ESE-16 on platelets.

Scanning electron microscopy was used to assess morphological changes in platelets after exposure to ESE-16 and no changes were observed in ESE-16-treated platelets. The possible induction of apoptosis and autophagy was determined by annexin V-FITC, measurement of caspase 3 activity, autophagy-related protein 5 levels, light chain 3-I to light chain 3-II conversion and monodansylcadaverine staining which indicated that there was no increase in apoptosis or autophagy when platelets were exposed to ESE-16. The expression of the angiogenic proteins namely vascular endothelial growth factor, platelet derived growth factor and matrix metallopeptidase-9 was also assessed and results showed that levels were significantly increased after platelets were added to MCF-7 cells.

This is the first ex vivo study to highlight possible involvement of angiogenesis, apoptosis, autophagy in platelets after exposure to this potential anti-cancer compound warranting further investigation concerning these signaling pathway targets on platelets of cancer patients.

Biography:

Abstract:

Background:  Breast  cancer  is  becoming  a  silent killer  amongst  women  of  younger  age due  to  negligence  and   belief  that  it  occurs only  in  old  women.  As  long  as there  are  presence  of  breast  tissues  in  a  female, breast  cancer  can occur  from  any  age.

Methods: A  qualitative  study  was  carried  out  for  1 week, offline  forms  were  filled  by   women  of different  races, ages   diagnosed  of  cancer. Data  was  compiled ,AGE 15-35 was  grouped  as  young  and 36 >  was  grouped  as  old.

Result: Among   the   participants, were   6   cases   of   younger   women   and   39   cases   of  older   women .  Most  women  of  the  young  age group  linked  their  diagnosis  to  genetic  predisposition  while  women  of  older  age  groups  could  not  determine  a   link  to  their diagnosis  which  rarely  occurs.   

Conclusion: Prevalence   of   breast  cancer  in  younger  women   is  quite  low  and  can  be  linked  to family  history, unlike  in  older   women  it   is  very  high and  can be  due  to  various  risk  factors  which  cannot  be  stated  specifically.