It’s no secret that most bright minds in the cancer research space are joined by competing priorities of funding, budget and other issues of safety, side effects, impact and risk factors.
As Europe’s leading conference on cancer research, advances and challenges in the field, we at the European Congress on Clinical Oncology or ECCO are driven by the goal to bring the global cancer coThe current status of colorectal cancer in Chinmmunity together. We take pride in creating a space that cultivates the exchange of the latest, most promising findings as well as the pressing issues in our field today and the future.
So without further ado, here are the full details of the conference proceedings:
Presentation Topics (with speaker details and synopsis)
1. Cyclic peptide derived from flax inhibits cell proliferation of giant cell tumor of bone
Speaker: Yuta Taniguchi, Department of Orthopaedic Surgery, Kanazawa University Hospital
Synopsis: In recent years, the effectiveness of anti-receptor activator of NF-κB ligand (RANKL) therapy on giant cell tumours of the bone (GCTB) has been reported. Flax (botanical name: Linum usitatissimum) is a member of the family of Linaceae and raw material for linseed oil. Cyclolinopeptide (CL), cyclic peptide derived from flax, suppresses the RANKL signal and osteoclast differentiation from myeloid progenitor cells. However, the anti-tumour effects of CL remain poorly understood. This study aimed to evaluate the anti-tumour effects of CL on GCTB in vitro.
Materials and methods: Three cases of GCTB tissue were collected from a surgical specimen. The GCTB tissues were treated with collagenase and sub-cultured several times in D-MEM medium supplemented with 10% FBS. Three kinds of GCTB cell lines were established. Immunofluorescence of the GCTB cells were evaluated for RANKL expression and transmutation of histone H3F3A, a driver gene mutation in GCTB. GCTB cell growth inhibition by CL was evaluated using water-soluble tetrazolium salt (WST)-8 cell proliferation assay and 5-ethynyl-2’-deoxyuridine (EdU) cell proliferation assay. The mRNA expression levels of RANKL and RUNX 2 were evaluated using real-time polymerase chain reaction (PCR) before and after administration of CL.
Results: During immunofluorescence, RANKL expression and transmutation of histone H3F3A were observed in all cell lines. In WST-8 cell proliferation assay, dose-dependent inhibition of GCTB cells was observed in the CL-administered group, compared to non CL-administered group (P<0.05). During EdU cell proliferation assay, the ratio of EdU positive cells decreased in the CL-administered group (P<0.05). During real-time PCR testing, expressions of RANKL and RUNX2 mRNA were decreased within the CL-administered group (P<0.05).
Conclusion: Our study suggests that CL has anti-tumour effects on GCTB in vitro.
2. The current status of colorectal cancer in China
Speaker: Jin Gu, M.D., FACS, FASCRS Peking University Cancer Hospital , GI 3 department
Synopsis: Colorectal cancer (CRC) is the fourth most common carcinoma in China. For economic reasons, a national colorectal cancer registry system has not been established and a large scale screening programme has not yet been implemented. Therefore, accurate statistical data concerning the incidence of colorectal cancer covering the whole country cannot be obtained. In China, the majority of hospitals in central cities and even in county hospitals are able to provide medical care for CRC patients. Due to socioeconomic disparities, medical conditions and skill levels, there is a wide variation in the treatment. Most oncologists make their clinical decisions based on the National Comprehensive Cancer Network (NCCN) guidelines although some domestic guidelines are now available. In October 11, 2011, the China Ministry of Health released the National Guideline of colorectal cancer treatment. This will give a degree of standardization of the treatment of CRC nationwide and will ensure that higher quality care will be available, especially in rural areas. Owing to language difficulties, research on CRC in China has only had a limited exposure in the international literature, due in some part to lack of understanding of the current position in the country. Chinese colorectal surgeons urgently need to exchange their knowledge and experience with international colleagues. In this article, the current situation regarding surgical treatment of rectal cancer in China is summarized.
3. Drug repositioning: New hope and opportunities for cancer patients and pharmaceutical companies
Speaker: Weiguang Wang
Synopsis: There are over 200 types of cancer reported all over the globe. The risk of getting cancer is as high as 1:2 -1:3 in the West but WHO predictions suggest cancer risks are also dramatically increasing in low-medium income countries likely to lead to estimated 21 million deaths world wide by 2030. Although the outcomes of cancer treatment have been improved in the last three decades most of them remain ‘incurable’. The complexity of this disease at genetic and phenotypic levels leads to its clinical diversity and therapeutic resistance. The recent discovery that many cancers are probably driven by a small sub-population of cancer stem cells (CSCs), suggests that the therapeutic outcomes will be significantly improved by effectively targeting CSCs.
The medical need for better cancer therapies is urgent while drug development is slow and costly, mainly due to the large risk of toxicity of novel molecules. Development of a new drug takes on average 15 years and US$1.5bn with only 5-25% of new oncology drugs in clinical development actually reaching the market. This has led to an increasing appreciation of the potential of repurposing of known drugs.
We have shown that disulfiram, an anti-alcoholism drug used in clinic for over 60 years, shows specific activity against a wide range of cancers. Importantly, we have been able to demonstrate that disulfiram specifically destroys cancer-stem-like cells and enhances the cytotoxicity of several conventional first-line anticancer drugs. Although disulfiram shows strong anticancer activity in laboratory, clinical use of disulfiram as an anti-cancer drug is limited by its rapid degradation and extensive metabolic conversion in the bloodstream.
To overcome this bottleneck, we recently used nano-technology to wrap disulfiram into nanoparticles and extend its half-life in the blood from 4 minutes to over 7 hours and obtained very promising anticancer activity in cell culture and in brain, breast, liver, lung cancer and mesothelioma animal models. Nano-wrapped disulfiram blocks tumour growth and metastasis in mouse models. We also developed skin penetrating derma gel formulation. The preliminary clinical studies manifested very promising outcomes in lung, breast, pancreatic cancer and lymphoma patients with multiorgan metastasis. All patients tolerated the treatment very well with no significant side effect.
Disulfiram is a Food and Drug Administration approved drug. Our invention will quickly lead it into cancer treatment. The success of our study will significantly benefit our cancer patients and economy.
4. A parallel deep learning network framework for whole-body bone scan image analysis
Speaker: Xiaorong Pu, University of Electronic Science and Technology of China
Synopsis: Whole-body bone scan image analysis in nuclear medicine is a common method assisting physicians in bone metastases detection of cancer. As the increasing need for diagnostic examinations in the huge and elderly population in China, physicians are facing a significant growth of workload but must still manage to read the diagnostic images carefully and avoid errors in interpretation. In this study, we proposed a parallel deep learning network framework for bone-scan interpretations of the presence or absence of bone metastases. The whole-body bone scans (anterior and posterior views) of 707 patients who are suspected bone metastatic disease were studied. The physicians were asked to classify each case for the presence or absence of bone metastasis manually. Each bone scan image was automatically segmented into 26 different anatomical regions of homogeneous bones based on the skeletal frame. The corresponding 26 deep learning networks made a diagnosis by inspecting each region and searching for abnormal lesion activity simultaneously. To estimate the performance of each anatomical sub-region identification models, a ten-fold cross testing scheme was applied where the data set was divided into ten parts of equal size randomly. The sensitivity, specificity and the mean number of false lesions detected were adopted as performance indices to evaluate the proposed model. The best sensitivity and specificity of an individual network corresponding to each sub-region are 99.9 % and 97.3% respectively. The overall mean sensitivity and specificity of the parallel model are 99.2% and 71.8% respectively, as well as 2.0 false detections per patient scan image within millisecond. With an extremely high sensitivity, specificity and a low false lesions detection rate, this proposed parallel deep learning network model is demonstrated as useful for detecting metastases in bone scans. Our proposed framework appears to have significant potential as a clinical decision support tool in assisting physicians in their clinical routine.
5. Adjuvant chemotherapy of early prostate cancer
Speaker: Pirkko-Liisa Kellokumpu-lehtinen
Stay tuned for more details on this topic!
6. Igf2bp3 in gonadal differentiation and the testis cancer development
Speaker: Guijun Guan, Shanghai Ocean University
Presentation Details: Gsdf as one of TGF- factors is essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes), with an unknown mechanism. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf-deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf-deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Moreover, Igf2bp3 and relevant proteins were abnormally expressed in human testis cancer, indicating the important role of TGF/Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla.
7. Up-regulated LGMNP1 mediated radiotherapy resistance in glioblastoma
Speaker: Li Ren
Objective To study the function of legumain pseudogene 1 (LGMNP1) on the radioresistant in glioblastoma.
Methods RT-qPCR detected the relative expression of LGMNP1 in glioma cell lines after radiotherapy. Lentiviral vector-mediated LGMNP1 gene overexpression. Clone formation test was used to estimate the clonogenic formation ability following radiotherapy. Comet assay, flow cytometry (FCM) and western blot were applied to detect the ability of DNA repairment, apoptosis cell, and apoptotic proteins, respectively. Result LGMNP1 was significantly up-regulated in glioma cells after radiation. The model of overexpression of LGMNP1 in glioma cells were stably constructed. Overexpression of LGMNP1 in glioma cells elevated DNA repair processes and reduced the percentage of apoptotic cells after radiotherapy. In addition, overexpression of LGMNP1 in GBM cells decreased apoptotic protein after radiotherapy. Conclusion Up-regulated LGMNP1 mediated radiotherapy resistance by increasing the ability of DNA repairment and reducing the apoptosis cells in glioma cells.
8. Gliolastoma Multiforme (GBM) Microvesicles: Biomarkers of cancer stem cells (CSCs) and tumor invasion/progression
Speaker: Sarah Crawford, Southern Connecticut State University New Haven, CT, USA
Synopsis: Research in our laboratory on microvesicles (MVs) secreted by glioblastomsa multiforme (GBM) astrocytoma cells suggests that these intermediate sized (100-100nm) vesicles play an important role in microtumor formation, mediating cell-to-cell interactions to form tumor aggregates that coalesce to condensed bodies with physiological parameters comparable to micrometastases in vivo. MVs are dynamic, flexible membrane bound bodies that can fuse to produce end-to-end tubules that connect solid tumor masses to other satellite tumors. Western blot analysis of the protein composition of the tumor associated MVs showed that they contain significant amounts of alpha-v-integrin, a trans-membrane adhesion protein that binds the extracellular matrix (ECM). Patient tumor studies have shown that this biomarker is selectively expressed in GBM, but not in lower grade gliomas, normal glia or neurons in the cortex and cerebral white matter where aggressive GBM tumors commonly arise. Moreover, tumor biopsy studies link alpha- v – integrin to more highly invasive and proliferating tumor areas. Cadherins, calcium regulated transmembrane cell-to-cell adhesion proteins, were also present in MVs secreted by GBM cells in culture. Lower levels of other cell surface proteins implicated in local tumor spread and invasion were detected in GBM MVs, including CD63, CD47, Tsg101 and flotillin-2. In addition, several proteins identified previously as neural stem cell markers, including neurolignin-3 and beta-III tubulin, were identified in the tumor cell membrane and associated microvesicles. Neurolignin-3 has been identified as a growth promoting activator of GBM tumors. Beta-III is present at high levels in the developing central and peripheral nervous systems, but not in mature brain tissue, except in malignant tumors.
It is highly significant that GBM tumor MVs contain proteins specifically linked to the invasive and progressive properties of glioblastoma, suggesting that the MVs may play an important role in tumor invasion and spread. I will present a model, “insertional membrane editing” to explain how tumor MV/stromal interactions may facilitate tumor progression by reprogramming adjacent stromal tissue. MVs may serve as an intricate intercellular communication platform for coordinating homeostasis within the tumor microenvironment. In the context of the tumor microenvironment, changes in cell-to-cell adhesion parameters, such as those involved in epithelial to mesenchymal transitions (EMTs), may promote the production of MVs that further contribute to tumor invasion and spread by remodeling the tumor invasion zone to facilitate tumor cell migration, ECM attachment and invasion.
The presence of highly expressed stem cell biomarkers on both tumor cells and associated MVs suggests that astrocyte “dedifferentiation” is a critical component of GBM malignancy. Using a novel tumor invasion assay recently developed in our laboratory, the activities of each of the MV components identified will be assayed for their specific roles in brain tumor progression.
9. The progress of Limb-Salvage Surgery for Osteosarcoma
Speaker: Hiroyuki Tsuchiya, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University
Synopsis: The progress of musculoskeletal sarcoma treatment has been providing the improvement of limb-saving surgery and survival rate in patients with those tumors. Recently, limb-saving tumor surgery, which is not limited for merely saving, aims at much better functional results. The goal of limb-saving tumor surgery is normalization of the affected limbs in function and appearance.
Biological reconstruction after tumor resection is classified into two sub-types. One is reconstruction with living bone such as vascularized bone transfer and distraction osteogenesis. The other one is reconstruction with devitalized bone such as allograft, irradiated autogarft, autoclaved autograft and frozen autograft treated by liquid nitrogen. Each reconstruction method has both advantages and disadvantages. Living bone can provide structure, cells, proteins and blood supply while most of devitalized bones can provide only structure and proteins. Biological healing of bone and excellent attachment between bone and soft-tissue can be specifically expected in biological reconstruction.
In this lecture, I would like to introduce reconstruction methods with distraction osteogenesis, massive frozen autograft and vascularized fibular graft, and also talk about tips how to make the best use of those methods based on our experience of more than 30 years.
10. Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma
Speaker: Huidi Liu, Harbin Medical University
Synopsis: Ovarian Clear Cell Carcinoma (OCCC) displays distinctive clinical and molecular characteristics with the worst prognosis among all ovarian carcinoma types. IGF2BP3 is a member of an evolutionarily conserved protein family. In this study, we investigated the roles of IGF2BP3 in the progression of OCCC. A total of 328 OCCCs from the AOVT (the Alberta Ovarian Tumor Type study) and COEUR (the Canadian Ovarian Experimental Unified Resource) cohorts were used to elucidate the associations between IGF2BP3 expression and clinicopathological parameters, with positive IGF2BP3 expression defined as diffuse block staining being more frequently observed at stage III (P=0.0056) and significantly associated with unfavorable overall survival cases ((HR=1.59, 95% CI 1.09 – 2.33) in multivariate analysis.). Meanwhile bioinformatic methods revealed IGF2BP3 gene expression levels were markedly increased in OCCC compared to normal ovarian surface epithelium (NOSE). We chose the IGF2BP3-overexpression cell lines ES2 and OVMANA for further knockdown in vitro and in vivo experiments by siIGF2BP3-1/-2. The proliferation and viability of both cell lines were significantly inhibited by siIGF2BP3-1/-2 and similar suppression was observed in cell migration and invasion by Wound Healing and Transwell assays. The percentage of apoptotic cancer cells was enhanced by both siIGF2BP3-1 and siIGF2BP3-2. With in vivo experiments, compared to those in the left side (negative controls), siIGF2BP3-1 delayed tumors starting point in the right side(P<0.05), and all animals treated with siIGF2BP3-1 gradually gained body weight. Furthermore, cancer metastasis-indicators MMP2 and MMP9 were down-regulated as seen in western blots, ELISA assays and by immunohistochemistry. In conclusion, our studies of IGF2BP3 by both in-vivo and in-vitro experiments suggest that IGF2BP3 may be an important prognostic biomarker for clinicopathological diagnosis in OCCC.
11. Effects of herbal medicine for xerostomia in head and neck cancer patients: an observational study in a tertiary cancer hospital
Speaker: Ren Jye Lim, Traditional and Complementary Medicine Unit, National Cancer Institute Malaysia.
Synopsis: More than 80% head and neck cancer patients endured radiotherapy-induced xerostomia which impacts their quality of life (QoL). This observational study evaluated the effect of herbal treatment on head and neck cancer patients’ xerostomia and QoL.
Methods:Head and neck cancer patients were recruited from July 2016 till March 2017 at National Cancer Institute, Ministry of Health, Malaysia. All study participants continued their standard oncology surveillance. Treatment group participants additionally received Chinese herbal treatment. The assessments included unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and QoL questionnaire.
Results: Of 42 recruited participants, 28 were in the treatment group and 14 were in the control group. Participants were mainly Chinese (71.4%), stage III cancer (40.5%), and had nasopharynx cancer (76.2%). The commonly used single herbs were Wu Mei, San Qi, and Tian Hua Fen. Sha Shen Mai Dong Tang, Liu Wei Di Huang Wan, and Gan Lu Yin were the frequently prescribed herbal formulas. The baseline characteristics, USFR, SSFR, and QoL between control and treatment groups were comparable (p > 0.05). USFR between control and treatment groups were similar throughout the 6-month study period. SSFR for the treatment group significantly improved from 0.15 ± 0.28 ml/min (baseline) to 0.32 ± 0.22 ml/min (p = 0.04; at the 3rd month) and subsequently achieved 0.46 ± 0.23 ml/min (p = 0.001; at the 6th month). The treatment group had better QoL in terms of speech (p = 0.005), eating (p = 0.02), and head and neck pain (p = 0.04) at the 6th month.
Conclusion:Herbal treatment may improve xerostomia and QoL in post-radiotherapy head and cancer patients.
12. Irradiated tumor cells with lactic acid stimulation can enhance the anti-tumor immunity
Speaker: Jiayun Yu, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Synopsis: Low pH and lactate accumulation are characteristic features of the tumor microenvironment. With the finding in our study that high concentrations of lactic acid can inhibit tumor growth, it is conceivable that the administration of lactic acid could promote the antitumor immunity of a tumor vaccine. To test this concept, we studied the anti-tumor effect of irradiated tumor cells which were stimulated by lactic acid in mouse xenografts models to potentially improve whole-cell tumor vaccines. In this study, we found that lactic acid could obviously inhibit tumor growth and the inhibition function was enhanced with the increase of lactic acid concentration. The effect of lactic acid stimulated tumor cells on DCs included enhancing phagocytosis function, stimulating maturation and aggregation. Moreover, lactic acid could potentiate the immunogenicity of UV-irradiated whole tumor vaccine and then inhibit tumor growth. We further verified that the antitumor immune response was mediated by CD8+ T cells. Besides, interferon–γ expressing CD4+ and CD8+ T cells in spleen and lymph nodes of mice immunized by cells with irradiation and lactic acid stimulation increased. furthermore, the tumor microenvironment change was also observed in this study. Reduction of Myeloid-derived suppressor cells and increase of activated CD8+T cells were proved in tumor tissues. Reduced Treg cells and increase of activated CD8+T cells were observed in para-tumor lymph nodes. Our findings may be helpful for seeking a new strategy for cancer therapy.
13. Aging of Hematopoietic Stem Cells, Warburg Effect and Clonal Hematopoiesis
Speaker: Anthony Ho, Department of Medicine V, University of Heidelberg, Germany
Synopsis: Aging entails functional decline of tissues and cells in the organism and especially of stem cells. Applying -omics analyses, we have studied the molecular features of aging in human hematopoietic stem cells (HSC) as a model for other stem cell systems. The most prominent finding is that the sugar metabolism of HSC increases with age – a change reminiscent of the Warburg effect. This is coupled with lineage skewing of HSC towards myeloid differentiation.
Methods: We recruited 59 healthy human subjects aged between 20 and 60, who donated bone marrow for the study. In contrast to other studies performed in HSC from mouse models of aging, we examined especially the proteomes, i.e. all protein changes over time not only in HSC, but also in other cells that comprise the bone marrow environment called the “niche”.
Results: Among all diverse alterations within the aging process, the most remarkable and significant change is an enhanced metabolic and anabolic activity of older HSC. The abundance of enzymes catalyzing the upper part of glycolysis, e.g. hexokinase 1 (HK1) and phosphorfructokinase M (PFKM), aldolase C (ALDOC) and triosephosphate isomerase 1 (TPI1) was found. The second phase as well as the Krebs cycle, remained unaffected. This is reminiscent of the Warburg effect, where excess of glycolytic carbon is redirected to pathways that branch out of glycolysis. Simultaneously we have found a continual and significant decrease in abundance of proteins essential for lymphoid differentiation with aging, and an increase in abundance of proteins for myeloid and platelet differentiation. Transcriptomic analyses of single sorted CD34+ cells showed that the increase in glycolytic enzymes in older HSC is found only in myeloid-primed CD34+ cells and is associated with the lineage skewing of the HSC at the expense of the lymphoid-primed CD34+ cells. This gradual loss of functional lymphoid cells with aging has been described in murine models and is proven unequivocally by our present study.
Conclusions: Our discovery implies that we might be able to influence the changes associated with aging by intervening in sugar metabolism. Controlled inhibition of glucose metabolism might restore the balance between the myeloid and lymphoid cells. These rare human datasets will serve as an important reference for further studies on the molecular mechanisms of aging and age-related diseases such as myelodysplasia and hematologic malignancies.
14. Cerenkov Lumicenscence Imaging, a new challenge in prostate cancer surgery
Speaker: Marcel Stokkel, NKI-AVL, Amsterdam, Netherlands
Synopsis: Prostate cancer is one of the most common cancer types in male patients. Standard treatment options in this tumor type are radiotherapy, wait and see, hormonal treatment or surgery. all depending on factors as tumor stage, age and patient’s condition. It has been noticed, however, that in case of surgery, complete resection of the tumor is achieved in 70-80% of the patients. In approximately 25% of the patients, additional treatment is required. In this respect, it would be very helpful to have better techniques to assess tumor margins during surgery in order to have better results.
Gallium68-PSMA PET/CT scanning is a very important technique nowadays for prostate cancer staging, with both high sensitivity and specificity. Initial results were related to the detection of recurrent disease, whereas over the past 2 years primary staging has become the second important indication in PCa patients with a high risk profile. It is known that PET tracers, and especially Fluor 18 and Gallium-68, not only emit annihiliation photons, but also induce the production of Cerenkov light. This blue light is very typical and can be detected with special devices. Furthermore, this light can be dimmed by a thin layer of tissue, which may be indicative for a complete or non-complete resection of tumors. When Ga68-PSMA is injected prior to prostatectomy, this light therefore may be used to assess tumor margins. In case of a complete resection in which the tumor is covered by normal tissue, this blue light will not be detected anymore, whereas in case of an incomplete resection, there will be a glimp of this blue light. In the latter case, reresection can be performed immediately. Theory behind this technique and first pre-clinical results will be presented. Finally, since it is known that the waiting time between diagnostic procedures and prostatectomy may be up to 5 week, we have to be sure that Ga68-PSMA uptake in the primary tumor will not change during this period. Therefore, we have performed a test/re-test study analyzing this feature with an interval of 4 weeks between the two scans. It was demonstrated that kinetics and absolute uptake do not change over time. As a consequence it can be stated that the Ga68-PSMA administration prior to surgery can be done in the operation room without the need of extra PET/CT scanning. The ultimate goal is to apply this technique to other tumor types using other radiopharmaceuticals.
15. Optimization of Medical Accelerators
Speaker: Carsten Welch, University of Liverpool
Synopsis: Proton and heavy ion beam cancer therapy promises significant advantages over other forms of radiation therapy. However, to assure the best possible cancer care for patients, further R&D into novel beam imaging and patient diagnostics, enhanced biological and physical models in Monte Carlo codes, as well as clinical facility design and optimization is required.
Within the pan-European Optimization of Medical Accelerators (OMA) project, collaborative research has been carried out since 2015 between universities, research and clinical facilities, as well as industry partners in all of these areas. This contribution gives an overview of the research results of this major European initiative. It will present the characteristics of the new sensor technologies that have been developed for online beam and patient monitoring, the results from Monte Carlo techniques for therapy planning and beam modelling purposes, as well as improved beam delivery schemes for state-of-the-art proton and heavy ion therapy. A summary of the interdisciplinary approach to training of early stage researchers that was pioneered by the OMA consortium will also be given.