BrainMap

Mrs. Laura Georgiana Necula

PhD

- INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Web of Science ResearcherID: I-1668-2015

Expertise & keywords

Mechanisms and biomarkers of response and resistance to current targeted therapies in gastric cancer Call name: P 4 - Proiecte Complexe de Cercetare de Frontieră
PN-III-P4-ID-PCCF-2016-0158 2018 - 2022

Role in this project:

Coordinating institution: INSTITUTUL CLINIC FUNDENI

Project partners: INSTITUTUL CLINIC FUNDENI (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE CRAIOVA (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: https://cemt.ro/proiect/therres/

Abstract:

Gastric cancer (GC) is a heterogeneous disease with almost one million new cases occurring annually worldwide. Recent developments provide the unprecedented opportunity to make substantial progress in GC therapy. Targeted therapies have revolutionized the therapy of GC, but the benefits remain limited to a few months of increased survival.

The challenge is now how to best stratify patients for therapy, and to identify ‘druggable’ primary and acquired resistance.

Limited studies have been performed to evaluate biomarkers for predicting response to anti-HER2, anti-MET, anti-VEGFR2 therapy in GC, and immune checkpoints that contribute to tumor resistance. Moreover, combining targeted strategy with immune checkpoint inhibition – the most exciting and active area of research currently because of durable responses seen in melanoma and lung cancer – are among the new frontiers of research in the cancer treatment and could represent a quantum leap in the therapy of GC.

The project specific objectives are:

Objective 1: To explore potential biomarkers and targets for therapy in GC subtypes defined based on contemporary disease classifications

Objective 2: To examine biomarkers of response and resistance to standard anti-HER2, anti-MET, and anti-VEGF therapy in GC

Objective 3: Characterization of the particular features of GC vascular stroma, including the study of the potential role of immune checkpoints in GC subtypes

As a key output, the project will generate decision making tools for treatment and management of GC patients in a personalized approach. The results of the present project will help improve the performance, quality and international visibility of Romanian scientific results in oncological field.

Evaluation of the exploatation potential Potential of Porous Materials in the tREatment of Microbiota-related dISeasEs - PREMISE Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-4018 2020 - 2022

Role in this project:

Coordinating institution: UNIVERSITATEA POLITEHNICA DIN BUCURESTI

Project partners: UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: https://www.micronanotech.ro/evaluarea-potentialului-de-exploatare-a-materialelor-poroase-in-tratarea-disbiozelor-microbiotei/

Abstract:

The scope of the current project proposal is to develop novel micro- and mesoporous materials (MMMs) using recent synthesis methods and to further functionalize these materials for developing better performances in order to be used as drug delivery systems (DDS), especially for microbiota-related diseases. These drug delivery systems are developed for oral administration and are expected to be protected within the stomach and maintain their activity until reach the desired site. Even if these drug delivery platforms are extensively exploited in the literature for several types of applications as DDS (hosting anticancer, anti-infectious or analgesic agents), the field of microbiota is only marginally treated. Nowadays, especially in the case of children, the awareness about the importance of the microbiota is well known, therefore after an antibiotic treatment, the prescription of probiotics is frequently needed. In the project’s boundaries, natural substances (polyphenols and vitamins) used as biological active agents will be loaded into the porous platforms, in order to assure a positive feedback to the microbiota due to the antioxidant, antimicrobial, anti-inflammatory and anticancer activities. In recent years, great emphasis has been placed on the development of micro and mesoporous materials loaded with biological active agents, but few research papers discuss the impact of functionalized MMMs on microbiota. In the current project, the main goal is to develop innovative MMMs with enhanced pore system able to host and deliver biological active agents (vitamins and polyphenols are expected to be used) for the treatment of the microbiota-related diseases. because most polyphenols have low solubility, two innovative delivery systems will be developed in order to assure triggering delivery / smart delivery.

Evaluation of COL10A1 as potential therapeutic target and early diagnosis biomarker in gastric cancer Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-1864 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.virology.ro/ro/cercetare/proiecte/proiect-pn-iii-p1-1-1-te-2019-1864-col-dia-ther

Abstract:

The project “Evaluation of COL10A1 as potential therapeutic target and early diagnosis biomarker in gastric cancer” aims to analyze the involvement of COL10A1 in gastric carcinogenesis in order to evaluate his potential as biomarker for gastric cancer diagnosis and, also, to assess him as molecular target for development of new cancer therapeutic strategies. Recent studies, including a project conducted by our group suggested that modification of COL10A1 gene expression is associated with neoplastic transformation of gastric tissue and also with tumor progression. The project objectives include the validation of COL10A1 as possible therapeutic target by analysis of his oncogenic effects through loss- and gain-of-function experiments in tumoral and normal gastric human cells, and evaluation of circulating COL10A1 in plasma of the patients with gastric cancer in order to identify his potential as diagnostic biomarker for gastric cancer. The results of the project are assumed to have a significant social impact by reducing individual suffering and social costs due to chronic patients care, and these might also be applicable to the early diagnosis of the disease. The project results could also offer the basis for identifying new molecular targets and developing solid therapeutic approaches for gastric cancer that will be highly interesting for pharmaceutical companies.

Composite hydrogels based on inorganic nanoparticles and collagen with prolonged antimicrobial activity for the prevention of wound infections Call name: P 2 - SP 2.1 - Proiect de transfer la operatorul economic
PN-III-P2-2.1-PTE-2016-0177 2016 - 2018

Role in this project:

Coordinating institution: SANIMED INTERNATIONAL IMPEX S.R.L.

Project partners: SANIMED INTERNATIONAL IMPEX S.R.L. (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://nanocolagel.sanimed.ro/

Abstract:

Chronic wounds represent a good niche for biofilm development because the impaired immune response promotes infection susceptibility whilst necrotic tissue and debris favor bacterial attachment. Collagen hydrogels represent one of the most efficient treatments in case of both chronic and acute wounds due to their ability to maintain optimal humidity and aeration parameters. Currently, at a national level there is no production of collagen hydrogels aimed for the treatment of chronic wounds, hence these types of products are being imported. In this context, the present project proposal aims to design and obtain new types of multifunctional collagen hydrogels harboring antimicrobial properties in order to favor the healing process of chronic wounds. As a novelty element in comparison to products currently available on the international market, we will design and produce collagen hydrogels containing nanoparticles. Thus, Sanimed International Impex S.R.L will develop a simple and rapid technology to obtain hydrogels functionalized with metalic and oxidic nanoparticles (collagen hydrogels with Ag nanoparticles, collagen hydrogels with ZnO hydrogels and collagen hydrogels with SiO2@ZnO nanoparticles). The novel hydrogels will be tested for their antimicrobial and antibiofilm properties using in vitro and in vivo methods and also for the host response after hydrogel treatment on wounded cells and in vivo lesion murine models, for achieving market preparation.

Knowledge Transfer on investigation of the anti-infective and antitumoral activity of novel cosmetic and pharmaceutical formulations based on natural extracts Call name: P 2 - SP 2.1 - Transfer de cunoaștere la agentul economic „Bridge Grant”
PN-III-P2-2.1-BG-2016-0369 2016 - 2018

Role in this project:

Coordinating institution: UNIVERSITATEA BUCURESTI

Project partners: UNIVERSITATEA BUCURESTI (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); HOFIGAL EXPORT IMPORT SA (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: https://icubresearch.wordpress.com/2018/10/19/bg-369/

Abstract:

The present project proposal aims the development of an innovative methodology for testing the antimicrobial, antiviral, anti-tumor and immunomodulatory activity, and to elucidate the mechanisms of action at the cellular and molecular level of natural bee and plant extracts with the purpose of introducing them în new cosmetic and pharmaceutical formulations, for expanding the marketed products range of the economic agent participating în the project - Hofigal S.A.

The addressed strategy is based on abundant scientific literature and original experimental results of all involved partners regarding the characterization and marketing of natural products / compounds with therapeutic or prophylactic value.

The proposed project falls into a major research direction aimed at the discovery of complementary therapeutic solutions based on natural compounds, for the treatment of different pathologies (i.e., infectious diseases and cancer), which are currently found în the top of causes of global morbidity and mortality.

The therapeutic alternatives that will be investigated în this project are based on natural compounds of vegetal and bee origin, with high therapeutic and preventive potential, due to the following properties: complex composition that allows simultaneous action on multiple biological targets; decreased risk for selecting resistance, both în case of infectious agents, such as viral, bacterial and fungal, and în the case of tumor cells; immunomodulatory effect; high biocompatibility; minimal or no side effects.

Implementation of a complex genome profiling diagnostic algorithm for patients with congenital and developmental abnormalities Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-2240 2014 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU"

Project partners: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); INSTITUTUL NATIONAL PENTRU SANATATEA MAMEI SI COPILULUI "ALESSANDRESCU-RUSESCU" BUCURESTI (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "GR. TH. POPA" (RO); PERSONAL GENETICS S.R.L. (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.virology.ro/ro/congen-proiect

Abstract:

The proposed project will set up a consortium in genomics, aiming at the implementation of new investigation methods in clinical practice that could contribute to the elucidation of the molecular mechanisms of congenital and developmental abnormalities with a final practical goal in prophylaxis and better clinical management of patients. The project corresponds to the direction 4 - HEALTH and its objectives refer to the national implementation of new prevention and intervention methods in accordance with European standards (4.1.6). The major objectives of the project are:

1) Investigation of genetic abnormalities in Romanian patients with congenital/developmental disorders aiming to identify possible new genomic variants;

2) Integration in the international endeavor of identifying and confirming new genomic variants for these rare disorders through active participation and inclusion of the Romanian data in the multi-center international consortia.

3) Implementation of a complex genome profiling diagnostic algorithm for patients with congenital and developmental abnormalities and use the integrated results for improving diagnostic yield, genetic counseling and clinical management.

The partnership consists of Stefan S. Nicolau IVN Bucharest, that will set-up the cells/DNA/RNA sample bank and perform PCR, MS-MLPA, sequencing analysis; Alfred Rusescu IOMC Bucharest and Grigore T. Popa UMF Iaşi that will recruit the patients, perform the phenotype/formal-genetic analysis and clinical management of the patients, and Personal Genetics Ltd. which will perform aCGH and next generation sequencing, will integrate the results of the analysis and will apply the resulting algorithm, firstly in their practice, and next will disseminate it to a clearly defined target market. The consortium represents a specialized and complementary team, capable to advancing the knowledge on clinical management, prevention, and eventually, therapy of congenital and developmental abnormalities, and to join international research effort in this direction.

PELL AMAR – A NAME IN SEARCH OF ITS LOST FAME Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-1470 2014 - 2017

Role in this project:

Coordinating institution: PELL AMAR COSMETICS S.R.L.

Project partners: PELL AMAR COSMETICS S.R.L. (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE CHIMICO - FARMACEUTICA - I.C.C.F. BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" RA (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" RA (RO)

Project website: http://www.pellamar.com/dermatocosmetice/cercetare.php

Abstract:

PELL AMAR – A NAME IN SEARCH OF ITS LOST FAME

Finding that sapropelic mud has biotrophic, regenerating, sedative, analgesic, anti-inflammatory properties, Dr Ionescu Călineşti had two ideas that led to a Romanian brand of great success in 1970:

a) he inferred the synergistic effect of the combination of minerals, enzymes and organic substances, mainly its holistic healing action;

b) he obtained by atomization, a concentrate with enhanced curative effects.

The extract was called PELL AMAR and was used in over 40 products: pharmaceuticals (including injectables), cosmetics, food supplements. After some clinical trials (1980) PELL AMAR products were used for treating ailments such as rheumatoid polyarthritis, ankylosing spondylitis, cervical, dorsal, lumbar vertebro-peripheral osteoarthritis, gonarthrosis, coxarthrosis, scapulo-humeral periarthritis, tendonitis, synovitis, bursitis, sprains, bruises, dislocations, contusions, psoriasis and localized scleroderma, burns.

After 1990 the products disappeared from the market, at the same time with their production infrastructure, and with the legislative changes which cancelled the old authorizations. In 2010, the products reappeared with the establishment of SC PELL AMAR COSMETICS SRL, which in the last 3 years has demonstrated that the sapropelic mud extract can successfully cope with the technical and commercial demands of the cosmetics market.

This project aims to increase the quality and competitiveness of PELL AMAR - COSMETICS range, which are already produced and initiate a new category of PELL AMAR – PHARMA range, by significant changes in the technology, base product and derived products and also by upgrading the approach of production, verification and control process,.

The basic ideas are:

• Upgrading the technology by:

1) replacing the atomization concentration with the lyophilisation concentration;

2) introducing a new stage of irradiation treatment of the lyophilized extract;

• Upgrading and improving the base product - microbial sapropelic mud extract, because both elements of technology modernisation will have consequences in product upgrading.

• Introducing regulatory elements that improve the Quality Management System of SC PELL AMAR: standardizing the solid extract and establishing a set of physical, chemical, biological tests that unequivocally characterize the product, by following the model in the European Pharmacopoeia and thus facilitating the authorization of the products in the pharmaceutical range.

• Establishing and demonstrating the manufacturing technology on its range of derived products:

- Cosmetics (biotrophic effect, regenerating, sedative);

- Food supplements (boost immunity, relieve rheumatic pain)

• Demonstrating the therapeutic effect of a product with topical application (ointment in rheumatic diseases) and initiating the studies necessary to the documentation for changing its categorization from cosmetics to pharmaceuticals.

The dissemination of the project results will be one of the tasks of all members of the partnership. It will be focused on two target groups: a) persons and institutions having specialized technical & scientific knowledge - scientific articles, patents, national seminar, project’s site; here the focus will be on the technical & scientific results); b) the general public - articles, interviews in the media, brochures, newsletters, movies, showrooms; here the focus will be on improving the quality of life).

The consortium partners have been chosen according to three criteria: competence, complementarity and cohesion. Competence is proven by certification, accreditation, licensing.

Complementarity is needed for solving all the problems that the project will be facing, and cohesion is based on the previous relationships between the partners.

Project coordination is undertaken by the economic partner and the project director, an economist, is also the general manager of the economic partner.

PROTEOMIC AND GENOMIC METHODS IN EVOLUTION AND PERSONALIZED TREATMENT OF HIGH RISK PROSTATE CANCER USING BIOMARKERS PANEL APROACH Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-1851 2014 - 2017

Role in this project:

Coordinating institution: INSTITUTUL CLINIC FUNDENI

Project partners: INSTITUTUL CLINIC FUNDENI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" RA (RO); INSTITUTUL NATIONAL DE ENDOCRINOLOGIE "C.I.PARHON" BUCURESTI (RO); CYTOGENOMIC MEDICAL LABORATORY SRL (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" RA (RO)

Project website: http://www.urologie-prometeu.ro

Abstract:

Prostate cancer is the most commonly diagnosed cancer and a leading cause of cancer death in European men. Curative treatment for clinically localized prostate cancer may produce acceptable oncological control of the disease and for selective group of patients can be sufficient. Despite that, prostate cancer exhibits considerable variability in clinical behaviour, ranging from indolent to lethal disease. At present there is no means that can predict aggressive behaviour of prostate tumors. Thus, development of reliable biomarkers and a personalized clinical approach is critical in the management of clinically relevant disease.

The purpose of this project is to identify new urinary and genetic biomarkers and a set of reliable biomarkers by proteomic and genomic analysis that can predict aggressive behavior of prostate cancer and to validate the use of a panel of markers for treatment stratification of prostate cancer patients (n=100) versus benign prostate hypertrophy (n=50) proposed for radical prostatectomy, with localized disease at the time of diagnosis using nomogram analysis. The proposed markers are in urine, plasma, genomic and tissue DNA, as follows: in urine, prostate cancer antigen 3 (PCA3) RNA and the transmembrane protease, serine 2 v-ets erythroblastosis virus E26 oncogene homolog (avian) (TMPRSS2:ERG) gene fusion, decreased β-microseminoprotein (MSMB); in blood (PSA, free PSA); in genomic DNA (BRCA2 mutation and HOXB13 mutation, risk SNPs, (KLK2-KLK3 SNP rs2735839, 17p12 SNP rs4054823, androgen metabolism SNPs, SLCO2B1,SLCO1B3 (androgen transport) SNPs); in tissue, by immunohistochemistry: p53, Ki67, PTEN loss (plus SMAD4, cyclin D1, SPP1) and in metastatic tissue (AR, SPINK1, Her2/neu).

Main objective of this prospective, non-interventional project is to improve the predictive classification of prostate cancer allowing differentiation between indolent and aggressive tumors and the identification of patients who will most benefit from diagnosis and therapeutic intervention. In addition, nomograms will help patients to better understand their disease and will assist physicians with difficult clinical-making decision.

Expected outcomes are: 1) identification of new biomarkers involved in aggressive forms of prostate cancer and in higher disease recurrence rate after radical prostatectomy; 2) development of an innovative predictive model for treatment stratification of patients with localized prostate cancer; 3) validation of this model that could potentially be used for patients proposed for other primary treatment of prostate cancer. The results of this study will have a major impact in increase knowledge in clinical-making decision and management of prostate cancer patients treated by radical prostatectomy in particular, with immediate positive clinical (survival, quality of life) and socioeconomic impact.

The high level of interdisciplinary of the suggested activities justifies the consortium composed by institutes of complementary areas of research: Fundeni Clinical Institute (Departments of Urology and Pathology), “Victor Babes” National Institute of Pathology (Biochemistry Proteomics Department), “C.I.Parhon” National Institute of Endocrinology and CytoGenomic medical laboratory as private partner.

GENOMEWIDE STUDY OF BIPOLAR I DISORDER AND GUIDE FOR ASSESSING THE GENETIC RISK FOR BIPOLAR I DISORDER IN THE ROMANIAN POPULATION Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-1628 2012 - 2016

Role in this project:

Coordinating institution: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA

Project partners: SPITALUL CLINIC DE PSIHIATRIE PROF.DR.ALEXANDRU OBREGIA (RO); INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO); UNIVERSITATEA BUCURESTI (RO); PERSONAL GENETICS S.R.L. (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE "STEFAN S.NICOLAU" (RO)

Project website: http://www.bio.unibuc.ro/index.php?option=com_content&view=article&id=212%3

Abstract:

Medicine develops into three directions: prevention, prediction and personalization. Bipolar I disorder (BPI) is a chronic major psychiatric disease with a polygenic basis not yet elucidated. The objectives of the project are: 1) fine mapping of two haplotypes in NCAN and MAD1L1 genes found associated with BPI in a previous genomewide association study (GWAS) (Cichon et al, Am J Hum Genet, 2011) in which the project coordinator was involved; 2) a GWAS of the response to lithium therapy aiming at detecting the genotypes linked to positive response; 3) estimating morbid risks (MR) for relatives of BPI patients valid for the Romanian population; 4) determining the structure of Mad1 and Mad2 molecules and their neurobiological consequences with potential impact on drug development; 5) development of a guide for genetic counseling containing genotypes associated with BPI in the Romanian population, MR for relatives of patients, phenotypic variables that increase MR and genotypes predicting the positive response to lithium. The study will be conducted in an international consortium including Romanian partners. A Romanian sample of about 550-570 patients and 550-570 controls will be integrated in an international sample of several thousands of patients and controls that will be genotyped with high-throughput methods (Illumina, Sequenom) by Romanian researchers at the German partner and with next generation sequencing technology atone of the Romanian partners. Probands and their available first degree relatives will be investigated with DIGS and FIGS interviews and will provide psychiatric family history necessary for estimating MR. The response to lithium therapy in patients treated at least one year will be rated with the Alda scale. Our sample of lithium-patients will be integrated in the international lithium sample for genotyping. The biometric and molecular results of the study will be implemented in personalized medicine by a private health care company and disseminated among specialists.

FINDING AND VALIDATING MOLECULAR TARGETS IN GASTRIC TUMOR STEM CELLS FOR DEVELOPMENT OF NOVEL ANTI-CANCER THERAPEUTIC STRATEGIES. Call name: Projects for Young Research Teams - TE-2010 call
PN-II-RU-TE-2010-0062 2010 - 2013

Role in this project:

Coordinating institution: INSTITUTUL DE VIRUSOLOGIE STEFAN S NICOLAU DIN BUCURESTI

Project partners: INSTITUTUL DE VIRUSOLOGIE STEFAN S NICOLAU DIN BUCURESTI (RO)

Affiliation: INSTITUTUL DE VIRUSOLOGIE STEFAN S NICOLAU DIN BUCURESTI (RO)

Project website: http://www.virology.ro/ro/cercetare/proiecte/tinte-moleculare

Abstract:

Cellular heterogeneity, present in most solid tumors, represents an enormous challenge for cancer eradication. Present strategies for inducing cell death usually target only the most rapidly proliferating cells within a tumor, and are unable to destroy tumor stem cells that are more resistant to standard chemotherapeutic agents and have the ability to regenerate the tumor. It became increasingly obvious that it is necessary to develop strategies targeted to the mechanisms of survival and regeneration characteristics of tumor stem cells.

A recent study published in 2009, which identify gastric tumor stem cells (GTSC) based on surface antigen CD44, opens new directions for the management of gastric carcinoma, disease that is the second cause of death worldwide (700,000 deaths/year worldwide ; 17/6.6 m / f deaths/100000 people/year in Romania).

Given the opportunity to identify and isolate gtsc, and our laboratory experience in the field of stem cells and anti-tumor therapy, we intend to use small interferece rna technology to specifically inhibit certain genes overexpresed in gastric cancer which can be promoters of processes such as: cell proliferation, interaction with the matrix, motility, metastasis, angiogenesis.

The objectives are:

1. Identification, isolation and characterization GTSC. Testing their tumoral capacity on immunodeficient animal models

2. Identification of molecular targets by testing gene expression in the gtsc, and selection of genes significantly modified

3. Specific inhibition of selected gene expression using siRNA methodology

4. Analysis of molecular target therapy-induced effects on GTSC functionality.

The project will lead to consolidation of a young specialists team in a leading field of the research: anti-tumor therapy, based on modern biotechnological methods of gene therapy.

Hepatocellular carcinoma stratification based on noninvasive markers Call name: EEA Research Programme under EEA Financial Mechanism 2009-2014
EEA-JRP-RO-NO-2013-1-0363 2013 -

Role in this project:

Coordinating institution: INSTITUTUL CLINIC FUNDENI

Project partners: INSTITUTUL CLINIC FUNDENI (RO); UNIVERSITATEA "TITU MAIORESCU" (RO); UNIVERSITATEA OVIDIUS (RO); Norwegian University of Science and Technology (NO); Nuclear Organization and Oncogenesis Unit (INSERM U993) at the Institut Pasteur (FR)

Affiliation: UNIVERSITATEA "TITU MAIORESCU" (RO)

Project website:

Abstract:

The major goal of the project “Hepatocellular carcinoma stratification based on noninvasive markers” (HEPMARK) in accordance the EEA Research Programme objectives is to stimulate multidisciplinary research by creating and supporting a network for translational science that brings together scientists from Romania, Norway and France.

HEPMARK proposes a concept of research that would identify using expression miRNAs expression, a high-risk group of patients with liver cancer who may develop intrahepatic recurrence/ distant metastasis. Currently is an unmet need to improve the accuracy of hepatocellular carcinoma (HCC) score stratification by incorporation of new non-invasive molecular assays. Moreover, the possibilities to develop the new systems that predict the likelihood of recurrence after curative treatment, including miRNA and angiogenetic factors are needed. Thus, our hypothesis is that primary liver cancers release miRNAs within exosomes transported in the peripheral blood that facilitate the metastatic niche. We intend to use miRNA circulating and angiogenic panel for HCC patients’ stratification. More accurate preoperative selection criteria will allow better patient selection and better allocation of the HCC patients in case of curative treatment.

The project specific objectives are:

Obj_1: To quantify the expression of microRNA species in serum exosomes from patients with non-metastatic HCC and distant metastases/ intrahepatic recurrence

Obj_2: To characterize angiogenic plasma biomarker patterns of HCC and imaging biomarkers in correlation with microRNA markers

Obj_3: To characterize epigenetic changes (DNA and histones) resulting in microtranscriptomic alterations

Obj_4: To create new clinical guidelines for the use of serum and tissue tumor markers for early detection, as well as for differentiation between HCC patients (patients’ stratification).

The project will achieve the following results with practical relevance:

1. Identification of circulating microRNAs as biomarkers of HCC for detection and evaluation of disease aggressiveness in patients at risks

2. Development of a panel of circulating microRNAs, proteins and imaging parameters as biomarkers of response in HCC

3. To test prospectively biomarker candidates for optimization and future translation in clinical practice guidelines for patient’s stratification depending on selected markers

4. Integration of Romanian research groups into a strong network with proficiency in HCC translational research

The strong points that guarantee the success of the project are:

- the proposed project continues the research interest of consortium in the field of molecular biology of HCC which have investigated molecular predictive factors from tissue specimens. One of the strengths of the current project is that it expands the pannel of molecular markers with microRNA species in serum exosomes quantified in patients’ blood samples.

- the consortium has already created a functional network that may easily sustain the fulfillment of present project.

- The consortium is formed by renowned scientists in the field of molecular biology, genomics and clinical practice as sustained by their recent publications in Nature Genetics, PlosOne, Cancer Res. etc, which is the guarantee for a good management of the research outputs.

- The sample size is statistically valid

The results of this project will impact directly the strategic area of health care by improving the quality of clinical decision –making for a specific group of HCC patients.

Our findings may have significant translational relevance for development of new molecularly targeted therapies for patients with HCC. We intend to exploit this knowledge to develop targeted therapies of HCC based on the microRNA dysregulation.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects