GRANTS LIST: CELLULAR AND MOLECULAR PATHOLOGY DEPARTMENT

P2X receptors as a therapeutic opportunity (PRESTO, 2022-2026; EU- COST, COST CA21130), Principal investigator: for IVN Carmen C. Diaconu, PhD

The evaluation of anti-SARS-CoV-2 protection in convalescent and vaccinated subjects in the light of newly emerging variants (IMMUN_SARS_CoV, 2022-2024; PN-III-P1-1.1, PD-2021-0825); Principal investigator: Lilia Matei, PhD

Wastewater-based epidemiology concept as an early warning system for sars-cov-2 trend and its circulating variants in a defined catchment (WARNING, 2022-2024; PN-III-P2-2.1 PED-2021-4131); Principal investigator: Coralia Bleotu PhD

Pan-European Response to the Impacts of COVID-19 and future Pandemics and Epidemics (PERISCOPE, 2020 – 2023; EU-Horizon 2020 101016233 H2020-SC1-PHE-CORONAVIRUS-2020-2-RTD); Principal investigator: for IVN Carmen C. Diaconu, PhD

Molecular Profiling of Myeloproliferative Neoplasms and Acute Myeloid Leukemia for Designing Early Diagnostic, Prognostic and Treatment Strategies (MYELOAL – EDIAPROT, 2015-2023; POC 2014-2020 149/2018 SMIS 106774 Project ID P_37_798); Principal investigator: Prof. Stefan N Constantinescu MD, PhD; Executive coordonator: Carmen C. Diaconu, PhD

Mechanisms and biomarkers of response and resistance to current targeted therapies in gastric cancer (THERRES, 2018-2022; PN-III-P4-ID-PCCF-2016-0158); Principal investigator: for IVN Mihaela Economescu (Chivu) PhD

Evaluation of the potential of the porous material in the treatment of microbiota (2020-2022; PN-III-P2-2.1-PED-2019-4018); Principal investigator: Coralia Bleotu PhD

Evaluation of COL10A1 as a potential therapeutic target and early diagnostic biomarker in gastric cancer (COL-DIA-THER; 2020-2022; PN-III-P1-1.1-TE-2019); Principal investigator: Laura Necula PhD

Knowledge transfer on the investigation of the anti-infective and antitumoral activity of novel cosmetic and pharmaceutical formulations based on natural extracts (2016–2018; PN-III-P2-2.1-BG-2016-0369); Principal investigator: Coralia Bleotu PhD

Composite hydrogels based on inorganic nanoparticles and collagen with prolonged antimicrobial activity for the prevention of wound infections (2016–2018; PN-III-P2-2.1-PTE-2016-0177); Principal investigator: Coralia Bleotu PhD

Implementation of a complex genome profiling diagnostic algorithm for patients with congenital and developmental abnormalities (CONGEN; 2014–2017; PN-II-PT-PCCA-2013-4-2240); Principal investigator: Carmen Cristina Diaconu PhD

Genome-wide study of bipolar disease and genetic risk assessment guide for bipolar I disorder in the Romanian population (GWASBP, 2012-2015; PN-II-PT-PCCA-2011-3.2; 89) – Principal investigator: for Carmen Cristina Diaconu PhD

Finding and validating molecular targets in gastric tumor stem cells for development of novel anti-cancer therapeutic strategies (2010-2013; PNII-RU-TE-100/1020); Principal investigator: Mihaela Economescu (Chivu) PhD.

Specialization for performance, efficiency and results in organ transplant field (S.P.E.R.; 2010-2012; POS-DRU/81/3.2/S/59616); Principal investigator: for IVN Mihaela Economescu (Chivu) PhD.

Alternative therapies for healing of major tissue defects (2008-2011; PNII 42-136); Principal investigator: Bleotu Coralia PhD

Research regarding pharmacogenomic and pharmacokinetic investigations used for the individualization of antituberculosis therapy in particular clinical situations (2008-2011; PNII 42-148); Principal investigator: Bleotu Coralia PhD

Tumor neural stem cells a new therapeutic target in the multimodal treatment of gliomas (TUMORSTEM, 2007-2010, CEEX- PNII 41-035) Principal investigator: Bleotu Coralia PhD

Intracellular signaling in gastric and esophageal adenocarcinoma (GECS, 2007-2010, PN-II-41-036); Principal investigator: Mihaela Economescu (Chivu) PhD

Genotype–phenotype correlation for some candidate gene in bipolar disorder (2007-2010, PN-II-42-151)- Principal investigator: for Carmen Cristina Diaconu

PhD

Study of the cytokines profile involved in the humoral and cellular response in patients with herpetic keratitis (2007; GAR116); Principal investigator: Irina Alexiu

Establishing an integrated network for the study of microbial biofilms on cellular and prosthetic substrates in order to improve the diagnosis and treatment of infections caused by biofilms(2006-2008, PNII 142); Principal investigator: Bleotu Coralia PhD

The polymorphisms profile of cytokines involved in graft rejection and in the production of viral infections in transplant recipient patients (2006-2008, CEEX 148); Principal investigator: Carmen Cristina Diaconu PhD

The complex, cellular, molecular and genetic approach to new pathogenic mechanisms in malignant myeloproliferative (2006-2008, CEEX 111); Principal investigator: Carmen Cristina Diaconu PhD

New cell therapy strategies using hematopoietic progenitors from umbilical cord blood (2006-2008, CEEX 85); Principal investigator: Mihaela Economescu (Chivu) PhD

The therapeutic potential of hematopoietic stem cells in liver diseases. (2006-2008, CEEX 65); Principal investigator: Mihaela Economescu (Chivu) PhD

Tissue engineering techniques with applications in treating intestinal fistulas (2006-2008, CEEX 85); Principal investigator: Mihaela Economescu (Chivu) PhD

Promotion of psychiatric genetics research in Romania through international partnership in genetic and epigenetic studies of bipolar disease (2006-2008, CEEX 122); Principal investigator: Carmen Cristina Diaconu PhD

Definition of a homogeneous phenotype of bipolar disease for genetic studies based on family aggregation. Participation in an international genetic study (GAR 2006-2007); Principal investigator: Carmen Cristina Diaconu

Studies on the involvement of cytomegalovirus in the pathology of graft rejection(GAR 2006-2007); Principal investigator: Alexiu Irina MD, PhD

Evaluation strategies and amplification of the proliferative potential of hematopoietic stem cells – Therapeutic implications (2004 -2006; VIASAN 343) – Principal investigator: Mihaela Economescu (Chivu) PhD

The significance of persistent EBV and HPV infections in laryngopharyngeal cancer, (2003-2005; VIASAN 223) – Principal investigator: Bleotu Coralia PhD

Study of the effects of intra-arterial chemotherapy and systemic radiochemotherapy in patients with ENT lymphomas (2003-2005; VIASAN 276) – Principal investigator: Bleotu Coralia PhD

Quantification of the biological effects of some cell cycle inhibitors (2003-2004; GAR 294/2003; 136/2003/AR; 128/2004/AR) – Principal investigator: Bleotu Coralia PhD

Effects of maternal inheritance in bipolar disease. Biometric and molecular study (2002-2005, VIASAN 170); Principal investigator: Carmen Cristina Diaconu PhD

The significance of the molecular mechanisms involved in HPV transformation for the monitoring of some human cancers (2001-2002; GAR 311/2001; 76/2001/AR; 54/2002/AR); Principal investigator: Bleotu Coralia PhD

Evaluation of the molecular mechanisms involved in supporting hematopoiesis in order to develop a suitable culture system for the ex vivo expansion of hematopoietic stem cells (2002-2003; CNCSIS grant AT 33466/2002; AT 33954/2003); Principal investigator: Mihaela Economescu (Chivu) PhD

Research on the role of endogenous and exogenous glucocorticoids in the modulation of peripheral lymphocyte apoptosis in HIV infection (2000-2002, ANSTI Grant C); Principal investigator: Florica Toparceanu PhD

Study of the dynamics of some glucocorticoid hormones and proinflammatory cytokines during the acute phase response in patients with influenza infections (2001-2002, ANSTI Grant C); Principal investigator: Florica Toparceanu PhD

Cellular factors involved in multiple drug resistance, rational evaluation strategies and chemoprevention(2001- 2004; VIASAN 051); Principal investigator: Carmen Cristina Diaconu PhD

The prevalence of the 32BP deletion in the CCR5 chemokine receptor gene in patients with HIV infection in Romania – Correlations with the rate of disease progression (1999-2000, ANSTI-AT Grant); Principal investigator: Tardei Gratiela MD, PhD

The rational design and biological evaluation of new classes of anti-HIV agents (1999, GAR); Principal investigator: Carmen Cristina Diaconu PhD

GRANTS DETAILS

MOLECULAR PROFILING OF MYELOPROLIFERATIVE NEOPLASMS AND ACUTE MYELOID LEUKEMIA FOR DESIGNING EARLY DIAGNOSTIC, PROGNOSTIC AND TREATMENT STRATEGIES (MYELOAL – EDIAPROT, 2015-2023)

De preluat:

https://www.virology.ro/ro/myeloal-ediaprot

Project title: THE EVALUATION OF ANTI-SARS-COV-2 PROTECTION IN CONVALESCENT AND VACCINATED SUBJECTS IN THE LIGHT OF NEWLY EMERGING VARIANTS

Acronym: IMMUN_SARS_CoV.

Aim: This project aims to evaluate the persistence of anti-SARS-CoV-2 immune response developed post-infection or post-vaccination to different SARS-CoV-2 variants in order to better understanding the natural adaptive immune response to SARS-CoV-2.

Partners: Coordinator: Institute of Virology Stefan S. Nicolau – project director Dr. Lilia Matei

Funding: 250.000 RON

Working team: Lilia Matei, Simona-Maria Ruta

Project financed by UEFISCDI program PN-III-P1-1.1-PD-2021-0825, contract no. PD13/2022

Implementation period: 01.04.2022 – 31.03.2024

Summary: Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is a serious disease that has resulted in widespread global morbidity and mortality. Globally, at the beginning of July 2021, there have been more than 183 million confirmed cases of COVID-19, including almost 4 million deaths, reported to WHO. With the COVID-19 pandemic outbreak spreading worldwide, immunity to SARS-CoV-2 infection is central to long-term control of the current pandemi. The recent development of different types of vaccines (mRNA or adenoviral vector-based technology) opens new perspectives in the fight against COVID-19. Still, one of the most important question is how long humoral and cellular immunity will last and whether it will protect the population from recurrent SARS-CoV-2 infections, especially in the context of new emerging variants in the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1) and India (B.1.617). The same question applies to those who have had a natural infection with SARS-CoV-2. In this context, our project aims to evaluate the persistence of anti-SARS-CoV-2 immune response developed post-infection or post-vaccination to different SARS-CoV-2 variants in order to better understanding the natural adaptive immune response to SARS-CoV-2.

Results:

Articles:

  1. Chivu-Economescu M., Vremera T., Ruta S.M., Grancea C., Leustean M., Chiriac D., David A., Matei L., Diaconu C.C., Gatea A., Ilie C., Radu I., Cornienco A.M., Iancu L.S., Cirstoiu C., Pop C.S., Petru R., Strambu V., Malciolu S., Popescu C.P., Florescu S.A., Rafila A., Furtunescu F.L., Pistol A. Assessment of the Humoral Immune Response Following COVID-19 Vaccination in Healthcare Workers: A One Year Longitudinal Study. Biomedicines 2022, 10, 1526. doi: 10.3390/biomedicines10071526. IF = 4.757  

Book Chapter:

  1. Diaconu C.C., Pitica I.M., Chivu-Economescu M., Necula L.G., Botezatu A., Iancu I.V., Neagu A.I., Radu E.L., Matei L., Ruta S.M., Bleotu C. SARS-CoV-2 Variant Surveillance in Genomic Medicine Era. In: Rodriguez-Morales A.J. editor. Current Topics in SARS-CoV-2/COVID-19 – Two Years After [Working Title] [Internet]. London: IntechOpen; 2022. Available from: https://www.intechopen.com/chapters/83524 doi: 10.5772/intechopen.107137


Project title: WASTEWATER-BASED EPIDEMIOLOGY CONCEPT AS AN EARLY WARNING SYSTEM FOR SARS-COV-2 TREND AND ITS CIRCULATING VARIANTS IN A DEFINED CATCHMENT

Acronym: WARNING

Aim: The project aims to demonstrate that the early detection of an increasing trend in total SARS-CoV-2 concentration and the assessment of its circulating variants in wastewater represent the key factors in the pandemic containment. The main objectives are to develop and establish a surveillance procedure in order to track the dissemination of total SARS-CoV-2 concentration in untreated wastewater, to identify the specific circulating variants based on signature mutations and to demonstrate SARS-CoV-2 infectivity in untreated wastewater samples.

Partners: Coordinator: Institute of Virology Stefan S Nicolau – project director Dr. Coralia Bleotu

Partner 1: National Institute for Research and Development in Industrial Ecology ECOIND – responsible Dr. Mihai Nita-Lazar

Funding: 598.795,00 RON

Working team: Coralia Bleotu, Elena Radu, Carmen C. Diaconu, Denisa Dragu, Lilia Matei, Saviana Nedeianu, Marius Ataman, Ioana Pitica.

Project financed by UEFISCDI program PN-III-P2-2.1-PED-2021-4131, contract no. 705PED/2022

Implementation period: 21.06.2022 – 20.06.2024

Summary: Covid-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019 and gave rise to a worldwide health emergency after only 2 months. Currently, more than 226 million cases have been confirmed and over 4.6 million deaths worldwide. In Romania, the numbers are raising with over 1.1 million confirmed cases and more than 35k deaths. The well-known lineages, B.1.1.7 (Alpha variant), B.1.351 (Beta variant), P.1 (Gamma variant) and B.1.617.2 (Delta variant) assigned as variants of concern (VOCs), show an increased transmissibility and higher infectivity. Lately, it has been observed that the VOCs exhibit an increased resistance towards the vaccines and therapies, especially the Delta variant. Considering the ascending number of infections with SARS-CoV-2 variants and the necessary time for the symptoms onset in infected individuals, a delay of the real active cases reported per day can be observed. Wastewater based epidemiology (WBE) proved to be a powerful tool for the early detection of SARS-CoV-2 concentrations in a certain catchment and to provide a quick snapshot about the circulating variants before they are seen in clinical cases. The scope of the project is to demonstrate that the early detection of an increasing trend in total SARS-CoV-2 concentration and assessment of its circulating variants in wastewater represent the key factor in the pandemic containment. Furthermore, the present proposal aims to demonstrate the infectivity of SARS-CoV-2 in untreated wastewater samples from Bucharest, which is of paramount importance for the public health. Noteworthy, the study aims to support the collective efforts of the EU Sewage Sentinel System by implementing a wastewater-based surveillance approach in Romania as recommended by the European Commission. EU strongly encourages the member states to implement the wastewater surveillance system for SARS-CoV-2 and its variants before October 1st 2021.

Results:

Book Chapter:

  1. C.C. Diaconu, I. M. Pitica, M. Chivu-Economescu, L. G. Necula, A. Botezatu, I. V. Iancu, A. I. Neagu, Elena L. Radu, L. Matei, S. M. Ruta, C. Bleotu, 2022, “SARS-CoV-2 variant surveillance in genomic medicine era” in SARS-CoV-2 Variants – Two Years After, IntechOpen, ISBN 978-1-80356-234-6, Book edited by: Prof. Alfonso J. Rodriguez-Morales.


Project title: MECHANISMS AND BIOMARKERS OF RESPONSE AND RESISTANCE TO CURRENT TARGETED THERAPIES IN GASTRIC CANCER

Acronym: THERRES.

Aim: The main objective is to identify and characterize the regulators of immune function activation (immune checkpoints) within a new, updated molecular classification system for gastric cancer, for the implementation of a personalized treatment in order to improve the survival rate of patients.

Partners: Coordinator: Fundeni Clinical Institute – principal investigator Prof. Dr. Irinel Popescu

Partner 1: Craiova University of Medicine and Pharmacy – principal investigator Prof. Dr. Adrian Saftoiu

Partner 2: Institute of Virology Stefan S. Nicolau – principal investigator Dr. Mihaela Economescu;

Funding: 2.000.000 RON

Working team: Mihaela Economescu, Carmen C. Diaconu, Coralia Bleotu, Laura Necula, Denisa Dragu, Lilia Matei, Ana Iulia Neagu.

Project financed by UEFISCDI program PN-III-P4-ID-PCCF2016-0158, contract no. PCCF17/2018

Implementation period: 01.01.2018 – 30.11.2022

Summary: Functional in vitro studies were carried out on primary cultures generated from gastric cancer tissue fragments to create study models on the identified immune targets. Such models are useful to validate both immune targets and specific inhibitors or therapeutic combinations consisting of immunotherapy + chemotherapy or targeted therapy.

The analysis mainly focused on the changes induced at the level of signalling pathways following the co-culture of gastric cancer cells with increased expression of PD-L1 with human T lymphocytes with PD1 expression in the presence of inhibitors of the PD1/PD-L1 interaction +/ VEGFR2 inhibitor.

Combining the targeted strategy with immunotherapy represents the most interesting and active field of research today due to the durable responses observed in other malignant types such as melanoma and lung cancer. This strategy could represent a quantum leap in gastric cancer therapy.

Results:

Articles:

  1. Chivu-Economescu M, Necula LG, Matei L, Dragu D, Bleotu C, Sorop A, Herlea V, Dima S, Popescu I, Diaconu CC. Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis. International Journal of Molecular Sciences 2022; 23(6):3214. https://doi.org/10.3390/ijms23063214 IF=6.208/2021
  2. Necula L, Matei L, Dragu D, Pitica I, Neagu A, Bleotu C, Diaconu CC, Chivu-Economescu M. Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer. Int. J. Mol. Sci. 2022, 23, 12415. https://doi.org/10.3390/ijms232012415 IF=6.208/2021
  3. Chivu-Economescu M, Necula L, Matei L, Dragu D, Bleotu C, Diaconu CC. Clinical Applications of Liquid Biopsy in Gastric Cancer. Front Med (Lausanne). 2021;8:749250. doi: 10.3389/fmed.2021.749250. IF 3.9
  4. Necula L, Matei L, Dragu D, Pitica I, Neagu AI, Bleotu C, Dima S, Popescu I, Diaconu CC, Chivu-Economescu M. High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients. World J Gastroenterol. 2020 Jun 14;26(22):3024-3033. doi: 10.3748/wjg.v26.i22.3024. PMID: 32587446; IF=3.665.
  5. Chivu-Economescu M, Necula LG, Matei L, Dragu DL, Neagu AI, Alexiu I, Bleotu C, Diaconu CC. Gastrointestinal cancer stem cells as targets for innovative immunotherapy. World J Gastroenterol. 2020 Apr 14;26(14):1580-1593. doi: 10.3748/wjg.v26.i14.1580. PMID: 32327907; IF= 3.665.
  6. Necula L, Matei L, Dragu D, Neagu AI, Mambet C, Nedeianu S, Bleotu C, Diaconu CC, Chivu-Economescu M. Recent advances in gastric cancer early diagnosis. World J Gastroenterol. 2019 May 7;25(17):2029-2044. doi: 10.3748/wjg.v25.i17.2029. PMID: 31114131; IF= 3.411.

Communications at national/international congresses

  1. Chivu-Economescu M, Necula L, Matei L, Dragu D, Neagu A , Bleotu C, Sorop S, Herlea V, Dima S, Popescu I, Diaconu C. PD-L1 solubil ca biomarker pentru progresia și prognosticul în cancerul gastric. Zilele Științifice ale Institutului Clinic Fundeni, 7-9 decembrie 2022.
  2. Chivu-Economescu M, Necula L, Matei L, Dragu D, Neagu AI, Bleotu C, Sorop A, Herlea V, Dima S, Popescu I and Diaconu C. Soluble PD-L1 Level is Correlated with its Expression in Tissue and is Associated with Poor Overall Survival in Gastric Cancer. The 3rd Immuno-Oncology World Congress, 2-3 noiembrie 2022, Copenhaga, Denemarca.
  3. Chivu-Economescu M,Matei L, Necula L, Dragu D, Neagu AI, Sorop A, Bleotu C, Dima S, Irinel P. Evaluation of tumor immune microenvironment to predict and guide immunotherapeutic response, prezentare în cadrul Congresului Național de Citometrie a XIIIa Ediție, sesiunea de Imunologie, 16-18 decembrie 2020
  4. Chivu-Economescu M. High PD-L1 expression in Epstein-Barr virus positive and microsatellite unstable cancers, prezentare în cadrul Conferinței Webinar „Tratamente Inovative în Oncologie” – ediția a VII-a, 27 noiembrie 2020
  5. Chivu-Economescu M, Necula LG, Dragu D, Matei L, Neagu AI, Bleotu C, Sarbu M, Dima SO, Diaconu CC, Popescu I. New molecular classification of gastric cancer opens new avenues to novel therapeutic strategies, prezentare orală în cadrul “The 12th National Pathology Symposium, sesiunea Omics in pathology, 21-23 noiembrie 2019, București, România.
  6. Necula LG, Matei L, Dragu D, Neagu AI, Pitica I, Nedeianu S, Mambet C, Bleotu C, Dima S, Popescu I, Diaconu CC, Chivu-Economescu M. Plasma level of COL10A1 is associated with tumor stage and survival in patients with Gastric Cancer, prezentare în cadrul “Advances in Cancer Research and Therapy”, 11-12 noiembrie 2019, Madrid, Spania.
  7. Matei L, Dragu D, Necula LG, Neagu AI, Pitica I, Nedeianu S, Mambet C, Bleotu C, Dima S, Popescu I, Diaconu CC, Chivu-Economescu M. Classification of Gastric Cancer samples according to protein expression and MSI status based algorithm, prezentare în cadrul “Advances in Cancer Research and Therapy”, 11-12 noiembrie 2019, Madrid, Spania.
  8. Sîrbu M, Șorop A, Chivu-Economescu M, Dima L, Chiosa A, Dima S, Popescu I. Molecular classification of gastric cancer opens new opportunities into personalized treatment, poster în cadrul ediției a XIVa a Simpozionului Academician Nicolae Cajal, 17-19 octombrie 2019, București, România.
  9. Necula LG, Matei L, Dragu D, Neagu AI, Pitica I, Mambet C, Bleotu C, Dima S, Popescu I, Diaconu CC, Chivu-Economescu M. Diagnostic role of circulating COL10A1 in gastric cancer, prezentare în cadrul ediției a XIVa a Simpozionului Academician Nicolae Cajal, 17-19 octombrie 2019, București, România.

Project title: EVALUATION OF COL10A1 AS A POTENTIAL THERAPEUTIC TARGET AND EARLY DIAGNOSTIC BIOMARKER IN GASTRIC CANCER

Acronym: COL-DIA-THER.

Aim: The main objective was to analyze the involvement of COL10A1 in gastric carcinogenesis in order to evaluate its potential as a biomarker for the diagnosis of gastric cancer and molecular target for the development of new therapeutic strategies.

Coordinator: Institute of Virology Stefan S. Nicolau – principal investigator Dr. Laura Georgiana Necula

Funding: 431.900 RON

Working team: Laura Georgiana Necula, Mihaela Economescu, Lilia Matei, Denisa Dragu, Ioana Pitica.

Project financed by UEFISCDI program PN-III-P1-1.1-TE-2019, contract no. TE36/2020

Implementation period: 01.09.2020 – 30.08.2022

Summary: The results obtained within this project regarding the correlation between the increased circulating COL10A1 level and tumor progression suggest the possibility of using COL10A1 as a diagnostic and prognostic biomarker in patients with gastric cancer. Also, the results related to the involvement of COL10A1 in tumor development processes such as proliferation, suppression of apoptosis and invasion of gastric cells can significantly influence the scientific field, suggesting that this molecule could represent a therapeutic target. In conclusion, the results obtained in this study could represent the basis for the development of new methods of prevention, diagnosis and treatment of patients with gastric cancer, improving the survival rate in the case of this disease.

Results:

Articles:

  1. Chivu-Economescu M, Necula LG, Matei L, Dragu D, Bleotu C, Sorop A, Herlea V, Dima S, Popescu I, Diaconu CC. Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis. International Journal of Molecular Sciences 2022; 23(6):3214. https://doi.org/10.3390/ijms23063214 IF=6.208/2021
  2. Necula L, Matei L, Dragu D, Pitica I, Neagu A, Bleotu C, Diaconu CC, Chivu-Economescu M. Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer. Int. J. Mol. Sci. 2022, 23, 12415. https://doi.org/10.3390/ijms232012415 IF=6.208/2021

Project title: FINDING AND VALIDATING MOLECULAR TARGETS IN GASTRIC TUMOR STEM CELLS FOR DEVELOPMENT OF NOVEL ANTI-CANCER THERAPEUTIC STRATEGIES.

Acronym: –

Aim: The main objective of the project was to employ siRNA technology to target particular genes that are overexpressed in gastric cancer and have the potential to promote processes such as cell proliferation, interaction with the matrix, motility, metastasis, and angiogenesis, and specifically inhibit their expression.

Contractor: Stefan S. Nicolau Institute of Virology– principal investigator Mihaela Economescu (Chivu) PhD.

Funding: 735.000 RON

Working team: Mihaela Economescu, Laura Necula, Denisa Dragu, Cosmin Ilie

Project financed by PNII-RU-TE-100/1020

Implementation period: 12.08.2010 – 11.08.2013

Summary:

This project aimed to identify, isolate, and characterize stem cells in gastric tumor cell lines and primary cultures of gastric adenocarcinoma. In order to achieve this, we tested the tumorigenic capacity of isolated gastric tumor stem cells in immunodeficient animal models and identified molecular targets by testing gene expression in gastric tumor stem cells, ultimately selecting genes significantly dysregulated.

As a result, the project contributed to the identification of two molecular targets, S100A2 and KRT17, which are crucial for the development of new antitumor therapeutic strategies. The molecular targets were validated using RNA interfering technology in both in vitro and in vivo studies were the biological role of each target on the functionality of gastric tumor stem cells was analysed. The findings of this project may be valuable to pharmaceutical companies for the development of new antitumor products. Overall, this project provides important insights into potential new therapeutic strategies for treating gastric adenocarcinoma.

Results:

Articles:

Mihaela Chivu Economescu, Laura G. Necula, Denisa Dragu, Liviu Badea, Simona O. Dima, Stefan Tudor, Anca Nastase, Irinel Popescu, Carmen C. Diaconu, Identification of potential biomarkers for early and advanced gastric adenocarcinoma detection, Hepato-Gastroenterology 2010; 58(104): 1453-1464 (ISSN: 0172-6390). IF 0.677 (reprint anexat)

  1. Yamanaka S, Olaru AO, An F, Luvsanjav D, Jina Z, Agarwal R, Tomuleasa C, Popescu I, Alexandrescu S, Dima S, Chivu-Economescu M, Montgomery EA, Torbenson M, Meltzer SJ, Selaru FM. MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer. Digestive and Liver Disease 2012, Jul;44(7):589-96. (ISSN 1590-8658). IF 2.805.
  2. Dima SO, Tanase C, Albulescu R, Herlea V,Chivu-Economescu M, Purnichescu-Purtan R, Dumitrascu T, Duda DG, Popescu I. An exploratory study of inflammatory cytokines as prognostic biomarkers in ductal pancreatic adenocarcinoma patients. Pancreas 2012, 41: 1001-1007.(ISSN 0885-3177). IF 2.067.
  3. Erno Duda, Elena Codrici, Daniela Ionela Popescu, Laura Necula, Radu Albulescu, Protein biomarkers in cancers of the digestive tract – a step towards personalized medicine, Current Proteomics 2013,10(3): 228 – 236. ISI, ISSN: 1570-1646, IF 0.748.

Communications at national/international congresses

  1. M. ChivuEconomescu, et al. Potential biomarkers for gastric adenocarcinoma detection, Simpozionului de Tehnologii Avansate în Medicina 2010 (www.stam2010.ro), 11-12 noiembrie 2010, Bucuresti, organizat în cadrul Institutului National de Statistica, p20.
  2. Mihaela Chivu-Economescu, et al. In search of a gastric cancer molecular signature, Simpozionul Academician Nicolae Cajal Symposium, 28-30 March 2012, Bucuresti, Romania.
  3. Mihaela Chivu-Economescu, et al. New insights into the molecular etiology of gastric cancer, Congresul National de Oncologie Medicala si Radioterapie organizat in cooperare cu ESMO, 18-20 octombrie 2012, Sinaia, Hotel International – publicat in Journal of Radiotherapy and Medical Oncology, vol. 18 supliment, 2012, pag. 36.
  4. Dragu DL, et al. New molecular markers associated with gastric adenocarcinoma development and progression, Poster prezentat in cadrul 9th International Symposium on Targeted Anticancer Therapies, Paris, Franta, 07-09 martie 2011, si publicat sub forma de abstract in Annals of oncology Vol. 22, Suppl.3, pp: 26-26, mai 2011.
  5. Denisa Laura Dragu et al. New potentially targets to for inhibition the of metastatic and invasion capacity of gastric cancer cells, poster prezentat in cadrul Congresului FEBS, Saint Petersburg 2013.
  6. Lilia Matei, et al, Synthesis and evaluation of antitumoral activity of some new pyrazolic compounds, poster prezentat in cadrul Congresului FEBS, Saint Petersburg 2013.

Project title: INTRACELLULAR SIGNALING IN GASTRIC AND ESOPHAGEAL ADENOCARCINOMA

Acronym: GECS

Aim: This project aimed to perform an etiopathogenetic study on the role of gp130 co-receptor and Jak1, STAT3 signaling pathways in gastric and esophageal carcinoma.

Partners: Coordinator: Stefan S. Nicolau Institute of Virology– principal investigator Mihaela Economescu (Chivu) PhD.

Partner 1 – Floreasca Emergency Clinical Hospital, principal investigator Gabriel CONSTANTINESCU, MD, PhD

Partner 2: Fundeni Clinical Institute – principal investigator Prof. Irinel Popescu MD, PhD

Funding: 750.000 RON

Working team: Stoian Mihai, Diaconu Carmen Cristina, Anton Gabriela, Zaharia Corneliu Nicolae, Bleotu Coralia, Irina Alexiu, Neagu Ana Iulia, Nastasie Alina, Dragomir Laura, Dragu Denisa, Stancu I Cosmin, Dragusel Roxana, Matei Lilia, Fratilescu Milica, Ivan Doina, Marginean Georgeta, Mustatea Steluta, Harcu Lucica, Petre Niculina, Tiron Brenda, Badea Ion.

Project financed by MEC, PN-II contract no. 41-036/2007

Implementation period: September 2007 – September 2010

Summary: This study aimed to characterize changes in the gene expression profile in patients with gastric adenocarcinoma, based on tumor stage, and identify candidate genes involved in tumor progression and metastasis. In order to obtain a molecular-level image of gastric tumorigenesis, significantly modified genes were examined in terms of molecular functions, interactions, and their involvement in signaling pathways. Gene expression data was obtained using immunoblot, ELISA, sequencing, microarray, and quantitative RT-PCR techniques. The results showed several changes in normal biological processes that were associated with the primary or advanced stage of gastric adenocarcinoma. In primary lesions, intense metabolic processes were observed (with regard to triglycerides, collagen, and glycerol), as well as an increase in expression level of protease, genes related to morphogenesis and biosynthesis processes. Additionally, in advanced gastric adenocarcinoma, overexpressed genes known to be involved in cytoskeleton rearrangement, cell migration, regulation of phosphorylation processes, and anti-apoptosis were found. Moreover, in this study, a significant association was identified between tumor stage and mRNA expression level for 7 genes: IL11, S100A2, MMP3, KRT17, SPP1, KIAA1199, and COL10A1, which may become markers of tumor progression. Thus, COL10A1 and KRT17, together with SALL4, can be used as biomarkers in early detection because their increased expression occurs in the early stage of the tumor and remains elevated during tumor progression. All these results led to the development of a molecular screening protocol for evaluating disease progression and prognostic index in gastric ADK, which will be recommended to medical facilities for improving medical services. Another direct result of the project is the tumor bank, which contains samples from 61 cases (tumor and adjacent normal tissue fragments, plasma, extracted nucleic acids, primary cell cultures). The bank has a computerized database that can be quickly accessed for extracting different indicators. The bank can be a starting point for future studies, being particularly useful due to the well-characterized and preserved biological material stored.

Results:

Articles:

  1. Mihaela Chivu Economescu, Laura G. Necula, Denisa Dragu, Liviu Badea, Simona O. Dima, Stefan Tudor, Anca Nastase, Irinel Popescu, Carmen C. Diaconu, Identification of potential biomarkers for early and advanced gastric adenocarcinoma detection, Hepato-Gastroenterology, 2010, 58(104): 1453-1464 (ISSN: 0172-6390, ISI, IF=0.677
  2. Necula LG, Chivu-Economescu M, Stanciulescu EL, Bleotu C, Dima SO, Alexiu I, Dumitru A, Constantinescu G, Popescu I, Diaconu CC. IL-6 and IL-11 as markers for tumor aggressiveness and prognostic in gastric adenocarcinoma patients without mutations in gp130 subunit. Journal of Gastrointestinal and Liver Diseases 2012, 21(1), 23-29. (ISSN: 1841-8724). IF=1.855

Communications at national/international congresses

  1. Mihaela Chivu, Laura G. Necula, Adriana Dumitru, Liliana Dumitru, Simona O. Dima, Anca Nastase, Liviu Badea, Gabriel Constantinescu, Irinel Popescu, Carmen C. Diaconu. IL11 and STAT3 as potential biomarkers for gastric adenocarcinoma progression, FEBS Special Meeting: JAK/STAT signaling: From Basics to Disease, 10-13 February 2010, Vienna, Austria, p64.
  2. Laura G. Necula, Mihaela Chivu, Coralia Bleotu, Adriana Dumitru, Liliana Dumitru, Gabriel Constantinescu, Simona O. Dima, Irinel Popescu, Carmen C. Diaconu. Evidence of STAT3 hyperactivity in serum and mucosa of patients with gastric cancer, FEBS Special Meeting: JAK/STAT signaling: From Basics to Disease, 10-13 February 2010, Vienna, Austria, p113.

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