Finding and validating molecular targets in gastric tumor stem cells for development of novel anti-cancer therapeutic strategies

Principal investigator: Mihaela Economescu (Chivu) PhD.

(2010-2013; PNII-RU-TE-100/1020) – Principal investigator: Mihaela Economescu (Chivu) PhD.

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.

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