Rolul microRNA



Rolul microRNA in modularea imuna dupa splenectomia

totala si partiala (The role of microRNAs in immune regulation after total and

partial splenectomy)

 

PROJECT NO: 22/2013

PROJECT CODE: PN-II-ID-PCE-2012-4-0018

TITLE: “The role of microRNAs in immune regulation after total and

partial splenectomy”

PROJECT DIRECTOR: Conf. Dr. Catalin Vasilescu, INSTITUTUL CLINIC FUNDENI BUCURESTI

DATE OF BEGINNING THE PROJECT: 02/09/2013

DATE OF FINALISING THE PROJECT: 30/09/2016

TOTAL VALUE OF THE PROJECT: 1.124.999 ron

FINNANCING AUTHORITY: UEFISCDI

 

PROJECT OBJECTIVE:

 

The main objective of the study will be to identify the microRNAs expressed in plasma/serum of patients that underwent subtotal or total splenectomy and play a key role in modulating the immune response.

 

ABSTRACT:


 

 

 

Understanding the potential role of microRNA may be of a great clinical importance in predicting and early treatment of possible septic complications which can occur after the surgical intervention of spleen removal. This will allow us further to establish the diagnostic and prognostic significance of the plasma/serum miRNAs in patients that underwent splenectomy. Because subtotal splenectomy was shown to preserve the immune function of the spleen, we hypothesize that in the plasma/serum of the patients that underwent subtotal splenectomy, the levels of microRNAs are significant different from that of total splenectomy patients. Furthermore, we will correlate the levels of microRNAs with the specific findings in the immune response in total and subtotal splenectomized patients. The study will have a prospective component as it will include searching for specific features of the immune response (as descried bellow) in three different categories of selected patients (healthy control group, the group of patients that will be subject to subtotal splenectomy and total splenectomy group). Also, the study will have a retrospective component as the same parameters will be evaluated in patients already splenectomized and subject to a follow-up.  The research will have two major components:

 

  1. to evaluate the endotoxin tolerance phenomenon as an expression of innate immunity, by determining the mononuclear cell cytokine release (TNF alpha, IL-1, IL – 6, IL -10) using ELISA techniques(cytokine releasing capacity of the whole blood after LPS stimulation)
  2. to identify the levels of microRNAs differentially expressed in plasma/serum of patients after total and partial splenectomy. We will correlate the plasma levels of microRNAs with the levels of proinflammatory cytokines after LPS stimulation and with the presence of different subsets of lymphocytes present in the circulation of the patients selected. Furthermore we would like to use the microRNAs as markers in order to find the differences between the immune response after subtotal and total splenectomy in order to demonstrate the immune advantages of partial splenectomy.

The possible control of microRNAs expression and function in patients who underwent total or subtotal splenectomy is a completely unexplored field.  If identified, such marker(s) could be of great clinical value, orienting the clinician in preventing or early treatment of the possible post-splenectomy life-threatening infections, like OPSI.


 

PERSONNEL LIST:


 

 

 

1. Catalin Vasilescu

2. Dan Coriu

3. Stefan Tudor

4. Monica Popa

5. Tudor Tuhari

6. Adina Ghita

7. Valeria Tica

8. Emilia Grigore

9. Dana Giza

10. Livia Procopiuc

11. Bogdan Trandafir

12. Vlad Nacev

13. Popa Ioana

14. Herlea Vlad

15. Olteanu Mircea

16. Lazarescu Valentina

17. Manuc Mircea

18. Diculescu Mircea

19. Babes Alexandru

20. Simona Manciu

21. Daniel Gavrila

22. Laura Costin

 

 

PHASES:


 

Phase 1 (31/12/2013) – FINISHED
Phase 2 (31/12/2014) – FINISHED
Phase 3 (31/12/2015) – FINISHED
Phase 4 (30/09/2016) – FINISHED


 

SCIENTIFIC REPORT:


ORAL PRESENTATION:

  1. MicroRNAs and the Dysfunction of the Innate Immune System in Sepsis. C. Vasilescu. MD Anderson Cancer Center Seminars, November 2013

 

  1. Minimally invasive splenectomy – twenty years, single team experience. C. Vasilescu, S. Tudor, Monica Lacatus, Dana Elena Giza. MINIMALLY INVASIVE SURGERY WEEK 2014 ANNUAL MEETING & ENDO EXPO, 10-13 Septembrie, 2014. USA.

 

  1. Robotic Versus Laparoscopic Splenectomy. Overcoming Technical Challenges with Robotic Surgery in Minimally Invasive Splenectomy. C. Vasilescu, S. Tudor, Monica Lacatus, V. Nacev. The International Congress of Endoscopic and Laparoscopic Surgeons of Asia (ELSA 2014). 8-11 Octombrie, 2014. Indonesia

 

  1. Partial laparoscopic splenectomy C. Vasilescu. 23rd INTERNATIONAL CONGRESS OF THE EUROPEAN ASSOCIATION FOR ENDOSCOPIC SURGERY (EAES), 4 – 6 iulie, 2015. Romanin.

 

  1. Minimally Invasive Partial Splenectomy – from laparoscopic to robotic surgery. C. Vasilescu, S. Tudor, B. Trandafir MINIMALLY INVASIVE SURGERY WEEK 2014 ANNUAL MEETING & ENDO EXPO, 2-5 Septembrie, 2015. USA.

 

  1. Robotic Partial and Total Splenectomy – Experience of a Single Team in a Series of 95 Cases. Monica Lacatus, C. Vasilescu. THE 4TH INTERNATIONAL CONGRESS IN ROBOTIC SURGERY. 29-31 Octombrie, 2015, Romania

 

  1. Why Do We Love da Vinci? Robotic Surgery: Myths and Realities. C. Vasilescu. CONFERINȚA NAȚIONALĂ  DE CHIRURGIE. 14-17 Octombrie 2015, Romania

 

  1. Chirurgia in bolile hematologice. C. Vasilescu. A XXIII-A CONFERINTA NATIONALA DE HEMATOLOGIE CLINICA SI MEDICINA TRANSFUZIONALA. 15-18 Octombrie, 2015, Romania

 

  1. Splenectomia  la pacientul cu PTI. C. Vasilescu. ACTUALITĂŢI ÎN MANAGEMENTUL AFECŢIUNILOR HEMATOLOGICE RARE. 21 Noiembrie, 2015. Romania
  1. Minimally invasive splenectomy – experience in a series of 530 cases. Vasilescu, S. Tudor, Simona Manciu, Monica Lacatus. 13º Congresso Brasileiro de Videocirurgia SOBRACIL, 11-14 Mai 2016, Brazilia

 

  1. Minimally invasive treatment of splenic cysts: the role of robotic surgery in partial splenectomy C. Vasilescu, D. Gavrila, B. Trandafir, L. Costin. 24th International congress of the EAES, 15-18 iunie, Olanda

 

  1. The Role of Robotic Surgery in Partial Splenectomy. C Vasilescu, B. Trandfir, S. Tudor Minimally Invasive Surgery Week 2016 SLS Annual Meeting, SRS Annual Meeting, 31 August-3 Septembrie 2016 USA

 


PUBLICATION LIST:

 

  1. Fractal-like kinetics of intracellular enzymatic reactions: a chemical framework of endotoxin tolerance and a possible non-specific contribution of macromolecular crowding to cross-tolerance., autori: Vasilescu C, Olteanu M, Flondor P, Calin GA in Theor Biol Med Model. 2013 Sep 14;10:55. doi: 10.1186/1742-4682-10-55. IMPACT FACTOR 1,46, SCOR RELATIV DE INFLUENTA 0,753.

 

  1. Robotic Splenectomy: What is the Real Benefit? Giza DE, Tudor S, Purnichescu-Purtan RR, Vasilescu C. World J Surg. 2014 Dec;38(12):3067-73. doi: 10.1007/s00268-014-2697-6. IMPACT FACTOR 2,348, SCOR RELATIV DE INFLUENTA 1,793

 

  1. MicroRNAs and ceRNAs: therapeutic implications of RNA networks. Giza DE, Vasilescu C, Calin GA. Expert Opin Biol Ther. 2014 Sep;14(9):1285-93. doi: 10.1517/14712598.2014.920812. IMPACT FACTOR 3,653, SCOR RELATIV DE INFLUENTA 1,36

 

  1. Cellular and Kaposi’s sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma: Stefan Tudor, Dana Elena Giza, Catalin Vasilecu et. al. Cell Death & Disease, (2014)5, e1559; doi:10.1038/cddis.2014.515. IMPACT FACTOR 5,014, SCOR RELATIV DE INFLUENTA 1,639.

 

  1. From mobility to crosstalk. A model of intracellular miRNAs motion may explain the RNAs interaction mechanism on the basis of target subcellular localization. Vasilescu C, Tanase M, Dragomir M, Calin GA. Math Biosci. 2016 Oct;280:50-61. doi: 10.1016/j.mbs.2016.07.012. Epub 2016 Aug 4 IMPACT FACTOR 1,64, SCOR RELATIV DE INFLUENTA 1,337.

 

  1. Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications Dana Elena Giza, Enrique Fuentes-Mattei, Marc D Bullock, Stefan Tudor, Mathew Goblirsch, Muller Fabbri, Florea Lupu, Sai-Ching Jim Yeung, Catalin Vasilescu and George A Calin. Cell Death and Differentiation (2016), 1–12 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1350-9047/16; Received 21.11.15; revised 30.7.16; accepted 02.8.16. IMPACT FACTOR 8,385, SCOR RELATIV DE INFLUENTA 3,674.

 

  1. Patients after splenectomy: old risks and new perspectives. Mihnea Dragomir, George Emil Dragoș Petrescu, Grațiela Elena Manga, George A. Călin. Revista Chirurgia, Bucuresti

 

  1. Book „Splina. De la laparoscopie la chirurgia robotica si inapoi.” La Editura Medicala, ISBN 978-973-39-0815-9.