Analysis of mutant p53 gene in Chronic Lymphocytic Leukemia -CLL

Created on 18 May 2016
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Dr. Aurel

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ABSTRACT

 

 Apoptosis is an energy related process, in contrast with necrosis that occurs in the absence of adenosine-triphosphate (ATP). The main objective of the study was to assess intracellular ATP concentrations in B lymphocytes from patients with chronic lymphocytic leukemia (CLL), in comparison with ATP concentrations from B and T cells from patients with malignant diseases or non-malignant diseases, with allergic conditions.

 

Material and method

Using a Luminometer LKB analyzer, on principle of bioluminescence, we examined 75 patients (50 males and 25 females) with the following diagnoses: 25 patients (mean age 55 ± )) with allergic diseases (chronic allergic rhinitis, allergic dermatitis, chronic allergic asthma), 25 patients (mean age 58 ±) with nonhematopoietc malignant diseases (lung cancer, bone metastasis) and 25 patients with confirmed diagnosis of CLL. Control group consisted of 120 healthy patients (mean ages ±).

 

Results

 In the healthy male and female subjects, the mean concentration of ATP in 1 x 106 lymphocytes /ml of normal peripheral blood, T lymphocytes had was µM ATP and in B lymphocytes the concentration was µM ATP/ml [SD = , p= ]. The mean concentration of ATP in 1 x 106 activated peripheral blood T lymphocytes from patients with allergic diseases was µM ATP/ml and in B lymphocytes the mean concentration was µM ATP/ml [SD= , p = ]. From patients with malignant diseases, the concentration of ATP in 1 x 106 activated peripheral blood T lymphocytes/ml had a mean value of µM ATP and the mean concentration of ATP in activated 1 x 106 peripheral blood B lymphocytes/ml was µM ATP [SD= , p = ]. The mean concentration of ATP in 1 x 106 activated peripheral blood malignant CLL B lymphocytes/ml was µM ATP but was only µM ATP [SD= , p< ] in T lymphocytes from these patients. A strong correlation was observed between the concentration of ATP of T lymphocytes from patients with malignant diseases and ATP concentration of B lymphocytes from samples of patients with CLL (r= ) and a good correlation was observed between T lymphocytes (Th) from allergic diseases and T lymphocytes (Ts) from malignant diseases (r = ).

Conclusion

 

Blocked apoptosis from malignant diseases may be due to high ATP concentration originating from anaerobic metabolism. The difference of energy between anaerobic ATP in B lymphocytes from CLL and aerobic ATP in T lymphocytes from normal status in value of µM ATP, as an energetic transfer between B and T cells, initiates carcinogenesis by suppression of anti oncogene proteins, especially p53 protein.

 

Further studies are necessary to detect to patients with high concentrations of ATP and the mutations, translocations or deletions of the p53 gene, which is located on chromosome 17, using FISH technology and to discovery izoforms of Proteine P-53, in agresive malignant diseases, for application of personalised medicine at the patients with diagnosis of Leukemia.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Keywords (publishable, recommended: 3-5 keywords[l1] ):

Adenosine-triphosphate, Chronic Lymphocytic Leukemia, FISH-Fluorescence in situ hybridization, Hypoxia inducible factor -1, Phosphoinositide-3 kinase, Tumor necrosis factor

 

 

 

 

Table of content

Ensure to update the pagination of the following table of contents

1         Section 1: Relevance to the call. 4

;      Relevance to the general call objectives. 4

;      Federative character of the proposed activities. 4

;      Transformative character of the proposed activities. 4

;      Long-term plans beyond the project 4

;      Relevance to the topic. 4

2         Section 2: S/T Quality. 5

;      Objectives of the project 5

;     State of the art and expected progress beyond state of the art 5

;     Description of the project approach and method. 5

3         Section 3: Implementation. 6

;      Work plan and work packages. 6

;         Work plan. 6

;        Work Packages 7

;     Organisational and management structure. 8

;     Consortium. 9

;        Description of the consortium. 9

;      Added value of the collaboration, including multidisciplinarity and European dimension. 12

;      Consortium agreement principles (partner’s rights and duties, IPR management) 12

;      Organisations interested in the project beyond the consortium members. 12

;      Significant facilities and equipment 12

;     Financial plan. 12

;     Link with on-going projects. 12

;     Risks and mitigation plans. 12

4         Section 4: Impact. 13

;      Expected impacts. 13

;     Dissemination and exploitation of results. 13

5         Ethical issues. 13

6         References. 13

7         Appendix. 14

 

 

General recommendation:

  1. Please follow the recommended length for each section. The total recommended length for the core proposal is about 40 pages. Additional documents can be included in appendix to support the core proposal, but the role of the appendix is not to extend the proposal, and evaluation will be essentially based on the core proposal (cf. section 7).
  2. Please complete all sections. For the evaluation criteria, please refer to the call announcement. Your proposal should include all details required.

 

 

1 Section 1: Relevance to the call

;    Relevance to the general call objectives

;         Overall concept of the project

(~ ½ page)

Describe the concept of the project: why a Flagship-proof-of-concept project is needed, what is the rationale of your project to address the overall goals of this Call, what are the key innovative factors of your project.

 

   Interests of doctors in all specialties, medical students , staff working in clinical laboratories based on the fact that this work rests on a solid scientific information , rigorously confronted with the author's own experience gained in basic medical education in the country and abroad.

;         Federative character of the proposed activities

(~ ½ page)

Describe how the proposed project can attract, leverage or federate other initiatives, programmes and projects at the regional, national, European or international level.

TOPIC :

Diagnostic characterisation of rare diseases, 
Topic identifier:
    
SC1-PM-03-2017

;         Transformative character of the proposed activities

(~ 1 page)

Describe how the proposed activities are complementary with existing initiatives and have a transformative character with a high potential impact, in particular through changes of organisation and practices (, by bringing together different disciplines or by developing new methodologies, evaluation metrics, benchmarking protocols, data production and sharing protocols, test platforms, and other tools supporting coordination of efforts and reproducibility of experiments, novel approaches to academia-industry co-operation for enabling disruptive product and process innovation, creation of new markets, new companies, etc.).

 

 

    A dysfunctional apoptotic pathway may lead to the development of cancers. Due to the sensitivity of the intrinsic pathway, tumors arise more often through the intrinsic pathway than the extrinsic pathway . A very common cause of malignant tumors through the intrinsic pathway is a mutation in the p53 protein (tumor-suppressor protein). Besides regulating apoptosis, p53 also regulates the checkpoints of the cell cycle, DNA repair, senescence, and genomic integrity.

     A mutation causes the p53 gene to lose any of its functions will inevitably lead to carcinogenesis by letting the cell grow indefinitely, without any regulation. The p53 gene has been mapped in chromosome 17. In the cell, p53 protein binds DNA, stimulating another gene to produce the protein p21 that interact with cycle cell in division, stimulating a protein of stop division (cdk2). Another important factor in carcinogenetic process is the balance between the pro-apoptotic and anti-apoptotic members of the Bcl-2 family. In a tumor cell, a mutation in the Bcl-2 gene results in increased expression will suppress the normal function of the pro-apoptotic proteins BAX and BAK, leading to malignancy.

 

     In the normal cell, the p53 protein binds DNA, stimulating another gene to produce a protein called p21, which interacts with a cell division stimulating protein (cdk2) [11]. When p21 forms a complex with cdk2, the cell cannot pass through to the next stage of cell division, and remains arrested in G1.

    The p53 protein product of a TP53 mutant gene cannot bind DNA in an effective way, and as a consequence, the p21 protein is not made available to act as the stop signal for the cell cycle/cell division. Therefore, cells divide uncontrollably and form tumors [4] Not surprisingly, there is an increased frequency in the amplification of the ubiquitin ligases protein (MDM2) involved in the mechanism for the down regulation of p53 activity through ubiquitin-dependent proteosomal degradation of p53.

;         Long-term plans beyond the project

(~ 1 page)

Describe long-term plans to further develop research and innovation in the domain beyond the proposed project, and how these plans can be updated at the end of the project by taking into account its outcomes.

 

      Further studies are necessary to detect to patients with high concentrations of ATP the mutations, translocations or deletions of the p53 gene, using molecular complex technologies, in the discovery of mechanisms in the carcinogenesis process

;   Relevance to the topic

(~ 1 page)

Explain how the proposal addresses the specific scope of the topic.

 

     P53 has been shown to promote hematopietic stem cells (HSCs) quiescence and self-renewal with recent studies showing that deficiency of p53 likely promotes acute myeloid leukemia (AML) by eliminating its ability to limit aberrant self-renewal in hematopoietic progenitors. Micro RNAs (miRNAs) are small non-protein-coding RNAs that regulate gene expression by inhibiting the translation or catalyzing the degradation of target mRNAs. Since the first miRNA, lin-4, was identified in 1993, miRNAs have been shown to play critical roles in the regulation of many biological processes including cell differentiation, proliferation, and apoptosis, with significant influences on normal and malignant hematopoiesis.

     In this context the nuclear p-53 proteine was showed that protect the cell of a malignant process, and only citoplasmatic p-53 proteine, by its izoforms, in modified citoplsmatic medium, by high concentration of anaerobic ATP, drives at cancer.

2Section 2: S/T Quality

;   Objectives of the project

(~ 2-3 pages)

Describe the specific objectives for the project. These objectives should be clear, measurable, realistic and achievable within the duration of the project. Provide a SWOT table to outline which are the main strengths, weak points, opportunities and threats of your project in its 3-year timeframe.

 

This strategy could be particularly beneficial in treating cancers that do not harbor TP53 mutations. For example in hematologic malignancies, such as multiple myeloma, chronic lymphocytic leukemia (CLL).

;   State of the art and expected progress beyond state of the art

(~ 1 page)                    

Describe background, state of the art and expected progress beyond state of the art. Quantitative information must be provided.

 

Statement

  - My Book written in Clinical Laboratory Medicine, “ Hematological and Metabolical Aspects from Laboratory Medicine” , confirm the aria of my interest in discovery of carcinogenesis mechanisms, especially in onco-haematology field, Leukemia.

Seller , ;  

 

-Also, my new e-Book: e-BOOK: Hematological and Metabolical Aspects of Laboratory Medicine (Hematological and Metabolical Aspects from Laboratory Medicine) ( Second Edition ) [Large Print] [Paperback].

 

-Publisher: Aurelian Udristioiu, 2 edition (September 9, 2013) Full Color on White paper, 122 pages. ISBN-13: 978-1492186816 (CreateSpace-Assigned) ISBN-10: 1492186813, BISAC: Medical / Laboratory Medicine, USA. Sold by ;  

 

-Please, see the Blog of my Medical Book :

;          

 

Thanks.~!

-           Aurelian Udristioiu, ,

-           Lab Director, EuSpLM,

-           City Targu Jiu, Romania

- Member of National Academy of Biochemical Chemistry (NACB) , Washington , ;

 -Fellow PhD, Molecular Biology, Titu Maiorescu University, General Medicine Faculty, Bucharest, Romania,

-Man of Medical Year/2015, Certificate International Biographic Center, IBC, Cambridge, UK.

;   Description of the project approach and method

(~ 1 page)

Describe the overall approach and methodology, and explain their relevance to the objectives. Describe in particular the balance between pure coordination and networking activities and scientific and technical activities serving the goals of the project and of the call.

 

 

 Please, consult the following offer, on link : An interphase nucleus of normal human lymphocyte was stained with HER2/CEN17q FISH Probe, for about 100 cases.

HER2/CEN17q FISH Probe
FG0006

 

3Section 3: Implementation

;   Work plan and work packages

;   Work plan

(~ 1 page)

Describe the general work plan. Please provide a general overview of the work plan and a timing of the different work packages and their components (Gantt chart or similar) and a graphical presentation of the components showing how they inter-relate (Pert chart or similar).

   I wish to continue and develop the fundamental research on the Onco-Hematology field entitled, "The correlation between the cellular energy expressed in ATP and levels of mutant p53 protein in CLL.

  In this respect, I revealed the different levels of concentration anaerobic ATP in leukemia cells, T and B lymphocytes, of certain categories of this ;

    In this  highlighted research I quoted; Blocked apoptosis from malignant diseases may be due to high concentration ATP originating from anaerobic difference of energy from anaerobic ATP in B lymphocytes in CLL and aerobic ATP in T lymphocytes in the same case of CLL, was   μM ATP, and this level can initiate the carcinogenesis process by suppression of anti-oncogenic proteins, especially protein p53.

    Further studies have to necessary to detect high concentrations of ATP patients with the mutations and, translocation or deletions of the p53 gene, on chromosome 17 in which is located this gene, using FISH technology, and must done a correlation in this regard.   

    Lately, researchers in other countries have discovered the importance of the p53 gene mutated in malignant diseases, gene which, in the process of carcinogenesis becomes the active gene in ;

  Initially, it was found that P-53 mutant protein would be present in malignant cells, only 30%, but over the years, with the improvement molecular inspection techniques, PCR and FISH technology, the percentage of protein P- 53 mutant has increased to 70-80%. Also recently, oncologists experiment new medicines, the cytostatics of  bio-drugs category for malignant cells which act in the high levels of anaerobic glycolysis and hypoxic microenvironment, characteristic of cancer cells that destroy these cells.

   I believe that this research upon completion using FISH molecular technique could contribute to a new breakthrough in treating cancer, especially in CLL, the most common form of leukemia among adults.

;   Milestones

(~½ page)

 

List of milestones[1]:

No of Milestone

Delivery month

WP involved

Title

M1

June/2016

Undersign

Role of Gene and P-53 Protein in onco-genesis of LLC

M2

September/2016

Undersign

Apoptosis and autoimmunity in cancer

M3

May/2017

Undersign

Susceptibility of patients at P-53 mutant in LLC

Use as many lines as needed but try to limit the number of milestones.

;   Work Packages

Provide a description of each work package and a list of work packages (templates provided).

 

(up to 1 page per WP)

WP 1

WP Title

Start month

End month

Contribution of project partners

Partner number[2]

1

2

3

4

5

6

7

8

Total effort per partner (Person*months)

Full

Full

Full

Full

 

 

September 2016

May/

2017

Aim of the WP

Description of the objectives and expected results of the WP and the interrelation with other WPs.

 

   Recent evidences suggest that metabolites themselves can be oncogenic by altering cell s The advances in cancer metabolism research, over the last decade, have enhanced our understanding regarding the aerobic glycolysis and other metabolic alterations that  are associated with cell growth and proliferation.

 

   The objective of this work is to demonstrate that, under condition of changes of cellular microenvironment , the product of gene P-53, protein p-53 lost the role of stopping division cells and become aggressive in the carcinogenesis process.

 

 

 

 

 

 

 

3

 

 

June/2016

September/2016

 

Use as many lines as needed

 

Chronic Lymphocytic Leukemia derived from Syndrome congenital Li-Fraumeni disease

 

 

Deliverable

 

Month of delivery

Title of deliverable

June/2017

Pathogenesis of Chronic Lymphocytic Leukemia

September 2016

Gene an protein p53 in pathogenesis of

  Chronic Lymphocytic Leukemia

 

 

Use as many lines as needed














 

Use as many WP templates as needed

 

 

 

 

Work package overview: Total effort per WP and partner (in Person-Months)

project-partner

WP1

WP2

WP3

WP4

WP5

WP6

total

1

Full

Full

Full

Full

 

 

 

2

 

 

 

 

 

 

 

3

 

 

 

 

 

 

 

4

 

 

 

 

 

 

 

5

 

 

 

 

 

 

 

6

 

 

 

 

 

 

 

total

 

 

 

 

 

 

 

Use as many lines and columns as needed

 

;   Organisational and management structure

(~ 1 page)

Describe the organisational structure, management structure and decision-making procedures.

 

Titu Maiorescu University, Faculty of Medicine, Physiology Department, Bucharest, Romania;

 

 

;   Consortium

;   Description of the consortium

Describe expertise and role in the project for each partner (max. 1 page per partner). The information provided here will be used to judge the operational capacity.

 

Use this template for the coordinator

 

For now and until  the project deadline to my proposal, 11 April 2017 17:00:00,  in particularly for the proposal my project,  on personal Site Cordis, have expressed interest, but only as partners on, the site AUDRISTOIU2 Cordis, finder in  CORDIS page as Partnerships finder, Aurelian Udristoiu:

-Dr. Wang Yi, lecturer, PhD, Msc, School of Materials, University of Manchester, UK
-Dr. Paloma Gonzalez, Santander, Cantabria, Spain, EU Partners and Partnerships finder page on CORDIS,
-Dr. Liam Good, UK, EU Partners and Partnerships finder page on CORDIS.
Svetlana, Assistance Service, Institute of pulmonology Chisinau, Moldova.

 If I will receive founds I can become the Manager and resposible of this project.

 

 

se this template if this partner is not requesting funding but still essential to the project and committed to sign the project consortium agreement (cf. section for other organisations interested in the project).

 

 

Partner n

 

Organisation Full name / Department

Emergency County Hospital Targu Jiu

Expertise:

 

Expertise of the organisation related to the project objectives.

 

None

 

 

 

 

 

 

 

 

 

 

 

 

For the principal investigators give a brief CV highlighting research experience and list the 5 most important publications of the last three years

Curriculum Vitae

 

PERSONAL DETAILS:    

 

First name:

AURELIAN

Surname:

UDRISTIOIU

Specialty:

European Specialist in Laboratory Medicine

Age:

61

Gender:

Male

Date of Birth:

/05/11/

Citizenship:

Romanian

Home Address:

Traian Street, No: 26, City: Targu-Jiu, Romania

Telephone:

40723621414;  40723565637.

Email Address:

Reason for applying to work abroad:

Passion for works of researches in onco-hematology field

Available From (Month, Year):

October First,  / 2015

 

 

LANGUAGE SKILLS:

 

Language

Level

ENGLISH                                                           

8

ITALIAN

9

RUSSIAN

5

ARABIC 

3

 

MEDICAL AUTHORITY REGISTRATIONS:

 

Medical Authority

Registration Number

European Specialist in Biochemistry and Laboratory Medicine, License to practice in: EUROPEN UNION-EU

Certificate of Conformity, BUCHAREST, ROMANIA.

                        

My GMC Reference Number in UK: 7480781

NO. VIII. d / 55001 / 19. 10. 2007

 

 

 

 

 

education AND POST GRADUATE EXAMS PASSED:

 

-High School, Liceul Pedagogic, (Teacher), City Targu Jiu, County Gorj,  Romania, 1972-1\

 

-Faculty of General Medicine CRAIOVA, Romania, September 1977-September 1983

 

-Practitioner Medic of General Medicine (Stage), in University Hospital Grivita,  (Sfanta Maria), Bucharest, District 1, Romania, October 1983-November 1986.

 

-General Practitioner  in County Gorj, Hospital Motru,City Motru, Romania, December -1986-November 1989

-Physician Resident in Laboratory Medicine and Microbiology,-14 November 1989 to 14 November 1992.

--Master in Hematology, Laboratory Medicine, University Hospital Careggi, Agienda Carregy, Universita degli Studi Firenzze, Florence, Italy, January 1995-June 1995.

 

Fellow PhD in molecular biology, Titu Maiorescu University, General Medicine Faculty, Bucharest, Romania.

COURSES COMPLETED:

 

Name of course

Date Completed

Laboratory  Onco-Hematology , University Hospital Fundeni, Romania/780,MS

Ian 1993-Mai 1993

Screening , col cancer uterine , Babes Papanicolau

10 Oct 2013-13 Oct 2013

 

Course of Mass-Spectrometry IPC-MS

 

9 Sept. 2012-15 Sept. 2012.

 

current employment:

 

From: Month, Year

To: Month, Year

Hospital

Country

Position Title

August, 1998

May/2015 and in present

EMERGENCY COUNTY HOSPITAL

TARGU JIU

Romania

Primary Physician in Laboratory Medicine

 

Name and address of the hospital:

Emergency County Hospital TARGU-JIU,.Progresului Street ,Gorj, Postal Code:Zip 210218,Romania;  Fax :00-40-253-210432 ;Phone :00-40-723621414.

Hospital DESCRIPTION

Specialties

Internal Medicine, Gynecology, Neurology, Oncology, Emergency Medicine.

No. of hospital beds

1200

Outpatient services offered:

Diagnostics Diseases, Treatment, Laboratory Investigations.

previous employment:

 

Physician Specialist of Laboratory Medicine, in Hospital Rovinari, County Gorj, Romania, December 1992-September 1993

 

-Physician Specialist of Laboratory Medicine September 1993-1995, in Hospital City Nalut and Kabaw, Lybia.

 

- September 1996-1998, 31 August, Physician Specialist of Laboratory Medicine and Primary Physician of Laboratory Medicine ( from 18-09-1997) in University Hospital Bucharest, Romania

 

-Primary Physician of Laboratory Medicine, from 31-08-1998 until present/2015, in Emergency County Hospital Targu Jiu, City Targu Jiu, Romania.

SUMMARY OF EXPERIENCE- BY SKILL

Skill

Number of procedures undertaken:

From: (Month,Year)

To:

(Month,Year)

 

-Perform and Validation of Laboratory Analyses.

 

-I Assure the Quality Control of medical laboratory analyses, QC,  PT ( Proeficiency Testing),

 

-Auditor Accredited on the  International Standard; ISO: 15189/2013.

 

 

I performed in Departments of Laboratory Medical Analyses:

-HEMATOLOGY, Analysis of Laboratory, per every year/15 000.

- MICROBIOLOGY, Analysis of Laboratory, per every year/500

- CLINICAL CHEMISTRY, Analysis of Laboratory, perevery year/20 000.

August, 1998

March, 2015

Works of researches, in Laboratory medicine field

11

August, 1998

June, 2015

 

 

 

 

 

 

 

 

 

 

 

RECENT WORK OF RESEARCHES

 

1. Udristioiu A. The Assessment of Uncertainty in Measurement of Cholesterol; A Model of Calculation. Biophysical Journal; Volume 96, Issue 3, Supplement 1, February 2009; Page 504a.

 

2. Udristioiu A, Florescu Cristina, Popescu Manuela Andrei. “High Concentration of anaerobic ATP implicated in aborted apoptosis from CLL”. LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript 09-08-LM-S-SCI-0122R1, Published in 04-05/2010.

 

3. Aurelian Udristioiu. First Hematological Signal of Latent Anemia to Aging Population. Nature Publishing Group. Advance Search npre Creative Common Attribution License, accepted for the work online posted.

 

4. Udristioiu A, Cojocaru M, Florescu C. Screening Tests for Latent Anemia in Hospitalized Adults Over ;  LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript  ,  Published  in 07-05 American Journal of Clinical Pathology p-ISSN: 0002-9173 ICV LabMedicine ; Ascp Press) , Impact Factor ISI, IF = , 18 Index Copernicus Journals Master List 2006.

 

5. PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ANTIBIOTIC RESISTANCE PATTERNS IN ACINETOBACTER BAUMANNII STRAINS ISOLATED IN A ROMANIAN HOSPITAL. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2,SIMONA ENACHE-SOARE3, GABRIELA BANCESCU2, AURELIANUDRISTOIU4, MANOLE COJOCARU5, CODRUTA VAGU6

1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy, Department of Microbiology, Traian Vuia 6, Sect. 2, 020956,Bucharest, Romania.

6“Stefan S. Nicolau” Virology Institute, Bucharest, Romania. FARMACIA 2010; (57); 3: 420-427 IMPACT FACTOR ISI THOMSON .

 

6. Moleular Biological  Tchiniques  user for identification  of Candida SPP. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2, SIMONA ENACHE-SOARE3,  AURELIAN UDRISTOIU4. 1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy. FARMACIA 2010; (58); 4: 422-429

 

7. Udristioiu A. Role of Mg2+ ion as cofactor ATP in assurance of energetic environment cells( Abstract). Magnesium Research 2011; 24 (1): 22-6.

 

8. -Aurelian Udristioiu, Radu G. Iliescu, Cristina Popescu. Variability of bilirubin values in serum samples with high triglycerides; interference or congenital liver syndromes. J Biosci Tech Volume 2, Issue 4 (JULY 2011).

 

9. Aurelian Udristioiu¹*,Radu G. Iliescu², Lucian Udristioiu¹ and Manole Cojocaru. A new approach of abnormal apoptosis as a cause of autoimmunity and malignancy. Biotechnology and Molecular Biology Review Vol. 6(8), pp. 166-171, November 2011 . Available online at < ;

 

10. Aurelian Udristioiu, Cristina Popescu, Manole Cojocaru, Sorina Comisel, Valentina Uscatescu. Relation between LDH and Mg as Factors of Interest in the Monitoring and Prognoses of Cancer. Journal of Bioanalysis & Biomedicine. Ref.:  Ms. No. JBABM-11-48R1 accepted on Jan 27, 2012

 

11. UDRISTIOIU A. Florescu C, Popescu C, Cojocaru M "Significance of Neutrophil Alkaline Phosphatase versus Isoenzymes ALP in Acute or Chronic Diseases,"accepted for publication in LabMedicine, LabMedicine Manuscript

 

12. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Errors in Counting Platelets in Hemodialysis 12PatAurients by Use of Optical Microscopy. Review of Applied Physics (RAP) Volume 2 Issue 1, March 2013; p: 17-22

 

13. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Energetic Levels of Metabolic Pathways in Malignant B and T Cells Mini-Review. Advances in Chemical Science Volume 2 Issue 4, December 2013; 2; 90-95

 

14. Aurelian Udristioiu¹, Manole Cojocaru² Hemolytic Anemia Drugs Induced by Antihypertensive Agents: A case of Laboratory. 13 Scholars Journal of Medical Case Reports ISSN 2347- 6559. Sch J Med Case Rep 2013; 1(1):8-11

 

;Rapid Diagnosis of Acute Respiratory Infections by Multiplex Endpoint PCR Technology to International Journal of Life Science and Engineering on December 14, 2014.

                           

16. Aurelian Udristioiu1*, Radu G. Iliescu2, Manole Cojoraru Molecular mechanisms of bone reconstruction in new dental implant technology. Integrated Journal of British. Volume 1 2014 Issue 1(5-6), pg: 1-7; IJBRITISH.

 

17. Aurelian Udristioiu¹, Staniloiu Mihail¹, Manole Cojocaru², Sorina Comisel³.

 Molecular mechanisms of bone reconstruction in new dental implant technology.

 App. Sci. Report. 10 (2), 2015: 50-54.

 

18. Aurelian Udristioiu. Infrared Spectrum of Human Bio-energetic Field. . Open Science Journal of Bioscience and Bioengineering 2015; 2(6): 63-67. Published online October 13, 2015 ()

 

19.  Aurelian Udristioiuᶪ, Manole Cojocaru². Risk of Dis-lipids Syndrome in Modern Society.  International Journal for Research in Health Sciences and Nursing.  VOL 2 ISSUE 1 January 2016 Paper 4

 

 

WRITEN BOOKS:

 

Udristioiu. “Fitness Bike and Health”. Ed. Medicala 1990, Bucuresti. ISBN: 973-39-01105-9; Formatul 16/10 x 100; Nr pagini: 78.

 

Udristioiu. “Bioenergetics of malign and normal cells” Ed. Academica Brancusi 2002, Targu Jiu, Bun de tipar, Bucuresti, Tipografia Everest 2001; ISBN 973 85342-6-7; Formatul 16/14 x 100; Nr. Pagini: 307.

 

3. Aurelian Udristioiu, Manole Cojocaru, Radu Iliescu., “Hematological and Metabolic Aspects from Laboratory Medicine" (ISBN 978-3-8473-0775-4). LAP LAMBERT Academic Publishing GmbH & Co. KG Heinrich-Böcking-Str. 6-8 , 66121, Saarbrücken, Germany, 2012.

 

4. Book title: Renal Diseases / Book 2 (ISBN 979-953-307-704-7). Chapter title: Variability of Biological Parameters in Blood Samples between Two Consecutive Schedules of Hemodyalsis
Authors:
Aurelian Udristioiu, Manole Cojocaru, Victor Dumitrascu, Daliborca Cristina Vlad, Alexandra Dana Maria Panait and Radu Iliescu, Publishing Group 2011.
Volume 2, Issue 4 (JULY 2011)

 

5. e-BOOK: Hematological and Metabolical Aspects of Laboratory Medicine (Hematological and Metabolical Aspects from Laboratory Medicine) ( Second Edition ) [Large Print] [Paperback].

Publisher: Aurelian Udristioiu; 2 edition (September 9, 2013); Full Color on White paper, 122 pages. ISBN-13: 978-1492186816

 

 6. Book:” Recent Developments in Biotechnology, Volume 9: Diseases and Theranostics”, Author: Surender Singh. Chapter 21, Energetic Levels of Metabolic Pathways in Malignant B and T Cells Mini-review, Author Aurelian Udristioiu, Manole Cojocaru, ISBN: 9781626990241, Pages: 530, Publisher: Studium Press LLC, Year: 2014

 

 

TEACHING RESPONSIBILITIES:

 

Speciality/area of responsibility

From: (Month,Year)

To:

(Month,Year)

Lab Director of Laboratory Analyses

August 1998

April 2015

 

NATIONAL AND INTERNATIONAL AWARDS

 

 - Aurelian Udristioiu, Member in :National Academy of Clinical Biochemistry, NACB, Washington, , USA. 

 

- Aurelian Udristioiu. Anti-miocard Antibodies in Rheumatic Fever, Measured by Immunofluorescence, Medical Days, Craiova – May 1983. – Premium III Diploma.

 

- Aurelian Udristioiu. International Travel Grant AACC:

Winner/56-th Annual Meeting AACC, 08/25-29/2004, Los Angeles, California, USA.

 

-Aurelian Udristioiu. International Travel Grant AACC,

 Winner/57-th Annual Meeting AACC, 07/24-28/2005, Orlando (FL), USA.

- Aurelian Udristioiu. Award: Clinical Chemist`s Recognition Award/2007-2008 and Award/2009, AACC, Washington al Society, since 2008, Columbus, (OH), USA.

 

-Aurelian Udristioiu, ‘ Who is Who in Romania/2009’Romanian Personality in Book Enciclopedy

-Aurelian Udristioiu. Award: Clinical Chemist`s Recognition Award/2007-2008 and Award/2009, AACC, Washington .

- Aurelian Udristioiu, ‘ Who is Who in medical departments USA/ 2011-2012:  Who's Who in Medicine and Healthcare

 2011-2012-2013-2014-2015 (8th Edition)

” MarquisWho'sWho” , 300 ConnellDrive, Suite 2000, Berkeley Heights, N0: 07922 USA1-908-673-1000 ,

 

-Professional 1 Member in American Society of Clinical Laboratory(ASCLS), Bethesda, USA, since 07/31/2006; Member ID#= 219762.

 

- Aurelian Udristioiu, Certificate as Award Academic Editor International UK: SCIENCEDOMAIN international Journal/2015.

 

- Aurelian Udristioiu, Certificate as Award Academic, IBC, International Bibliographic Centre, Cambridge, UK, 2015.

 

- Aurelian Udristioiu, Man of medicine on year/2015, Certificate as Award Academic, IBC, International Bibliographic Centre, Cambridge, UK, 2015.

REFERENCE

Name:

Hospital:

Contact phone number:

Email address:

Manole Cojocaru

 

Titu Maiorescu University, Faculty of Medicine, Physiology Department, Bucharest, Romania;

40723326663

Dana Alexandra Maria Panait

Titu Maiorescu University, Faculty of Medicine, Microbiology Department, Bucharest, Romania

40720949055

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Role in project:

 

Doctoral thesis as Fellow PhD in Molecular Biology, UTM, Titu Maiorescu University, Medicine Faculty, Bucharest, Romania

 

 

 

 

 

 

Funding:

Explain how the partner is able to secure its own funding (a letter of commitment or documentation about the funding can be provided in appendix if deemed relevant)


Dear Aurelian Udristioiu,

my contact follows the call for participants published on the Cordis
portal "Diagnostic characterisation of rare diseases".

I'm a Professor and Researcher at Computer Science, University of
Coimbra, Portugal. I have developed a computational model to
understand the infection mechanism of pathogen factor (virus;
Bacteria,..) over time condition. We have tested and experimentally
validated the model using flu and HIV data (paper under review).

At the moment we are looking for other domains to apply our model, and
the Personalised Medicine seems a perfect domain.
I would like to ask to share more detailed information about the
project proposal that you envision.

All the best,
-- 
____________________________________
Joel Arrais, Assistant Professor
DEI/CISUC - University of Coimbra
~jpa

 

 

 

 

Use as many partner template as needed

 

;         Added value of the collaboration, including multidisciplinarity and European dimension

(~ ½ page)

Describe the added value of the consortium as a whole (including complementarity, balance). Indicate the contribution of the project, at the European and/or international level, to the expected impacts.

 

FISH deletion hematologic Neoplasms 7q bone marrow with delivered in  peripheral #39;d be interested hematological disease Chronic Lymphocytic Leukemia derived from Syndrome congenital Li-Fraumeni disease which can be included in rare  malignant diseases, and can be diagnosed by Technology Test FISH deletion 5q,  or Test 
    In proposal project on site Cordis, that I did not find a Manager in charge of the project, which to access European Community funds by acquiring and filling the Guide European program online Call Project Proposal, the site FP7 / Horizon 2020.

;         Consortium agreement principles (partner’s rights and duties, IPR management)

(~ ½ page)

  For now and until  the project deadline to my proposal, 11 April 2017 17:00:00,  in particularly for the proposal my project,  on personal Site Cordis, have expressed interest, but only as partners on, the site AUDRISTOIU2 Cordis, finder in  CORDIS page as Partnerships finder, Aurelian Udristoiu:

-Dr. Wang Yi, lecturer, PhD, Msc, School of Materials, University of Manchester, UK
-Dr. Paloma Gonzalez, Santander, Cantabria, Spain, EU Partners and Partnerships finder page on CORDIS,
-Dr. Liam Good, UK, EU Partners and Partnerships finder page on CORDIS.
Svetlana, Assistance Service, Institute of pulmonology Chisinau, Moldova

-

CORDIS is managed by the Publications Office of the European Union.

Dear Partner,

 I am contacting you from the Lithuanian Association “Institute of Advanced Society” regarding the new calls for proposals. Also, we’re looking for new partnerships in the framework of EU programmes to innovate our activities and fully exploit the potential of transnational cooperation, with particular regard to main objectives: § Encourage long life learning of society members, provide them with the best possible conditions to improve, widen interests; § Develop work and art abilities, educate cultural and other valuables in order to create innovative, creative civil personality; § Maintain communication and collaboration of Institute and society members in order to ensure sustainable, impartial and overall human and social development network of partners; § Educate the public about responsibilities of citizens; I am sure that Institute of advanced society as educational institution could be competitive partner for your consortium. We are working a lot with youths, social risk groups for involving them in active society, helping in finding a job, also for business startup and self-employment. If you considered us as a partner I could send you more information which you need. Also we would give a hand while preparing proposal for European Commision. Feel free to get in touch with me for joint project proposals and partnerships! Sincerely, Reda Zakarauskaitė CEO tel.:+370 601 07135 e‘mail.: Association „Institute of Advanced Society“Organisations interested in the project beyond the consortium members

 (~ ½ page)

Mention organisations which have expressed interest in the project and are willing to participate to some of its activities, while not being consortium members. Letters of support can be provided in appendix. Such organisations can typically be invited to meetings and workshops organised by the project. However, the core scientific and technical objectives of the project should not rely on such invited partners.

Research within the Cancer Genetics Program is wide ranging. It includes identifying and studying genes associated with childhood cancer risk; analyzing molecular and cell biology pathways associated with development and progression of cancers; identifying molecules that might represent viable targets for novel drug therapies; and developing practical applications of genetic testing of children and families at risk. It receives more than 190 new referrals each year and to date has consulted on over 1200 families.

Individuals with mutations in the TP53 gene, a condition known as Li-Fraumeni Syndrome (LFS), are one particular focus of the Cancer Genetics Program.

LFS sufferers are predisposed to a wide spectrum of cancers that often develop when they are children. TP53 mutations are also found in women who have developed breast cancer under age 30. Many people with LFS will be diagnosed with cancer two or more times during their lifetime.

Childhood cancer is largely a genetic disease, although its pattern of inheritance is not always clearly defined. It is these genetic mechanisms of susceptibility that are the focus of research for the Cancer Genetics Program at the Hospital for Sick Children (SickKids) in Toronto, Canada.

Nardin Samuel, an MD/PhD candidate at the Faculty of Medicine, University of Toronto working at the Hospital for Sick Children, Genetics and Genome Biology, Ontario Institute for Cancer Research, is using Qlucore’s Omics Explorer in her PhD work focusing on the epigenetics of LFS cancers.

Epigenetics is the study of the chemical reactions that activate and deactivate specific parts of living organism’s the genome as it develops and the factors that influence these reactions.

Various sequencing approaches are applied to understand how cells are primed to transform and become malignant and in particular, how they can be targeted therapeutically.

Epigenetics is a growing field in the arena of cancer susceptibility syndromes and approaches to analyzing genome-scale data are essential for surveilance cells.

 

 

 

;         Significant facilities and equipment

 (~ ½ page)

Describe any significant facilities and large equipment available to the consortium to perform the project.

 

The p53 gene is responsive to a large number of environmental stressors and regulates maintenance of genomic stability, changes in oxidative stress and mtDNA copy number, and adjacent regions to p53 encode for proteins with important roles cellular function.

"In the presence of some type of environmental stressor, the tumor suppressor p53 stops cell division to allow the repair of damaged DNA.

 

;   Financial plan

(~ 2 pages)

Describe the overall project costs and requested funding, for each partner and each type of resource (Personnel, Consumables, Equipment, Travel, Subcontracting, Provisions, Licensing fees, other), and justify the requested funding. Note that figures for each project partner and type of resource must also be filled in directly in the Evaluation and Submission System (ESS) by the coordinator.

 

 Please, consult the following offer, on link : An interphase nucleus of normal human lymphocyte was stained with HER2/CEN17q FISH Probe, for about 100 cases.

 

  • Specification
  • Product Description:
  • Labeled FISH probes for identification of gene translocation using Fluorescent In Situ Hybridization Technique. (Technology).

 

4       PML/RARA DY Translocation FISH Probe

  • Catalog # : FT0004
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  • 200 uL
  • USD $ 2,060
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  • order now, ship in 5 days
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  • The price is valid only in USA. Please select country.

 

Abnova is offering 20% off on 330+ research and 15% off on 43 GMP-graded cytogenetic probes enablingyou to detect specific targets in cells or in tissues. Manufacturedand validated through rigorous controlprocesses, our FISH probes are ensured toprovide researchers the best tool to confirm various genetic amplification,rearrangements, deletions, and aneuploidy. View details below for more information:
 

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  • Quality Control Testing:
  • Representative images of normal human cell (lymphocyte) stain with the dual color FISH probe. The left image is chromosomes at metaphase, and the right image is an interphase nucleus.

 

;   Link with on-going projects

(~ 1 page)

Indicate if on-going projects are linked to the proposed project and how such cooperation will be developed and managed, which activities will be coordinated with other projects, which results will be shared, how relationships will be managed to ensure proper management of resources and intellectual property rights, etc.

 

A basic medical education in the country and abroad with the interests of doctors in all specialties , medical students , staff working in clinical laboratories from 21 countries.

;   Risks and mitigation plans

(~ 1 page)

Describe the main risks associated both to the networking activities and to the scientific and technological activities of the project in its 3-year timeframe. For each of the identified risks, provide a short description of an appropriate mitigation plan which could keep the project in line with its overall goals.

 

Risk

Likelihood (low, medium, high)

Impact (low, medium, high)

Mitigation plan

Descovery of translocations and deletions of the p53 gene, using molecular complex technologies, in percent ratio from 30-40% to 70-80% in function of used techologies

Medium

Medium

User of Technology Test FISH with very high sensitivity and specifity.

 

 

 

 

 

 

 

 

Use as many lines as needed

 

 

5Section 4: Impact

;   Expected short-term impacts

(~ 1 page)

Describe the expected scientific or societal impacts of the proposed project, providing only information that applies to the proposal and its objectives. Wherever possible, use quantified indicators and targets.

 

The anabolic metabolism in B and T cells from malignant diseases there is under a complex regulatory control directed of membrane receptors, associated with growth factors signals of transduction in transformed cells.

      This energetic level could initiate the process of carcinogenesis, by the supression of anti-oncogene proteins, from its normal activity.

Management of bionergy cells,  from cancer cells,  on glicolitic pathway, can stop the processs of carcinogenesis.

 

;   Expected long-term impacts

(~ 1 page)

Provide a synthetic description of what the impact could be n a 10-year perspective assuming the proposed effort for promoting a long-term federation the research community to focus on the proposed research and innovation roadmap is successful.

 

   Most important cell-regulatory mechanisms of energetic metabolic pathways, in mammalian T cells and B cells are: death receptors, caspases, mitochondria, the Bcl-2 family proto-oncogene, tumor suppressor gene TP53, TNF, and nuclear translocation factor, NF-Κb and recently Micro RNAs (miRNAs) which are small non-coding RNAs that act at the posttranscriptional level to regulate protein expression [38, 39, 40].

    High concentrations of anaerobic ATP could impair the apoptosis from CLL. Further studies are necessary to detect to patients with high concentrations of ATP the mutations, or translocations deletions of the p53 gene, using molecular complex technologies, in the discovery of mechanisms in the carcinogenesis process.

The research community to focus on the proposed research and innovation roadmap become successful because is very near to discovery the final treatment of cancer, in specially on LLC.

;   Dissemination and exploitation of results

(~ 1 page)

Provide a plan for disseminating and exploiting the project results.

I wish to continue and develop fundamental research on the Onco-Hematology,, entitled: " Correlation between the cellular energy expressed in ATP and levels of mutant p53 gene in Chronic Lymphocytic Leukemia". In this regard we have prepared a summary on this issue that may put him at your disposal for verification and other data (CV, list of papers published in academic journals International and list of books written addressing issues hematologic and metabolic medicine Laboratory.

 

High concentrations of anaerobic ATP implicated in aborted apoptosis from CLL

 

 ¹Udristioiu Aurelian, ²Cristina Florescu, ³Manuela Anda Radu-Popescu, 4 Manole Cojocaru ¹Emergency County Hospital TARGU-JIU,.Progresului Street ,Gorj, Postal Code:Zip 210218,Romania, ²Central Laboraotry Synevo, Clinical Trial, District 1, Bucharest, Romania ³UMF Carol Davila, Medicine Faculty, Department of Farmacy, Bucharest, Romania 4Titu Maiorescu University, Faculty of Medicine, Physiology Department, Bucharest, Romania

 

 ABSTRACT

Apoptosis is an energy related process, in contrast with necrosis that occurs in the absence of adenosine-triphosphate (ATP). The main objective of the study was to assess intracellular ATP concentrations in B lymphocytes from patients with chronic lymphocytic leukemia (CLL), in comparison with ATP concentrations from B and T cells from patients with malignant diseases or non-malignant diseases, with allergic conditions.

Material and method

The mean concentration of ATP in 1 x 106 activated peripheral blood malignant CLL B lymphocytes/ml was µM ATP but was only µM ATP [SD= , p< ] in T lymphocytes from these patients. A strong correlation was observed between the concentration of ATP of T lymphocytes from patients with malignant diseases and ATP concentration of B lymphocytes from samples of patients with CLL (r= ) and a good correlation was observed between T lymphocytes (Th) from allergic diseases and T lymphocytes (Ts) from malignant diseases (r = ).

 Conclusion

 

 Blocked apoptosis from malignant diseases may be due to high ATP concentration originating from anaerobic metabolism.

 The difference of energy between anaerobic ATP in B lymphocytes from CLL and aerobic ATP in T lymphocytes from normal status in value of µM ATP, as an energetic transfer between B and T cells, initiates carcinogenesis by suppression of anti oncogene proteins, especially p53 protein. Further studies are necessary to detect to patients with high concentrations of ATP and the mutations, translocations or deletions of the p53 gene, which is located on chromosome 17, using FISH technology.

 

Abbreviations APTT-Adenosine-triphosphate; CLL-Chronic Lymphocytic Leukemia; FISH-Fluorescence in situ hybridization; HIF-1 -Hypoxia inducible factor 1; PIK3- Phosphoinositide-3 kinase; TNF-Tumor necrosis factor; TNFĄ, TGFħ

 

 

 

6Ethical issues

Describe any foreseeable ethical issue that may arise during the course of the research project. Describe all mitigation strategies employed to reduce ethical risk, and justify the research methodology with respect to ethical issues.

 

The work is an original research and I have contributed as single author to the intellectual content of this paper.

Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest for chapter 1”

 

Author,

Aurelian Udristioiu, Emergency County Hospital Targu Jiu, Clinical Laboratory,

                      Fax; 40253210432, Phone; 40723621414, E-mail;

 

7References

(Recommended maximum: 30 references)

 

Adela Joanta, Division of Clinical Research, Department of Neurology, Columbia University, New York, USA.

 

3. Cristina Florescu, Central Medical Synevo, Clinical Trial, District 1, Bucharest.

 

4. Dana Alexandra Maria Panait, TituMaiorescu University, Faculty of Medicine, Physiology Department, City Bucharest, Romania

 

5. Delia. Nica Badea, Constantin Brancusi University, Faculty of Medical Science and Behaviors, City Targu Jiu, Romania

 

6.  Florin Mitu, Mecro System SRL, Bucharest,

 

7. Lucian Udristioiu,  Emergency County Hospital Targu Jiu, Clinical Laboratory, Gorj, Romania

 

8. Manole Cojocaru, Titu Maiorescu University, Medicine Faculty, Department Physiology, Bucharest, Romania

 

9. Mihail Staniloiu,  Emergency County Hospital Targu Jiu & UCB University, Romania

 

10. Radu G. Iliescu, Polytechnic Institute of New York University, Department of Researches, Brooklyn, USA.

11. Sorina Comisel, UMF Craiova, Medicine Faculty, Endocrinology, Craiova, Romania

 

 

 

 

 

8Appendix

Provide any additional document supporting the core proposal, such as letters of commitment from self-funded consortium partners or letters of support from potential associated partners not included in the consortium. This appendix is not counted in the 40 page length recommendation. However, its role is not to extend the proposal, and evaluation will be essentially based on the core proposal. In particular, information provided in the appendix which is essential for the evaluation should appear in the core proposal, with a pointer to the relevant part of the appendix. As an example, if copies of letters of support are provided in appendix, the list and main features of these letters should appear in the core proposal.

 

 

- Energy levels of the metabolic pathways in malignant B and T lymphocytes in Review" ,the chapter presents the latest evidence from the literature on cellular metabolites that may be oncogenic by modifying cell signaling and blocking cellular differentiation. Advances in cancer metabolism research in the last decade have increased our understanding on aerobic glycolysis, anaerobic and other metabolic ch"anges that are associated with cell growth and proliferation.

Blocking apoptosis in malignant diseases may be due to the high concentration of ATP from anaerobic metabolism. Energy difference between anaerobic ATP B and T lymphocytes in peripheral blood samples from hematopoietic malignancies measured by bioluminescence was μM ATP, a value that appears as an energy transfer between normal B cells and T cells. The energy level can initiate the process of carcinogenesis by suppressing the activity of anti-oncogene proteins.

    It is concluded that anabolic metabolism in B and T cells in hematological malignancies are under complex regulatory control, directed by receptors on the cell membrane associated with an increase in signal transduction in cells transformed into malignancy.

 

- Energy levels of the metabolic pathways in malignant B and T lymphocytes in Review" ,the chapter presents the latest evidence from the literature on cellular metabolites that may be oncogenic by modifying cell signaling and blocking cellular differentiation. Advances in cancer metabolism research in the last decade have increased our understanding on aerobic glycolysis, anaerobic and other metabolic ch"anges that are associated with cell growth and proliferation.

Blocking apoptosis in malignant diseases may be due to the high concentration of ATP from anaerobic metabolism. Energy difference between anaerobic ATP B and T lymphocytes in peripheral blood samples from hematopoietic malignancies measured by bioluminescence was μM ATP, a value that appears as an energy transfer between normal B cells and T cells. The energy level can initiate the process of carcinogenesis by suppressing the activity of anti-oncogene proteins.

    It is concluded that anabolic metabolism in B and T cells in hematological malignancies are under complex regulatory control, directed by receptors on the cell membrane associated with an increase in signal transduction in cells transformed into malignancy.

 

Biochim, PhD, Sorin Gijiu, Emegency Hospital Clinical University, City Timisoara, Romania

Member of American Academy of Clinical Biochemistry, (AACC/NACB) Washington , USA

 

 

 

[1] A milestone is a major and visible achievement in the project. It should be SMART (Specific, Measurable, Attainable, Relevant, Time-bound).

[2] Bold the partner number of the work package leader

 [l1]


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