Universitatea de Medicină si Farmacie din Craiova
PN-II-ID-PCE-2007-1 (nr. 257/01.10.2007)

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THE STUDY OF ANGIOGENESIS AND LYMPHANGIGENESIS IN ORAL SQUAMOUS CELL CARCINOMAS
Period: 2007-2010
Project Manager: Associate Professor Claudiu Margaritescu, MD, PhD
Participant: University of Medicine and Pharmacy from Craiova
budget: 536 349 RON
Financial support: UEFISCSU

 

Grant's abstract:

 

Oral cancers is one of the major worldwide health problem due to high incidence, reduce survival rate and also to functional and cosmetic deficiency that accompany the disease and her treatment.

Since for the development and metastasis of oral squamous cell carcinoma (OSCC) is crucial to acquire an angiogenic and lymphangiogenesis phenotype by the malignant cells, we pursue the following objectives: 1)the angiogenic and lymphangiogenic phenotype for different OSCC variants; 2)identification of some statistics meaningful differences between sanguine and lymphatic vessels microdensity in OSCC variants, and also between intra- and peritumoral vessels microdensity; 3)quantification of proangiogenic and lymphangiogenic factor expression in tumoral cells and their stromal cellular partners and the expression rate of their receptors in endothelial cells.

To carry out all these desideratum we will use the following methods: 1)histopathological analysis for the estimation of OSCC variants, the degree of differentiation, the depth and pattern of invasion; 2)simple and double immunohistochemical analysis to investigate the phenotype of newborn vessels, involvement of proangiogenic and lymphangiogenic factors and cellular stromal partners in OSCC neovasculogenesis; 3) morphometrical analysis for the estimation of sanguine and lymphatic vessels microdensity and cellular stromal partners; 4)statistic analysis for identification of meaningful statistic correlations between morphoclinical parameters and vessels microdensity, the degree of proangiogenic and lymphangiogenic factor expression and cellular stromal partners density in different OSCC variants.

Carrying out these objectives we hope to establish the degree by which sanguine and lymphatic vessels microdensity and also the expression rate of major proangiogenic and lymphangiogenic factor and their target receptors has prognostic value in oral carcinogenesis.

 

 

 

 

The involvement of the each research team member in achievement of the proposed objectives

 

Activities

Month

Team member

2007

1*

2**

3**

4***

5***

1.1. Thoroughly studies on tumor and nontumoral angiogenesis and lymphangiogenesis process.

X-XII

X

X

X

X

X

1.2. Literature studies regarding oral squamous cell carcinoma angiogenesis and lymphangiogenesis

X

X

X

X

X

1.3. Literature studies regarding blood and lymphatic endothelial cell markers, pro- and antiangiogenic and pro- and antilymphangiogenic factors implicated in oral carcinogenesis

X

X

X

X

X

1.4 Workshop of the research team for homogenization of knowledge and to establish of the future research phases

X

X

X

X

X

1.5 Establishing of the research criteria and the statistics selection methods

X

X

X

X

X

1.6. Made of a site for results dissemination

X

 

 

X

X

 

2008

 

1.1. Retrospective studies for selection of the clinical cases and the registration of its in the data base

I-III

X

 

 

X

X

1.2 Prospective studies for identification of new clinical cases and the registration of its in the data base

X

 

 

X

X

1.3. Sample prelevation, histopathological processing and sample storage

X

 

 

X

X

1.4. Clinical and histopathological statistics process of the acquired data

X

 

 

X

X

1.5. Identification of the concerning cases which will be process by immunohistochemistry and morphometry

X

X

X

X

X

1.6. Workshop of the research team for homogenization of knowledge and to establish of the future research phases

X

X

X

X

X

2.1. Immunohistochemical identification of the main blood new vessels from oral squamous cell carcinoma (OSCC)

IV-VI

X

X

X

X

X

2.2. Establishing of the new blood vessels maturity from OSCC

X

X

X

X

X

2.3. The evaluation of the intra- and peritumoral new vessel microdensity in OSCC

X

X

X

X

X

2.4. Evaluation of the implication degree of pro- and antiangiogenic factors in OSCC

X

X

X

X

X

2.5. Statistical process of the acquired data

X

X

X

X

X

3.1. Immunohistochemical identification of the lymph new vessels from OSCC

VII-IX

X

X

X

X

X

3.2. Quantification of the proliferation degree for lymph endothelial cells from OSCC

X

X

X

X

X

3.3. The evaluation of the intra- and peritumoral new lymph vessel microdensity from superficial and deep parts of OSCC

X

X

X

X

X

3.4. Evaluation of the implication degree of pro- and anti lymph angiogenic factors in OSCC

X

X

X

X

X

3.5. Statistical process of the acquired data

X

X

X

X

X

4.1. Workshop of the research team for elaboration of the future articles that will be publishes.

X-XII

X

X

X

X

X

4.2. The site actualization.

X

X

X

X

X

 

2009

 

1.1. Continuing of the clinical monitoring of the selected cases and their inclusion in data base

I-III

X

 

 

X

X

1.2. Continuing the sampling prelevation and their histopathological processing.

X

 

 

X

X

1.3. The histopathological analysis and the results statistical processing.

X

X

X

X

X

2.1. Continuing of the immunohistochemical processing and of the main new blood vessels evaluation in OSCC

IV-VI

X

X

X

X

X

2.2 Evaluation of the of the new blood vessels maturity from OSCC

X

X

X

X

X

2.3. The evaluation of the intra- and peritumoral new vessel microdensity in OSCC

X

X

X

X

X

2.4. Evaluation of the implication degree of pro- and antiangiogenic factors in OSCC

X

X

X

X

X

2.5. Statistical process of the acquired data

X

X

X

X

X

3.1. Immunohistochemical evaluation of the new lymph vessels from OSCC

VII-IX

X

X

X

X

X

3.2. Continuing of the endothelial lymph cell proliferate degree evaluation in OSCC

X

X

X

X

X

3.3. The evaluation of the intra- and peritumoral new lymph vessel microdensity from superficial and deep parts of OSCC

X

X

X

X

X

3.4. Evaluation of the implication degree of pro- and anti lymph angiogenic factors in OSCC

X

X

X

X

X

3.5. Statistical process of the acquired data

X

X

X

X

X

4.1. Workshop of the research team for elaboration of the future articles that will be publishes

X-XII

X

X

X

X

X

4.2. The site actualization

X

 

 

X

X

 

2010

 

1.1. Continuing of the clinical monitoring of the selected cases

I-VI

X

 

 

X

X

1.2. Comparative morphometrical analysis of blood and lymph microvessels density from inside and periphery, respective from superficial and deep parts of the OSCC

X

X

X

X

X

1.3. Comparative immunohistochemical analysis of the main pro angiogenic and pro lymph angiogenic factors and for their receptors at the endothelial blood and lymph vessel in OSCCC

X

X

X

X

X

1.4. Comparative immunohistochemical analysis of the main anti angiogenic and anti lymph angiogenic factors in OSCC

X

X

X

X

X

1.5. Statistical process of the acquired data

X

X

X

X

X

1.6. The angiogenic phenotype characterization in different variants of OSCC

X

X

X

X

X

1.7. The lymph angiogenic phenotype characterization in different variants of OSCC

X

X

X

X

X

1.8. Establishing of the most significant statistical correlations between morfoclinical parameters and blood and lymph microvessels density, the expression degree of pro-angiogenic and pro-lymph angiogenic factors and their receptors in OSCC

X

X

X

X

X

1.9. Establishing of the main function of antiangiogenic and anti-lymph angiogenic factors in OSCC

X

X

X

X

X

1.10. Quantification of the prognostic value of angiogenesis and lymphangiogenesis in OSCC

X

X

X

X

X

2.1. Workshop of the research team for elaboration of the future articles that will be publishes

VII-IX

X

X

X

X

X

2.2. The site actualization

X

 

 

X

X

2.3. Programming and organize of a conference for dissemination of the final results

X

X

X

X

X

2.4. Identification of the following methods for the following researches

X

X

X

X

X

 

*- project manager;

**- Research experts;

***- Research in training