“Analysis of the E1a gene”
Principal Investigator: Santiago Ramón i Cajal Agüeras.
Invasiveness and metastatic potencial are two main properties that characterize tumor malignancy. The E1a gene has been proved to have a dual effect, acting both as tumor promoter as well as a tumor suppressor gene by decreasing the growth and the metastatic potential of the malignant cells. By microarray analysis, it has been found that genes of the plasminogen activator family, such as uPA, uPAr, tPA and PAI-1, are downregulated. In contrast, the gene PAI-2, that belongs to the same family, has been found to be upregulated. We propose that E1a regulates the expression of most of the members of the plasminogen activator family by repressing genes eventually involved in invasion and upregulating PAI-2, that correlates with a better prognosis in human tumors.
“Role of cyclin K as therapeutic factor”
Principal Investigator: Santiago Ramón i Cajal Agüeras.
Overexpression of certain genes such as bcl-2 increases the resistance to chemotherapeutic treatments, as the CDDP (cisplatinum). In addition, proteins such as the cyclin K (with viral origin) display lethal effects in human malignant cells. In ovary cells, it has been shown that the resistance induced by bcl-2 overexpression to chemotherapeutic agents is reverted by cyclin K overexpression. Cyclin K therapeutic effect could be beneficial in those patient tumors that, overexpressing bcl-2, were resistant to chemotherapy.
“Improvement of HVB expression by atomic microscopy”
Principal Investigator: Santiago Ramón i Cajal Agüeras.
In collaboration with Dr. Cenaro (Padova, Italy), we have identified the expression of hepatitis B and C viruses by atomic microscopy in DNA samples from patients in which the expression of these viruses had been previously assessed by quantitative PCR. This work has been performed in collaboration with the Biochemistry Department of the HUVH.
“Analysis of the expression of senescence genes in human tumors”
Principal Investigator: Santiago Ramón i Cajal Agüeras.
mRNA expression of senescence genes identified by Dr. R. Bernards has been studied both in normal tissues as well as in tumoral tissues from cancer patients. This study has identified for the first time RSK 4 and KIAA0828 as genes with a putative relevant role in cancer. Currently we are investigating the expression of these genes at protein level by Western blot and immunohistochemistry techniques.
“Analysis of the PI3K-Akt-mTOR pathway in human tumors”
Principal investigator: Federico Rojo Todo
In collaboration with the Oncology Department, activation levels of the PI3K-Akt-mTOR pathway have been characterized in a broad selection of solid tumors. This selection was performed based on high activation levels of mTOR and of their downstream proteins (p70S6K, S6 and 4EBP1), and the aim of the work was to identify the best candidates to be treated with mTOR inhibitors based on rapamycin analogs.
“Analysis of new genes involved in proliferation”
Principal Investigator: Matilde Esther Lleonart Pajarín.
Six millions cDNAs library has been used to infect MEFs primary cells, and the cellular clones with a proliferative advantage have been selected. These clones presumably contain genes involved in proliferation, and are able to escape to replicative senescence. We are currently identifying these genes and we will proceed to their characterization. This work is carried out in collaboration with Dr. Beach (London, UK) and Dr. Carnero (CNIO, Madrid).
“Tumor markers identification for endometrial adenocarcinoma after the isolation by microarray hybridization analysis of 297 differentially expressed sequences”
Principal investigator: Angel García Jiménez.
Immunohistochemistry performed by tissue array indicates that RUNX/AML1 overexpression correlates with different stages of the tumorogenesis process, from the normal atrophic endometrium to the complex hyperplasia and the carcinoma. These studies indicate for the first time that RUNX1/AML1 overexpression in endometrial cancer correlates with the initial steps of the myometrial infiltration.
“Expression of the angiogenic factors VEGF and bFGF and their receptors FLT-1 and FLK/KDR in Prostate Intraepithelial Neoplasia (PIN). Relationship with human prostate invasive carcinoma development.”
Principal investigator: Inés de Torres Ramírez.
The role for the angiogenesis in PIN lesions evolution towards the carcinoma development has been previously shown. Overexpression VEGF, Bfgf, flk/kdr and Flt-1, as well as a higher vascular density in the prostate adenocarcinoma versus the intraepithelial neoplasia of high degree, determines the angiogenic evolutive pattern in the different stages of the tumoral development from the initial pre- malignant phase to the invasive carcinoma.
“Thymidylate synthetase analysis in adjuvant therapy with 5-FU for colorectal carcinomas”
Principal investigator: Míriam Cuatrecasas Freixas.
We have studied expression levels and genetic alterations of the Thymidylate synthetase (TS) induced by the adjuvant treatment with 5-Fluorouracyl in colorectal carcinoma patients. The results obtained showed the predictive use of these levels to evaluate the response to the chemotherapeutic treatment, being effective for predicting a worse response in the case of tumors with TS overexpression detected by immunohistochemistry, and with genetic alterations in TS polymorphisms, in TS 6-bp from 1494 and in the TS promoter region (TSER).
“Identification of molecular targets associated with the tumoral progression and chemoresistance in colorectal carcinoma”.
Principal investigator: Míriam Cuatrecasas Freixas.
Our aims are directed towards the study of the central signal transduction pathways in colorectal carcinoma, the identification putative molecular alterations that could be used as therapeutic targets and the characterization of the genetic instability degree present in the regulation and activation of five central cellular processes (cell cycle, apoptosis, signal transduction, angiogenesis and invasiveness).
“Prognosis and biologic value of the expression of extracellular matrix degrading molecules and the epidermal growth factor receptor (EGFR) in colorectal carcinoma, by using immunohistochemistry, RT-PCR and laser tissue microdissection techniques”.
Principal investigator: Carmela Iglesias Felip.
We are focused in analyzing catepsines and EGFR expression in neoplastic transformation process of the colonic tissue: normal mucosa, hyperplasia, adenoma and carcinoma. Clinicopathological correlation analysis allows the evaluation of their putative prognostic role specifically in stage II tumors. Our working hypothesis, based on an increased expression of this factor in the metastasis compared to the primary tumor, is that the evaluation of immunohistochemical and morphologic parameters in the primary tumor could indicate the probability of the lesion to progress.