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A Coruña, Spain

Medina Villaamil V.,INIBIC | Aparicio Gallego G.,INIBIC | Santamarina Cainzos I.,INIBIC | Valbuena Ruvira L.,Modelo Hospital | And 3 more authors.
International Journal of Biomedical Science | Year: 2011

Introduction: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. Methods: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson's correlation coefficient test. Results: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. Conclusion: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression. © 2011 Villaamil et al. Source

De Mendoza C.,University Hospital | Caballero E.,Hospital Vall DHebron | Aguilera A.,Hospital Conxo CHUS | Piron M.,Catalonian Blood and Tissues Bank | And 80 more authors.
AIDS Reviews | Year: 2014

The annual workshop of the Spanish HIV-2/HTLV Study Group was held at the Instituto de Salud Carlos III in Madrid on December 11, 2013. Nearly 100 experts and researchers in retroviruses other than HIV-1, the classical AIDS agent, convened for a one-day meeting devoted to updating knowledge on the epidemiology of HIV-2 and HTLV-1 infections and discussing new diagnostic and therapeutic strategies, with special attention to non-endemic regions such as Spain. The Group was funded 25 years ago and since then has been responsible for the national registry of cases, recording all relevant information for each subject and inviting them to enroll in a prospective cohort and biobank. Up to the end of 2013, a total of 297 individuals with HIV-2 infection were reported in Spain. All but 10 carry HIV-2 subtype A, with the rest being infected with subtype B. Overall, 71% came from sub-Saharan Africa. During the last decade, the incidence of new HIV-2 infections in Spain has remained fairly stable with around 20 cases per year. At the time of diagnosis, plasma HIV-2 RNA was undetectable in 61% of individuals and values in viremic subjects tended to be low (2.8 logs on average). To date, only 26% of HIV-2 individuals have been treated with antiretrovirals. The CD4 counts, however, only increased above 200 cells/mm3in 42% of them. On the other hand, 74% of non-treated HIV-2 individuals have > 500 CD4+ T-cells/mm3. As in HIV-1 infection, X4 tropism in HIV-2 is associated with lower CD4 counts. A total of 253 individuals with HTLV-1 infection were reported in Spain by the end of 2013. Overall, 58% came from Latin America. HTLV-1-associated myelopathy was diagnosed in 29 patients and adult T-cell leukemia/lymphoma in 18. The highest incidence occurred in 2013, with 34 new HTLV-1 diagnoses, largely as result of expanding HTLV screening in blood banks. Attempts to reduce HTLV-1 proviral load in symptomatic or asymptomatic patients with elevated HTLV-1 DNA using antiretrovirals have produced poor results, although integrase inhibitors could be more successful. Although no cases of HTLV-3 or-4 have been identified so far in Spain, 769 individuals have been diagnosed with HTLV-2 infection. Up to 85% of the latest cases are coinfected with HIV-1 and are former intravenous drug users. Source

Medina Villaamil V.,INIBIC | Alvarez Garcia A.,CHU A Coruna | Aparicio Gallego G.,INIBIC | Diaz Prado S.Ma.,INIBIC | And 2 more authors.
Molecular Medicine Reports | Year: 2011

The aim of this study was to provide a methodology to make a clear distinction between malignant tumors and morphologically similar benign processes, by examining the expression of EGFR, VEGF, HIF1-α, survivin, Bcl-2 and p53 proteins. Four groups of patient samples were studied: group 1, low-grade astrocytomas (WHO grades I-II) (n=6); group 2, peripheral area of high-grade astrocytomas (WHO grades III-IV) (n=5); group 3, gliomatosis cerebri (n=11); and group 4, reactive gliosis (n=6). Tissue arrays (TAs) were designed to study apoptosis, angiogenesis and invasion-related proteins by immunohistochemistry (IHC). By means of non-parametric analysis (Mann-Whitney Uu test), EGFR staining was shown to be significantly lower in reactive gliosis than in the low- and high-grade astrocytomas (p=0.015 and p=0.030, respectively); Bcl-2 immunoreactivity was significantly higher in the gliomatosis cerebri samples than in the reactive processes (p=0.005); and finally, Bcl-2 presented significantly lower expression levels in reactive gliosis compared to the peripheral areas of high-grade astrocytomas (p=0.004). The results indicate that Bcl-2 and EGFR may be useful in conducting differential diagnosis between the above groups, while the expression of the remaining antibodies does not appear to aid in distinguishing between the samples analyzed. The use of TAs to identify the protein expression profiles of biological markers related to different pathways was verified, and its potential as a discriminatory technique for everyday pathology procedures was demonstrated. Source

Medina Villaamil V.,INIBIC | Aparicio Gallego G.,INIBIC | Santamarina Cainzos I.,INIBIC | Valladares-Ayerbes M.,INIBIC | Anton Aparicio L.M.,Medical Oncology Service
Clinical and Translational Oncology | Year: 2012

Introduction Kidney tumours are frequently characterised by hypoxic conditions due to a local imbalance between oxygen (O2) supply and consumption. Hif1-α regulates angiogenesis, tumour growth, tumour progression, metastatic spread, and glucose metabolism by acting as a transcription factor for relevant genes. Here, we describe an immunohistochemical study of Hif1-α, a comprehensive computational study of Hif1-α interacting proteins (HIPs), an analysis correlating expression levels of Hif1-α with upstream and downstream proteins, and an analysis of the utility of Hif1-α for prognosis in a cohort of patients with renal cell carcinoma. Materials and methods The patient cohort included 80 patients. For immunohistochemistry evaluation, tissue microarrays were constructed. The IntAct, MINT, and BOND databases were used for the HIP approach. The Kruskal-Wallis test was used for comparing protein expression with pathology measurements. Correlation was expressed as the Pearson coefficient. Results Hif1-α expression correlates significantly with the "clear" histological subtype of renal cell carcinoma (p<0.01). The samples with the worst prognoses related to the pathological variables analysed showed the highest levels of Hif1-α expression. Significant correlations were found with Bcl-2, CAIX, C-kit, EGFR, TGF-β, proteins of the VEGF family, proteins related to differentiation (such as Notch1 and Notch3) and certain metabolic enzymes. Bioinformatic analysis suggested 45 evidence-based HIPs and 4 complexes involving protein Hif1-α. Conclusions This work summarises the multifaceted role of Hif1-α in the pathology of renal cell carcinomas, and it identifies HIPs that could help provide mechanistic explanations for the different behaviours seen in tumours. © 2012 Federación de Sociedades Españolas de Oncología (FESEO). Source

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