José M González

Fundación Hospital de Jove, Gijón, Asturias, Spain

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Publications (6)19.49 Total impact

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    ABSTRACT: The aim of the present work was to perform a comparative study of stromal cell expressions of MMPs and TIMPs between benign and malignant prostate tissues. An immunohistochemical study was performed using specific antibodies against metalloproteases (MMPs) -1, -2, -7, 9, 11, 13, 14 and their tissue inhibitors (TIMPs) -1, 2 and 3, on prostate specimens from 133 patients with clinical localized prostate carcinoma and from 50 patients with BPH. Our results showed higher percentages of expressions of MMPs and TIMPs by fibroblasts or by mononuclear inflammatory cells (MICs) in prostate carcinomas compared to these cells in BPH. The detection of MMP-2 expression by stromal fibroblasts and/or MMP-2, 9 and TIMP-3 expression by stromal MICs was associated with a 100% of specificity for diagnoses of prostate cancer. We found that the combination of MMP-2 expression by fibroblasts and/or MMP-9 by MICs and/or TIMP-2 by MICs yielded a sensitivity of 47.4%. Despite of a limited sensitivity (50%), the combination of MMP-TIMPs expression in stromal cells (MMP-2 by fibroblasts and TIMPs by MICs) in our study provided a specificity of 100% for prostate cancer diagnosis.
    Journal of Cancer Research and Clinical Oncology 03/2011; 137(3):551-5. DOI:10.1007/s00432-010-0906-8 · 3.01 Impact Factor
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    ABSTRACT: Matrix metalloproteases (MMPs) and their inhibitors (TIMPs) play an essential role in the degradation of stromal connective tissue and basement membrane components. The aim of this study was to determine whether the dynamic analysis of these components can help to predict tumour aggressiveness. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13 and -14 and TIMPs -1, -2 and -3. More than 5000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed on the tumour centre core as well as on the invasive front. Immunostaining for MMPs/TIMPs on mononuclear inflammatory cells (MICs) was evaluated. To identify specific groups of tumours with distinct expression profiles, data obtained from both MICs populations were analysed by unsupervised hierarchical cluster analysis. When compared with MICs at the invasive front, intratumour MICs more frequently showed expression of MMP-7 and -1 and TIMP-3, but less frequently expression of MMP-9 and -11 and TIMP-2. Our data led us to consider the need of further studies in order to identify subsets of MICs and other protein elements of the microenvironment as attractive targets for new therapeutic strategies against cancer.
    Histopathology 12/2010; 57(6):862-76. DOI:10.1111/j.1365-2559.2010.03723.x · 3.30 Impact Factor
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    ABSTRACT: To investigate the possible clinical value of the expression of MMPs and their tissue inhibitors (TIMPs) by the different cellular types of the tumor scenario to predict biochemical recurrence in patients undergoing radical prostatectomy due clinically localized prostate cancer. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13 and 14 and TIMPs-1, 2 and 3 on cancer specimens from 133 patients with clinical localized prostate carcinoma. Immunostaining for all the proteins studied was localized predominantly in tumor cells, but also in stromal cells in a significant percentage of prostate carcinomas, ranged from 20 to 50% for several proteins in fibroblast-like cells and in mononuclear inflammatory cells. Multivariate analysis according to a Cox model demonstrated that tumor stage (P < 0.0001) and Gleason grading (grades 7-10: 2.08 (1.1-3.9); P < 0.05) were significantly and independently associated with biochemical recurrence. Additionally, the expression of MMP-9 by fibroblast-like cells (P < 0.01) and MMP-13 by tumor cells (P < 0.05) were also variables significantly and independently associated with biochemical recurrence. MMP-13 expression by tumor cells and MMP-9 by stromal fibroblast-like cells were independent factors of biochemical recurrence in prostate cancer.
    World Journal of Urology 10/2010; 29(5):657-63. DOI:10.1007/s00345-010-0595-6 · 3.42 Impact Factor
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    ABSTRACT: Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, and 9 in prostate cancer. The expression levels of TLR3, TLR4, and TLR9 were analyzed on tumors from 133 patients with prostate cancer. The analyses were performed by immunohistochemistry on tissue arrays and real time-PCR. Cancerous cells showed high expression levels of TLRs compared with controls. Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4, and TLR9. In addition, the tumors that showed high TLR3 or TLR9 expression levels were significantly associated with higher probability of biochemical recurrence. TLR expression is associated with prostate cancer with recurrence and the role of TLR receptors in the biology of malignancy merits study. Therapeutic strategies to boost or block TLRs may be of interest.
    Cancer Immunology and Immunotherapy 10/2010; 60(2):217-26. DOI:10.1007/s00262-010-0931-0 · 3.94 Impact Factor
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    ABSTRACT: To investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in patients who develop local recurrence (LR) after mastectomy. We analyzed the expressions of MMP-1, -2, -7, -9, -11, -13, -14, TIMP-1, -2, and -3, using immunohistochemical techniques, in primary tumors from patients without tumoral recurrence (n = 50), patients who developed distant metastasis (n = 50), and from patients who develop LRs (n = 25). LRs of the latter group were also analyzed for MMPs expression. All the patients underwent mastectomy. Score values for all MMPs and TIMPs were significantly higher in primary tumors of patients with distant metastasis. Primary tumors from patients with LR have lower expressions of MMPs and TIMPs compared with those from patients who developed distant metastasis, and with patients without recurrence for some MMPs. Remarkably, however, primary tumors from patients with LR showed significantly higher percentage of TIMP-1 and 2 expression in stromal cells compared to primary tumors from patients with distant metastasis or primary tumors from patients without tumoral progression. Furthermore, LRs had significantly higher MMP-9 expression than their corresponding primary tumors. Our data indicate differences in MMPs/TIMPs expression between primary tumors of patients with LRs and of those with distant metastasis, both after mastectomy for breast cancer.
    Journal of Cancer Research and Clinical Oncology 07/2010; 136(7):1049-58. DOI:10.1007/s00432-009-0750-x · 3.01 Impact Factor
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    ABSTRACT: We assessed differences in the patterns of expression of matrix metalloproteases and their inhibitors (tissue inhibitors of metalloproteases) in ductal carcinoma in situ alone and admixed with invasive ductal carcinomas (n = 40), as well as in pure invasive ductal carcinomas (n = 40), immunohistochemically and using tissue arrays. The invasive ductal carcinoma components showed higher expression of matrix metalloprotease-9 and -13 than did the admixed ductal carcinoma in situ, whereas stromal fibroblasts of the invasive components showed higher expression of matrix metalloprotease-2, -7, -9, -13, and -14 and tissue inhibitor of metalloprotease-1 and -3 than did fibroblasts around the neoplastic ducts of the admixed ductal carcinoma in situ. Expression of matrix metalloprotease-14 and tissue inhibitor of metalloprotease-3 was significantly higher in the mononuclear inflammatory cells of the invasive components. By contrast, matrix metalloprotease-1 expression was significantly higher in stromal cells of the ductal carcinoma in situ admixed with invasive ductal carcinoma. The pure invasive ductal carcinomas had significantly higher expression of matrix metalloprotease-1, -9, -11, and -14 and tissue inhibitor of metalloprotease-1 and -3 than the invasive ductal carcinomas admixed with ductal carcinoma in situ. Our findings indicate a significant association of matrix metalloprotease expression by the periductal stromal cells of the ductal carcinoma in situ component of mixed tumors and the occurrence of distant metastasis. Our data suggest that the molecular matrix metalloprotease/tissue inhibitor of metalloprotease profile can contribute to better characterization of early breast carcinomas.
    Human pathology 03/2010; 41(7):980-9. DOI:10.1016/j.humpath.2009.08.027 · 2.81 Impact Factor