[Show abstract][Hide abstract] ABSTRACT: Fibronectin (Fn) and tenascin-C (TnC) are two extracellular matrix proteins associated with remodeling changes. Fn and TnC gene and protein expression in lung tissue, including their predominant location in bronchial and pulmonary artery structures, have not yet been fully evaluated. The aim of the present study was to assess: (1) gene expression of Fn and TnC in lung samples from chronic obstructive pulmonary disease (COPD) and non-COPD subjects; and (2) protein content and location of Fn and TnC in both groups.
Consecutive subjects requiring lung resection due to lung cancer surgery were included. Lung specimens were examined for gene expression by quantitative real-time PCR (values expressed as fold change ratio). The analysis of their protein content and location was performed by western blot and immunohistochemical studies, respectively. Patients were divided into two cohorts according to COPD status.
A total of 41 patients (20 with COPD and 21 without COPD) were included. An enhanced Fn gene expression was observed in the COPD group compared to the non-COPD group (4.73 ± 0.54 vs. 2.65 ± 0.57; P = 0.012), whereas no differences in gene TnC expression were observed (2.91 ± 0.44 vs. 2.60 ± 0.48; P = 0.633). No differences in lung protein content and location were found between groups. Immunohistochemical evaluation showed a predominantly vascular and bronchial location of Fn and TnC in both groups.
An enhanced lung gene expression of Fn was observed in COPD subjects compared to non-COPD subjects. No differences were found in Fn protein expression or in TnC gene or protein expression among groups.
Beiträge zur Klinik der Tuberkulose 03/2015; 193(3). DOI:10.1007/s00408-015-9717-7 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs.
ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.
A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA.
The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.
BMC Pulmonary Medicine 07/2014; 14(1):120. DOI:10.1186/1471-2466-14-120 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objectives:
Some types of cancer tend to spread to certain organs. In the case of melanoma, uveal melanoma spreads almost exclusively to the liver, while cutaneous melanoma spreads to the liver and other organs. Although important advances have been made in our understanding of the molecular mechanisms underlying melanoma, few recent studies have focused on the patterns of visceral metastasis in cutaneous melanoma. The aim of this study was to retrospectively investigate whether clinicopathologic variants of cutaneous melanoma and primary tumor site might be associated with pattern and time of onset of metastasis to visceral sites, including the central nervous system (CNS).
Materials and methods:
We included patients diagnosed with cutaneous melanoma between 1988 and 2009 with at least 2 years' follow-up.
Of the 1083 patients studied, 92 developed visceral metastasis. The CNS was affected in 21 cases, the lungs in 24, the liver in 17, the digestive tract in 7, and multiple organs simultaneously in 23. Metastasis to the lungs, the liver, and the digestive tract occurred within 5 years in most cases, while metastasis to the CNS and multiple organs occurred later (>5 years in 38% and 43% of cases, respectively).
Unlike uveal melanoma, cutaneous melanoma spreads to different organs without any particular predilection. We observed no significant associations between the site of visceral metastasis and either clinicopathologic variant or location of the primary tumor. Metastasis occurred within 5 years of diagnosis in most cases, but it can occur after 10 years.
[Show abstract][Hide abstract] ABSTRACT: Epidermal keratinocytes and hair follicle (HF) stem cells (SCs) expressing oncogenes are competent at developing squamous cell carcinomas (SCCs) in epidermis and HFs, respectively. To determine whether bulge and hair germ (HG) SCs from HF contribute to SCC generation at distant epidermis, the most frequent epidermal region where these lesions arise in human skin, we used a skin cancer mouse model expressing E6 and E7 oncoproteins from Human papillomavirus (HPV) 16 in SCs and basal keratinocytes. This previously described mouse model recapitulates the human skin papillomavirus-induced SCC pathology. We show that E6 and E7 expression promote the expansion of keratin 15 (K15)-expressing cells. These K15(+) aberrant cells exhibit some HGSC markers and diminished expression of Tcf3 and Sox9 hair SC specification genes, which are accumulated in HFs and mislocalized to interfollicular epidermis. Leucine-rich G-protein-coupled receptor 5 (Lgr5)-expressing SCs, localized in the bulge and HG, are the origin of the expanded K15(+) cell population. A large subset of the Lgr5(+) SC progeny, expressing K15 and P-cadherin, is aberrantly mobilized to the upper region of HFs and the epidermis, and accumulates at E6/E7-induced pre-neoplastic lesions and epidermal tumors. These findings indicate that aberrant accumulation of altered SCs in HFs and their subsequent migration to the epidermis contribute to HPV-induced tumor development.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.375.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the molecular events occurring in the metastases of human tumors. Epigenetic alterations are dynamic lesions that change over the natural course of the disease, and so they might play a role in the biology of cancer cells that have departed from the primary tumor. Herein, we have adopted an epigenomic approach to identify some of these changes. Using a DNA methylation microarray platform to compare paired primary tumor and lymph node metastatic cell lines from the same patient, we observed cadherin- 11 promoter CpG island hypermethylation as a likely target of the process. We found that CDH11 DNA methylation-associated transcriptional silencing occurred in the corresponding lymph node metastases of melanoma and head and neck cancer cells, but not in the primary tumors. Using in vitro and in vivo cellular and mouse models for depleted or enhanced CDH11 activity, we also demonstrated that CDH11 acts as an inhibitor of tumor growth, motility and dissemination. Most importantly, the study of CDH11 5'-CpG island hypermethylation in primary tumors and lymph node metastases of cancer patients showed this epigenetic alteration to be significantly confined to the disseminated cells. Overall, these results indicate the existence of metastasisspecific epigenetic events that might contribute to the progression of the disease.
The Journal of Pathology 02/2012; · 7.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objectivesFew studies have addressed cutaneous recurrence of melanoma. The aim of this retrospective study was to analyze the characteristics and prognostic significance of the different patterns of cutaneous recurrence.
[Show abstract][Hide abstract] ABSTRACT: The primary intranodal schwannoma is an uncommon variant of schwannomas and extremely rare. We report the case of a 70-year-old woman who was found to have a soft tissue opacity in the right hemithorax on chest posteroanterior radiography and significant uptake of (18)F-fluorodeoxyglucose on positron emission tomography. We performed thoracoscopic resection, and a definitive diagnosis of intranodal schwannoma was made from the pathological findings.
General Thoracic and Cardiovascular Surgery 12/2011; 59(12):819-21. DOI:10.1007/s11748-010-0773-x
[Show abstract][Hide abstract] ABSTRACT: Few studies have addressed cutaneous recurrence of melanoma. The aim of this retrospective study was to analyze the characteristics and prognostic significance of the different patterns of cutaneous recurrence.
Patients diagnosed with melanoma between 1988 and 2008 at Hospital de Bellvitge, Barcelona, Spain and for whom data were available for at least 2 years of follow-up were included in the study. Local recurrence was defined as melanoma invasion of the skin adjacent to the scar left by excision of the primary tumor, regional metastasis or recurrence as metastasis restricted to the area drained by a regional lymph node station, and distant cutaneous metastasis as metastasis occurring outside this area. The relationship between cutaneous recurrence pattern and age, sex, primary tumor site, tumor subtype, Breslow depth, and ulceration was assessed.
Eighty-five out of 1,080 patients (7.87%) had cutaneous recurrence. In 71 of those patients (83.53%; 27 men and 44 women; mean age, 60.68 years), this was the first indication of melanoma recurrence. Thirty-two patients had local recurrence, 32 regional metastasis, and 7 distant metastasis. Significant differences were observed in survival time from diagnosis of the primary tumor (P=.044) and from diagnosis of cutaneous recurrence (P<.001) according to the type of recurrence.
Our results suggest that the pattern of cutaneous recurrence is prognostically significant and related to the site of the primary tumor given that the majority of local and regional recurrences occurred in primary tumors located on the lower limbs and head.
[Show abstract][Hide abstract] ABSTRACT: Uveal melanoma metastases develop in 6.5-35% of patients, most commonly to the liver. Metastatic uveal melanoma (MUM) survival is poor, with 5-7 months of median survival. We reviewed retrospectively all patients with MUM diagnosed between January 1990 and December 2008 at our institution. We analyzed a total of 58 patients with a median age of 61 years (31-84 years). Median time for metastases development was 25.63 months (0.17-102.43 months). Fifty-six patients had hepatic involvement, 63.8% bilobar and 51.7% had more than or equal to five hepatic metastatic lesions. Sixteen patients (27.6%) had two or more organs involved. Six patients (10.71%) were treated with surgery, 25 patients (44.67%) received systemic chemotherapy, and 23 (41.07%) had best supportive care (BSC). The median overall survival (OS) for all the patients was 10.83 months [95% confidence interval (CI): 6.92-14.74]. Patients who had undergone chemotherapy presented 10.83 months (95% CI: 5.35-16.308) of median OS whereas the patients who did not undergo this treatment had an OS of 8.033 months (95% CI: 2.46-13.61). There were more patients with poor survival characteristics such as worse Eastern Cooperative Oncology Group performance status in the BSC group. OS was poor in treated and BSC patients. Differences in survival are more likely to be related to patient characteristics rather than to a chemotherapy effect. Patients with MUM should be included in clinical trials evaluating other options with newer agents.
Melanoma research 04/2011; 21(3):217-22. DOI:10.1097/CMR.0b013e3283457726 · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Giant cell arteritis, Takayasu arteritis, and Horton disease are rare, idiopathic diseases that cause chronic inflammation and obliteration of large arteries, mainly the aorta and its major branches. Histological examination reveals multinucleated giants cells and clinical presentation is characterized by general symptoms and/or symptoms related to stenosis or occlusion of vessels. A case of a 50-year-old woman with neurological symptoms, cervicothoracic tumour with severe stenosis of the right subclavian artery and complete occlusion of common carotid artery is presented.
Interactive Cardiovascular and Thoracic Surgery 09/2010; 11(3):337-9. DOI:10.1510/icvts.2010.239772 · 1.16 Impact Factor