Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

OBJECTIVES: Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. METHODS: Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. RESULTS: AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). CONCLUSIONS: Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC.

Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53-p21 axis.

Glyoxalase 2 (Glo2), a metabolic enzyme, is overexpressed in some human cancers which suggests this enzyme may play a role in human tumorigenesis. In prostate cancer (PCa), the role of Glo2 has been scarcely investigated and there are no studies addressing a causative involvement of this protein in this neoplasia. Here, we examined the immunohistochemical profile of Glo2 in human PCa and benign adjacent tissues and investigated Glo2 involvement in PCa development in human prostate cell lines. PCa and matched adjacent normal tissues were obtained from paraffin sections of primary PCa from 20 patients who had undergone radical prostatectomy. Histopathological diagnosis was confirmed for each sample. Glo2 expression analysis was performed by immunohistochemistry in prostate tissues, and by qRT-PCR and immunoblotting in prostate cell lines. The causative and mechanistic role of Glo2 in prostate tumorigenesis was demonstrated by Glo2 ectopic expression/silencing and employing specific activators/inhibitors. Our results showed that Glo2 was selectively expressed in PCa but not in the luminal compartment of the adjacent benign epithelium consistently in all the examined 20 cases. Glo2 expression in PCa was dependent on androgen receptor (AR) and was aimed at stimulating cell proliferation and eluding apoptosis through a mechanism involving the p53-p21 axis. Glo2 was intensely expressed in the basal cells of benign glands but was not involved in PCa genesis. Our results demonstrate for the first time that Glo2 drives prostate tumorigenesis and suggest that it may represent a novel adjuvant marker in the pathological diagnosis of early PCa.

Human Umbilical Cord Wharton Jelly-Derived Adult Mesenchymal Stem Cells, in Biohybrid Scaffolds, for Experimental Skin Regeneration.

The ultimate goal for skin tissue engineering is to regenerate skin lesions to allow the full restoration of morphological and functional properties as what they were before injury. To this end, we have assembled a new prototype of a biomimetic human umbilical cord adult mesenchymal stem cell (hUCMS)/fibrin-based scaffold. We have fully characterized the proposed dermal equivalent (DE) in vitro, to assess morphological, functional, and biological properties of the encased cells. We transplanted DE subcutaneously into immunocompetent rodents, to verify its full biocompatibility. Finally, we studied DE graft effects on full-thickness wounds, in immunocompetent mice to demonstrate its capability to drive the healing process in the absence of significant scarring tissue. The excellent outcome of these in vivo studies fuels hope that this new approach, based on a biohybrid DE, may be applied to the operative treatment of skin lesions (i.e., diabetic foot ulcers and burns) in man.

Mouse Thyroid Gland Changes in Aging: Implication of Galectin-3 and Sphingomyelinase.

Prevalence of thyroid dysfunction and its impact on cognition in older people has been demonstrated, but many points remain unclarified. In order to study the effect of aging on the thyroid gland, we compared the thyroid gland of very old mice with that of younger ones. We have first investigated the changes of thyroid microstructure and the possibility that molecules involved in thyroid function might be associated with structural changes. Results from this study indicate changes in the height of the thyrocytes and in the amplitude of interfollicular spaces, anomalous expression/localization of thyrotropin, thyrotropin receptor, and thyroglobulin aging. Thyrotropin and thyrotropin receptor are upregulated and are distributed inside the colloid while thyroglobulin fills the interfollicular spaces. In an approach aimed at defining the behavior of molecules that change in different physiopathological conditions of thyroid, such as galectin-3 and sphingomyelinase, we then wondered what was their behavior in the thyroid gland in aging. Importantly, in comparison with the thyroid of young animals, we have found a higher expression of galectin-3 and a delocalization of neutral sphingomyelinase in the thyroid of old animals. A possible relationship between galectin-3, neutral sphingomyelinase, and aging has been discussed.

e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease.

Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed.