miRNA expression profile of mucoepidermoid carcinoma.

OBJECTIVES: MicroRNAs (miRNAs) are single-stranded RNAs that have been implicated in cancer initiation and progression and act as tumour suppressors or oncogenes. In this study, miRNA profiling was conducted on the most frequent malignancy of salivary glands, mucoepidermoid carcinoma (MEC), in comparison with normal tissues. MATERIALS AND METHODS: The TaqMan Human miRNA Cards Array was used for the miRNA profiling of MEC and normal tissues. To validate the differentially expressed miRNAs in MEC, we used real-time PCR (qRT-PCR). RESULTS: miR-302a was the most significantly increased miRNA in cancer tissues (p < .05). Here, we demonstrate that the upregulation of miR-302a expression in SGT cell lines induced cancer cell invasion in vitro. CONCLUSIONS: These promising results suggest the need for further studies to establish mir-302a as a marker of invasion and aggressiveness in MEC.

Cytokines and tumor markers in potentially malignant disorders and oral squamous cell carcinoma: a pilot study.

OBJECTIVE: To evaluate serum levels of interleukin (IL)-1, IL-6, IL-8, IL-10, soluble IL-2 receptor (sIL-2R), squamous cell carcinoma antigen (SCCA), tissue polypeptide-specific antigen (TPS) and vascular endothelial growth factor (VEGF) in patients with potentially malignant disorders (PMD), oral squamous cell carcinoma (OSCC), or status-post (SP) OSCC. SUBJECTS AND METHODS: Blood was collected from 47 patients, either controls or diagnosed with PMD, OSCC, or SPOSCC. Levels of cytokines and tumor marker were evaluated by ELISAs. Normal levels were based on previous studies and pathology determined by chi-square and Fisher's exact tests. P ≤ 0.05 was considered statistically significant. RESULTS: Above normal levels of SCCA were found for OSCC and dysplasia patients (33.3% and 11.1%, respectively) and high range of normal (upper 20% of the normal range) for lichen planus, SPOSCC, and dysplasia patients (6.67%, 33.3%, and 22.2%, respectively), differences that approached statistical significance (P = 0.055). No differences were found between groups for other tested markers. A progression was seen for SCCA from high range of normal in SPOSCC to a mixture of high normal and elevated in dysplasia to elevated in active OSCC, suggesting that SCCA may be correlated with cancer progression. CONCLUSION: Higher levels of serum SCCA may serve as a marker for dysplasia and progression to oral carcinogenesis.

Biological activities and molecular targets of the human papillomavirus E7 oncoprotein.

The human papillomavirus (HPV) E7 protein is one of only two viral proteins that remain expressed in HPV-associated human cancers. HPV E7 proteins share structural and functional similarities with oncoproteins encoded by other small DNA tumor viruses such as adenovirus E1A and SV40 large tumor antigen. The HPV E7 protein plays an important role in the viral life cycle by subverting the tight link between cellular differentiation and proliferation in normal epithelium, thus allowing the virus to replicate in differentiating epithelial cells that would have normally withdrawn from the cell division cycle. The transforming activities of E7 largely reflect this important function.

The cytokines tumor necrosis factor-alpha (TNF-alpha ) and TNF-related apoptosis-inducing ligand differentially modulate proliferation and apoptotic pathways in human keratinocytes expressing the human papillomavirus-16 E7 oncoprotein.

Keratinocytes are the natural target cells for infection by human papillomaviruses (HPVs), most of which cause benign epithelial hyperplasias (warts). However, a subset of papillomaviruses, the "high risk" HPVs, cause lesions that can progress to carcinomas. Inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand (TRAIL) are produced by cells in response to a viral infection. To determine the effects of TNF-alpha and TRAIL on keratinocytes expressing the high risk HPV-16 oncoprotein E7, human foreskin keratinocytes stably expressing E7 were treated with TNF-alpha and TRAIL. Treatment with TNF-alpha alone, but not TRAIL, induced growth arrest and differentiation in keratinocytes that was almost completely overcome by expression of HPV-16 E7. Both cytokines induced apoptosis when administered in combination with the protein synthesis inhibitor cycloheximide, but the apoptotic response to TRAIL was significantly more rapid and efficient compared with the response seen after TNF-alpha treatment. HPV-16 E7-expressing keratinocytes were more prone to both TNF-alpha- and TRAIL-mediated apoptosis compared with vector-infected controls.

Degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 E7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of E7.

The steady-state level and metabolic half-life of retinoblastoma tumor suppressor protein pRB are decreased in cells that express high-risk human papillomavirus (HPV) E7 proteins. Here we show that pRB degradation is a direct activity of E7 and does not reflect a property of cell lines acquired during the selection process for E7 expression. An amino-terminal domain of E7 that does not directly contribute to pRB binding but is required for transformation is also necessary for E7-mediated pRB degradation. Treatment with inhibitors of the 26S proteasome not only blocks E7-mediated pRB degradation but also causes the stabilization of E7. Mutagenic analyses, however, reveal that the processes of proteasomal degradation of E7 and pRB are not linked processes. HPV type 16 E7 also targets the pRB-related proteins p107 and p130 for destabilization by a proteasome-dependent mechanism. Using the SAOS2 flat-cell assay as a biological indicator for pRB function, we demonstrate that pRB degradation, not solely binding, is important for the E7-induced inactivation of pRB.

Efeito da época do ano na transferência de embriöes em vacas holandesas superovualdas com PMSG / Effect of season on embryo transfer in superovulated Holstein cows with PMSG

Estudou-se a influência de fatores sazonais na performance de 21 vacas da raça Holandesa submetidas a 37 superovulaçöes com 3.000 U.I. de PMSG. Os resultados das transferências de embriöes foram analisados segundo o efeito da época do ano: chuvosa (outubro a março) com temperatura máxima média = 30,0 ñ 0,8ºC e precipitaçäo pluviométrica mensal = 153,1 ñ 78,8 mm elevado ao cubo e seca (abril a setembro) com temperatura máxima média = 26,5 ñ 1,6ºC e precipitaçäo pluviométrica mensal = 59,2 ñ 53,8 mm elevado ao cubo. Registrou-se variaçäo climática entre as estaçöes (p<0,05), mas näo houve diferença significativa (p>0,05) entre épocas do ano quando foi comparado o número médio de estruturas por superovulaçäo (5,4 ñ 2,63 e 4,3 ñ 4,00), o percentual de embriöes viáveis (50,0 por cento e 57,6 por cento) e o percentual de prenhezes obtidas: 44,4 por cento e 35,2 por cento, respectivamente. Concluiu-se, portanto, que as diferentes condiçöes climáticas das épocas do ano näo influíram nas transferências de embriöes em vacas holandesas superovuladas com PMSG