Global gene expression profiling of oral cavity cancers suggests molecular heterogeneity within anatomic subsites

Abstract Background Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis. Results Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis. Conclusion Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.

VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors

The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 μM) and 1 μMof propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p>0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production.

Valor da PET/CT na abordagem do câncer de cabeça e pescoço

OBJETIVO: Avaliar a PET/CT na abordagem de pacientes com câncer de cabeça e pescoço. MATERIAIS E MÉTODOS: Estudo retrospectivo de 63 prontuários e exames de PET/CT de pacientes com câncer de cabeça e pescoço. RESULTADOS: Foram encontradas alterações em 76% dos exames. Destes, 7 (11%) foram considerados falso-positivos, com SUV < 5,0. A PET/CT mostrou-se negativa em 15 situações (24%). Dos 14 casos nos quais se utilizou o exame para estadiamento, em 3 (22%) houve aumento no estadiamento. CONCLUSÃO: A PET/CT mostra-se como exame de potencial valor na rotina de avaliação de pacientes com câncer de cabeça e pescoço, entretanto, necessitamos de maior número de casos para definirmos protocolo de uso.

Brazilian blood donation eligibility criteria for dermatologic patients

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

Morphological alterations and gene and protein expression profiling of bladder tumor cells after treatment with gemcitabine.

Chemical agents used in cancer therapy are associated with cell cycle arrest, activation or deactivation of mechanisms associated to DNA repair and apoptosis. However, due to the complexity of biological systems, the molecular mechanisms responsible for these activities are not fully understood. Thus, studies about gene and protein expression have shown promising results for understanding the mechanisms related to cellular responses and regression of cancer after chemotherapy. This study aimed to evaluate the gene and protein expression profiling in bladder transitional cell carcinoma (TCC) with different TP53 status after gemcitabine (1.56 μM) treatment. The RT4 (grade 1, TP53 wild type), 5637 (grade 2, TP53 mutated) and T24 (grade 3, TP53 mutated) cell lines were used. PCR arrays and mass spectrometry were used to analyze gene and protein expression, respectively. Morphological alterations were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results of PCR array showed that gemcitabine activity was mainly related to CDKN1A, GADD45A and SERTDA1 overexpression, and BAX overexpression only in the wild type TP53 cells. Mass spectrometry demonstrated that gemcitabine modulated the protein expression, especially those from genes related to apoptosis, transport of vesicles and stress response. Analyses using SEM and TEM showed changes in cell morphology independently on the cell line studied. The observed decreased number of microvillus suggests low contact among the cells and between cell and extracellular matrix; irregular forms might indicate actin cytoskeleton deregulation; and the reduction in the amount of organelles and core size might indicate reduced cellular metabolism. In conclusion, independently on TP53 status or grade of bladder tumor, gemcitabine modulated genes related to the cell cycle and apoptosis, that reflected in morphological changes indicative of future cell death.