Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer. METHODS: In the present study, 200 individuals were separated into three groups: (i) 72 women constituting the control group who were selected according to rigorous and well-established criteria; (ii) 56 patients with benign breast tumors; and (iii) 72 patients with malignant breast cancers of different clinical stages. The miR-195 and let-7a expression levels in serum were evaluated by real-time PCR. The results were assessed alone and in combination, and the analysis included an estimation of sensitivity and specificity in ROC curves. RESULTS: Compared with the benign and control groups, both microRNAs were downregulated in the malignant breast cancer patient group. Compared with the malignant group, the combination of both biomarkers in the control and benign groups showed good sensitivity and specificity in the serum with AUCs of 0.75 and 0.72, respectively. The biomarker combination for the control group versus the malignant group exhibited a better sensitivity and specificity than for the benign group versus the malignant group. CONCLUSION: These findings support the evidence that the analysis of miR-195 and let-7a can be used as a non-invasive biomarker for breast cancer detection.

Association between Literacy, Compliance with Prostate Cancer Screening, and Cancer Aggressiveness: Results from a Brazilian Screening Study

Purpose Little is known about the effects of literacy levels on prostate cancer screening. This study evaluates the association between literacy, compliance with screening, and biopsy findings in a large Brazilian screening study. Materials and Methods We analyzed 17,571 men screened for PCa with digital rectal examination (DRE) and total and free prostate-specific antigen (PSA) from January 2004 to December 2007. Of those, 17,558 men had information regarding literate status. Full urological evaluation in a specialized cancer center was recommended in the case of: a) suspicious DRE, b) PSA > 4.0 ng/mL, or c) PSA 2.5-3.9 ng/mL and free/total PSA (f/tPSA) ratio < 15%. Transrectal ultrasound guided prostate biopsy (14 cores) was performed upon confirmation of these findings after the patient's consent. Patients' compliance with screening recommendations and biopsy results were evaluated according to literacy levels. Results an abnormal PSA, a suspicious DRE, or both were present in 73.2%, 19.7%, and 7.1% of those men who underwent biopsy, respectively. PCa was diagnosed in 652 men (3.7%). Previous PSAs or DREs were less common among illiterate men (p < 0.0001). Additionally, illiterate men were less prone to attend to further evaluations due to an abnormal PSA or DRE (p < 0.0001). PSA levels > 10 mg/mL (p = 0.03), clinical stage > T2a (p = 0.005), and biopsy Gleason > 7 (p = 0.02) were more common among illiterate men. Conclusions In a screened population, literacy levels were associated with prior PCa evaluations and with compliance with screening protocols. Illiterate men were at higher risk of being diagnosed with more advanced and aggressive PCa. .

Mechanisms and role of microRNA deregulation in cancer onset and progression

MicroRNAs are key regulators of various fundamental biological processes and, although representing only a small portion of the genome, they regulate a much larger population of target genes. Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. MicroRNA targeting is mostly achieved through specific base-pairing interactions between the 5' end ('seed' region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR diminish mRNA stability. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. Calin and Croce were the first to demonstrate a connection between microRNAs and increased risk of developing cancer, and meanwhile the role of microRNAs in carcinogenesis has definitively been evidenced. It needs to be considered that the complex mechanism of gene regulation by microRNAs is profoundly influenced by variation in gene sequence (polymorphisms) of the target sites. Thus, individual variability could cause patients to present differential risks regarding several diseases. Aiming to provide a critical overview of miRNA dysregulation in cancer, this article reviews the growing number of studies that have shown the importance of these small molecules and how these microRNAs can affect or be affected by genetic and epigenetic mechanisms.

Hypermethylation Pattern of COX-2 and Rb1 in Head and Neck Squamous Cell Carcinomas

Head and neck cancer is among the ten most common human cancers worldwide, being 90% of all cases squamous cell carcinoma histological subtype. These tumors are always associated with high rates of mortality and patients with disease presenting in the same site with the same stage that under go the similar treatment, may have different oncologic outcomes. These aspects show the necessity of developing effective molecular markers that may be able to increase survival rates. Epigenetic mechanisms contribute to the carcinogenesis process, especially by the methylation of cytosines in CpG islands. The identification of aberrantly methylated DNA may help carcinogenesis understanding as well as potential clinical targets for studies in cancer. We analyzed genes RB1 and COX-2 methylation status by the quantitative, high-throughput Q-MSP assay in cell lines, 30 tumor samples and 10 normal oral cavity mucosa samples. These two genes evaluation was not informative because the incidence of hypermethylation was completely absent (RB1) or ubiquitous (COX-2), RB1, regardless of tissue type. These results suggest that the hypermethylation pattern of both RB1 and COX-2 might not be a reasonable biomarker for head and neck squamous cell carcinomas.

Sarcoma sinovial de extremidades com doença localizada ao diagnóstico: tratamento e padrões de recidiva em 57 casos / Localized extremity sinovial sarcoma: treatment and patterns of recurrence in 57 cases

OBJETIVOS: Os sarcomas sinoviais são tumores raros e agressivos que acometem adultos jovens, com sobrevida doençaespecífica em cinco anos de 57 a 63 por cento. O presente estudo analisa a experiência institucional com este tumor, dando ênfase à associação entre variáveis clínicas, padrões de recorrência e sobrevida. MÉTODO: Entre 1970 e 2001 foram identificados 57 pacientes com sarcomas sinoviais. Fatores demográficos, clínicos e anatomopatológicos foram pesquisados. Associações entre variáveis clínicas e a sobrevida livre de recidiva local, livre de metástases e doença-específica em cinco anos foram calculadas. RESULTADOS: A idade mediana dos pacientes foi 26 anos, 56 por cento eram masculinos, 79 por cento eram brancos. Localizavam-se em membro inferior em 74 por cento, proximalmente em 53 por cento. O sintoma mais comum foi a presença de tumor em 42 por cento. Na admissão 18 por cento eram intactos, 42 por cento manipulados e 40 por cento recidivados. A maioria era maior que 5 cm., e três pacientes apresentavam metástase linfonodal. A cirurgia mais freqüente foi ressecção ampla, 30 por cento necessitou amputação. Margens amplas foram obtidas em 65 por cento, 51 por cento eram tumores bifásicos. Neoadjuvância foi utilizada em 46 por cento e adjuvância em 58 por cento dos casos. As sobrevidas livre de recidiva local , metástases e doença específica em cinco anos foram 60±8 por cento, 47±7 por cento e 58±7 por cento. A localização proximal do tumor associou-se com preservação de membro (p=-0,001), margens inadequadas (p=0,006) e subtipo bifásico (p=0,047). CONCLUSÕES: Os dados confirmam a hipótese de tratar-se de tumor agressivo, com altos índices de recidiva local e à distância. Os resultados do tratamento são comparáveis a outros centros especializados. Tratamento fora destes centros deve ser desencorajado.

Carcinoma adenóide cístico de traquéia: tratamento pela laringotráqueo-esofagectomia e traqueostomia mediastinal / Adenoid cystic carcinoma of the trachea: treatment by removing the larynx, trachea, and esophagus, and mediastinal tracheostomy

Os autores descrevem o caso de uma paciente de 54 anos de idade com carcinoma adenóide cístico de traquéia ao nível da cricóide, na qual foi realizada ressecçäo extensa, incluindo a laringe, parte da traqéia e esófago. A reconstruçäo do trato gigestivo foi através do tubo gástrico e a via aérea pela construçäo de uma traqueostomia mediastinal. Cinco anos mais tarde removida uma recorrência tumoral cutânea no pescoço. Sete anos depois do procedimento original, foi notada nova recorrência no mediastino, que respondeu à irradiaçäo. A paciente encontra-se muito bem atualmente, oito anos e cinco meses após o procedimento