The BRAFV600E mutation analysis and risk stratification in papillary thyroid carcinoma

ABSTRACT Objective: Although the prognostic role of BRAFV600E mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAFV600E mutation status on PTC risk stratification. Subjects and methods: PTC patients attending a university-based hospital who had the analysis of the BRAFV600E mutation were included. Persistent disease was defined as the presence of biochemical or structural disease. The performance of the ATA risk stratification system on predicting persistent disease with or without the BRAFV600E mutation status information was evaluated. Results: Of the 134 patients evaluated, 44 (32.8%) carried BRAFV600E mutation. The median tumor size was 1.7 cm (P25-75 1.0-3.0), 64 (47.8%) patients had lymph node, and 11 (8.2%) distant metastases. According to the ATA risk stratification system, patients were classified as low, intermediate, and high risk in 55 (41%), 59 (44%), and 20 (14%) patients, respectively. The data on BRAFV600E mutation reclassified 12 (8.9%) patients from low to intermediate risk. After a median follow-up of 8.5 years, the prevalence of persistent disease was similar in patients with and without BRAFV600E mutation (P = 0.42). Multivariate analysis failed to demonstrate an association between the BRAFV600E mutation and persistent disease status (RR 0.96; 95%CI 0.47-1.94). Notably, none of the patients reclassified from low to intermediate risk showed persistent disease on follow-up. Conclusion: Inclusion of BRAFV600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.

Prognostic value of long non-coding RNA TP73-AS1 expression in different types of cancer: a systematic review and meta-analysis

Background: TP73 antisense RNA 1 (TP73-AS1), a newly discovered long non-coding RNA (lncRNA), has been reported to be upregulated in various kinds of tumors, and shows a variable influence on living quality and prognosis of patients. Thus, we conducted a meta-analysis to evaluate the overall prognostic value of the lncRNA TP73-AS1 in cancer patients. Results: A systematic literature retrieval was carried out using the PubMed, Cochrane Library, EMBASE, and Web of Science databases. We calculated the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the association of TP73-AS1 expression with prognostic and clinicopathological parameters. A total of 15 studies including 1057 cancer patients were finally selected for the meta-analysis. The results demonstrated that high TP73-AS1 expression was significantly associated with shorter overall survival (OS) (HR = 1.97, 95% CI: 1.68­2.31, P b 0.001). According to a fixed-effects or random-effects model, elevated TP73-AS1 expression markedly predicted advanced clinical stage (OR = 3.30, 95% CI: 2.35­4.64, P b 0.001), larger tumor size (OR = 2.37, 95% CI: 1.75­3.22, P b 0.001), earlier lymph node metastasis (OR = 3.28, 95% CI: 1.59­6.76, P = 0.001), and distant metastasis (OR = 4.94, 95% CI: 2.61­9.37, P b 0.001). Conclusions: High lncRNA TP73-AS1 expression appears to be predictive of a worse OS and clinicopathologic features for patients with various types of malignant tumors. These results provide a basis for utilizing TP73- AS1 expression as an unfavorable indicator to predict survival outcomes.

MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

Identification of key genes involved in nasopharyngeal carcinoma / Identificação dos principais genes envolvidos no carcinoma nasofaríngeo

Abstract Introduction: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. Objective: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. Methods: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package. Using the BiNGO plugin in Cytoscape and pathway enrichment analysis in the PGS package, functional and pathway enrichment analyses were performed separately to predict potential functions of the differentially expressed genes. Furthermore, Transcription factor-differentially expressed gene pairs were searched, and then the transcription factor-differentially expressed gene regulatory network was visualized using Cytoscape software. Results: A total of 487 genes were screened as differentially expressed genes between the nasopharyngeal carcinoma samples and the normal nasopharyngeal tissue samples. Enrichment analysis indicated that PTGS2 was involved in the regulation of biological process and small cell lung cancer. ZIC2 and OVOL1 may function in nasopharyngeal carcinoma through targeting significantly up-regulated genes (such as PTGS2, FN1, CXCL9 and CXCL10) in the Transcription factor-differentially expressed gene regulatory network (e.g., ZIC2→PTGS2 and OVOL1→CXCL10). Conclusion: PTGS2, FN1, CXCL9, CXCL10, ZIC2 and OVOL1 might play roles in nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é o câncer mais comum originário da nasofaringe. Objetivo: Estudar os mecanismos do câncer de nasofaringe; dados do microarray GSE12452 foram analisados. Método: GSE12452 foi obtido da base de dados Gene Expression Omnibus e inclui 31 amostras de carcinoma nasofaríngeo e 10 amostras de tecido nasofaríngeo normal. Os genes diferencialmente expressos foram analisados por ANOVA no kit PGS. Usando o plugin BiNGO no Cytoscape e análise de enriquecimento da via no kit PGS, análises de enriquecimento funcional e da via foram realizadas separadamente para prever as potenciais funções dos genes diferencialmente expressos. Além disso, os pares Fator de Transcrição - genes diferencialmente expressos foram pesquisados e em seguida a sua rede reguladora foi visualizada usando o programa Cytoscape. Resultados: Um total de 487 genes foram analisados como genes diferencialmente expressos entre as amostras de carcinoma nasofaríngeo e amostras de tecido nasofaríngeo normal. A análise de enriquecimento indicou que PTGS2 estava envolvido na regulação do processo biológico e câncer pulmonar de pequenas células. ZIC2 e OVOL1 podem funcionar no carcinoma nasofaríngeo almejando-se de maneira significativa os genes suprarregulados (como o PTGS2, FN1, CXCL9 e CXCL10) na rede reguladora de fator de transcrição - genes diferencialmente expressos (p.ex., ZIC2→PTGS2 e OVOL1→CXCL10). Conclusão: PTGS2, FN1, CXCL9, CXCL10, ZIC2 e OVOL1 podem desempenhar alguns papéis no carcinoma de nasofaringe.

Analysis of gene expression changes associated with human carcinoma-associated fibroblasts in non-small cell lung carcinoma

BACKGROUND: This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC). METHODS: We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis. RESULTS: We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-ß signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%. CONCLUSION: Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.

Role of regenerating gene IA expression on local invasion and survival in nasopharyngeal carcinoma

BACKGROUND: Regenerating gene IA (REGIA) plays an important role in tissue regeneration and tumors prognosis of epithelium origin. However, the role of REGIA in nasopharyngeal carcinoma (NPC) is unclear. This study aims to investigate the expression and function of REG1A in NPC. RESULTS: We have found that there was 63 patients with REGIA positive expression of 155 patients in this study (40.65%). The positive expression rate of REGIA was 30.50, 44.44 and 47.83% in stage T2, T3 and T4 patients, respectively. The REGIA expression was significantly difference in T2 and T4 stage tumors or T2 and T3-T4 stage. The positive expression rate of REGIA was found to be higher in patients with cervical lymph node persistence than those with cervical lymph node complete regression. Patients with negative REGIA expression had a better overall survival and free survival than those with REGIA positive expression. In addition, according to the univariate and multivariate analysis, the REGIA expression was an independent adverse prognostic factor for NPC patients. CONCLUSION: REGIA expression was a useful biomarker in NPC patients for assessing T stage and survival.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Mutación V600E del oncogén BRAF en nódulos tiroideos en Argentina / BRAF V600E mutation in thyroid nodules in Argentina

Este estudio prospectivo analizó en una población argentina la frecuencia de la mutación V600E del oncogén BRAF en pacientes operados por nódulos tiroideos benignos y por carcinoma papilar de tiroides. En estos últimos se compararon las características clínicas y anatomopatológicas en relación a la presencia o ausencia de la mutación. Se estudiaron prospectivamente 25 pacientes consecutivos operados en nuestra institución. Se obtuvieron muestras histológicas de tejido nodular y el adyacente no nodular en fresco. Se extrajo ADN, se amplificó según técnica amplification refractory mutation system polymerase chain reaction (ARMS PCR). Se efectuó secuenciación directa del gen en 4 muestras. El 77% de los operados por carcinoma papilar resultaron BRAF+. Todas las muestras de tejido adyacente no tumoral y de los nódulos benignos fueron negativas para la mutación. La secuenciación directa confirmó los resultados obtenidos por ARMS PCR en las muestras en que fue efectuada. Los pacientes BRAF+ presentaron mayor edad al diagnóstico vs. aquellos BRAF- (47.7 ± 12.7 vs 24.7 ± 8.1 años, p < 0.01). Nueve de diez carcinomas papilares de tiroides con mutación de BRAF correspondieron a la variante histológica clásica, la cual no se observó en los tumores BRAF- (p < 0.02). En conclusión, comunicamos una elevada frecuencia de mutación V600E del oncogén BRAF en pacientes operados por carcinoma papilar de tiroides en Argentina. Estos resultados son acordes a lo referido en la bibliografía.

This prospective study analyzed the frequency of V600E mutation of oncogene BRAF in patients operated for benign thyroid nodules and for papillary thyroid cancer in an Argentine population. In patients with papillary thyroid cancer we compared clinicopathological characteristics between those harboring BRAF mutation and those without it. Twenty five consecutive patients operated for benign nodules and for papillary carcinoma were prospectively included. Fresh tissue samples of thyroid nodules and of adjacent thyroid parenchyma were obtained. DNA was extracted and amplified by amplification refractory mutation system polymerase chain reaction (ARMS PCR). Direct sequencing was performed in four samples. Of those patients operated for papillary thyroid cancer, 77% harbored BRAF mutation. All samples from adjacent thyroid parenchyma and from patients operated for benign nodules tested negative for the mutation. Direct sequencing confirmed the results obtained by ARMS PCR. Patients with BRAF mutation were significantly older at the time of diagnosis (BRAF+ 47.7 ± 12.7 years vs. BRAF- 24.7 ± 8.1 years, p < 0.01). Nine out of ten papillary carcinomas with BRAF mutation corresponded to the classic histological subtype, which was not observed in BRAF negative tumors (p < 0.02). In conclusion, we found a high frequency of BRAF V600E mutation in this population of patients operated for papillary thyroid carcinoma in Argentina. These results are consistent with those reported in the literature.

Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer

BACKGROUND AND OBJECTIVE: Long non-coding RNAs can regulate tumorigenesis of various cancers. Dys-regulation of lncRNA-AFAP1-AS1 has not been studied in colorectal carcinoma (CRC). This study was to examine the function involvement of AFAP1-AS1 in tumor growth and metastasis of CRC. METHODS: Relative expression of AFAP1-AS1 in CRC tissues and CRC cells lines was determined using quantitative real-time PCR (qRT-PCR). Functional involvement of AFAP1-AS1 in tumor proliferation and metastasis was evaluated in AFAP1-AS1-specific siRNA-treated CRC cells and in CRC cell xenograft. Expression of epithelial-mesenchymal transition (EMT)-related gene expression was determined using western blot. RESULTS: Relative expression of AFAP1-AS1 was significantly elevated in CRC tissues and CRC HCT116 and SW480 cell lines. AFAP1-AS1 knock-down suppressed SW480 cell proliferation, colony formation, migration and invasion. Also AFAP1-AS1 knock-down inhibited tumor metastasis-associated genes expression in terms of EMT. This carcinostatic action by AFAP1-AS1 knock-down was further confirmed by suppression of tumor formation and hepatic metastasis of CRC cells in nude mice. CONCLUSION: lncRNA-AFAP1-AS1 knock-down exhibits antitumor effect on colorectal carcinoma in respects of suppression of cell proliferation and metastasis of cancer cells.

Serological under expression of microRNA-21, microRNA-34a and microRNA-126 in colorectal cancer

PURPOSE: This paper describes the ability of miRNA value predict oncological outcomes in CRC patients and correlates to clinical and pathologic variables. METHODS: We prospectively analyzed the serological expression of microRNA-21, microRNA-34a, and microRNA-126 in 37 stage II - IV CRC patients and correlate to seven fit counterparts. Serological microRNAs were extracted using the miRNeasy Mini Kit(r) (Qiagen, Hilden, Germany). Quantification of microRNAs was performed using TaqMan Master Mix(r) reagent (Applied Biosystems, USA). RESULTS: We obtained serological underexpression microRNA-21, microRNA-34a, and microRNA-126 in CRC group. However, miRNAs serological values do not impact prognosis. Furthermore, miRNAs was not influenced by CEA values, TNM staging, and histological subtype. CONCLUSION: Despite lower expression of miR-21, miR-34a and miR-126 in the CRC group, no association with poor prognosis was found.

The role of immunohistochemistry in the Muir-Torre Syndrome

Muir-Torre Syndrome is defined by the coexistence of sebaceous skin tumors and internal malignancies. Mutations in the DNA mismatch repair genes are found in the inherited form of the disease, resulting in the absence of crucial enzymes involved with DNA replication process. This case describes a patient with sebaceous adenoma and colorectal carcinoma, meeting the criteria for Muir-Torre Syndrome. The immunohistochemical analysis of the skin lesion was an important tool to confirm the diagnosis, as it revealed nuclear negativity for MSH2 and MSH6.

Transnational dialogues between specialist and institutional knowledge in occupational accident legislation, first half of the twentieth century / Diálogos transnacionales entre los saberes técnicos e institucionales en la legislación sobre accidentes de trabajo, primera mitad del siglo XX

In the early twentieth century, Argentina began legislating occupational safety. Law no.9.688 legislated accidents in the workplace (1915) and granted legal jurisdiction to work-related problems. The approval of this legislation was in dialogue with proposals being produced in other regions. The links established between local figures and colleagues elsewhere are useful for examining the circulation, reception and legitimation of knowledge on a regional scale. The objective of this article is to examine the transnational references in local discussions about occupational accidents in Peru and Chile during the first half of the twentieth century.

A partir del siglo XX, se inició en la Argentina la legislación protectora del trabajo. La ley n.9.688 legisló sobre accidentes de trabajo (1915) y otorgó jurisdicción legal a los problemas relativos al trabajo. La sanción de este corpus estuvo en diálogo con las propuestas que se producían en otras latitudes. Los vínculos que se establecieron entre los referentes locales y sus colegas son de utilidad para abordar el estudio de circulación, recepción y legitimación de los saberes dentro de una escala regional. Así pues, el objetivo de este trabajo es revisar las referencias transnacionales en las discusiones locales sobre los accidentes laborales en Perú y Chile durante la primera mitad del siglo XX.

Detection of Plasma BRAF(V600E) Mutation Is Associated with Lung Metastasis in Papillary Thyroid Carcinomas

PURPOSE: The BRAF(V600E) mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF(V600E) in predicting the advanced disease of PTC. MATERIALS AND METHODS: Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF(V600E) mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). RESULTS: The BRAF(V600E) mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF(V600E) mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF(V600E) mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis. CONCLUSION: These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF(V600E) mutation in large prospective studies.

Micro RNA expression and prognosis in low-grade non-invasive urothelial carcinoma

Purpose To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. Materials and Methods Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. Results There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found. Conclusion We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except miR-10a, over-expressed in most of cases, seeming to have increased levels in tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice. .

Cyclin D1 expression in prostate carcinoma

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in REPLACE_GT5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≧7), 86% of patients demonstrated cyclin D1 immunostaining of REPLACE_GT5% (PREPLACE_LT0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (PREPLACE_LT0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

HER-2 gene expression in atypical ductal hyperplasia associated with canine mammary carcinomas / Expressão gênica de HER2 em hiperplasias ductais atípicas associadas a carcinomas mamários caninos

O presente estudo apresenta o comportamento do gene HER2, a partir do uso da técnica de hibridização cromogênica in situ, em hiperplasias ductais atípicas associadas a carcinomas mamários caninos positivos para HER2. Aparentemente, uma fraca expressão da proteína HER2 foi observada nas hiperplasias ductais atípicas, bem como uma ausência de amplificação do seu gene codificador nessas hiperplasias e nos carcinomas mamários associados. O comportamento da proteína HER2 e do seu gene em carcinomas mamários caninos é similar ao observado em alguns subtipos histológicos de tumores mamários humanos, e a ausência dessas alterações sugerem que esse gene poderia aparentemente não estar envolvido com os estágios iniciais de proliferação celular atípica...

B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1

B-RafV600E mutant is found in 40-70% of papillary thyroid carcinoma (PTC) and has an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein that mediates active iodide transport into the thyroid follicular cells, and B-RafV600E has been known to be associated with the loss of NIS expression. In this study, we found that B-RafV600E inhibited NIS expression by the upregulation of its promoter methylation, and that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC were highly methylated compared with surrounding normal tissue. Although DNA methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1 expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes. Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-kappaB activation. These results led us to conclude that NIS promoter methylation, which was induced by B-RafV600E, is one of the possible mechanisms involved in NIS downregulation in PTC.

Incremento en la expresión del ARNm del receptor c-Met en el cáncer gástrico / Increased expression of the c-Met receptor mRNA in gastric cancer

El cáncer gástrico es una de las patologías malignas más frecuentes en el mundo. En las últimas décadas la atención se ha centrado en posibles alteraciones de factores genéticos que incluyen la activación de proto-oncogenes y/o la inactivación de genes supresores tumorales. El producto del C-MET proto-oncogen y su ligando, el factor de crecimiento del hepatocito (HGF), han sido implicados en la proliferación y migración celular en el cáncer gástrico. En este estudio se analizó a nivel molecular la amplificación del ARNm del receptor c-Met a partir del tejido tumoral gástrico de pacientes a quienes se les practicó gastrectomías, utilizando el método del ácido guanidina-tiocianato-fenol-cloroformo, y el método semicuantitativo de la Reacción en Cadena de la Polimerasa con Transcriptasa Reversa (RT-PCR), encontrándose que los elevados niveles del ARNm del receptor c-Met en las muestras tumorales de los pacientes están relacionados con mayor invasión en la profundidad de la pared gástrica (r = 0,762, p<0,01), incremento en la metástasis a los ganglios linfáticos (r = 0,766, p<0,01), alta frecuencia en tumores pocos diferenciados o indiferenciados (r = 0,912, p<0,001), aumento en el estadiaje del cáncer gástrico (r = 0,838, p<0,001), y en la sobreexpresión por el método inmunohistoquímico (IHQ) de la estreptavidina-biotina marcada de su receptor a nivel proteico (r = 0,858, p<0,001). La amplificación del ARNm y/o la sobreexpresión a nivel proteico del receptor c-Met, pudieran ser utilizados como factores pronósticos en el cáncer gástrico.

Gastric cancer is one of the most common malignancies in the world. In the last decades, the attention has been focused in possible alterations of genetic factors that include proto-oncogene activation and/or the tumor suppressor gene inactivation. The product of the proto-oncogene c-MET and its ligand, hepatocyte growth factor (HGF), have been implicated in cell proliferation and migration in gastric cancer. In this study we analyzed at the molecular level, the amplification of c-Met receptor mRNA from gastric tumor tissue of patients who underwent gastrectomy, using the acid guanidinium-thiocyanate-phenol-chloroform method and the semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) method. It was found that high levels of c-Met receptor mRNA in tumor samples from patients are associated with greater depth of invasion in the gastric wall (r = 0.762, p<0.01), increase in metastases to lymph nodes (r = 0.766, p<0.01), high frequency of poorly differentiated or undifferentiated tumors (r = 0.912, p<0.001), increase in the gastric cancer staging (r = 0.838, p<0.001), and the overexpression, by the immunohistochemistry method (IHC) of the labeled streptavidin-biotin, of the c-Met receptor at the protein level (r = 0.858, p<0.001). The amplification of mRNA and/or protein level overexpression of the c-Met receptor could be used as prognostic factors in gastric cancer.

PGC and PSMA in prostate cancer diagnosis: tissue analysis from biopsy samples

Purpose The discovery of new diagnostic tools for the diagnosis of prostate cancer (PCa) has become an important field of research. In this study, we analyzed the diagnostic value of the expression of the pepsinogen C (PGC) and prostate-specific membrane antigen (PSMA) genes in tissue samples obtained from prostate biopsies. Materials and Methods This study was comprised of 51 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies between January 2010 and March 2010. The biopsies were performed with 12 cores, and an additional core was randomly retrieved from the peripheral zone from each patient for study purposes. The expression of the PGC and PSMA genes was analyzed from the cDNA from the samples via the qRT-PCR technology. The expression patterns of patients with PCa were compared with those of patients without a PCa diagnosis. Results PSMA was overexpressed in only 43.4% of PCa cases, and PGC was overexpressed in 72.7% of cases. The median expression of PSMA was 1.5 times (0.1 to 43.9) and the median PGC expression was 8.7 times (0.1 to 50.0) the expression observed in prostatic tissue from TRUS-guided biopsies of normal patients. Analysis of patients with high-risk PCa indicated that PGC was overexpressed in 71.4% of cases (with a median expression of 10.6 times), and PSMA was overexpressed in only 35.7% of cases (with a median expression of 4.5 times). Among patients with low-risk PCa, PGC was also overexpressed in 71.4% of cases (with a median expression of 5.9 times), and PSMA was overexpressed in only 42.8% of cases (with a median expression of 2.5 times). Conclusions PGC gene expression is significantly higher in prostatic tissue in men affected by PCa when compared to normal prostates. Further analyses are necessary to confirm our results. .