Detección de ARNm de oncoproteínas E6/E7 del Virus del Papiloma Humano en cáncer de cuello uterino / Detection of Human Papillomavirus E6/E7 mRNA in cervical cancer / Detecção de RNAm de oncoproteínas E6/E7 do Vírus do Papiloma Humano em câncer de colo de útero

La infección de transmisión sexual por el Virus del Papiloma Humano (VPH) es una de las más comunes en el mundo. Los VPH se clasifican en bajo riesgo y alto riesgo. Los VPH de bajo riesgo son los causantes de lesiones benignas como verrugas genitales y condilomas acuminados, mientras que los VPH de alto riesgo pueden originar la transformación maligna de las células del epitelio cervical por la acción de las oncoproteínas E6 y E7, lo que puede dar origen al cáncer de cuello uterino. La detección de los niveles de ARN mensajero (ARNm) de E6 y E7 de VPH en las células del epitelio cervical está siendo evaluada como un marcador predictivo del cáncer de cuello uterino como alternativa a las técnicas de detección del ADN de VPH. En este artículo se realizó una revisión crítica acerca de la relación existente entre la detección de la expresión de ARNm de E6 y E7 del virus del papiloma humano y el cáncer de cuello uterino. Además, se revisaron las técnicas aprobadas actualmente por la FDA (Food and Drug Administration) para la detección de ARNm de las oncoproteínas E6 y E7 de VPH y el estado del arte del VPH en Colombia.

The sexually transmitted infection by the Human Papillomavirus (HPV) is one of the most common in the world. Human papillomaviruses are classified as low risk and high risk. Low-risk HPVs are the cause of benign lesions such as genital warts and condylomata acuminata, while high-risk HPV types can cause malignant transformation of cervical epithelial cells by the action of oncoproteins E6 and E7, which could result in the development of cervical cancer. The detection of levels of HPV E6 and E7 mRNA (messenger RNA) in cervical epithelial cells is being evaluated as a predictive marker of cervical cancer as an alternative to HPV DNA detection techniques. In this article, a critical review was made about the relationship between the detection of E6 and E7 mRNA expression of human papillomavirus and cervical cancer. Furthermore, the techniques currently approved by the Food and Drug Administration (FDA) for the detection of mRNA from the HPV E6 and E7 oncoproteins and the state of the art of HPV in Colombia were reviewed.

A infecção sexualmente transmissível pelo Vírus do Papiloma Humano (HPV) é uma das mais comuns no mundo. Os HPV são classificados em tipos de baixo e de alto risco. Os HPV de baixo risco são a causa de lesões benignas, tais como verrugas genitais e condilomas acuminados, enquanto que os HPV de alto risco podem causar a transformação maligna das células do epitélio cervical pela ação das oncoproteínas E6 e E7, o que pode dar origem ao câncer de colo de útero. A detecção dos níveis de RNA Mensageiro (RNAm) E6 e E7 de HPV nas células do epitélio cervical está sendo avaliada como marcador preditivo do câncer de colo de útero como alternativa às técnicas de detecção de DNA do HPV. Neste artigo, foi realizada uma revisão crítica sobre a relação entre a detecção da expressão de RNAm E6 e E7 do vírus do papiloma humano e o câncer do colo de útero. Do mesmo modo, foram revisadas as técnicas aprovadas pela FDA (Food and Drug Administration) para detecção de ARNm das oncoproteínas E6 e E7 de HPV e o estado da arte do HPV na Colômbia.

Association between the p53 arginine/arginine homozygous genotype at codon 72 and human papillomavirus E6/E7 mRNA expression

ABSTRACT Objective: To evaluate the association between p53 polymorphisms and human papillomavirus (HPV) E6/E7 mRNA expression. Methods: We analyzed 175 cervical samples from women aged 16-69 years old who were tested for HPV E6/E7 mRNA expression (NucliSENS® EasyQ® HPV). The samples were divided into three groups: positive (n = 75) those with positive HPV E6/E7 mRNA expression and positive high-risk HPV Hybrid Capture (HR-HC) test; negative (n = 52) those with negative HPV E6/E7 mRNA expression and positive HR-HC; and control (n = 48) those with negative HPV E6/E7 mRNA expression and negative HR-HC. The p53 polymorphisms at codons 11, 72, and 248 were evaluated through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the arginine/arginine homozygous genotype at codon 72 was significantly higher in the positive (49.3%) than in the negative (32.7%) and control groups (20.8%, p = 0.002*). The frequency of the arginine allele was also significantly higher in the positive (67.3%) than in the negative (53.8%) and control groups (38.5%, p < 0.001*). The arginine/arginine homozygous genotype was significantly associated with positive HPV E6/E7 mRNA expression (positive group) compared with negative and control groups (odds ratio: 2.633; 95% CI, 1.399-4.954, p = 0.003). The frequency of arginine/arginine homozygous genotype at codon 72 remained significantly more frequent in the positive group of women aged ≥30 years than in the other two groups. Conclusion: The presence of the p53 arginine/arginine homozygous genotype at codon 72 was significantly associated with the positive HPV E6/E7 mRNA expression.

Efeito da infecção por HPV nas vias de sinalização por toll like receptors / Effects of HPV infection on TLR signaling pathway

As oncoproteínas E6 e E7 do Papilomavírus Humano (HPV) estão envolvidas na desregulação do sistema imune inato, provocando alterações na expressão dos receptores do tipo Toll (TLR). Considerando-se a função da via de sinalização iniciada por TLR, haveria uma vantagem para o vírus capaz de manipular a resposta desta via de modo que possa persistir nas células sem ser detectado pelo sistema imune ou ainda modulando essa resposta e criando um ambiente mais propício à manutenção da infecção. No entanto, muitos dos mecanismos que levam à eliminação da infecção ou persistência do HPV ainda são pouco conhecidos. O objetivo principal desse trabalho é investigar o papel das vias de TLR no processo de carcinogênese mediado por HPV. Inicialmente, foi analisada a expressão de genes da via de TLR em linhagens de tumores cervicais e em células expressando as oncoproteínas virais. Foram identificados vários genes diferencialmente expressos entre linhagens de células tumorais e queratinócitos normais, incluindo moléculas adaptadoras da via de TLR e genes associados à via da MAP quinase, ativação de NFkappaB e resposta imune antiviral. Cerca de 90% destes genes foram regulados negativamente. Entre eles, destacamos HMGB1, que apesar de possuir menos RNAm nas células tumorais possui um nível proteico muito maior, além de ter-se mostrado de grande importância para a viabilidade e proliferação das células tumorais, conforme demonstrado através de experimentos de supressão gênica. Em conjunto, os nossos dados indicam que E6 e E7 de HPVs de alto risco inibem proteínas da via de sinalização de TLR

Previous studies have shown that E6 and E7 HPV oncoproteins are involved in innate immune system dysregulation, causing alterations on Toll-like receptors (TLR) expression. Considering TLR pathway function, it would be advantageous for a virus to manipulate the response of this pathway so it can persist in cells without being detected by the immune system or to modulate this response to create a better environment for persistence of infection. However, many of the mechanisms leading to HPV infection clearance or persistence are still unknown and matter of active investigation. We analyzed in cervical cancer cell lines expression of genes from TLR pathway; several were differentially expressed between tumor cells lines and normal keratinocytes, including TLR adaptors molecules and genes associated with MAP kinase pathway, NFkappaB activation and antiviral immune response. About 90% of these genes were down regulated. Among them, we selected HMGB1 for further characterization due to its interference with tumor cell viability and proliferation. Altogether, our data indicate that high risk HPV E6 and E7 can inhibit TLR signaling pathway

Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor gamma (PPARgamma) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians.

Study on the Expression of PTENmRNA,P73mRNA and Clinicopathological Significances in the Benign and Malignant Lesions of Mammary Gland / 医学研究杂志

Objective To study on the expressions of PTENmRNA and P73mRNA and detect their clinicopathological significances in the benign and malignant lesions of mammary gland. Methods In situ hybridization method was used on the routinely paraffin-embedded sections for 40 cases with breast cancer and 30 ones with breast benign lesions. Results The positive rates of PTENmRNA was significantly lower in the breast cancer than that in breast benign lesions(P2cm and with-metastasis of lymphnode in breast cancer, but those of P73mRNA were opposite. The closely negative correlation was found between the expression of PTENmRNA and P73mRNA in breast cancer. Conclusions The pression of PTENmRNA or P73mRNA might be an important biological marker for the reflecting the carcinogenesis, progress, biological behaviors and prognosis of breast cancer. The detections of PTENmRNA and P73mRNA in the breast begin lesions might be important clinical values for early-stage prevention and treatment of breast cancer.

The Expression of PTEN,p73 Oncoprotein and Its Significance in Gastric Cancer Tissues / 中国医师杂志

Objective To study the expressions of PTEN,p73 oncoproteins and their chinicopathological significances in gastric cancer tissues.Method Immunohistochemical method of avidin-biotin complex was used to the routinely paraffin-embedded sections.Results The positive rates of PTEN,p73 in 57 cases with gastric cancer were 51% and 37% ,respectively.The positive rate of PTEN was higher in adenocarcinoma(63%) than that in mucoadenocarcinoma(43%) or signet ring cell carcinoma(38%) and that p73 was lower in adenocarcinoma(26%) than that in mucoadenocarcinoma(57%) or signetring cell carcinoma(44%).The positive rates of PTEN were significantly higher in the cases of histological grade Ⅰ and without Iymphnode metastasis than those in the cases of histological graed Ⅲ and with Iymphnode metastasis,but those of p73 were opposite.The negative correlation was found between the expression of PTEN and p73.Conclusions The expressions of PTEN,p73 mihgt be related to the clinicopathological characteristics and biological behaviors of gastric cancer,they might be important biological markers