Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell.

The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ.

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.

Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo.

Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-ß. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo. Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer.

Conocimiento y creencias de mujeres del estado de Morelos sobre el virus del papiloma humano / Knowledge and beliefs of women from the state of Morelos about the human papilloma virus

Introducción: una enfermedad de transmisión sexual que afecta a un alto porcentaje de mujeres jóvenes de todo el mundo es la infección producida por virus papiloma humano. La falta de información asociada a diversos factores culturales, favorece el desarrollo de creencias que dificultan la prevención y diagnóstico oportunos. Objetivo: identificar el nivel de conocimiento y las creencias que tienen las mujeres del Estado de Morelos, México, sobre la transmisión, detección y tratamiento de la infección por virus del papiloma humano de acuerdo con la edad y el grado de escolaridad. Métodos: estudio descriptivo transversal a partir de un cuestionario aplicado a 690 mujeres en el estado de Morelos. Resultados: el nivel de conocimientos entre la mayoría de la población femenina fue de nivel medio, se incrementa en mujeres jóvenes y con mayor escolaridad. La creencia de que la detección de infección implica mayor gasto económico se presenta sin distinción de edad o nivel escolar. Conclusiones: los aspectos más conocidos sobre la infección por virus papiloma humano, es que es una infección de transmisión sexual, asociada a la aparición de verrugas en genitales y causante de cáncer cérvico uterino. Los menos conocidos son: que la infección es asintomática y que no existe tratamiento para eliminarla(AU)

Introduction: A sexually transmitted disease affecting a high percentage of young women worldwide in the infection produced by the human papilloma virus (HPV). The lack of information associated with different cultural factor favors the development of beliefs that limit timely prevention and diagnosis. Objective: Identify the level of knowledge and beliefs of women from the state of Morelos, Mexico, about the transmission, detection and treatment of HPV infection in accordance with their age and school level. Methods: Cross-sectional, descriptive study with a survey conducted on 690 women on the state of Morelos. Results: The level of knowledge among most of the female population was average, increased in young women and those with higher school level. The belief that infection detection implies higher economic spends is present regardless age and school level. Conclusions: The most known aspects about HPV are that it is a sexually transmitted infection, associated to the onset of genital warts and causing cervical cancer. The least known are that the infection is asymptomatic and that there is no treatment to eliminate it(AU)

Conocimiento y creencias de mujeres del estado de Morelos sobre el virus del papiloma humano / Knowledge and beliefs of women from the state of Morelos about the human papilloma virus

Introducción: una enfermedad de transmisión sexual que afecta a un alto porcentaje de mujeres jóvenes de todo el mundo es la infección producida por virus papiloma humano. La falta de información asociada a diversos factores culturales, favorece el desarrollo de creencias que dificultan la prevención y diagnóstico oportunos. Objetivo: identificar el nivel de conocimiento y las creencias que tienen las mujeres del Estado de Morelos, México, sobre la transmisión, detección y tratamiento de la infección por virus del papiloma humano de acuerdo con la edad y el grado de escolaridad. Métodos: estudio descriptivo transversal a partir de un cuestionario aplicado a 690 mujeres en el estado de Morelos. Resultados: el nivel de conocimientos entre la mayoría de la población femenina fue de nivel medio, se incrementa en mujeres jóvenes y con mayor escolaridad. La creencia de que la detección de infección implica mayor gasto económico se presenta sin distinción de edad o nivel escolar. Conclusiones: los aspectos más conocidos sobre la infección por virus papiloma humano, es que es una infección de transmisión sexual, asociada a la aparición de verrugas en genitales y causante de cáncer cérvico uterino. Los menos conocidos son: que la infección es asintomática y que no existe tratamiento para eliminarla(AU)

Introduction: A sexually transmitted disease affecting a high percentage of young women worldwide in the infection produced by the human papilloma virus (HPV). The lack of information associated with different cultural factor favors the development of beliefs that limit timely prevention and diagnosis. Objective: Identify the level of knowledge and beliefs of women from the state of Morelos, Mexico, about the transmission, detection and treatment of HPV infection in accordance with their age and school level. Methods: Cross-sectional, descriptive study with a survey conducted on 690 women on the state of Morelos. Results: The level of knowledge among most of the female population was average, increased in young women and those with higher school level. The belief that infection detection implies higher economic spends is present regardless age and school level. Conclusions: The most known aspects about HPV are that it is a sexually transmitted infection, associated to the onset of genital warts and causing cervical cancer. The least known are that the infection is asymptomatic and that there is no treatment to eliminate it(AU)

In vivo Antitumor Effect of an HPV-specific Promoter driving IL-12 Expression in an HPV 16-positive Murine Model of Cervical Cancer.

Human papillomavirus (HPV) is a DNA virus that infects epithelial cells and has been implicated in the development of cervical cancer. Few therapeutic strategies have been designed for the treatment of cervical intraepithelial neoplasia, a precursor of cervical cancer. In these early stages, the HPV E2 protein is the most important viral factor involved in viral gene expression and plays crucial roles during the vegetative viral cycle in epithelial cells. Papillomavirus E2 binds specifically to palindromic ACCN6GGT sequences, referred to as the E2 binding sites (E2BS), which are concentrated within the viral long control region, and which are responsible for regulation of the HPV protein's expression. Here, we consider E2BS as a candidate sequence to induce the expression of antiviral therapeutic genes selectively in HPV-infected cells expressing the E2 protein. This study focuses on the use of an HPV-specific promoter comprised of four E2BS to drive the expression of IL-12, leading to an antitumor effect in an HPV-positive murine tumor model. The therapeutic strategy was implemented via viral gene therapy using adenoviral vectors with recombinant E2 and IL-12 genes and E2BS-IL-12. We demonstrate that the HPV-specific promoter E2BS is functional in vitro and in vivo through transactivation of HPV E2 transcription factor.

Inhibitory activity of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes) on transformed cells by human papillomavirus.

In this study, we investigated the effects of the aqueous extracts of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum, obtained from three localities (China; and Morelos and Michoacan, Mexico) on cervical cells transformed by human papillomavirus (HeLa and SiHa) and C-33A cancer cells. The cells were plated in DMEM medium supplemented, and were incubated in the presence of different concentrations of G. lucidum for 24 h. Cell proliferation was determined by MTT colorimetric assay and viability by trypan blue assay. Inhibitory dose was determined (IC50) of the three different extracts of G. lucidum in the culture cell lines mentioned above. The apoptosis process was confirmed by nuclear DNA fragmentation and the cell cycle was determined by flow cytometry. The results showed that aqueous extracts G. lucidum obtained from three localities produced inhibition in the proliferation of VPH transformed cells; they also induced apoptosis and cell cycle arrest in HeLa, SiHa, and C-33A cancer cells. Therefore, it was found that aqueous extracts G. lucidum obtained from three different locations produced inhibitory effect on cancer cells and may have a potential therapeutic use for the prevention and treatment of this disease.

The relationship between the antitumor effect of the IL-12 gene therapy and the expression of Th1 cytokines in an HPV16-positive murine tumor model.

OBJECTIVE: The goal of the present study was to investigate the effect of IL-12 expressed in plasmid on the Th1 cytokine profile in an experimental HPV16-positive murine tumor model and the association with the IL-12's antitumor effect. METHODS: Mice were injected with BMK-16/myc cells to establish HPV16-positive tumor and then pNGVL3-mIL-12 plasmid; pcDNA3 plasmid or PBS was injected directly into tumor site. The antitumor effect of the treatment was evaluated and the cytokines expression profile in each tumor tissue was analyzed. RESULTS: Treatment with pNGVL3-mIL-12 plasmid had a significant antitumor effect, and a Th2-Th3-type cytokines prolife was detected in the murine tumor model with expression of the cytokines IL-10, IL-4, and TGF-ß1. However, after the tumor was treated with three intratumoral injections of plasmid containing IL-12 cDNA, it showed a cytokine profile associated with Th1 with expression of IL-2, IL-12, and IFN-γ cytokines and reduced expression of IL-10, IL-4, and TGF-ß1. CONCLUSIONS: The treatment with the IL-12 gene in the experimental HPV16-positive tumor model promoted the activation of the cellular immune response via expression of a Th1-type cytokine profile and was associated with the inhibition of tumor growth. Thus, IL-12 treatment represents a novel approach for gene therapy against cervical cancer.