RESUMEN
Protein phosphorylation is a posttranslational modification that is essential for normal cellular processes; however, abnormal phosphorylation is one of the prime causes for alteration of many structural, functional, and regulatory proteins in disease conditions. In cancer, changes in the states of protein phosphorylation in tyrosine residues have been more studied than phosphorylation in threonine or serine residues, which also undergo alterations with greater predominance. In general, serine phosphorylation leads to the formation of multimolecular signaling complexes that regulate diverse biological processes, but in pathological conditions such as tumorigenesis, anomalous phosphorylation may result in the deregulation of some signaling pathways. Cervical cancer (CC), the main neoplasm associated with human papillomavirus (HPV) infection, is the fourth most frequent cancer worldwide. Persistent infection of the cervix with high-risk human papillomaviruses produces precancerous lesions starting with low-grade squamous intraepithelial lesions (LSIL), progressing to high-grade squamous intraepithelial lesions (HSIL) until CC is generated. Here, we compared the proteomic profile of phosphorylated proteins in serine residues from healthy, LSIL, HSIL, and CC samples. Our data show an increase in the number of phosphorylated proteins in serine residues as the grade of injury rises. These results provide a support for future studies focused on phosphorylated proteins and their possible correlation with the progression of cervical lesions.
Asunto(s)
Progresión de la Enfermedad , Proteómica , Neoplasias del Cuello Uterino/fisiopatología , Adulto , Cuello del Útero/fisiopatología , Cuello del Útero/virología , Clusterina/metabolismo , Femenino , Proteínas de Choque Térmico/metabolismo , Humanos , Queratina-19/metabolismo , Queratina-8/metabolismo , México , Persona de Mediana Edad , Chaperonas Moleculares/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/fisiopatología , Infecciones por Papillomavirus/virología , Fosforilación , Lesiones Precancerosas/virología , Serina/metabolismo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/complicaciones , Lesiones Intraepiteliales Escamosas de Cuello Uterino/fisiopatología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Treonina/metabolismo , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
Despite the essential role of Human Papillomavirus (HPV) in cervical carcinogenesis, other factors are required for cancer establishment, like miRNAs. Such molecules present a complex biogenesis, being diversely distributed across tissues and biological fluids, as cell-free miRNAs or miRNAs present in extracellular vesicles (EV). After HPV infection, an interplay between HPV and the miRNA network occurs in cervical cells. As the virus persists and cellular transformation occurs, specific patterns of miRNA expression are found in different stages of cervical disease. Thus, defining promising miRNAs/specific miRNA signatures - especially circulating miRNAs - represents an interesting strategy for screening (diagnosis, prognosis, etc.) those stages. Despite the limited number of studies investigating circulating miRNAs in distinct biological fluids, accumulating data have pointed to some promising candidates, both as cell-free or EV-derived miRNAs. Here we highlight some of these promising non-invasive biomarkers and bring attention to the urgent need for efforts in this field.
Asunto(s)
MicroARNs/sangre , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Neoplasias del Cuello Uterino/etiología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Progresión de la Enfermedad , Vesículas Extracelulares/genética , Femenino , Humanos , Lesiones Intraepiteliales Escamosas de Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/virologíaRESUMEN
The studies for the prevention of uterine cervical cancer in Panama City began in a private institute, impelled by the high incidence of cancer. The preventive programs were initiated with the support of the Obstetrics and Gynecology Institute of the University of Padua in Italy. In these studies, we applied the methodological diagnostics of this Institute with certain modifications adapted to our needs. The diagnosis, treatment, and follow-up were carried out under the protocol of the University of Padua. We achieved a diagnosis of oncogenic risk (OR) in 6,411 patients which corresponded to 5,498 cases of human papillomavirus (HPV), 1,150 cases of dysplasia, 210 cases of cancer, and 794 cases of OR. From 2011, polymerase chain reaction (PCR) was also applied with the aim to improve the accuracy of the diagnosis. With this method the prevalence of pathologies were HPV infections both in healthy patients or in patients cured from HPV. Patients were treated by means of local destructive treatments (LDT), basically with cryotherapy and cauterization. We can consider these results as successful prevention and suggest to extend a preventive program to all the population.
Asunto(s)
ADN Viral/genética , Detección Precoz del Cáncer/tendencias , Infecciones por Papillomavirus/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/prevención & control , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cauterización , Niño , Colposcopía , Criocirugía , Electrocoagulación , Femenino , Humanos , Persona de Mediana Edad , Panamá , Prueba de Papanicolaou , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Reacción en Cadena de la Polimerasa , Lesiones Intraepiteliales Escamosas de Cuello Uterino/complicaciones , Lesiones Intraepiteliales Escamosas de Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/cirugía , Frotis Vaginal , Adulto Joven , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/cirugíaRESUMEN
BACKGROUND: The progression of the cervical squamous intraepithelial lesion (SIL) is associated with many cofactors, and nutritional aspects are gradually assuming an important role in understanding the physiopathogenesis. OBJECTIVE: To assess the serum levels of retinol in women from a poor region of Brazil with a histological diagnosis of cervical high-grade SIL (HSIL). METHODS: A cross-sectional study was conducted in 62 women aged 14-48 years who had a cervical biopsy and were treated at the Federal University of Ceara in Fortaleza, Brazil. Serum retinol levels were measured in peripheral blood by a spectrophotometry technique. Values were categorized as subnormal (<20 µg/dl) or normal (≥20 µg/dl). Multivariate logistic regression was used to determine the association between serum levels of retinol and HSIL for a confidence interval of 95%. RESULTS: Twenty-six out of 62 women (42%) had a negative histopathological result for SIL and 36 (58%) were diagnosed with SIL (20 low SIL and 16 high SIL). The level of retinol was more frequently low in women with HSIL, but there was no statistical significance [p = 0.409, OR: 2.26 (0.33-15.59)]. CONCLUSION: There was no association between high SIL and low levels of retinol in peripheral blood.