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1.
PLoS One ; 15(6): e0234518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525936

RESUMO

BACKGROUND/OBJECTIVE: Human papillomavirus (HPV) genotyping and cytology have been recommended for colposcopy triage, but it is unclear which combinations of high-risk HPV (hrHPV) types and cytology with various thresholds provide clinically useful information for the triage after primary HPV screening on self-collected samples. METHOD: Chinese Multi-site Screening Trial (CHIMUST) database focused on self-collected samples was reviewed using the results of Cobas4800 HPV assay. Absolute risks of each genotype for cervical intraepithelial neoplasia 2 or worse/ 3 or worse (CIN2+/CIN3+) were calculated. Triage of atypical squamous cells of undetermined significance (ASCUS) or worse cytology was used as the comparator, and diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar's test. RESULTS: A total of 10, 498 women were included, the overall prevalence of hrHPV, HPV16, HPV18, and Other hrHPV genotypes were 13.7%, 2.4%, 0.8%, and 10.5%, respectively. HPV16-positive women had the highest absolute risk among various genotypes for CIN2+/CIN3+ whether in normal or abnormal cytology (ASCUS or worse) and among all age groups. When compared with the comparator, combining HPV16 positivity and/or high-grade squamous intraepithelial lesion (HSIL) or worse yielded higher specificity (97.7% vs. 97.0%, p<0.0001), similar sensitivity (90.7% vs. 96.3%, p = 0.256) for detection of CIN3+, and a decrease in colposcopy referral rate from 3.5% to 2.7%, similar results were found for CIN2+. Positivity for HPV16 and/or (ASCUS or worse), and positivity for (HPV16 and/or HPV18) and/or (ASCUS or worse) achieved favorable sensitivity compared with the comparator (80.6% and 81.3% vs. 70.1% respectively for CIN2+, p<0.0001; both 96.3% vs. 96.3% for CIN3+, p = 1.000), these algorithms would reduce the colposcopy referral rate to 5.0% and 5.6% respectively, compared with 13.7% of that for HPV alone. CONCLUSIONS: Triage of HPV-positive women on self-collected samples by combining HPV16 or HPV16/18 genotyping with different thresholds of cytology could provide tradeoffs in sensitivity for detecting cervical lesions and colposcopy referral rates, and tailor management in various circumstances of clinical practice.


Assuntos
Técnicas de Genotipagem/métodos , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Triagem/métodos , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Adulto , Biópsia/estatística & dados numéricos , Colo do Útero/citologia , Colo do Útero/patologia , Colo do Útero/virologia , Colposcopia/estatística & dados numéricos , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Humanos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Encaminhamento e Consulta/estatística & dados numéricos , Medição de Risco/métodos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Triagem/estatística & dados numéricos , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(1): 7-12, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-32343058

RESUMO

This study proposes an image segmentation method based on bottleneck detection and watershed algorithm to solve the problem of overlapping cervical cell image. First, we use polygon approximation to get all feature points on the cell contour and then use bottleneck detection and ellipse fitting to obtain the correct split point pairs. Therefore, the approximate range of the overlapping region was determined. The watershed algorithm was used to obtain the internal boundary information for the gradient image of the region. Finally, the segmentation results of the overlapped cells were obtained by superimposing with the outer contour. The experimental results show that this algorithm can segment the contour of a single cell from the overlapping cervical cell images with good accuracy and integrity. The segmentation result is close to that of doctors' manual marking, and the segmentation result is better than other existing algorithms.


Assuntos
Algoritmos , Colo do Útero/citologia , Processamento de Imagem Assistida por Computador , Feminino , Humanos
3.
Cancer Invest ; 38(4): 228-239, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32208057

RESUMO

The aim of this study was to characterize both by flow cytometry analysis and immunohistochemistry cervix uteri cells of nulliparous women screened for cervical intraepithelial neoplasia (CIN) in comparison to a group without CIN by using mesenchymal stem cell-like and hematopoietic lineage markers. A significant expression for CD29, CD38, HLA-I, and HLA-II was correlated positively to the CIN degree and it was more relevant in patients positive for human papilloma virus (HPV). Thus, identification and detailed characterization of pluripotent resident in uteri cells could be a promising therapeutic target.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/citologia , Células-Tronco Neoplásicas/patologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , ADP-Ribosil Ciclase 1/análise , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/imunologia , Colo do Útero/patologia , Colo do Útero/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Integrina beta1/análise , Integrina beta1/imunologia , Integrina beta1/metabolismo , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Gradação de Tumores , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/virologia , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
4.
Adv Exp Med Biol ; 1219: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130694

RESUMO

Several aspects of the human physiology are controlled by the microbiota that plays a key role in health and disease. In fact, microbial dysbiosis is associated with numerous diseases, including several types of cancer such as colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas.Metabolic symbiosis between non-malignant cells and the resident microbita is crucial for the host homeostasis. However, cancer cells are able to repurpose the pre-existing metabolic symbiosis, being able to recycle those relations and also create novel metabolic symbiosis, leading to profound alterations on the local microenvironment.In here we will explore some of these symbiotic metabolic interactions between bacteria and non-malignant cells in two different contexts: colon and uterine cervix. The way malignant cells are able to recycle these normal interactions and also create novel types of symbiotic metabolic relations will also be discussed.The knowledge of these complex interactions and recycling mechanisms is of extreme importance for cancer treatment, as new therapeutic targets could be developed.


Assuntos
Bactérias/metabolismo , Células Epiteliais/metabolismo , Neoplasias/metabolismo , Neoplasias/microbiologia , Simbiose , Colo do Útero/citologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo/citologia , Colo/metabolismo , Colo/microbiologia , Feminino , Humanos , Microbiota/fisiologia
5.
Rev. habanera cienc. méd ; 19(1): 112-124, ene.-feb. 2020. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1099150

RESUMO

Introducción: La citología cervical constituye la principal herramienta para la detección y tratamiento del cáncer de cérvix. Algunos estudios llevados a cabo en población urbana han relacionado la realización y adherencia con los conocimientos, las actitudes y las prácticas favorables de las mujeres con respecto a esta prueba. Objetivo: evaluar los conocimientos, actitudes y prácticas con respecto a la citología cervical en mujeres pertenecientes a un grupo poblacional del ámbito rural. Material y Métodos: estudio de corte transversal-analítico en una población de aproximadamente 3148 mujeres en edad fértil, de ellas se obtuvo una muestra representativa. Se utilizó una encuesta anónima, validada, dirigida, y aplicada por personal de salud capacitado que labora en centros de salud del primer nivel de atención de los distritos de la provincia de Bolívar, La Libertad. Resultados: El 80 por ciento de las mujeres encuestadas tuvo un nivel de conocimiento alto e intermedio, el 70 por ciento una actitud favorable, mientras que el 44 por ciento reportó prácticas correctas en relación con la prueba de citología cervical. El nivel de conocimiento alto e intermedio estuvo asociado a la edad mayor de 30 años (p:0.02), estado civil casada (p:0.05), el mayor grado de instrucción (p:0.00) y el uso de métodos anticonceptivos (p:0.01); no se encontró relación con la edad de inicio de relaciones sexuales (p:0.98). Conclusiones: Existe un alto nivel de conocimientos, actitudes y prácticas correctas hacia la citología cervical en la población rural de la provincia de Bolívar, pero una baja adherencia hacia la misma(AU)


Introduction: Cervical cytology is the main tool for the detection and treatment of cervical cancer. Some studies carried out in the urban population have associated the realization and adherence with knowledge, attitudes and favorable practices of women with respect to this test. Objective: The aim of this study was to determine the level of knowledge, attitudes and practices towards cervical cytology in women of childbearing age in a rural Peruvian province. Material and Methods: A cross-sectional analytical study was conducted in a population of approximately 3148 women of childbearing age, a representative sample was obtained. An anonymous, validated, directed survey was used; it was applied by trained health personnel working in health centers of the primary care level in the districts of the province of Bolívar, La Libertad. Results: A total of 400 surveys were carried out. The results showed that 80 percent of the women surveyed had high and intermediate levels of knowledge, 70 percent had a favorable attitude, while 44 percent reported correct practices related to the cervical cytology test. The high and intermediate levels of knowledge were associated with age over 30 years (p: 0.02), married marital status (p: 0.05), the highest level of instruction (p: 0.00) and the use of contraceptive methods (p: 0.01); no relationship was found with the age of onset of sexual intercourse (p: 0.98). Conclusions: There is a high level of knowledge, attitudes and correct practices towards cervical cytology in the rural population of the province of Bolívar, but a low adherence to it(AU)


Assuntos
Humanos , Feminino , Adulto , Colo do Útero/citologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Saúde da População Rural/educação , Peru , População Rural , Estudos Transversais , Saúde da Mulher
6.
Prog. obstet. ginecol. (Ed. impr.) ; 63(1): 3-5, ene.-feb. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-197725

RESUMO

OBJECTIVE: Cervical cancer has become an important public health concern, with 84% of cases and related deaths ocurring in developing countries. MATERIAL AND METHODS: Between the years 2005 and 2016, 75 rural communities of the state of Jalisco, Mexico, were visited, with cytological examinations granted to those women who solicited them, and collection of subsequent hystopathological data. RESULTS: 24,537 cytologies were conducted, finding 185 (0.75%) cases of intraepithelial lesions. CONCLUSIONS: Primary prevention is particularly important in rural communities due to their contribution to the global morbidity and mortality of cervical cancer


OBJETIVO: el cáncer cervicouterino es un problema importante de salud pública, 84% de los casos y defunciones ocurren en países en vías de desarrollo. MATERIAL Y MÉTODOS: en el transcurso del año 2005 al 2016 se visitaron 75 comunidades rurales en el estado de Jalisco, México, realizando citologías cervicales a quienes las solicitaran y recabando los resultados del análisis histopatológico. RESULTADOS: se realizaron 24.537 citologías, encontrando 185 (0,75%) con lesiones intraepiteliales. CONCLUSIONES: la prevención primaria es particularmente importante en comunidades rurales por su contribución a la morbimortalidad global del cáncer cervicouterino


Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Neoplasias do Colo do Útero/prevenção & controle , Colo do Útero/citologia , Estudos Retrospectivos , População Rural , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Incidência , México/epidemiologia
7.
Virol J ; 17(1): 8, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959186

RESUMO

The separation of exfoliated cells from the brushes used during cervico-vaginal smears is difficult, a problem which may affect the quality of ribonucleic acid (RNA) extracted. We compared the results of RNA extraction from cervico-vaginal cytology samples according to the type of tubes, preservative solutions, and storage temperature. The samples included exfoliated cervico-vaginal cytological specimens from patients with human papilloma virus 16, positive for cervical intraepithelial neoplasia or cervical cancer. Exfoliated cells were obtained by shaking a brush in a conventional rigid vial tube or squeezing the brush in a soft vial tube. RNA quantity and quality were compared between the two tubes. The concentration and purity of RNA (A260/A280 and A260/A230 ratios) was compared amongst five groups: Group 1, standard frozen storage; Group 2-4, RNA stabilization reagents with room temperature [RNAlater RNA Stabilization Reagent, RNAprotect cell Reagent and AllProtect Tissue Reagent]; and Group 5, Surepath Preservative fluid. To demonstrate the utility of the extracted RNA for PCR-based cDNA synthesis, GAPDH and E6 were targeted and gel band densities of GAPDH and E6 were measured. The median RNA concentration was significantly higher in the soft tubes compared with the rigid tubes (100.2 vs. 7.1 ng/µL, p = 0.0209). The purity of the RNA was higher in soft vial tubes than in rigid vials, as measured by A260/280 and A260/230 ratios. The RNA concentration, purity, and GAPDH density of groups 1, 2 and 3 were significantly higher than those of groups 4 and 5. Moreover, E6 density of group 1 and 2 was significantly higher than that of group 3, 4 and 5. The use of soft tubes enhanced the mRNA quantity and quality in cervico-vaginal cytology. The products of mRNA extraction using RNAlater RNA Stabilization Reagent and RNAprotect Cell Reagent at room temperature were comparable to those obtained by conventional frozen storage. Our protocol improved the yield and quality of RNA and might produce better results for molecular analysis in cervico-vaginal cytology.


Assuntos
Colo do Útero/virologia , Papillomavirus Humano 16/genética , RNA Mensageiro/análise , Vagina/citologia , Adulto , Neoplasia Intraepitelial Cervical/complicações , Colo do Útero/citologia , Feminino , Humanos , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/complicações , Vagina/virologia , Esfregaço Vaginal/métodos
8.
J Infect Dis ; 221(3): 449-453, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31541571

RESUMO

L-lactate is an abundant metabolite in a number of niches in host organisms and represents an important carbon source for bacterial pathogens such as Neisseria gonorrhoeae. In this study, we describe an alternative, iron-sulfur cluster-containing L-lactate dehydrogenase (LutACB), that is distinct from the flavoprotein L-lactate dehydrogenase (LldD). Expression of lutACB was found to be positively regulated by iron, whereas lldD was more highly expressed under conditions of iron-limitation. The functional role of LutACB and LldD was reflected in in vitro studies of growth and in the survival of N gonorrhoeae in primary cervical epithelial cells.


Assuntos
Proteínas de Bactérias/metabolismo , Colo do Útero/citologia , Células Epiteliais/microbiologia , Gonorreia/metabolismo , L-Lactato Desidrogenase/metabolismo , Viabilidade Microbiana/genética , Neisseria gonorrhoeae/enzimologia , Proteínas de Bactérias/genética , Feminino , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Gonorreia/microbiologia , Humanos , Ferro/metabolismo , L-Lactato Desidrogenase/genética , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/crescimento & desenvolvimento , RNA Viral/genética
9.
Diagn Cytopathol ; 48(1): 10-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31587527

RESUMO

The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aid in the classification of atypical cells in cervical cytology. Anyway, AGC diagnosis remains challenging, due to low frequencies of this finding (approximately 0.5%-1% of Pap test results), abundance of AGC mimics, and significant interobserver variability. We developed an algorithm based on nuclear areas parameter that can help to differentiate AGC from Normal and Reactive glandular cells. Nuclear areas and perimeters were measured on 16 Pap smears with AGC and 18 with Reactive glandular cells of women aged between 30 and 77. Glandular cells from nonpathological Pap smears were used as controls. For each case, the means, medians, standard deviations, and the minimum and maximum values of both nuclear areas and perimeters of the cells of interest were calculated. The nuclear area analysis showed a 100% specificity in discriminating Normal from Altered cells (either Reactive or AGC), whereas the nuclear perimeter analysis showed a lower specificity (87.5%). Both nuclear area and perimeter variability analysis resulted in high specificity values in distinguishing Reactive cells from AGC. Therefore, a stepwise two-step algorithm using nuclear areas to discriminate Normal from Altered cells, and nuclear area variability to distinguish Reactive from AGC, allowed us to reliably classify the cells into these three categories. The morphometric analysis of nuclear area is a valuable and reliable aid in AGC diagnosis and standardization, easily integrable into common automatic algorithms.


Assuntos
Células Escamosas Atípicas do Colo do Útero/citologia , Neoplasia Intraepitelial Cervical/diagnóstico , Colo do Útero/citologia , Teste de Papanicolaou/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Algoritmos , Células Escamosas Atípicas do Colo do Útero/patologia , Colo do Útero/patologia , Células Epiteliais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Esfregaço Vaginal/métodos
10.
Diagn Cytopathol ; 48(1): 35-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31639288

RESUMO

BACKGROUND: Although the Pap test has been the standard screening method for cervical precancer/cancer detection, it has been criticized for having a relatively low sensitivity and a low reproducibility between pathologists. There is limited knowledge about inter-rater agreement and what clinical and demographic factors are associated with disagreements between pathologists reading the same Pap smear. METHODS: This study aimed to assess inter- and intra- rater agreement of the Pap smear in 1619 cytologic slides with biopsy confirmation, using kappa statistics. Clinical and demographic factors associated with higher odds of inter-rater agreement were also examined and stratified by histologic diagnosis grade. RESULTS: Using a five grade classification system, the overall kappa statistics for total, inter-rater, and intra-rater samples were 0.62, 0.57, and 0.88 (unweighted) and 0.83, 0.81, and 0.95 (weighted), respectively. In stratified analyses by histologic grade, total kappas ranged from 0.40 (atypia) to 0.64 (human papilloma virus/CIN 1). Factors such as referral for abnormal Pap test (diagnostic vs screening population), recruiting site, and parity were found to be associated with higher agreement between the two cytologic readings. CONCLUSIONS: We observed relatively higher levels of agreement compared with other studies. However, variability was considerable and agreement was generally moderate, suggesting that cervical screening test accuracy and reproducibility needs to be improved.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Colo do Útero/citologia , Detecção Precoce de Câncer/métodos , Teste de Papanicolaou/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Feminino , Humanos , Programas de Rastreamento/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Esfregaço Vaginal/métodos
11.
Rev. bras. cancerol ; 66(1)20200129.
Artigo em Português | LILACS | ID: biblio-1088000

RESUMO

Introdução: O exame citopatológico é utilizado para detecção precoce das lesões precursoras do câncer do colo uterino. Objetivo: Avaliar os indicadores de qualidade de acordo com o Manual de Gestão da Qualidade para Laboratório de Citopatologia. Método: Verificaram-se os laudos das fichas de requisição dos exames citopatológicos do laboratório clínico da Pontifícia Universidade de Goiás (LC-PUC-Goiás) entre janeiro de 2013 e dezembro de 2017. Resultados: Do total de 6.809 diagnósticos, observaram-se 99,4% (6.768/6.809) satisfatórios, sendo 91,3% (6.215/6.809) resultados negativos, 8,1% (553/6.809) diagnósticos com anormalidades citológicas e 0,6% (41/6.809) de exames insatisfatórios. O índice de positividade dos anos de 2013 a 2017 foram 10,5%, 7,9%, 8,6%, 6,8% e 5,3%, respectivamente. O percentual de exames compatíveis com lesão intraepitelial de alto grau (HSIL) entre os exames satisfatórios no ano de 2013 foi de 1,3%; 2014: 1,0%; 2015: 0,5%; 2016: 0,6%; e 2017: 0,7%, resultados dentro do estabelecido, ≥0,4%. A relação de células escamosas atípicas (ASC)/satisfatórios demostrou valores acima do estabelecido nos anos de 2013 com 6,8% e 2015 com 6,1%. Segundo o Manual de Gestão para Controle de Qualidade, espera-se que, no máximo, 4% a 5% de todos dos exames sejam classificados como ASC. Valores acima de 5% necessitam de uma atenção diferenciada. Conclusão: É de suma importância a educação continuada dos profissionais que participam de todas as etapas do processo, da fase pré-analítica à analítica, para que possíveis erros possam ser corrigidos e medidas preventivas tomadas para uma melhor qualidade na interpretação dos exames citopatológicos.


Introduction: The cytopathological examination is used for early detection of cervical cancer precursor lesions. Objective: Evaluate the quality indicators according to the Quality Management Manual for the Cytopathology Laboratory. Method: The results of the request forms of cytopathological examinations of the Clinical Laboratory of the Pontifical University of Goiás (LC-PUC-Goiás) were verified between January 2013 and December 2017. Results: Of 6,809 diagnoses in total, 99.4% (6,768/6,809) were satisfactory, 91.3% (6,215/6,809) were negative, 8.1% (553/6,809) presented cytological abnormalities and 0.6% (41/6,809) were unsatisfactory. The Positivity Index from 2013 to 2017 was 10.5%, 7.9%, 8.6%, 6.8% and 5.3%, respectively. The percentage of examinations with high-grade intraepithelial lesion (HSIL) among satisfactory examinations in 2013 was 1.3%, in 2014, 1.0%, in 2015, 0.5%, in 2016, 0.6 % and in 2017, 0.7%, results within the established ≥ 0.4%. The atypical squamous cells (ASC)/satisfactory ratio showed values above the standard figures in 2013 with 6.8% and 2015 with 6.1%. According to the Quality Control Management Manual, it is expected that, at the most, 4% to 5% of all exams be classified as ASC. Values above 5% demand differentiated attention. Conclusion: It is of the utmost importance the continued education of professionals who participate in all stages of the process, from the pre-analytical to the analytical phase, so that possible errors can be avoided and preventive measures taken for better quality interpretation of the cytopathological examinations.


Introducción: El examen citopatológico se utiliza para la detección temprana de lesiones precursoras de cáncer cervical. Objetivo: Evaluar los indicadores de calidad de acuerdo con el Manual de Gestión de Calidad para el laboratorio de citopatología. Método: Se verificaron los informes de los formularios de solicitud para los exámenes citopatológicos del Laboratorio Clínico de la Pontificia Universidad de Goiás (LC-PUC-Goiás), de enero de 2013 a diciembre de 2017. Resultados: Del total de 6.809 diagnósticos, se observarán 99,4% (6.768/6.809) diagnósticos satisfactorios, 91,3% (6.215/6.809) resultados negativos, 8,1% (553/6.809) diagnósticos con anomalías citológicas y 0,6% (41/6.809) exámenes insatisfactorios. El índice de positividad de 2013 a 2017 fue de 10,5%, 7,9%, 8,6%, 6,8% y 5,3% respectivamente. El porcentaje de exámenes compatibles con lesiones intraepiteliales de alto grado (HSIL) entre los exámenes satisfactorios en 2013 fue de 1,3%; 2014: 1,0%; 2015: 0,5%; 2016: 0,6%; y 2017: 0,7%, resultados dentro de lo establecido, ≥0,4%. La relación células escamosas atípicas (ASC)/satisfactorio fue más alta que la establecida en 2013 con 6,8% y 2015 con 6,1%. Según el Manual de Gestión de Control de Calidad, se espera que un máximo del 4% al 5% de todos los exámenes se clasifiquen como ASC. Los valores superiores al 5% requieren una atención diferente. Conclusión: Es de suma importancia la educación continua de los profesionales que participan en todas las etapas del proceso, desde la fase preanalítica hasta la analítica, para que se puedan corregir los posibles errores y se tomen medidas preventivas para una mejor calidad en la interpretación de los exámenes citopatológicos.


Assuntos
Humanos , Feminino , Controle de Qualidade , Neoplasias do Colo do Útero/diagnóstico , Colo do Útero/citologia , Garantia da Qualidade dos Cuidados de Saúde , Brasil , Neoplasias do Colo do Útero/prevenção & controle , Programas de Rastreamento/normas , Estudos Retrospectivos , Técnicas Citológicas , Citodiagnóstico/normas , Teste de Papanicolaou/normas
12.
Cells ; 8(8)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375021

RESUMO

Despite the significant advances in the last decades, low implantation rate per transferred embryo still remains a major concern in assisted reproductive techniques, highlighting a need to better characterize endometrial receptivity also by mean of specific biomarkers. Based on physiology and on the intimate contact with endometrium as the tissue of interest, in this study we developed and validated an optimized protocol that uses extracellular vesicles (EVs) recovered from uterine flushings and from a cervical brush, the latter never used until now as an EVs source, as surrogates for endometrial biopsies. This method combines the safety of sampling with the ability to study the expression profile across the uterine cycle. We have compared the yield and composition of EVs recovered from different biofluids samples and fractions thereof, opting for chemical precipitation as the EV isolation procedure, assuring the highest yield without introducing any bias in specific EV recovery. Moreover, collected EVs, in particular exosome-like vesicles, express putative endometrial markers, such as glycodelin A and receptors for estrogen and progesterone, thus confirming their endometrial origin. We also identified uterine flushing EVs, in particular those recovered from its mucous fraction, as the richest source of endometrial transcripts, likely correlated to cellular (epithelial) origin of these vesicles. Finally, our pilot quantitative assessment of three endometrial gene profiles, in samples collected at different time points along the luteal phase, revealed the fluctuations apparently recapitulating gene expression variability prior reported during the menstrual cycle. Unlike tissue biopsy that is subjected to inter- and intra-sample differences, our data suggest that EVs from liquid biopsies (from uterine flushings and a cervical brush) obtained through less-invasive procedures, can be substrate to detect and track the tissue representative expression profiles, better depicting the total endometrium complexity.


Assuntos
Biomarcadores/metabolismo , Colo do Útero/metabolismo , Endométrio/metabolismo , Exossomos/metabolismo , Fase Luteal/metabolismo , Colo do Útero/citologia , Endométrio/citologia , Feminino , Glicodelina/metabolismo , Voluntários Saudáveis , Humanos , Biópsia Líquida/métodos , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Técnicas de Reprodução Assistida
13.
Sci Rep ; 9(1): 12115, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431640

RESUMO

Extravillous trophoblasts (EVTs) have the potential to provide the entire fetal genome for prenatal testing. Previous studies have demonstrated the presence of EVTs in the cervical canal and the ability to retrieve a small quantity of these cells by cervical sampling. However, these small quantities of trophoblasts are far outnumbered by the population of cervical cells in the sample, making isolation of the trophoblasts challenging. We have developed a method to enrich trophoblast cells from a cervical sample using differential settling of the cells in polystyrene wells. We tested the addition of small quantities of JEG-3 trophoblast cell line cells into clinical samples from standard Pap tests taken at 5 to 20 weeks of gestation to determine the optimal work flow. We observed that a 4 min incubation in the capture wells led to a maximum in JEG-3 cell settling on the surface (71 ± 10% of the initial amount added) with the removal of 91 ± 3% of the cervical cell population, leading to a 700% enrichment in JEG-3 cells. We hypothesized that settling of mucus in the cervical sample affects the separation. Finally, we performed a proof-of-concept study using our work flow and CyteFinder cell picking to verify enrichment and pick individual JEG-3 and trophoblast cells free of cervical cells. Ultimately, this work provides a rapid, facile, and cost-effective method for enriching native trophoblasts from cervical samples for use in subsequent non-invasive prenatal testing using methods including single cell picking.


Assuntos
Separação Celular/métodos , Colo do Útero/citologia , Trofoblastos/citologia , Linhagem Celular , Dermoscopia , Feminino , Humanos , Teste de Papanicolaou , Gravidez , Estudo de Prova de Conceito
14.
J Biomech Eng ; 141(9)2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374123

RESUMO

The cervix is essential to a healthy pregnancy as it must bear the increasing load caused by the growing fetus. Preterm birth is suspected to be caused by the premature softening and mechanical failure of the cervix. The objective of this paper is to measure the anisotropic mechanical properties of human cervical tissue using indentation and video extensometry. The human cervix is a layered structure, where its thick stromal core contains preferentially aligned collagen fibers embedded in a soft ground substance. The fiber composite nature of the tissue provides resistance to the complex three-dimensional loading environment of pregnancy. In this work, we detail an indentation mechanical test to obtain the force and deformation response during loading which closely matches in vivo conditions. We postulate a constitutive material model to describe the equilibrium material behavior to ramp-hold indentation, and we use an inverse finite element method based on genetic algorithm (GA) optimization to determine best-fit material parameters. We report the material properties of human cervical slices taken at different anatomical locations from women of different obstetric backgrounds. In this cohort of patients, the anterior internal os (the area where the cervix meets the uterus) of the cervix is stiffer than the anterior external os (the area closest to the vagina). The anatomic anterior and posterior quadrants of cervical tissue are more anisotropic than the left and right quadrants. There is no significant difference in material properties between samples of different parities (number of pregnancies reaching viable gestation age).


Assuntos
Colo do Útero/citologia , Análise de Elementos Finitos , Teste de Materiais , Fenômenos Mecânicos , Adulto , Anisotropia , Fenômenos Biomecânicos , Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Imagem Molecular , Estresse Mecânico
15.
J Antimicrob Chemother ; 74(11): 3245-3251, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424547

RESUMO

OBJECTIVES: Cell-penetrating peptides (CPPs) have been evaluated for intracellular delivery of molecules and several CPPs have bactericidal activity. Our objectives were to determine the effect of a 12 amino acid CPPs on survival and on the invasive and inflammatory potential of Neisseria gonorrhoeae. METHODS: Survival of MDR and human challenge strains of N. gonorrhoeae grown in cell culture medium with 10% FBS was determined after treatment with the CPP and human antimicrobial peptide LL-37 for 4 h. Confocal microscopy was used to examine penetration of FITC-labelled CPP into bacterial cells. The ability of the CPP to prevent invasion of human ME-180 cervical epithelial cells and to reduce the induction of TNF-α in human THP-1 monocytic cells in response to gonococcal infection was assessed. Cytotoxicity of the CPP towards the THP-1 cells was determined. RESULTS: The CPP was bactericidal, with 95%-100% killing of all gonococcal strains at 100 µM. Confocal microscopy of gonococci incubated with FITC-labelled CPP revealed the penetration of the peptide. CPP treatment of N. gonorrhoeae inhibited gonococcal invasion of ME-180 cells and reduced the expression of TNF-α induced in THP-1 cells by gonococci. The CPP showed no cytotoxicity towards human THP-1 cells. CONCLUSIONS: Based on these promising results, future studies will focus on testing of CPP in the presence of other types of host cells and exploration of structural modifications of the CPP that could decrease its susceptibility to proteolysis and increase its potency.


Assuntos
Antibacterianos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Penetradores de Células/química , Colo do Útero/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Feminino , Humanos , Monócitos/efeitos dos fármacos , Monócitos/microbiologia , Células THP-1 , Fator de Necrose Tumoral alfa/análise
16.
Cancer Sci ; 110(9): 2992-3005, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265190

RESUMO

Cervical clear cell carcinoma (cCCC) constitutes an extremely rare subtype of cervical cancer. Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of cCCC organoids, from biopsy samples of a 23-year-old patient diagnosed with cCCC. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient-derived cell line (PDC) for more than 6 months as organoids. This PDC tolerated cryopreservation and proliferated either as spheroids or adherent cells, and developed xenografts in immunodeficient mice, ensuring robust utility as a cell line. Intriguingly, the resected tumor focally contained serous carcinoma (SC) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the CCC component of the original tumor in histology, immunostaining profile, and genome-wide copy number changes, including focal gain of MET. Genomic analysis revealed that both organoids and the CCC component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the SC component showed a mutator-phenotype and prominent genome instability along with biallelic inactivation of TP53, but none of them were found in organoids or the CCC component. The PDC proved sensitive to major chemotherapeutic agents and MET inhibitors. These observations clearly indicated that the PDC, designated as YMC7, can be used as a novel cCCC cell line and provide novel insights into the pathogenesis of mixed cervical adenocarcinoma. As a valuable resource for rare cancer, it will likely contribute to investigations in many fields.


Assuntos
Adenocarcinoma de Células Claras/patologia , Colo do Útero/patologia , Organoides , Cultura Primária de Células , Neoplasias do Colo do Útero/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Animais , Linhagem Celular Tumoral , Colo do Útero/citologia , Colo do Útero/cirurgia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Esferoides Celulares , Neoplasias do Colo do Útero/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
17.
mBio ; 10(4)2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289181

RESUMO

Neisseria gonorrhoeae is a significant threat to global health for which a vaccine and novel treatment options are urgently needed. Glycans expressed by human cells are commonly targeted by pathogens to facilitate interactions with the host, and thus characterization of these interactions can aid identification of bacterial receptors that can be exploited as vaccine and/or drug targets. Using glycan array analysis, we identified 247 specific interactions between N. gonorrhoeae and glycans representative of those found on human cells. Interactions included those with mannosylated, fucosylated, and sialylated glycans, glycosaminoglycans (GAGs), and glycans terminating with galactose (Gal), N-acetylgalactosamine (GalNAc), and N-acetylglucosamine (GlcNAc). By investigating the kinetics of interactions with selected glycans, we demonstrate that whole-cell N. gonorrhoeae has a high affinity for mannosylated glycans (dissociation constant [KD ], 0.14 to 0.59 µM), which are expressed on the surface of cervical and urethral epithelial cells. Using chromatography coupled with mass spectrometric (MS) analysis, we identified potential mannose-binding proteins in N. gonorrhoeae Pretreatment of cells with mannose-specific lectin (concanavalin A) or free mannose competitor (α-methyl-d-mannopyranoside) substantially reduced gonococcal adherence to epithelial cells. This suggests that N. gonorrhoeae targets mannosyl glycans to facilitate adherence to host cells and that mannosides or similar compounds have the potential to be used as a novel treatment option for N. gonorrhoeae IMPORTANCE Multidrug-resistant strains of Neisseria gonorrhoeae are emerging worldwide, and novel treatment and prevention strategies are needed. Glycans are ubiquitously expressed by all human cells and can be specifically targeted by pathogens to facilitate association with host cells. Here we identify and characterize the N. gonorrhoeae host-glycan binding profile (glycointeractome), which revealed numerous interactions, including high-affinity binding to mannosyl glycans. We identify gonococcal potential mannose-binding proteins and show that N. gonorrhoeae uses mannosyl glycans expressed on the surface of cervical and urethral epithelia to facilitate adherence. Furthermore, a mannose-binding lectin or a mannoside compound was able to reduce this adherence. By characterizing the glycointeractome of N. gonorrhoeae, we were able to elucidate a novel mechanism used by this important pathogen to interact with human cells, and this interaction could be exploited to develop novel therapeutics to treat antibiotic-resistant gonorrhea.


Assuntos
Aderência Bacteriana/fisiologia , Colo do Útero/citologia , Células Epiteliais/microbiologia , Interações Hospedeiro-Patógeno , Neisseria gonorrhoeae/metabolismo , Polissacarídeos/metabolismo , Uretra/citologia , Aderência Bacteriana/efeitos dos fármacos , Células Cultivadas , Concanavalina A/farmacologia , Células Epiteliais/efeitos dos fármacos , Feminino , Gonorreia/microbiologia , Humanos , Masculino , Lectina de Ligação a Manose/metabolismo , Metilglicosídeos/farmacologia , Análise em Microsséries , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/patogenicidade
18.
Artigo em Inglês | MEDLINE | ID: mdl-31152639

RESUMO

INTRODUCTION: The aim of the study was to compare the results of two human papillomavirus (HPV) diagnostic techniques: human papillomavirus deoxyribonucleic acid (HPV DNA) testing and human papillomavirus E6/E7 messenger ribonucleic acid (HPV E6/E7 mRNA) testing in women with squamous cell abnormalities of the uterine cervix. MATERIAL AND METHODS: Comparative prospective study, conducted in the period from January 2016 to June 2017 of 128 sexually active women, age groups of 20 to 59 years (40.50 ± 10.85) with squamous cell abnormalities on the cervical cytology. All patients were subject to: HPV DNA testing, HPV E6/E7 mRNA testing and colposcopic cervical biopsy with endocervical curettage for histopathologycal analysis. HPV DNA testing was done using multiplex polymerase chain reaction (PCR) and reverse hybridization methods. HPV E6/E7 mRNA testing was done using real-time PCR method. RESULTS: Data analysis showed an association between the results of HPV DNA testing and HPV E6/E7 mRNA testing (p˂0.0001). The concordance between the results of both tests was moderate (55.47%). The results show that HPV E6/E7 mRNA testing had a higer specificity 88.89% and positive predictive value (PPV) 93.59% for HSIL + invasive squamous cell carcinoma compared to HPV DNA testing that had specificity of 55.56% and PPV 84.61%, respectively. CONCLUSION: The results of our study suggested that HPV E6/E7 mRNA testing is more specific and has a higher positive predictive value than HPV DNA testing and that viral oncoproteins E6 and E7 are superior biomarkers for the detection of high-risk HPV-associated squamous intraepithelial lesions of the uterine cervix.


Assuntos
Colo do Útero/anormalidades , Células Epiteliais/patologia , Testes de DNA para Papilomavírus Humano/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Adulto , Colo do Útero/citologia , Células Epiteliais/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Mensageiro/genética , RNA Viral/genética , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
19.
J Virol ; 93(17)2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31189705

RESUMO

Epidemiological data confirm a much higher incidence of high-risk human papillomavirus 16 (HPV16)-mediated carcinogenesis of the cervical epithelium than for other target sites. In order to elucidate tissue-specific responses to virus infection, we compared gene expression changes induced by productive HPV16 infection of cervical, foreskin, and tonsil organotypic rafts. These rafts closely mimic persistent HPV16 infection, long before carcinogenesis sets in. The total number of gene expression changes varied considerably across the tissue types, with only 32 genes being regulated in common. Among them, we confirmed the Kelch-like family protein KLHL35 and the laminin-5 complex to be upregulated and downregulated, respectively, in all the three tissues. HPV16 infection induces upregulation of genes involved in cell cycle control, cell division, mitosis, DNA replication, and DNA damage repair in all the three tissues, indicative of a hyperproliferative environment. In the cervical and tonsil epithelium, we observe significant downregulation of genes involved in epidermis development, keratinocyte differentiation, and extracellular matrix organization. On the other hand, in HPV16-positive foreskin (HPV16 foreskin) tissue, several genes involved in interferon-mediated innate immunity, cytokine signaling, and cellular defenses were downregulated. Furthermore, pathway analysis and experimental validations identified important cellular pathways like STAT1 and transforming growth factor ß (TGF-ß) to be differentially regulated among the three tissue types. The differential modulation of important cellular pathways like TGF-ß1 and STAT1 can explain the sensitivity of tissues to HPV cancer progression.IMPORTANCE Although the high-risk human papillomavirus 16 infects anogenital and oropharyngeal sites, the cervical epithelium has a unique vulnerability to progression of cancer. Host responses during persistent infection and preneoplastic stages can shape the outcome of cancer progression in a tissue-dependent manner. Our study for the first time reports differential regulation of critical cellular functions and signaling pathways during productive HPV16 infection of cervical, foreskin, and tonsil tissues. While the virus induces hyperproliferation in infected cells, it downregulates epithelial differentiation, epidermal development, and innate immune responses, according to the tissue type. Modulation of these biological functions can determine virus fitness and pathogenesis and illuminate key cellular mechanisms that the virus employs to establish persistence and finally initiate disease progression.


Assuntos
Colo do Útero/virologia , Prepúcio do Pênis/virologia , Perfilação da Expressão Gênica/métodos , Papillomavirus Humano 16/patogenicidade , Tonsila Palatina/virologia , Infecções por Papillomavirus/genética , Diferenciação Celular , Linhagem Celular Tumoral , Colo do Útero/química , Colo do Útero/citologia , Feminino , Prepúcio do Pênis/química , Prepúcio do Pênis/citologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Papillomavirus Humano 16/genética , Humanos , Queratinócitos/química , Queratinócitos/citologia , Queratinócitos/virologia , Masculino , Análise em Microsséries , Especificidade de Órgãos , Tonsila Palatina/química , Tonsila Palatina/citologia , Infecções por Papillomavirus/virologia , Transdução de Sinais , Replicação Viral
20.
Eur J Obstet Gynecol Reprod Biol ; 238: 157-163, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31158573

RESUMO

OBJECTIVE: Cervical ripening resembles an inflammatory process in many aspects, involving invasion of inflammatory cells, collagen breakdown and remodelling of the extracellular matrix. Mast cells produce a variety of inflammatory agents and are attributed a functional role in cervical ripening. The aim of this study was to examine if cervical mast cells are increased in number and stimulated during pregnancy. STUDY DESIGN: Cervical biopsies were obtained with a biopsy needle prior to surgical termination of pregnancy in the first trimester, surgery for first-trimester miscarriage, elective caesarean section, and benign gynaecological surgery in non-pregnant women. After fixation, semithin sections were prepared and stained with toluidine blue. The number of mast cells was counted under a light microscope and their secretory activity was scored (0.5-4) according to specified criteria and further visualised with electron microscopy. For pairwise comparison between groups Fisher's nonparametric permutation test was used. RESULTS: The number of mast cells was increased from 3.4 ± 1.65 mast cells per 10 visual fields in non-pregnant women to 7.70 ± 0.35 per 10 visual fields in first trimester control women (p < 0.05). The highest number of mast cells was observed at term with 10.8 ± 2.1 per 10 visual fields, a number that was significantly higher than in first trimester control women (p < 0.05). At term mast cell activity scores were 3.39 ± 0.37 compared with 2.69 ± 0.27 in control first trimester women and 2.21 ± 0.86 in women with missed miscarriage (p < 0.05). The percentage of mast cells with activity score 4 was significantly higher at term compared with in the first trimester. Free mast cell granules were predominantly observed in areas with disorganized collagen fibres. CONCLUSION: The findings confirm that an increased influx of mast cells to the cervix occurs during pregnancy. The stimulated mast cell secretory activity in conditions associated with cervical tissue remodelling, such as term pregnancy and symptomatic miscarriage, provides further evidence that mast cells play a physiological role in cervical ripening.


Assuntos
Maturidade Cervical , Colo do Útero/citologia , Mastócitos/fisiologia , Aborto Retido/patologia , Adulto , Feminino , Humanos , Mastócitos/ultraestrutura , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
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