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Methods Mol Biol ; 1856: 87-101, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30178247


Acute leukemias are hematologic malignancies with aggressive behavior especially in adult population. With the introduction of new gene expression and sequencing technologies there have been advances in the knowledge of the genetic landscape of acute leukemias. A more detailed analysis allows for the identification of additional alterations in epigenetic regulators that have a profound impact in cellular biology without changes in DNA sequence. These epigenetic alterations disturb the physiological balance between gene activation and gene repression and contribute to aberrant gene expression, contributing significantly to the leukemic pathogenesis and maintenance. We review epigenetic changes in acute leukemia in relation to what is known about their mechanism of action, their prognostic role and their potential use as therapeutic targets, with important implications for precision medicine.

Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Metilação de DNA , Epigenômica/métodos , Estudos de Associação Genética , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Histonas/metabolismo , Humanos , Modelos Biológicos , Terapia de Alvo Molecular , Mutação , Processamento de Proteína Pós-Traducional , Resultado do Tratamento
Cancer Prev Res (Phila) ; 11(9): 581-592, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29991579


In 2012, Colombia launched human papillomavirus (HPV) vaccination program for girls ages 9 to 12, and in 2013, the target age was expanded to 9 to 17 years. Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs. However, the data on HPV prevalence in young ages are very limited. The purpose of this study was to determine the prevalence of HPV infection and the distribution of genotypes in a group of nonvaccinated women ages 18 to 25 years old in three Colombian cities as baseline for the monitoring of the HPV national vaccination program. A total of 1,782 sexually active women were included. Cervical smear samples were collected to perform the Pap smear and HPV DNA detection using a Linear Array HPV assay. Of the 1,782 specimens analyzed, 60.3% were positive for any HPV type; 42.2% were positive for high-risk HPV (HR-HVP) types, and 44.4% for low-risk HPV (LR-HPV) types. Multiple and single infections were identified in 37.1% and 23.2% of samples, respectively. HR-HPV types -16, -52, and -51 were the most predominant with proportions of 11.3%, 7.92%, and 7.9%, correspondingly. The prevalence for HR-HPV 16/18 was 14.4%. HR-HPV prevalence in women with abnormal cytology (75.16%) was higher than in women with normal cytology (38.6%). In conclusion, a high prevalence of HR-HPV was observed among younger women. This HPV type-specific prevalence baseline may be used to monitor postvaccination longitudinal changes and to determine its impact on HPV-related disease incidence in Colombia population. Cancer Prev Res; 11(9); 581-92. ©2018 AACR.

Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Colo do Útero/patologia , Colo do Útero/virologia , Colômbia/epidemiologia , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Técnicas de Genotipagem , Humanos , Teste de Papanicolaou , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vacinação , Esfregaço Vaginal , Adulto Jovem
Rev. colomb. cancerol ; 21(2): 113-125, abr.-jun. 2017. tab
Artigo em Espanhol | LILACS | ID: biblio-900460


Resumen El tratamiento para cáncer de próstata localizado (prostatectomía radical o radioterapia) ofrece unas altas tasas de curación; sin embargo, del 20 al 30% de los casos desarrollan recurrencia bioquímica. Actualmente, existen factores clínicos y patológicos que ayudan a predecir recurrencia; no obstante tanto el carácter heterogéneo de estos tumores, las diferencias en los tiempos de progresión de cáncer localizado a metastásico como la resistencia al tratamiento han dado lugar a imprecisiones en la predicción del pronóstico y a tratamientos insuficientes o excesivos. Debido a esto se han estudiado biomarcadores con el fin de estratificar más acertadamente el riesgo y mejorar las decisiones de tratamiento de una manera adecuada y oportuna. Este manuscrito presenta una revisión de marcadores moleculares de pronóstico que se han propuesto en los pacientes con cáncer de próstata localizado, lo que podría permitir establecer con mayor precisión el riesgo de recurrencia de la enfermedad.

Abstract Treatment for localised prostate cancer (radical prostatectomy or radiotherapy), offers high cure rates; nevertheless, 20% to 30% of the cases develop biochemical recurrence. There are clinical and pathological features that are currently being used to predict recurrence of the disease. However, tumour heterogeneity in prostate cancer, along with differences in time of progression to metastasis and treatment resistance, have led to inaccuracies in predicting the risk of biochemical relapse, and therefore, misleading in treatment decisions. Because of this, many genetic markers have been studied in order to refine risk stratification and improve treatment decisions in a suitable and opportune manner. This paper presents a review of molecular prognostic markers that have been proposed in patients with localised prostate cancer, which potentially could allow establishing the risk of recurrence of the disease more accurately.

Humanos , Neoplasias da Próstata , Biomarcadores , Marcadores Genéticos , Previsões , Metástase Neoplásica
J Exp Clin Cancer Res ; 36(1): 37, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28245840


BACKGROUND: Survival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction. METHODS: To improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples. RESULTS: Both techniques were correlated to stratify patients into prognostic groups. An inverse relationship between survival and expression of the three-genes signature was observed and an immunophenotypic profile associated with clinical outcome was identified. Markers CD10 and CD20 were correlated with simultaneous overexpression of ID1, ID3 and IGJ. Patients with simultaneous expression of the poor prognosis gene signature and overexpression of CD10 or CD20, had worse Event Free Survival and Overall Survival than patients who had either the poor prognosis gene expression signature or only CD20 or CD10 overexpressed. CONCLUSION: By utilizing the combined evaluation of these two immunophenotypic markers along with the poor prognosis gene expression signature, the risk stratification can be significantly strengthened. Further studies including a large number of patients are needed to confirm these findings.

Antígenos CD20/metabolismo , Cadeias J de Imunoglobulina/genética , Proteína 1 Inibidora de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas de Neoplasias/genética , Neprilisina/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/classificação , Adolescente , Adulto , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
Cancer Prev Res (Phila) ; 9(9): 766-71, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27417431


Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types. Cancer Prev Res; 9(9); 766-71. ©2016 AACR.

Colo do Útero/virologia , DNA Viral/análise , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Urina/virologia , Adulto , Colômbia , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Esfregaço Vaginal , Adulto Jovem
J Exp Clin Cancer Res ; 35: 64, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27044543


BACKGROUND: B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. METHODS: We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). RESULTS: We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. CONCLUSIONS: Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

Hispano-Americanos/genética , Cadeias J de Imunoglobulina/genética , Proteína 1 Inibidora de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Regulação para Cima , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
Rev. colomb. cancerol ; 18(1): 27-40, ene.-mar. 2014. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-726885


El cáncer es una enfermedad compleja de etiología desconocida. Factores genéticos y epigenéticos se asocian al incremento en el riesgo de desarrollar esta enfermedad. A pesar del avance en los tratamientos tradicionales contra el cáncer, el pronóstico de los pacientes no ha mejorado significativamente. Estudios en la patogénesis molecular del cáncer han evidenciado la existencia de dianas moleculares con potencial terapéutico que permiten trasladar los conocimientos de la investigación básica a la clínica implementando nuevas terapias para el beneficio del paciente. El conocimiento del genoma viral, su función, replicación y los mecanismos de infección a la célula tumoral han permitido el desarrollo de la terapia génica viral que puede ser la herramienta ideal para el tratamiento del cáncer. Este artículo revisa diferentes metodologias desarrolladas para el diseno de una terapia génica contra el cáncer, abordada desde diferentes contextos biológicos, y su aplicación clínica para el tratamiento del cáncer.

Cancer is a complicated disease of unknown etiology. Genetic and epigenetic factors are associated with an increased risk for developing this disease. Despite the progress in the traditional cancer therapies, the prognosis of patients has not improved significantly. Studies on the molecular pathogenesis of cancer have demonstrated the existence of molecular targets with therapeutic potential. Furthermore, knowledge of the viral genome function and replication, as well as of the mechanisms of tumor cell infection, have made it possible to develop an ideal tool for gene therapy against cancer and thus, enable the transfer of knowledge from basic to clinical research for the benefit of patients. This article reviews different methodologies developed to design a cancer gene therapy and its clinical application for treating cancer, addressed from various biological contexts.

Humanos , Terapêutica , Terapia Genética , Genes Neoplásicos , Neoplasias , Adjuvantes Imunológicos , Terapia Viral Oncolítica
Rev. colomb. cancerol ; 17(3): 103-110, jul.-sep. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-727561


Objective: To analyze whether the immune response to HPV-16, -18, -31, -45 and -58 capsids in women vaccinated with the quadrivalent vaccine induces cross-reactivity against other HPV virus-like particles (VLPs). Methods: A total of 88 women aged between 18 and 27 years attending the HPV clinic at the Instituto Nacional de Cancerología were enrolled and vaccinated against HPV. Follow-up visits were scheduled at months 7, 12, and 24. Samples were collected for cytology, HPV-DNA typing, and detection of HPV antibodies. IgG antibodies were measured by ELISA using HPV-16, -18, -31, -45, and -58 VLPs. HPV-DNA detection was done by GP5+/GP6+PCR-ELISA and HPV typing was performed by Reverse Line-Blot assay. Results: Pre-vaccination, the seroprevalence of HPV-16, -18, -31, -45, and -58 was 39%, 31.7%, 15.9%, 31.7%, and 23.2%, respectively. One month post-vaccination, the seroprevalence increased close to 100% for all types. At month 24, this response was maintained only for HPV-16 and -18. For HPV-31, -45 and -58, the seroprevalence decreased to below 50%. The prevalence of HPV DNA types 16, 18 and 58 before vaccination was little changed 1 month after vaccination. No new infections were observed at 24 months. For HPV-16 and -18 related types, no differences were observed before vaccination and at month 24. For other high-risk HPV types, the prevalence increased 18 months post-vaccination (15.5%) compared with pre-vaccination (9.8%). Conclusion: Immune response to all HPV types increased after vaccination, but this increase was maintained only for HPV-16 and -18. These results suggest a possible cross-reactivity against HPV types 31, 45 and 58, but this cross-reactivity wanes with time. © 2012 Instituto Nacional de Cancerología. Publicado por Elsevier España, S.L. Todos los derechos reservados.

Objetivo: Analizar si la respuesta inmune hacia las cápsides del VPH tipos 16, 18, 31, 45 y 58 en mujeres que recibieron la vacuna tetravalente induce reactividad cruzada hacia otros tipos virales. Métodos: Ochenta y ocho mujeres entre 18 y 27 años, asistentes al Grupo VPH del Instituto Nacional de Cancerología, recibieron la vacuna de VPH. Visitas de seguimiento en los meses 7, 12 y 24. Se tomaron muestras para prueba de Papanicolaou, tipificación de VPH y detección de anticuerpos. Los anticuerpos se detectaron por ELISA, usando VLP-VPH. La detección del ADN-VPH se realizó por Reverse Line Blot. Resultados: Prevacunación, la seroprevalencia de VPH tipos 16, 18, 31, 45 y 58 fue de 39, 31,7, 15,9, 31,7 y 23,2%, respectivamente. Al mes 7 aumentó cerca del 100% para todos los tipos. Al mes 24 esta respuesta se mantuvo para VPH tipos 16 y 18. Para VPH tipos 31, 45 y 58 disminuyó por debajo del 50%. La prevalencia de ADN-VPH tipos 16, 18 y 58 tuvo poca variación antes y un mes después de la vacunación. Al mes 24, no se observaron nuevas infecciones. Para VPH tipos 16 y 18, no se observaron diferencias antes ni al mes 24. En otros tipos de HR-VPH aumentó la prevalencia al mes 24 (15,5%), comparada con la prevacunación (9,8%). Conclusión: Se observó un aumento de la respuesta inmune a todos los tipos de VPH después de la vacunación, pero esta se mantuvo solamente para los VPH tipos 16 y 18. Los resultados sugieren una posible reactividad cruzada contra VPH tipos 31, 45 y 58. Sin embargo, esta reactividad cruzada disminuye con el tiempo.

Humanos , Feminino , Adolescente , Adulto , Papiloma , Estudos Soroepidemiológicos , Prevalência , Vacinação , Ensaio de Imunoadsorção Enzimática , Papillomavirus Humano 16 , Papillomavirus Humano 31
Rev. colomb. cancerol ; 16(1): 16-26, mar. 2012. graf
Artigo em Inglês | LILACS | ID: lil-662986


Objective: To understand the biologic and clinical importance of intratumoral natural killer cells CD16+CD56+CD3 and NKT CD16+CD56+CD3 cells in immune surveillance against cervical cancer. Methods: To understand the significance of NK (CD16+CD56+CD3-) and NKT (CD16+CD56+CD3-) in immune surveillance against cervical cancer, we analysed 39 peripheral blood and 30 biopsy samples from cervical cancer patients, and 40 peripheral blood and 5 biopsy samples from healthy women with normal cytology. The frequencies of NK and NKT and HLA-I expression in keratinocytes were analysed by flow cytometry. Results: In peripheral blood, a higher frequency of NK was observed in the patient group compared with the controls (p=0.002). However, this increase was not reflected in TILs (p=0,095). A significant reduction of HLA-I expression was observed in the patient group compared to the control group (p=0.019). A low number of NK infiltrated was observed in tumors of patients with HLA-I down regulation, but it was not significant (p=0.374). A low number of NK infiltration was associated with shorter survival, but it was not significant (p=0.275). Conclusions: Our results show that although in peripheral blood an increase in NK population was observed in patient group, this increase was not reflected in TILs. It is possible that this inefficient migration of NK´s into the tumor milieu could be related to the expression of immunosuppressive cytokines, in particular IL-10.

Objetivo: Entender la importancia biológica y clínica de las células intratumorales natural killer (NK) CD16+CD56+CD3- y de las células natural killer T (NKT) CD16+CD56+CD3- en la inmunovigilancia del cáncer de cuello uterino (CCU). Métodos: Para comprender el papel de las NK (CD16+CD56+CD3-) y de las células natural killer T (NKT) (CD16+CD56+CD3-) en la inmunovigilancia del CCU, se analizaron 39 muestras de sangre periférica (SP) y 30 biopsias de pacientes con CCU, así como de 40 muestras de SP y 5 biopsias de cuello uterino de mujeres con citología normal. Las frecuencias de NK y NKT y la expresión de HLA-I se analizaron por citometría de flujo. Resultados: Se observó una mayor frecuencia de NK en SP en el grupo de pacientes comparado con el grupo control (p = 0,002). Sin embargo, este aumento no se reflejó en TIL (p = 0,095). Una reducción significativa de HLA-I se observó en el grupo de pacientes (p = 0,019). Esta disminución se asoció una disminución en el número de NK, pero no fue significativa (p = 0,374). Un bajo número de NK se asoció con una menor supervivencia, pero no fue significativo (p = 0,275). Conclusiones: Nuestros resultados muestran que aunque en SP se observa un incremento de NK, este no se refleja en los TIL. Es posible que este tráfico ineficiente de células NK hacia el tumor esté alterado por la expresión de citoquinas inmunosupresoras, en particular IL-10.

Humanos , Feminino , Adulto , Estudos de Casos e Controles , Células Matadoras Naturais/citologia , Células Matadoras Naturais/classificação , Células Matadoras Naturais/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/sangue , Citometria de Fluxo/métodos , Citometria de Fluxo , Colômbia/epidemiologia
Pathobiology ; 79(2): 72-83, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22213066


Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.

Neoplasia Intraepitelial Cervical/imunologia , Antígenos HLA-G/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Interleucina-10/metabolismo , Neoplasias do Colo do Útero/imunologia , Adulto , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
Int J Gynecol Cancer ; 22(2): 303-10, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22228426


OBJECTIVE: The study's objective was to estimate human papillomavirus (HPV) genotype-specific seroprevalence to determine population HPV exposure and inform vaccine policy. METHODS: This study is a cross-sectional prevalence survey of 878 women of Pueblorrico, a rural town of Colombia. A standardized questionnaire was used to obtain information on demographic characteristics, sexual and reproductive history, and smoking habits. Seropositivity to HPV-16, -18, -31, and -58 was determined by virus-like particles in an enzyme-linked immunosorbent assay. RESULTS: Overall seropositivity to any HPV genotype was 27.9%. The combined seroprevalence of women 15 to 19 and 20 to 24 years old was 35.4% (95% confidence interval [CI], 25.9-46.2) and 36.0% (95% CI, 27.7-45.3), respectively. Seroprevalence for HPV-16 was 17% (95% CI, 14.6-19.6); for HPV-18, 9.8% (95% CI, 8.0-11.9); for HPV-31, 11.4% (95% CI, 9.5-13.7); and for HPV 58, 12.5% (95% CI, 10.5-14.9). Higher HPV seropositivity was associated with the lifetime number of occasional sexual partners (odds ratio, 3.05; 95% CI, 1.26-7.37) and having more than 2 regular sexual partners (odds ratio, 3.00; 95% CI, 1.21-7.45) in women younger than 44 and older than 45 years old, respectively. Use of oral contraceptives and tobacco/cigarettes was significantly associated with reduced HPV seropositivity in women older than 45 but not in women younger than 44 years old. CONCLUSIONS: Human papillomavirus seropositivity is associated with measures of sexual behavior, particularly a greater lifetime number of sexual partners. Hormonal and tobacco/cigarette use may be factors influencing the HPV seropositivity in women older than 45 years old.

Alphapapillomavirus/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Comportamento do Adolescente , Adulto , Idoso , Alphapapillomavirus/genética , Colômbia/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Papillomavirus Humano 31/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/virologia , População Rural , Estudos Soroepidemiológicos , Comportamento Sexual , Inquéritos e Questionários , Adulto Jovem
Biomedica ; 30(2): 251-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20890572


INTRODUCTION: Studies using Western Helicobacter pylori strains have shown that a risk factor for gastric cancer is the number of EPIYA-C motifs in the cytotoxin-associated A protein. CagA is delivered into epithelial cells, where it becomes tyrosine phosphorylated in their EPIYA repeats and induces cytoskeleton rearrangements. OBJECTIVES: The objective of this study was to evaluate H. pylori cagA positive strains isolated from Colombian patients with gastroduodenal diseases for the number of EPIYA-C repeats in cagA and their ability to induce cytoskeleton rearrangements in epithelial cells. MATERIALS AND METHODS: We analyzed the 3´ EPIYA repeats region of cagA by PCR in 93 H. pylori cagA positive strains from 49 patients with gastritis, 17 with gastric cancer, and 24 with duodenal ulcer. AGS cells exposed to the various H. pylori isolates were evaluated for rearrangements in their cytoskeleton. RESULTS: Strains with one EPIYA-C were the most frequent in gastritis and duodenal ulcer patients. Strains with three EPIYA-C were mainly found in gastric cancer. We found a significantly higher risk of gastric cancer for individuals infected with strains harboring three EPIYA-C motifs (OR=12.4, CI95%: 2.32-66.3). Strains from gastric cancer showed significantly higher percentages of induction of cytoskeleton rearrangements in comparison with those from gastritis (p Mann-Whitney<0.005). CONCLUSIONS: H. pylori strains with three EPIYA-C repeats can confer an increased risk of cancer to infected individuals.

Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Helicobacter pylori/genética , Adulto , Idoso , Colômbia , Células Epiteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estômago/citologia , Adulto Jovem
Biomédica (Bogotá) ; 30(2): 251-258, jun. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-560973


Introduction. Studies using Western Helicobacter pylori strains have shown that a risk factor for gastric cancer is the number of EPIYA-C motifs in the cytotoxin-associated A protein. CagA is delivered into epithelial cells, where it becomes tyrosine phosphorylated in their EPIYA repeats and induces cytoskeleton rearrangements. Objectives. The objective of this study was to evaluate H. pylori cagA positive strains isolated from Colombian patients with gastroduodenal diseases for the number of EPIYA-C repeats in cagA and their ability to induce cytoskeleton rearrangements in epithelial cells. Materials and methods. We analyzed the 3’ EPIYA repeats region of cagA by PCR in 93 H. pylori cagA positive strains from 49 patients with gastritis, 17 with gastric cancer, and 24 with duodenal ulcer. AGS cells exposed to the various H. pylori isolates were evaluated for rearrangements in their cytoskeleton. Results. Strains with one EPIYA-C were the most frequent in gastritis and duodenal ulcer patients. Strains with three EPIYA-C were mainly found in gastric cancer. We found a significantly higher risk of gastric cancer for individuals infected with strains harboring three EPIYA-C motifs (OR=12.4, CI95%: 2.32-66.3). Strains from gastric cancer showed significantly higher percentages of induction of cytoskeleton rearrangements in comparison with those from gastritis (p Mann-Whitney<0.005). Conclusions. H. pylori strains with three EPIYA-C repeats can confer an increased risk of cancer to infected individuals.

Introducción. En los aislamientos de Helicobacter pylori del hemisferio occidental, se ha observado que el número de repeticiones EPIYA-C en la proteína CagA es un factor de riesgo para cáncer gástrico. La proteína CagA es introducida en la célula epitelial y, posteriormente, es fosforilada en las tirosinas presentes en los motivos EPIYA e induce rearreglos en el citoesqueleto. Objetivos. Nuestro propósito fue evaluar el número de repeticiones EPIYA-C y la habilidad para inducir rearreglos en el citoesqueleto en los aislamientos de H. pylori positivos para cagA, provenientes de pacientes colombianos con enfermedad gastroduodenal. Materiales y métodos. Mediante PCR, se analizó la región 3´ que contiene las repeticiones EPIYA-C, en 93 aislamientos de H. pylori positivos para cagA provenientes de 49 pacientes con gastritis, 17 con cáncer gástrico y 24 con úlcera duodenal. Los rearreglos del citoesqueleto se evaluaron mediante cultivos simultáneos de células AGS con las cepas de H. pylori.Resultados. En gastritis y úlcera duodenal se observó la mayor frecuencia de aislamientos con EPIYA C; los aislamientos con tres repeticiones EPIYA-C se encontraron con mayor frecuencia en cáncer gástrico. Encontramos un riesgo de cáncer gástrico significativamente mayor para individuos infectados con cepas con tres repeticiones EPIYA-C (OR=12,4; IC95% 2,32-66,3). Los aislamientos provenientes de cáncer gástrico mostraron mayores porcentajes de inducción de rearreglos en el citoesqueleto que los observados con aislamientos provenientes de gastritis (prueba de Mann-Whitney menor de 0,005). Conclusiones. La infección con cepas de H. pylori con tres repeticiones EPIYA-C puede conferir un mayor riesgo de desarrollar cáncer gástrico.

Gastrite , Helicobacter pylori , Polimorfismo Genético , Úlcera Duodenal , Neoplasias Gástricas
Rev. colomb. cancerol ; 13(2): 77-87, jun. 2009. graf, tab
Artigo em Espanhol | LILACS | ID: lil-661678


Objetivo: Caracterizar la respuesta IgG e IgA hacia VLP (partículas semejantes a virus) del virus del papiloma humano (VPH) 16, 31 y 58 y determinar su asociación con la eliminación de la infección. Métodos: Se incluyeron 186 mujeres con citología normal participantes en un estudio de cohorte sobre la historia natural de la infección por VPH. Se evaluaron tres grupos: control (negativas para ADN VPH, n=146), eliminación (positivas al ingreso y negativas durante el seguimiento, n=25) y persistencia (positivas durante el seguimiento, n=15). Los anticuerpos IgG e IgA hacia VLP VPH 16, 31 y 58 se analizaron mediante ELISA. Resultados: En la primera visita, se observó en el grupo de eliminación una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16. Esta prevalencia estuvo acompañada de mayores niveles de anticuerpos en este grupo, en comparación con los niveles observados en el grupo de persistencia (media DO405 nm 0,665 vs. 0,290, respectivamente). En contraste, en la quinta visita, se observó una mayor seroprevalencia de anticuerpos IgG hacia VLP VPH 16 y 58 en el grupo de persistencia (p=0,001 y p=0,003, respectivamente). Esta respuesta se correlacionó con mayores niveles de anticuerpos en esta visita (media DO405 nm 0,653 y 0,532, respectivamente), en comparación con los niveles de anticuerpos observados en la primera visita (media DO405 nm 0,290 y 0,362, respectivamente). Conclusiones: La presencia de altos niveles de anticuerpos IgG hacia VPH 16 y 58 durante la infección podría estar asociada con la eliminación de la infección.

Objective: To profile IgG and IgA response to the VLP ( virus-like particles) of the human papillomaviruses (HPV) 16, 31 and 58 and to assess the possibility that they may be related to eliminating infection. Methods: A group of 186 women with normal cytology, participants in a cohort study on the natural history of HPV infection, were selected. Three groups were evaluated: control (DNA HPV, n=146 negative), elimination (positive at outset and negative during follow-up, n=25), and persistance (positive during follow-up, n=15). The IgG and IgA antibodies against HPV-VLP 16, 31, and 58 were submitted to ELISA analysis. Results: During the initial visit greater IgG antibody seroprevalence against HPV16-VLP was observed among the elimination group. This prevalence was combined with greater antibody levels in this group in comparison with the levels found among members of the persistence (mean DO405 nm 0.665 vs. 0.290, respectively). In contrast, during the fifth visit, there was greater IgG antibody seroprevalence against HPV-PLV 16 and 58 among the persistance group (p=0.001 and p=0.003, respectively). This response correlated with greater anitbody levels on this visit (mean DO 405 nm 0.653 and 0.532, respectively) in comparison with the antibody levels observed on the first visit (mean DO 405 nm 0.290 and0.362, respectively). Conclusion: High levels of IgG antibodies working against HPV 16 and 58 during infection phase may be associated with elimination of infection.

Humanos , Adulto , Feminino , Idoso , Estudos de Casos e Controles , Antígenos HLA-D , Imunoglobulina A , Imunoglobulina G , Controle de Infecções , Neoplasias do Colo do Útero , Colômbia , Ensaio de Imunoadsorção Enzimática/métodos , Reação em Cadeia da Polimerase/métodos
Rev. colomb. cancerol ; 12(4): 173-180, 20081200.
Artigo em Inglês | LILACS | ID: lil-507219


Objetivo: Examinar la asociación entre la respuesta celular anti-VPH y la expresión de HLA clase I, HLA-G e IL-10 en céluals tumorales. Materiales y métodos: Linfocitos fueron aislados de 18 pacientes con CCU y estimulados con células dendríticas pulsadas con la proteína E7VPH-16 o directamente con péptidos sintéticos: E751-70´E765-84yE779-98. La células fueron marcadas para CD4,CD69, citoquinas intracelulares IFN-y e IL-4 y analizadas por citometría. La expresión de HLA-G e IL-10 fue analizada por inmunohistoquimica. Resultados: Una pérdida total de la expresión de HLA clae I se observó en 11/18 y regulación negativamente en 4/18 pacientes. La expresión HLA-G se observó EN 11/18 y regulación negativamente en 4/18 pacientes mientras que la expresión IL-10 en 6/17 pacientes. Se observó una asociación inversa entre la expresión de IL-10 y la falta de una respuesta inmune especifica (p=0.041). Ninguna asociación fue observada entre la expresión de HLA clase I o la expresión de HLA-G con la respuesta inmune. Conclusiones: Nuestros resultados subrayan la importancia de otros factores inmunes, como la expresión de IL-10, que podrían influir en la respuesta antitumoral. Estos resultados pueden tener implicaciones importantes durante el desarrollo de nuevas estrategias inmunoterapéuticas.

Colo do Útero , Antígenos HLA , Neoplasias , Linfócitos T , Evasão Tumoral
Biomedica ; 25(1): 34-45, 2005 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-15962900


BACKGROUND: The hepatitis C virus (HCV) commonly causes persistent infection. One of the viral mechanisms in preventing viral clearance is the ability of HCV to induce functional alterations of the immune system cells, specifically of dendritic cells. Viral proteins producing the dendritic cell functional alterations have been identified as the HCV core protein, which makes up the capsid structural unit. OBJECTIVE: One of the limitations to evaluate core protein properties is the difficulty in obtaining and purifying the complete protein--consisting of 191 amino acids. The aim of the current study was to produce and purify the recombinant core protein in a eukaryotic system, and to evaluate its effect in human dendritic cell cultures. RESULTS: The core protein p23 isoform was expressed in a baculovirus system and purified using isoelectric point separation and electroelution. The purity of the core protein was confirmed by silver stain and Western blot. These analyses showed the presence of two bands that correspond to p23 and p21 isoforms of core protein as previously reported. CONCLUSION: The expressed protein differed from naive core protein is terms of molecular weight, isoforms and subcellular localization. The procedures developed for core protein are applicable for expression of other membrane-associated proteins produced in eukaryotic systems.

Hepacivirus/genética , Hepatite C/genética , Proteínas do Core Viral/biossíntese , Baculoviridae/química , Bioensaio , Western Blotting , Proteínas do Capsídeo/biossíntese , Proteínas do Capsídeo/genética , Hepacivirus/fisiologia , Hepatite C/fisiopatologia , Humanos , Proteínas do Core Viral/genética
Biomédica (Bogotá) ; 25(1): 34-45, mar. 2005. ilus
Artigo em Espanhol | LILACS | ID: lil-421511


Introducción. La infección por el virus de la hepatitis C (VHC) se caracteriza por la alta frecuencia de infección persistente. La capacidad del VHC para inducir alteraciones en la función de las células del sistema inmune, específicamente en las células dendríticas, parece ser una de las estrategias virales implicada en el establecimiento de la infección persistente. Esta estrategia parece estar mediada en gran parte por una de las proteínas estructurales codificada por el genoma del VHC, la proteína Core, unidad estructural de la cápside viral. Objetivo. Una de las limitantes para la evaluación de las propiedades de Core es la obtención y la purificación de la proteína nativa (191 aa). El objetivo de este estudio fue la producción y la purificación de la proteína Core completa en un sistema eucariote para evaluar las propiedades de la proteína en cultivos de células dendríticas humanas. Resultados. En este estudio se logró la producción de la proteína Core completa en el sistema de expresión de baculovirus y su purificación por la técnica de separación por punto isoeléctrico y electroelución. La pureza de la proteína obtenida se confirmó por Western blot y tinción con plata. Estos análisis mostraron dos bandas únicas correspondientes a las isoformas p23 y p21 de la proteína Core, previamente descritas en la literatura. Conclusiones. La proteína obtenida posee varias de las condiciones de la proteína Core nativa, como peso molecular, isoformas y localización subcelular. Los procedimientos descritos en este artículo son aplicables a proteínas asociadas a membranas producidas en sistemas de expresión eucarióticos

Baculoviridae , Hepacivirus , Focalização Isoelétrica , Proteínas do Capsídeo/isolamento & purificação , Bioensaio
Int J Cancer ; 107(3): 416-24, 2003 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-14506742


Human papillomaviruses (HPVs) are the cause of epithelial lesions, HPV type 16 and type 18 being associated with the development of anogenital cancer. The L1 Major Capsid Protein (L1) represents about 90% of total HPV protein and is involved in virus-host cell interaction, but little is known about this binding process. L1 sequences from HPV types 16 and 18 were synthesized in 56 20-mer peptides, covering the entire protein, HPLC-purified, (125)I-radiolabeled and tested in VERO and HeLa cell-binding assays to identify those peptides with high specific binding activity. Peptides 18283 (residues 54-77) and 18294 (274-308) from HPV16 L1, as well as 18312 (59-78) and 18322 (259-278) from HPV18 L1, presented high specific target cell binding activity. Peptide 18283 and 18294 affinity constants were 300 and 600 nM, respectively. Enzyme cell treatment before binding assay indicated that VERO and HeLa cell peptide receptor is a surface-exposed protein. There was a 60% reduction in peptide 18283 binding to heparin lyase-treated cells. Cross-linking assays showed that these proteins molecular weights were around 69 and 54 kDa. Peptides 18283 and 18294 specifically inhibited HPV-16 VLP binding to HeLa cells. According to the L1- and VLP-reported structure, both peptides are close on the VLP-surface, belonging to the outer surface broad pockets suggested as being potential receptor sites. Furthermore, it has been reported that a conserved motif from peptide 18294 is the target for neutralizing antibodies. These results suggest that such binding sequences are used by the virus as cell-binding regions.

Proteínas do Capsídeo , Capsídeo/fisiologia , Proteínas Oncogênicas Virais/fisiologia , Papillomaviridae/fisiologia , Fragmentos de Peptídeos/fisiologia , Vírion/fisiologia , Sequência de Aminoácidos , Animais , Chlorocebus aethiops , Células HeLa , Heparina/farmacologia , Humanos , Dados de Sequência Molecular , Células Vero
Rev. colomb. cancerol ; 7(1): 26-34, mar. 2003. tab, graf
Artigo em Espanhol | LILACS | ID: lil-342840


Introducción: En Colombia, el carcinoma de cérvix es la primera causa de muerte por cáncer de la mujer en edad reproductiva.Se ha demostrado una asociación etiológica entre los virus del papiloma humano (HPV) de alto riesgo y esta neoplasia. La proteína L1 de los HPV tiene la propiedad de autoensamblarse en cápsides vacías(VLP). En varios estudios basados en VLP DE hpv16 o HPV18 se ha observado que la infección por HPV genitales es seguida por una respuesta serológica o proteínas de la cápside. Objetivos: Evaluar la respuesta serológica hacia las VLP de los tipos virales oncogénicos 16,18,31,33,39,58 y 59 en mujeres colombianas con cáncer de cérvix, y en controles y compararlos con la presencia de ADN viral, la edad y el curso clínico. Materiales y Métodos: Se analizó la presencia de anticuerpos hacia las VLP de 7 tipos virales oncogénicos en 147 sueros de mujeres con citología normal apareados por edad, mediante ELISA. Resultados: Se detectaron anticuerpos anti-VLP en 82 por ciento de pacientes y en 56 por ciento de controles. La detección de anticuerpos contra múltiples tipos de HPV fue la regla; en pacientes jóvenes con cáncer de cérvix se observaron altos nivels de anticuerpos. En los casos con seguimiento serológico durante un año, en general, los anticuerpos se mantuvieron en el mismo nivel; sin embargo, en algunos hubo elevación o disminución simultánea de los anticuerpos contra varios tipos virales. Conclusiones:Nuestros resultados confirman (i) la alta tasa de infecciones por HPV en Colombia, tanto en pacientes con cáncer como entre población general, y las particularmente altas tasas de infección por los tipos virales 31 y 58,(ii) la validez de los anticuerpos anti-VLP como marcadores de infecciones en curso o pasadas. La aparición o desaparición simultánea de anticuerpos contra VLP de varios tipos virales sugiere que los anticuerpos detectados en ELISA no son siempre tipoespecíficos.

Anticorpos , Sondas de DNA de HPV , Neoplasias do Colo do Útero