Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

Immunity and COVID-19 vaccines. Revisiting the bases.

The COVID-19 pandemic is one of the challenges of the 21st century; science and technology were put to the test for the development vaccines, diagnostic techniques and treatments in record time. However, misinformation and misinterpretation have made the safety and efficacy of COVID-19 vaccines a subject of debate. This review addresses concepts on immunization mechanisms and vaccination, as well as evidence supporting that COVID-19 vaccines are immunogenic, efficacious and safe.

La pandemia de COVID-19 es uno de los retos del siglo XXI; la ciencia y la tecnología se pusieron a prueba para desarrollar vacunas, técnicas diagnósticas y tratamientos en tiempo récord. No obstante, la desinformación y mala interpretación han hecho que la seguridad y eficacia de las vacunas contra COVID-19 sean un tema de debate. En esta revisión se abordan conceptos sobre los mecanismos de la inmunización y la vacunación; así como la evidencia que sostiene que las vacunas contra COVID-19 son inmunogénicas, eficaces y seguras.

HPV infection profile in cervical lesions.

INTRODUCTION: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region. OBJECTIVE: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. METHODS: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. RESULTS: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. CONCLUSIONS: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.

INTRODUCCIÓN: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. OBJETIVO: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. MÉTODOS: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. RESULTADOS: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. CONCLUSIONES: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.

Inmunidad y vacunas contra la COVID-19. Revisando las bases / Immunity and COVID-19 vaccines. Revisiting the bases

Resumen La pandemia de COVID-19 es uno de los retos del siglo XXI; la ciencia y la tecnología se pusieron a prueba para desarrollar vacunas, técnicas diagnósticas y tratamientos en tiempo récord. No obstante, la desinformación y mala interpretación han hecho que la seguridad y eficacia de las vacunas contra COVID-19 sean un tema de debate. En esta revisión se abordan conceptos sobre los mecanismos de la inmunización y la vacunación; así como la evidencia que sostiene que las vacunas contra COVID-19 son inmunogénicas, eficaces y seguras.

Abstract The COVID-19 pandemic is one of the challenges of the 21st century; science and technology were put to the test for the development vaccines, diagnostic techniques and treatments in record time. However, misinformation and misinterpretation have made the safety and efficacy of COVID-19 vaccines a subject of debate. This review addresses concepts on immunization mechanisms and vaccination, as well as evidence supporting that COVID-19 vaccines are immunogenic, efficacious and safe.

Perfil de infecciones por VPH en lesiones cervicales / HPV infection profile in cervical lesions

Resumen Introducción: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. Objetivo: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. Métodos: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. Resultados: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. Conclusiones: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.

Abstract Introduction: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region Objective: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. Methods: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. Results: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. Conclusions: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.

The big challenge of SARS-CoV-2 latency: testes as reservoir.

In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.

En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.

The big challenge of SARS-CoV-2 latency: testes as reservoir / El gran desafío de la latencia de SARS-CoV-2: el testículo como reservorio

Abstract In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.

Resumen En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.

Expression of Pregnancy Specific ß-1 Glycoprotein 1 in Cervical Cancer Cells.

BACKGROUND: Cervical Cancer (CC) is a worldwide public health concern associated with genetic alterations, among these the gain of the 19q chromosome harboring the Pregnancy Specific Glycoproteins (PSG) gene family. These proteins play a critical role in pregnancy, with participation in immunotolerance, angiogenesis, and invasion processes, which are also observed in carcinogenesis. The aim of this study was to determine the molecular alterations of PSG1 and its relationship with CC. METHODS: PSG1 Copy Number Variation (CNV) was evaluated in 31 CC and eight normal cervical tissues by qPCR. PSG1 expression was correlated with HPV detection and IL-10 and TGF-ß expression in CC samples. Finally, PSG1 protein expression was evaluated by immunofluorescence in CC cell lines, by immunohistochemistry in a tissue microarray, and by immunoblotting in the sera of women with normal cervix, pre-invasive lesions, and CC. RESULTS: PSG1 showed a gain of 25.6% in CNV and gene expression in CC. There was a lack of PSG1 expression in normal cervical epithelium and positive immunostaining in 57% of CC tissues, while all CC cell lines expressed PSG1. Finally, PSG1 was immunodetected in 90% of pre-invasive lesions and in all CC serum samples, but not in healthy women. PSG1 expression correlates with the expression of IL-10 and TGF-ß in CC tissues, but not with the presence of HPV. CONCLUSION: These data show evidence of the differential expression of PSG1 in CC that could explain its participation in tumor-biology and immunotolerance mechanisms. Further, its immunodetection could provide early detection of this cancer.

Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells.

Cervical cancer (CeCa) produces large amounts of IL-10, which downregulates the major histocompatibility complex class I molecules (HLA-I) in cancer cells and inhibits the immune response mediated by cytotoxic T lymphocytes (CTLs). In this study, we analyzed the ability of CeCa cells to produce IL-10 through the CD73-adenosine pathway and its effect on the downregulation of HLA-I molecules to evade CTL-mediated immune recognition. CeCa cells cultured in the presence of ≥10 µM AMP or adenosine produced 4.5-6 times as much IL-10 as unstimulated cells. The silencing of CD73 or the blocking of A2BR with the specific antagonist MRS1754 reversed this effect. In addition, IL-10 decreased the expression of HLA-I molecules, resulting in the protection of CeCa cells against the cytotoxic activity of CTLs. The addition of MRS1754 or anti-IL-10 reversed the decrease in HLA-I molecules and favored the cytotoxic activity of CTLs. These results strongly suggest the presence of a feedback loop encompassing the adenosinergic pathway, the production of IL-10, and the downregulation of HLA-I molecules in CeCa cells that favors immune evasion and thus tumor progression. This pathway may have clinical importance as a therapeutic target.

Sensorial innovation for non-invasive breast cancer detection. / La innovación sensorial para detección no invasiva del cáncer de mama.

Breast cancer represents a great challenge due to the context of gender, social and cultural aspects, as well as of the possibility of making accessible early detection methods. Currently, detection mostly relies on image tests (invasive procedures). However, due to new and numerous cases detected in young women, and detected in such advanced stages that only palliative care may be offered, there is opportunity to develop new, innovative and promising detection tests. In order to find solutions to the organizational process of tumor cells, and adapt them for early detection, biomimesis eases the development of new non-invasive approaches and innovative designs. Nowadays, the volatile organic compounds detection (also called volatolome) emitted by tumoral cells can be detected with the use of biological and/or artificial intelligent noses. This approach may represent a real opportunity for the early detection of cancer and several pathologies. There is no doubt that novel test for early detection of different diseases will be soon reality.

El cáncer de mama representa un gran reto por el contexto de género, su "look", el contexto social y cultural, así como la probabilidad de que la detección oportuna sea de fácil acceso. Si bien en la actualidad contamos con pruebas de imagen para su detección, los nuevos y numerosos casos detectados tanto en mujeres jóvenes como en etapas avanzadas de la enfermedad, cuando no hay más que ofrecer que cuidados paliativos, abren oportunidad para desarrollar nuevos y prometedores sistemas de detección. Tratando de buscar soluciones al proceso organizativo de las células tumorales y adaptarlas para su detección oportuna, la biomimesis abre la oportunidad para nuevos enfoques no invasivos y desarrollos innovadores. En la actualidad, la detección de compuestos orgánicos volátiles (llamado también volatoloma), emitidos por las células tumorales mediante narices biológicas y narices con inteligencia artificial, podrían representar una realidad para la detección oportuna del cáncer y otras enfermedades. Es posible que una prueba de detección oportuna para las enfermedades incluyendo al cáncer esté pronta.

Biology of SARS-CoV-2: Towards understanding and treating COVID-19. / Biología del SARS-CoV-2: hacia el entendimiento y tratamiento de COVID-19.

During the last two decades, three different epidemics, caused by three different coronaviruses, have affected humankind. The most recent, known as COVID-19, has caused in only five months, more than 340,000 deaths worldwide. Knowing the biology of coronavirus is key, not just to face the current pandemic, but to prepare ourselves for future epidemics. With this in mind, this article is focused on the biology of coronaviruses emphasizing SARS-CoV-2, the agent that causes COVID-19. This is a comprehensive review article, which covers different topics, from the biology and taxonomy of viruses, to the molecular biology of SARS-CoV-2, its mechanisms of action, and the immune response this virus elicits. We have also addressed clinical aspects of COVID-19, its methods of detection, treatment, and vaccines.

Durante las últimas dos décadas, tres epidemias de gran magnitud, causadas por tres distintos tipos de coronavirus, han impactado a la humanidad. La más reciente, conocida como COVID-19, ha provocado en tan solo cinco meses, más de 340 000 muertes en todo el mundo. Conocer la biología de los coronavirus es fundamental, tanto para enfrentar la pandemia actual, como para prepararnos para futuras epidemias. En este contexto, el presente artículo está enfocado en la biología de los coronavirus con énfasis en el SARS-CoV-2, agente causal de COVID-19. La temática que se incluye es muy amplia, abarca desde la biología general de los virus y su taxonomía, hasta aspectos muy puntuales de la biología molecular de SARS-CoV-2, así como de sus mecanismos de acción y la respuesta inmune. También presentamos distintos aspectos clínicos de COVID-19, de los métodos para su detección y algunos enfoques terapéuticos, incluyendo tratamientos antivirales y vacunas.

Bacterias relacionadas con vaginosis bacteriana y su asociación a la infección por virus del papiloma humano / Vaginosis-associated bacteria and its association with HPV infection

Antecedentes y objetivo: En México y en el mundo cada vez son más frecuentes los casos de cáncer de cérvix y aunque se sabe que existen diversos factores de riesgo para padecer este tipo de cáncer, se ha sugerido que las alteraciones en el microbioma cervical pueden desempeñar un papel importante en el establecimiento y progresión del cáncer, específicamente hablando de la presencia de aquellas bacterias asociadas a vaginosis bacteriana como lo son Atopobium vaginae y Gardnerella vaginalis. Material y métodos: Se estudió el ADN de un total de 177 muestras de raspado de cérvix, de las cuales 104 pertenecían a mujeres sin alteraciones citológicas o colposcópicas y 73 muestras de lesiones precursoras con antecedente de infección por virus del papiloma humano (VPH). Todas las muestras fueron sometidas a detección de secuencias de Atopobium vaginae, Gardnerella vaginalis y VPH por medio de PCR. Resultados: El VPH fue encontrado en mayor proporción en las muestras precursoras, y poco más del 30% de las muestras sin lesión fueron positivas para VPH. La mayoría de las muestras contienen secuencias de ambas bacterias sin asociación con la presencia viral, lo que podría indicar que estos microorganismos serían parte del microbioma cervical en población mexicana. Conclusiones: Los resultados obtenidos indican que las bacterias analizadas potencialmente forman parte del bioma normal en las mujeres mexicanas por lo que es de especial importancia reconsiderar el papel patógeno de estos microorganismos

Background and objective: Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. Material and methods: DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. Results: High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. Conclusions: The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms

Vaginosis-associated bacteria and its association with HPV infection. / Bacterias relacionadas con vaginosis bacteriana y su asociación a la infección por virus del papiloma humano.

BACKGROUND AND OBJECTIVE: Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. MATERIAL AND METHODS: DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. RESULTS: High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. CONCLUSIONS: The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms.

The expression of transcription factor BORIS and its association with the estrogen receptor beta (ER-ß) in cervical carcinogenesis.

BORIS is a transcription factor aberrantly expressed in human cancers that can regulate the expression of estrogen receptors in endometrial cancer and breast cancer. We evaluated the expression of BORIS and the estrogen receptors alpha (ER-α) and beta (ER-ß) in ten cell lines derived from cervical cancer using RT-PCR and Western-blot. We also evaluated 54 cervical tissues: normal epithelia, low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL), and invasive squamous carcinomas (SC) using immunohistochemistry. In the cell lines, BORIS mRNA and protein expressions are associated with ER-ß expression but not with ER-α expression. In the normal cervical epithelium, ER-α and ER-ß were expressed but the BORIS protein was not detected. In the LSIL samples, BORIS, ER-α and ER-ß were expressed; however, in the HSIL samples, only the BORIS and ER-ß expressions were detected, but ER-α expression was minimal or null. In the SC, only BORIS and ER-ß were detected. In summary, the results show that the expressions of BORIS and ER-ß increase while the expression of ER-α decreases according to the severity of the lesions. These results suggest synergistic roles for BORIS and ER-ß during cervical cancer progression with a possible regulation of the estrogen receptors by BORIS in the development of cervical cancer; however, more detailed studies are needed to confirm this suggestion and to determine the precise role of BORIS in cervical cancer.

Volatolome of the Female Genitourinary Area: Toward the Metabolome of Cervical Cancer.

BACKGROUND AND AIMS: Different Volatile Organic Compounds (VOCs) obtained from several human fluids (volatolome) has been reported as potential biomarkers for a great variety of diseases including cancer. At present, volatolomic profile data of the female genital area is scarce. METHODS: To identify the VOCs related to the female genitourinary area of healthy and Cervical Cancer (CC)-affected women used a pad, as a non-invasive tool for sample gathering was necessary. Used pads were analyzed by Gas Chromatography-Mass Spectrometry. The data were subjected to Principal Component Analysis looking for a possible spectrum of VOCs that could help identify CC-affected patients. The diagnostic role of the VOCs was validated through Receiver Operating Characteristic (ROC) analysis. The area below the curve and the diagnostic sensitivity and specificity values were also evaluated. RESULTS: The data showed great differences between female cancer and healthy patients groups; most of these VOCs belonging to the alkanes chemical classes. A group of VOCs were identified as common among CC patients, while others VOCs for healthy females. The ROC curve showed an optimal reach to diagnosis (89%), returning a 93% rate for sensitivity and specificity, indicating the VOCs identified in the samples could differentiate cancer patients from healthy females. CONCLUSIONS: In summary, we have detected and identified specific VOCs from healthy women that are not present in CC-affected females and VOCs specific of CC-affected women. We are strengthening our findings to aid in the detection of VOCs that are potential biomarkers for cervical tumors.

Genotipificación del virus del papiloma humano en un grupo de mujeres mexicanas atendidas en un hospital de alta especialidad: las infecciones múltiples y su potencial trascendencia en el esquema actual de vacunación / Genotyping of the human papilloma virus in a group of Mexican women treated in a highly specialist hospital: Multiple infections and their potential transcendence in the current vaccination programme

Fundamento y objetivo: El virus del papiloma humano (VPH) es uno de los principales factores de riesgo para el desarrollo del cáncer cervicouterino y sus lesiones precursoras. Se ha mencionado que a nivel mundial los tipos VPH16 y 18 cubren aproximadamente el 70% del cáncer de cérvix; sin embargo, se ha reportado que estos porcentajes varían significativamente dependiendo de la población en estudio. Materiales y métodos: Se estudió el ADN de un grupo de 67 muestras de tejidos cervicales mediante el kit HPV Linear Array(R) que detecta 37 tipos diferentes de VPH, y que correspondieron a 19 lesiones escamosos invasivas del cérvix, 15 lesiones intraepiteliales escamosas de alto grado, 20 lesiones intraepiteliales escamosas de bajo grado y 13 muestras de cérvix uterino sin lesión, todas ellas previamente diagnosticadas. Resultados: En general, se encontraron 16 tipos distintos de VPH con una clara diferencia en sus frecuencias, siendo en el cáncer invasivo donde se encontró mayor variedad de VPH, seguido por las lesiones intraepiteliales escamosas de bajo grado y, posteriormente, las de alto grado. El VPH16 fue el tipo más frecuentemente distribuido en las lesiones estudiadas, seguido por el VPH52, evidenciando una variabilidad de tipos virales dependiendo de la zona geográfica de referencia. Conclusiones: Los resultados indicarían variabilidad en la presencia de los VPH en México, resaltando la importancia del VPH52, entre otros, en nuestra población. Estos datos, además, tendrían un potencial impacto en la actual campaña de vacunación anti-VPH (AU)

Background and objective: Human papilloma virus (HPV) is one of the main risk factors associated with the development of cervical cancer and its precursor lesions. It has been reported that HPV16 and 18 types cover approximately 70% of cervical cancer worldwide; however, significant variation in percentages of HPV infections could be related to specific populations. Materials and methods: Purified DNA of 67 cervical samples were analyzed by Linear Array(R) HPV genotyping kit. These analyzed samples correspond to 19 cervical tumors, 15 high-grade squamous intraepithelial lesions, 20 low-grade squamous intraepithelial lesions, and 13 cervical samples without injury were studied, all of them previously diagnosed. Results: In general, 16 different HPV types were found with differences in their frequencies, cervical invasive cancer being the richest in HPV sequences, followed by the low-grade squamous intraepithelial lesions and then high-grade lesions. HPV16 was the most frequently distributed type in neoplastic lesions of the cervix, followed by the HPV52, suggesting viral type variability, probably associated to the geographical region studied. Conclusions: The results could indicate variability in HPV presence in Mexico, underlining the important role for HPV52 among others in the Mexican population. This would also potentially have an impact on the current anti-HPV vaccination schemes (AU)

Genotyping of the human papilloma virus in a group of Mexican women treated in a highly specialist hospital: Multiple infections and their potential transcendence in the current vaccination programme. / Genotipificación del virus del papiloma humano en un grupo de mujeres mexicanas atendidas en un hospital de alta especialidad: las infecciones múltiples y su potencial trascendencia en el esquema actual de vacunación.

BACKGROUND AND OBJETIVE: Human papilloma virus (HPV) is one of the main risk factors associated with the development of cervical cancer and its precursor lesions. It has been reported that HPV16 and 18 types cover approximately 70% of cervical cancer worldwide; however, significant variation in percentages of HPV infections could be related to specific populations. MATERIALS AND METHODS: Purified DNA of 67 cervical samples were analyzed by Linear Array® HPV genotyping kit. These analyzed samples correspond to 19 cervical tumors, 15 high-grade squamous intraepithelial lesions, 20 low-grade squamous intraepithelial lesions, and 13 cervical samples without injury were studied, all of them previously diagnosed. RESULTS: In general, 16 different HPV types were found with differences in their frequencies, cervical invasive cancer being the richest in HPV sequences, followed by the low-grade squamous intraepithelial lesions and then high-grade lesions. HPV16 was the most frequently distributed type in neoplastic lesions of the cervix, followed by the HPV52, suggesting viral type variability, probably associated to the geographical region studied. CONCLUSIONS: The results could indicate variability in HPV presence in Mexico, underlining the important role for HPV52 among others in the Mexican population. This would also potentially have an impact on the current anti-HPV vaccination schemes.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs.

BACKGROUND: Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. METHODS: Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. RESULTS: The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. CONCLUSION: Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer.

Epithelial ovarian cancer is one of the most lethal of gynecological malignancies. Due to its lack of early symptoms, detection usually occurs when the tumor is no longer confined to the ovary. We previously identified Fbxw15, a gene encoding an F-box protein in the mouse ovary, and showed that its expression is developmentally regulated. Here we report the molecular analysis of its human homologue, FBXW12 in epithelial ovarian tumors. To search for FBXW12 gene mutations, we PCR-amplified and sequenced the coding region of FBXW12, the gene's 5-untranslated region and the proximal promoter in each of 30 EOC tumors. Promoter methylation was determined by DNA bisulfite conversion, followed by methylation specific PCR. FBXW12 intracellular localization was identified by means of immunohistochemistry. A complete deletion of the gene's coding region, the 5'-UTR and the proximal promoter, was observed in 3 EOC samples. Eight of the remaining 27, had a deletion of the 5'-UTR, and the proximal promoter. FBXW12 mRNA was detected in 2 of the 19 samples without deletions. The methylation specific PCR results demonstrated CpGs methylation in the FBXW12 proximal promoter. Immunohistochemistry assay revealed that within the normal ovary, FBXW12 has an oocyte specific expression, whereas in EOC samples it is present in the ovarian surface epithelium. Our results indicate that the FBXW12 gene is deleted in approximately ten percent of the EOC cases studied; such deletions comprised either the FBXW12 promoter or the mRNA-encoding region. Moreover, FBXW12 could be epigenetically silenced by CpGs methylation in some of these EOC cases.

[The role of developmental HOX genes in cervical cancer]. / El papel de los genes del desarrollo tipo HOX en el cáncer cervicouterino.

Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.

El cáncer cervicouterino (CaCU) es una enfermedad multifactorial que se asocia a factores genéticos, ambientales y epigenéticos, y cuyo principal agente etiológico es la infección por el virus del papiloma humano. Además, la alteración en la expresión de factores de transcripción ha sido considerada de importancia para el desarrollo de esta neoplasia. Los genes HOX codifican un grupo de factores de transcripción que participan en los procesos de proliferación y diferenciación celular durante el desarrollo de las estructuras embrionarias en los vertebrados; y su expresión aberrante ha sido asociada con oncogénesis y metástasis. Una serie de evidencias sugiere un papel importante para los genes HOX en el desarrollo neoplásico de la célula cervical. Estudios realizados en líneas celulares de CaCU, lesiones premalignas y tumores primarios han sugerido el involucramiento de HOXA1, HOXC5, C6, C8 y C10, HOXD9 y HOXD13 en el proceso de carcinogénesis cervical. Asimismo, la expresión de novo de los genes HOXB2, B4, B13 y HOXC11-C13 parece estar involucrada en el proceso de transformación maligna de la célula del epitelio cervical. Estos datos permitirían abrir un campo en la búsqueda de nuevos marcadores moleculares en cáncer cervical y en el desarrollo de nuevas estrategias terapéuticas para atender esta neoplasia.