Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Pleiotrophin and the Expression of Its Receptors during Development of the Human Cerebellar Cortex.

During embryonic and fetal development, the cerebellum undergoes several histological changes that require a specific microenvironment. Pleiotrophin (PTN) has been related to cerebral and cerebellar cortex ontogenesis in different species. PTN signaling includes PTPRZ1, ALK, and NRP-1 receptors, which are implicated in cell differentiation, migration, and proliferation. However, its involvement in human cerebellar development has not been described so far. Therefore, we investigated whether PTN and its receptors were expressed in the human cerebellar cortex during fetal and early neonatal development. The expression profile of PTN and its receptors was analyzed using an immunohistochemical method. PTN, PTPRZ1, and NRP-1 were expressed from week 17 to the postnatal stage, with variable expression among granule cell precursors, glial cells, and Purkinje cells. ALK was only expressed during week 31. These results suggest that, in the fetal and neonatal human cerebellum, PTN is involved in cell communication through granule cell precursors, Bergmann glia, and Purkinje cells via PTPRZ1, NRP-1, and ALK signaling. This communication could be involved in cell proliferation and cellular migration. Overall, the present study represents the first characterization of PTN, PTPRZ1, ALK, and NRP-1 expression in human tissues, suggesting their involvement in cerebellar cortex development.

High frequency of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico.

BACKGROUND: Human papillomavirus infection is an important factor associated with cervical cancer (CC) development. The prevalence and genotype distribution vary greatly worldwide. Examining local epidemiological data constitutes an important step towards the development of vaccines to prevent CC. In this work, we studied the prevalence of HPV genotypes in women from Western Mexico with the COBAS 4800 and/or Linear Array Genotyping Test (LA). METHODS: The samples analysed in this study represent a population from Western Mexico, which includes six different states. Our approach was first to test for HPV in cervical samples from women who attended their health clinic for routine gynaecological studies (open-population, n = 3000) by utilizing COBAS 4800. Afterwards, 300 of the HPV-positive samples were randomly selected to be genotyped with LA; finally, we genotyped samples from women with cervical intraepithelial neoplasia grade 1 (CIN 1, n = 71) and CC (n = 96) with LA. Sociodemographic data of the diverse groups were also compared. RESULTS: The overall HPV prevalence among the open-population of women as determined by COBAS 4800 was 12.1% (n = 364/3000). Among the HPV-positive samples, single infections (SI) with HPV16 were detected in 12.4% (n = 45/364), SI with HPV18 were detected in 1.4%, and infection with at least one of the genotypes included in the high-risk HPV pool was detected in 74.5% of the cases. LA analysis of the samples showed that in addition to HPV genotypes 16 and 18, there was a high prevalence of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico. With respect to the sociodemographic data, we found statistically significant differences in the number of pregnancies, the use of hormonal contraceptives and tobacco intake. CONCLUSIONS: Our data indicate that there is a high prevalence of HPV genotypes which are not covered by the vaccines currently available in Mexico; therefore, it is necessary to include HPVs 59, 66, 51, 39 and 56 in the design of future vaccines to reduce the risk of CC development. It is also essential to emphasize that the use of hormonal contraceptives and tobacco smoking are risk factors for CC development in addition to the presence of HPV.

Detection of Alpha, Beta, Gamma, and Unclassified Human Papillomaviruses in Cervical Cancer Samples From Mexican Women.

Background: Cervical cancer (CC) is associated to high-risk human papillomavirus (HPV) infections, for this reason it is crucial to have sensitive and accurate HPV diagnostic tests. To date, most research is focused on HPVs within the Alphapapillomavirus (α-PVs) genus and little attention has been paid to cervical infections with other HPV genotypes, like those of the Betapapillomavirus (ß-PVs) and Gammapapillomavirus (γ-PVs) genera. The aim of this study was to determine the HPV genotypes from different genera in women with CC using Next-Generation Sequencing (NGS). Methods: The study comprised 48 HPV positive CC samples evaluated with the Linear Array HPV Genotyping test and individually sequenced by 454 NGS using PGMY09/11 and FAP primers. To determine the HPV genotypes present in each sample, the obtained sequences were compared with all HPV L1 gene reference sequences from the Papillomavirus Episteme database (PaVE). Moreover, 50 HPV positive low-grade cervical lesion samples individually genotyped with NGS were also included to determine the genotypes present preferentially in CC patients. Results: Among the 48 CC samples, 68.75% consisted of multiple HPV infections, 51 different genotypes were detected, of which 7 are still unclassified, 28 belong to α-PVs (6, 11, 16, 18, 26, 30, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 54, 59, 62, 66, 68, 69, 70, 71, 74, 81, 102, 114), 10 to ß-PVs (5, 12, 21, 37, 38b, 47, 80, 107, 118, 122), and 6 to γ-PVs (101, 103, 123, 135, 147, 214). Among them, HPV16 was the most prevalent genotype (54.2%), followed by HPV18 (16.7%), HPV38b (14.6%), and HPVs 52/62/80 (8.3%). Some genotypes were exclusively found in CC when compared with Cervical Intraepithelial Neoplasia grade 1 (CIN1) samples, such as HPVs 5, 18, 38b, 107, 122, FA39, FA116, mSK_120, and mSK_136. Conclusions: This work demonstrates the great diversity of HPV genotypes detected by combining PGMY and FAP primers with NGS in cervical swabs. The relatively high attribution of ß- and γ- PVs in CC samples suggest their possible role as carcinogenic cofactors, but deeper studies need to be performed to determine if they have transforming properties and the significance of HPV-coinfections.

Molecular subtypes and clinicopathological features of breast cancer in Mexican women. / Subtipos moleculares y características clinicopatológicas de cáncer de mama en mujeres mexicanas.

BACKGROUND: Breast cancer is a multifactorial and heterogeneous disease with distinct molecular features and histopathologic subtypes involving different therapeutic responses and clinical outcomes. Classification of breast cancer in molecular subtypes has made possible an approach to develop therapeutic strategies in order to have a better understanding of the breast cancer development. Due to the heterogeneity of the disease, there are still features to be elucidated in the behavior, etiology and clinical outcomes of each molecular subtype in breast cancer. METHODS: Variables measured in 1,695 cases of invasive breast carcinoma were age, histopathological diagnosis, histopathological grade, expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), cell proliferation marker (Ki67) and basal cytokeratins (CK 5/6). P values were obtained using Chi square test and hazard ratios were calculated with 95% confidence intervals. RESULTS: An increase of aggressive molecular subtypes of breast cancer was observed. The mean age of incidence of breast cancer patients is decreasing, and breast cancer Patients younger than 40-years-old showed higher risk to exhibit Triple negative and Basal-like tumors. CONCLUSIONS: The mean age for this pathology is decreasing in our population and there is predominance in the differential occurrence of etiologically distinct entities of breast cancer affecting to the young women.

INTRODUCCIÓN: El cáncer de mama es una enfermedad heterogénea y multifactorial. Presenta distintas características clínicas, moleculares e histopatológicas, las cuales se asocian con la respuesta a los esquemas terapéuticos, así como al resultado clínico. La clasificación en subtipos moleculares (luminales, HER2, triple negativo y basales) ha permitido el desarrollo y aplicación de estrategias terapéuticas particulares. Sin embargo, dada la gran heterogeneidad de la enfermedad, existen aún características por elucidar en el comportamiento, etiología y resultados clínicos de cada subtipo molecular de cáncer de mama. MÉTODOS: Se obtuvieron datos de 1695 casos de cáncer de mama invasor. Se realizaron correlaciones entre las siguientes variables: edad, diagnóstico histopatológico, grado histológico, expresión del receptor de estrógenos (ER), receptor de progesterona (PR), receptor 2 del factor de crecimiento epidérmico humano (HER2), marcador de proliferación celular (Ki67) y citoqueratinas basales (CK 5/6). Los valores de p fueron calculados utilizando Chi cuadrada y el cociente de riesgo fue calculado con un intervalo de confianza de 95%. RESULTADOS: Se observó un incremento en la frecuencia de los subtipos moleculares más agresivos, así como una disminución en el valor de la media de la edad en las pacientes diagnosticadas con cáncer de mama. El análisis de la información indica que en pacientes menores de 40 años existe mayor riesgo a la presencia de tumores triple negativo o basales. CONCLUSIONES: En población mexicana, la media de edad para el diagnóstico primario de cáncer de está disminuyendo y hay mayor frecuencia de subtipos moleculares más agresivos en pacientes jóvenes.

Metástasis coroidea como manifestación inicial de adenocarcinoma de pulmón en paciente joven: informe de caso / Choroidal metastasis as an initial manifestation of lung adenocarcinoma in a young patient: case report

Introducción: se presenta el caso de un paciente de 36 años, a quien se le realizó el diagnostico de tuberculoma coroideo, otorgando tratamiento sin mejoría de los síntomas. Posteriormente fallece dilucidándose el diagnóstico de adenocarcinoma de pulmón con metástasis a coroides. Objetivo: informar el diagnóstico de metástasis coroidea como manifestación inicial, de adenocarcinoma de pulmón, en un paciente joven. Diseño de estudio: reporte de caso. Resumen del caso: masculino de 36 años de edad, antecedente de tuberculosis en la infancia, tabaquismo positivo no significativo. Presenta baja visual de ojo derecho, siendo diagnosticado con tuberculoma coroideo, asociado a sudoración nocturna, lumbalgia, tos y QuantiFERON-TB positivo. Se inicia tratamiento antituberculosis. Posterior, presenta deterioro respiratorio y neurológico requiriendo intubación orotraqueal, ulteriormente fallece. La autopsia elucida el diagnóstico de adenocarcinoma de pulmón con metástasis a coroides, hígado y riñón. Conclusión: las metástasis coroideas conllevan un mal pronóstico visual y sistémico, se requiere un alto índice de sospecha en pacientes menores de 50 años sin factores de riesgo. Se convierten en un reto diagnóstico, sobre todo en países donde predominan las enfermedades infecciosas. El papel del oftalmólogo es realizar el diagnóstico oportuno y correcto, evitando así retrasar el tratamiento.

Background: the case of a 36 year-old patient is presented, who was diagnosed with choroidal tuberculoma, giving treatment without improvement. Then, the diagnosis of pulmonary adenocarcinoma and choroidal metastases was elucidated. Objective: to report the diagnosis of metastasis as the initial manifestation of lung adenocarcinoma in a young patient. Study design: case report. Case summary: male, 36 years old, history of tuberculosis in childhood, positive smoking, but not significant. He presented visual loss of the right eye, being diagnosed with a choroidal tuberculoma, associated with night sweats, cough and positive QuantiFERON-TB test, treatment for tuberculosis was initiated. Later he had respiratory and neurological deterioration requiring orotracheal intubation, but unfortunately he died. Autopsy reveals lung adenocarcinoma with choroidal, liver and kidney metastases. Conclusion: choroidal metastases lead to poor visual and systemic prognosis, a high suspicion is required in patients under 50 years of age without risk factors. They become a diagnostic challenge, especially in countries where infectious diseases are predominat. The ophthalmologist's role is to make the diagnosis timely and correctly, thus avoiding delaying treatment.

Orientación empática en estudiantes de Medicina en una universidad de República Dominicana / Empathic orientation observed in medical students at one university in the Dominican Republic

Objetivo: determinar el nivel de orientación empática de los estudiantes de medicina de la Universidad Central del Este. Métodos: esta es una investigación no experimental, descriptiva, transversal y ex posfacto causa-efecto. La población estuvo constituida por 853 estudiantes (años: 1ro., 2do. 3ro., 4to. y 5to.), de la cual se tomó una muestra de 515 voluntarios (n = 108 del 1ro.; n = 151 del 2do.; n = 109 del 3ro.; n = 94 del 4to. y n= 53 del 5to.) Se aplicó, en 2012, la versión en español de la Escala de Empatía Médica de Jefferson (EEMJ) para estudiantes de Medicina (versión S), validada en México y Chile y adaptada culturalmente a República Dominicana por los autores del presente trabajo. Resultados: el nivel de orientación empática de los estudiantes fue bajo. No se encontraron diferencias significativas en las puntuaciones según nivel de la carrera. Sin embargo sí fue significativa la diferencia en las puntuaciones de género. Conclusiones: es necesario realizar más investigaciones para determinar cuáles son los factores que están influyendo en los resultados encontrados, por qué fueron bajos y cuáles son las condiciones (internas y externas) en que se desenvuelve el proceso de formación de los estudiantes de Medicina de la Universidad Central del Este de República Dominicana.

Objective: to determine the level of empathic orientation of the medical students in Universidad Central del Este in the Dominican Republic. Methods: non-experimental, descriptive, cross-section and ex posfacto cause-effect research study. The study population was 853 students from the first, second, third, fourth and fifth years of the career and the final sample consisted of 515 voluntary students (108 from 1st year, 151 from the 2nd, 109 from the 3rd, 94 from the 4th and 53 from the 5th. In 2012, the Spanish version of the Jefferson Scale of Physician Empathy was applied to medical students after being validated in Mexico and Chile and adapted from the cultural viewpoint by the authors of this paper to the Dominican Republic background. Results: the level of empathic orientation found in the Dominican students was low. There were no significant differences in scores by study year. However, the difference was significant in gender scores. Conclusions: it is required to carry out research studies in order to determine the factors that have an impact on the observed results, the reasons why these indexes were low and the internal and external conditions of the process of medical student formation in Universidad Central del Este in the Dominican Republic.

Empathic orientation among medical students from three universities in Barranquilla, Colombia and one university in the Dominican Republic.

OBJECTIVE: To compare empathic orientation among medical students from three schools of medicine in Colombia and one in the Dominican Republic. MATERIAL AND METHODS: Empathic orientation of medical students was measured using the Jefferson Scale of Physician Empathy (JSPE), Spanish version for students (the "S" version) validated in Mexico and Chile, and culturally adapted to Colombia and the Dominican Republic. Data were compared using a three-factor analysis of variance (model III) and a discriminant analysis. RESULTS: No differences in empathic orientation were observed among courses and between sexes, but differences were found in schools of medicine considered as a unit in each studied country. CONCLUSIONS: Empathic orientation levels tend to reduce as courses advance. This was observed in both male and female students and in all schools analyzed.

Orientación empática de estudiantes de medicina en tres universidades de Barranquilla, Colombia y en una universidad de República Dominicana / Empathic orientation among medical students from three universities in Barranquilla, Colombia and one university in the Dominican Republic

Objetivo. Comparar la orientación empática entre estudiantes de Medicina de tres facultades de Medicina de Colombia y una de República Dominicana. Material y métodos. Se midió la orientación empática de los estudiantes de Medicina mediante la escala de empatía médica de Jefferson, en la versión en español para estudiantes (versión S) validada en México y Chile, y adaptada culturalmente a Colombia y República Dominicana. Los datos se compararon mediante un análisis de varianza trifactorial (modelo III) y por un análisis discriminante. Resultados. No se encontraron diferencias de orientación empática entre los cursos ni entre los sexos, pero sí entre las facultades de Medicina consideradas como una unidad en cada uno de los países estudiados. Conclusiones. Los niveles de orientación empática tienden a disminuir a medida que los cursos avanzan. Este hecho se produce en estudiantes de ambos sexos y en todas las facultades analizadas.(AU)

Objective. To compare empathic orientation among medical students from three schools of medicine in Colombia and one in the Dominican Republic. Material and Methods. Empathic orientation of medical students was measured using the Jefferson Scale of Physician Empathy (JSPE), Spanish version for students (the "S" version) validated in Mexico and Chile, and culturally adapted to Colombia and the Dominican Republic. Data were compared using a three-factor analysis of variance (model III) and a discriminant analysis. Results. No differences in empathic orientation were observed among courses and between sexes, but differences were found in schools of medicine considered as a unit in each studied country. Conclusions. Empathic orientation levels tend to reduce as courses advance. This was observed in both male and female students and in all schools analyzed.(AU)

Orientación empática de estudiantes de medicina en tres universidades de Barranquilla, Colombia y en una universidad de República Dominicana / Empathic orientation among medical students from three universities in Barranquilla, Colombia and one university in the Dominican Republic

Objetivo. Comparar la orientación empática entre estudiantes de Medicina de tres facultades de Medicina de Colombia y una de República Dominicana. Material y métodos. Se midió la orientación empática de los estudiantes de Medicina mediante la escala de empatía médica de Jefferson, en la versión en español para estudiantes (versión S) validada en México y Chile, y adaptada culturalmente a Colombia y República Dominicana. Los datos se compararon mediante un análisis de varianza trifactorial (modelo III) y por un análisis discriminante. Resultados. No se encontraron diferencias de orientación empática entre los cursos ni entre los sexos, pero sí entre las facultades de Medicina consideradas como una unidad en cada uno de los países estudiados. Conclusiones. Los niveles de orientación empática tienden a disminuir a medida que los cursos avanzan. Este hecho se produce en estudiantes de ambos sexos y en todas las facultades analizadas.

Objective. To compare empathic orientation among medical students from three schools of medicine in Colombia and one in the Dominican Republic. Material and Methods. Empathic orientation of medical students was measured using the Jefferson Scale of Physician Empathy (JSPE), Spanish version for students (the "S" version) validated in Mexico and Chile, and culturally adapted to Colombia and the Dominican Republic. Data were compared using a three-factor analysis of variance (model III) and a discriminant analysis. Results. No differences in empathic orientation were observed among courses and between sexes, but differences were found in schools of medicine considered as a unit in each studied country. Conclusions. Empathic orientation levels tend to reduce as courses advance. This was observed in both male and female students and in all schools analyzed.

Empathic orientation among medical students from three universities in Barranquilla, Colombia and one university in the Dominican Republic. / Empathic orientation among medical students from three universities in Barranquilla, Colombia and one university in the Dominican Republic.

OBJECTIVE: To compare empathic orientation among medical students from three schools of medicine in Colombia and one in the Dominican Republic. MATERIAL AND METHODS: Empathic orientation of medical students was measured using the Jefferson Scale of Physician Empathy (JSPE), Spanish version for students (the "S" version) validated in Mexico and Chile, and culturally adapted to Colombia and the Dominican Republic. Data were compared using a three-factor analysis of variance (model III) and a discriminant analysis. RESULTS: No differences in empathic orientation were observed among courses and between sexes, but differences were found in schools of medicine considered as a unit in each studied country. CONCLUSIONS: Empathic orientation levels tend to reduce as courses advance. This was observed in both male and female students and in all schools analyzed.

Orientación empática en estudiantes de odontología de la Universidad Central del Este / Empathic orientation in dental students of Universidad Central del Este

Objetivo: determinar la orientación empática en estudiantes de odontología. Metodología: es una investigación no experimental, descriptiva, de corte transversal y ex post facto causa-efecto. La población estuvo constituida por 284 estudiantes de la carrera de odontología de la Universidad Central del Este (República Dominicana) y la muestra se conformó con 239 sujetos, quienes cursaban los niveles 1º, 2º, 3º, 4º y 5º (Años), durante 2012. Se utilizó la Escala de Empatía Médica de Jefferson (EEMJ), versión S, adaptada culturalmente para la República Dominicana. Resultados: se analizaron las variables año y género. Se encontró que el factor año fue altamente significativo (p<0,001), contrario a resultados del factor género (p>0,05), lo cual indica que existen diferencias entre los años estudiados, pero no entre los géneros. Conclusiones: es necesario realizar estudios que favorezcan la observación de las variables estudiadas y compararlas con modificaciones hechas a nivel de los programas académicos y mallas curriculares.

Purpose: To determine the empathetic orientation of dental school students. Methods: This is a non-experimental, descriptive, transversal and ex post facto cause and effect study. The population consisted of 284 dentistry students from the Universidad Central del Este (Dominican Republic). The sample size was of 239 subjects, who were enrolled in level 1º, 2º, 3º, 4º and 5º (years) during 2012. We applied a culturally adapted Spanish version of the Scale of Physician Empathy Jefferson (JSPE). Results: We analyzed variables year and gender, finding that year was highly significant (p <0.001), in contrast to gender (p> 0.05). This indicates that there are differences in empathetic orientation between years but not between genders. Conclusions: Further studies should be conducted that favor the observation of the variables studied. When possible, comparative analysis should be made to determine the impact of changes made at the academic programs and curricula.

[Sacrococcygeal teratoma: report of a case and review of the literature]. / Teratoma sacrococcígeo: reporte de un caso y revisión de la bibliografía.

Sacrococcygeal teratoma is the most common tumor in infants. About 80% of these tumors are types 1 and 2, and are unlikely to cause metastases whose incidence is 10% in the neonatal period, against nearly 100% at the age of 3 years. These tumors can acquire huge and contain large proportions depriving blood flows to the developing fetus, the tumor hypervascularity generates a hyperdynamic state in the fetus, and that as the tumor grows, it increases its flow to behave as a short circuit and to be similar to that of the lower limbs of the fetus, increasing venous return and cardiac output, heart failure causing fetal and maternal eclampsia.