Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion.

Cancer-associated fibroblasts (CAFs) are the main component of the tumor stroma and promote tumor progression through several mechanisms. Recent evidence indicates that small noncoding RNAs, microRNAs (miRNAs), play key roles in CAF tumor-promoting properties; however, the role of miRNAs in lung cancer-associated fibroblasts remains poorly defined. We characterized the differential miRNA expression profile of fibroblasts isolated from matched tumor front (F-CAFs), inner tumor (In-CAFs), and normal adjacent (NFs) tissues from four lung adenocarcinoma patients (ADs) using microarray analysis. Proliferation and invasion assays of A549 human lung cancer cells in the presence of conditioned medium from F-CAFs, In-CAFs or NFs were performed to assess tumorigenic properties. Ten identified candidate miRNAs in F-CAFs, In-CAFs and NFs from 12 ADs were then validated by RT-PCR. Both F-CAFs and In-CAFs enhanced the proliferation and invasion of A549 cells compared with NFs; moreover, F-CAFs showed a significantly stronger effect than In-CAFs. RT-PCR validation demonstrated three downregulated miRNAs in F-CAFs compared with NFs (miR-145-3p, miR-299-3p, and miR-505-3p), two in F-CAFs compared with In-CAFs (miR-410-3p and miR-485-5p), but no differentially expressed miRNAs between In-CAFs and NFs. Further target-gene prediction and pathway enrichment analysis indicated that deregulated miRNAs in F-CAFs showed significant associations with "pathways in cancer" (miR-145-3p, miR-299-3p and miR-410-3p), "Wnt signaling pathway" (miR-410-3p and miR-505-3p), and "TGF-beta signaling pathway" (miR-410-3p). Importantly, a tumor-promoting growth factor targeted by those miRNAs, VEGFA, was upregulated in F-CAFs compared with NFs, as judged by RT-PCR. In conclusion, deregulated miRNAs in F-CAFs are potentially associated with CAF tumor-promoting properties.

Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets.

Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.

Synergistic effect of air pollution and habitual smoking on the retention of inorganic fibers identified as ferruginous bodies in autopsy cases in Mexico City.

In order to evaluate the synergistic effect of habitual smoking and air pollution in Mexico City on the retention of inorganic fibers, ferruginous bodies (FB) were quantified as markers of exposure to inorganic fibers in lung digests from 426 autopsy cases. FB were isolated from 426 lung digests from cases with several lung diseases. The results revealed more retention of FB in the smokers group than in non-smokers: 38 FB per gram (FB/g) versus 11.2 FB/g, respectively (p < 0.05). Male smokers living in Mexico City increased their median to 54 FB/g. This contrasts with the median of outside residents: 11.2 FB/g (p < 0.002). Housewives and manual laborers increased their medians when the smoking habit was positive: from 11 to 14 FB/g, and from 16 to 21.5 FB/g, respectively. There is an effect of tobacco smoke on the retention of more fibers identified as FB when the individuals are males and Mexico City residents.

Primary Cardiac Epithelioid Angiosarcoma in a Latin American Patient: Case Report and Literature Review.

Cardiac angiosarcoma is a rare and clinically challenging pathology. It is a high-grade primary malignant tumor of the heart tissue that has many variants, of which the epithelioid variant is rarely present in the heart or the great vessels. As with many other cardiac tumors, it is mainly a diagnosis of exclusion and the initial diagnostic test is an echocardiogram followed by a biopsy with immunohistochemistry analysis to ascertain the type of tumor. The differential diagnosis of cardiac tumors is challenging due to the overlapping clinical manifestations with different cardiac tumors and systemic diseases. Cardiac angiosarcomas are often aggressive with a poor prognosis even with treatment. Herein, we present a case of the epithelioid variant of a cardiac angiosarcoma in addition to a thorough review of the recent literature on the clinical manifestation, diagnosis, and treatment of this type of tumors.

Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion.

OBJECTIVE: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. METHODS: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. RESULTS: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. CONCLUSIONS: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

Localization and level of expression of beta-catenin in human laryngeal squamous cell carcinoma.

OBJECTIVE: We studied the participation of beta-catenin in the histologic differentiation of laryngeal squamous cell carcinomas. STUDY DESIGN AND SETTING: At the National Institute of Respiratory Diseases, a tertiary referral center, localization and level of expression of beta-catenin were compared between normal epithelium (15 cases) and primary tumors in different degrees of differentiation (38 cases), using an immunohistochemical procedure. RESULTS: Cell membrane staining of beta-catenin was observed in normal epithelium and in well and moderately differentiated carcinomas. Cytoplasmic redistribution was observed in poorly differentiated carcinomas. Loss of beta-catenin correlated with tumor dedifferentiation. CONCLUSION: Reduction of cell membrane beta-catenin expression correlated with tumor dedifferentiation. SIGNIFICANCE: Loss of beta-catenin may lead to diminishing the strength of the intercellular adhesion system, thereby promoting the invasive phenotype of the squamous cell carcinoma of the larynx.

Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion / Exactitud de la biopsia pleural cerrada para el diagnóstico de derrame pleural maligno

ABSTRACT Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

RESUMEN Objetivo: Estudios previos demuestran que la biopsia pleural cerrada (BPC) para diagnóstico de malignidad tiene una sensibilidad menor al 60%, por lo que recientemente ha despertado controversia su valor como prueba diagnóstica. Nuestro objetivo fue evaluar la exactitud de la BPC para diagnóstico de malignidad en pacientes con derrame pleural. Métodos: Estudio prospectivo de 8 años en individuos que se sometieron a la realización de BPC para establecer la etiología del derrame. La información de cada paciente se tomó de los registros de anatomopatología y del expediente clínico. Cuando el resultado de la BPC demostró malignidad o tuberculosis, esto se tomó como biopsia diagnóstica y quedó éste como diagnóstico definitivo. En los casos en que el resultado del estudio histopatológico de la biopsia resultó inespecífico, el diagnóstico definitivo se estableció en base a otros procedimientos diagnósticos, como toracoscopia, toracotomía, fibrobroncoscopia, estudio bioquímico y celular del líquido pleural y/o pruebas microbiológicas. Mediante una tabla de contingencia de 2 × 2 se midieron los indicadores para una prueba diagnóstica. Resultados: Se estudiaron 1034 biopsias de pacientes con derrame pleural, de las cuales se excluyeron 171 (16.54%) por muestra inadecuada o información insuficiente. El desempeño para malignidad fue: sensibilidad, 77%; especificidad, 98%; valores predictivos positivo y negativo, 99% y 66%, respectivamente; índices de probabilidad positivo y negativo, 38.5 y 0.23, respectivamente; probabilidad antes y después de la prueba, 2.13 y 82, respectivamente. Conclusión: La BPC es útil como prueba diagnóstica en la práctica clínica, debido a que produce un cambio importante de la probabilidad antes de la prueba a la probabilidad después de la prueba.

Socioeconomic factors influencing hospitalized patients with pneumonia due to influenza A(H1N1)pdm09 in Mexico.

BACKGROUND: In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. METHODOLOGY AND PRINCIPAL FINDINGS: A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. CONCLUSIONS: Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These socioeconomic factors may explain the different patterns of morbidity and mortality for H1N1 influenza observed among different countries and regions.

Sensibilidad y especificidad diagnóstica entre citología e histología broncopulmonar en pacientes con cáncer pulmonar durante diez años / Diagnostico sensitivity and specificity between bronchial cytology and histology in patients with lung cancer. A ten year review

Introducción: El cáncer pulmonar es la segunda causa de mortalidad en México, por esta razón el objetivo principal de este artículo es conocer el grado de certeza diagnóstica de los estudios histológicos y citológicos empleados en la población que acude al Instituto Nacional de Enfermedades Respiratorias y donde además, se debe contar con un método de control de calidad para las muestras enviadas. Material y métodos: Se revisaron todos los lavados, cepillados y biopsias transbronquiales de los archivos del Servicio de Patología de 1989 a 1998. Resultados: Fueron 1,094 estudios completos, 430 mujeres y 664 hombres. La neoplasia más frecuente fue el adenocarcinoma en 501 casos. La sensibilidad y especificidad del lavado y cepillado bronquial es del 62, 58, 65 y 54 por ciento, respectivamente y su valor predictivo es del 83 y 80 por ciento. El coeficiente de correlación es del 97 por ciento. Conclusiones: Los tres estudios en conjunto, son de los métodos con mayor sensibilidad para la identificación de neoplasias pulmonares.

Mesotelioma y aplasia pura de serie roja / Malignant mesothellioma and pure red cell aplasia

La aplasia pura de serie roja (APSR) es un síndrome clínico definido por la disminución de precursores eritroides maduros. Los pacientes con esta enfermedad presentan reticulopenia pero su cuenta de plaquetas y granulocitos es normal. La patofisiología es heterogénea y puede ser congénita o adquirida. En su forma secundaria, se encuentra asociada con distintos tipos de tumores como los timomas, las leucemias y los linfomas. El interés del caso que presentamos es la presencia de una aplasia pura de serie roja en un paciente con un mesotelioma. El tratamiento utilizado para esta aplasia consistió en el uso de prednisona y eritropoyetina recombinante humana. Ninguno de los tratamientos utilizados mejoró la anemia, por lo que el paciente fue mantenido a base de transfusiones periódicas. Por otra parte, el mesotelioma es una neoplasia muy agresiva con una vida media de tan solo dos a ocho meses. El paciente presentó una sobrevida de 18 meses y un estado físico aceptable.

Mucormicosis pulmonar diseminada: informe de dos casos / Disseminated pulmonary mucormycosis: report of two cases

La mucormicosis es causada por hongos de la clase de los Zigomicetos, orden de los Mucorales, es una micosis oportunista. Los factores de riesgo son diabetes mellitus, neoplasias principalmente hematológicas, trasplante de órganos, uso de medicamentos citotóxicos e inmunosupresores. La localización pulmonar ocupa el segundo lugar en frecuencia después de la rinocerebral.Se informan dos casos: Caso 1. Hombre de 57 años de edad con diabetes mellitus de 10 años de evolución, con neumonía necrotizante, falleció y en la autopsia se encontró el lóbulo superior derecho con extensa necrosis, colonias de bacterias Gram positivas e hifas anchas no septadas que se identificaron como de Mucorales. Caso 2. Hombre de 43 años de edad diabético, cuadro neumónico con opacidad del hemitórax derecho, la gammagrafía ventilatoria-perfusoria mostró destrucción completa del pulmón derecho. Se hizo neumonectomía, el pulmón mostró lesiones semejantes al caso 1. No recibió tratamiento específico, falleció y en la autopsia no se encontraron lesiones micóticas en el pulmón izquierdo, hubo diseminación a bazo, riñones y tiroides.

Caso anatomoclíiico: hombre de 71 años de edad on tabaquismo intenso e imagen radiológica de cavitación

Hombre de 71 años de edad con diabetes mellitus tipo II de 10 años de evolución, con tabaquismo intenso. Inició con derrame pleural e imagen radiológica de cavitación en lóbulo superior izquierdo.

Male of 71 years with 10 years evolution of diabetes mellitus II, heavy smoker. The case began with pleural overflow and with X ray cavitation in the left upper lobe.

Fístula arteriovenosa pulmonar: informe de un caso / pulmonary arteriovenous fistula: a case report

La fístula arteriovenosa pulmonar es una malformación congénita de la vasculatura pulmonar con persistencia de una o más comunicaciones entre los capilares pulmonares; el efecto fisiopatológico es consecuencia de la falta de oxigenación por paso directo de la sangre a través del sistema venoso. Nosotros reportamos a un niño de siete años de edad, con fístula arteriovenosa pulmonar difusa. Se revisaron en la literatura las ventajas y desventajas de cada método diagnóstico, concluyendo que la angiografía pulmonar sigue siendo de oro para el diagnóstico de esta enfermedad

Indice de calidad en citología en una muestra probabilística en la Cd. de México / Quiality indez in cytology in Mexico Cyty acoording to a probability sample

Se realizó una evaluación externa de la calidad del espécimen en citología ginecológica (PAP) en el laboratorio de Citopatología del Hospital General de la Ciudad de México para lo cual se evaluaron 6011 pruebas de PAP seleccionadas en forma aleatoria de 31,378 estudios de PAP reportados previamente como negativos, en el período 1988-1989. Se construyó un índice de calidad del espécimen con base en la presencia de células encocervicales, moco y metaplasia epidermoide. El índice de calidad construido reveló que el 64.1 por ciento de los especímenes son de baja calidad. La correlación entre el error diagnóstico y la calidad del PAP fue de 0.87. Estos resultados muestran la necesidad de instrumentar programas de evaluación externa en el diagnóstico de PAP, así como adiestramiento permanente en registro, técnicas de monitoreo en obtención, fijación y transporte del material de citología en los laboratorios de detección de cáncer poblacional.