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Cancer registries are essential for monitoring cancer burden and patterns, and document changes in time for cancer control. Hereby, we present the first results of four years of the Merida population-based cancer registry in Mexico.The registry collects data on all new cancers diagnosed since 2015 using both active and passive methods including a total of 104 information sources. Definitions and coding follow international standards. Using CanReg5 software, age-standardized incidence rates (ASR/100,000 person years) were computed by direct method using the world standard population.A total of 5684 new cancer cases were registered during 2015-2018, 2321 in males and 3363 in females corresponding to age-adjusted incidence rates (ASR per 100,000) of 128.5, and 153.1, respectively. Most frequent cancers among males were prostate cancer (ASR 29.8), lymphomas (ASR 10.9) and colorectal cancer (ASR 9.7) while among females it was breast cancer (ASR 49.3), cervical cancer (ASR 17.5) and corpus uteri (ASR 11.5). Childhood cancers (0-14 year) represented 2.9% of all cancers, with leukemias accounting for 52% of the new cases. Overall, 87.6% of new cases were microscopically verified.The data reported provide information on the cancer profile in Merida. Prostate and breast cancer are the main incident cancers. Cervical cancers present high rates among women, while lymphomas and liver cancer data merit further exploration. Efforts to support the Merida cancer registry as well as other registries in Mexico need to be pursued in order to have locally recorded data to support cancer control measures.

Spreadsheet of counts of patients with SNV/indel mutations in each gene

PDF file of supplementary methods and materials, and supplementary figures and tables

Supplementary Table 1 from Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2

Supplementary Table 2 from Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2

Supplementary Figures 1-7 from Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2

Supplementary Figure Legends 1-7 from Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2

Introducción: Las alteraciones esqueléticas son variaciones que se presentan en los maxilares y en la oclusión. Además, estas pueden generar problemas en las vías aéreas faríngeas. (5) Para ello surgen entonces diferentes procedimientos para corregir los problemas óseos; como la cirugía ortognática. Sin embargo, estas técnicas quirúrgicas no comprueban a cabalidad cambios significativos en las vías aéreas faríngeas superior e inferior. Objetivos: Determinar los cambios dimensionales en sentido anteroposterior de las vías aéreas faríngeas superiores e inferiores en las radiografías laterales de cráneo de los pacientes sometidos a cirugía ortognática. Metodología: Se realizó un estudio Observacional Descriptivo de Corte Transversal. En la muestra se incluyeron 24 radiografías cefálicas laterales de los pacientes entre 18 y 60 años de edad sometidos a cirugía ortognática. Se calcularon proporciones para las variables cualitativas, medidas de tendencia central y de dispersión para las cuantitativas. En las variables cefalométricas antes versus después; se aplicó la prueba T de Student pareada o el Test de signos de Wilcoxon según la distribución de los datos, adicionalmente se aplicó el coeficiente de correlación de Pearson para relacionar los cambios dimensionales de las vías aéreas faríngeas con los Planos SNA y SNB. Para el análisis se consideró un nivel de significancia de α ≤ a 0,05. Resultados: Es importante destacar que para cirugía de retroceso del maxilar se evidenciaron diferencias estadísticamente significativa antes y después del proceso quirúrgico (p=0,0023) pues gracias a esta cirugía los pacientes tuvieron 1,7 mm más en su espacio faríngeo superior. Mientras que las cirugías de avance y también la de retroceso mandibular les permitieron ganar 1,5 (p=0,0108) y 1,8 mm (p=0,0184) en este mismo espacio faríngeo Conclusiones: Se evaluaron 24 radiografías laterales de cráneo, en las cuales fue posible determinar cambios en la amplitud de las vías aéreas faríngeas superior e inferior, que se pudo haber producido por el conjunto de procedimientos quirúrgicos al que cada uno de los pacientes fue sometido.

Gastric cancer is a leading cause of cancer mortality and health disparities in Latinos. We evaluated gastric intratumoral heterogeneity using multiregional sequencing of >700 cancer genes in 115 tumor biopsies from 32 patients, 29 who were Latinos. Analyses focused on comparisons with The Cancer Genome Atlas (TCGA) and on mutation clonality, druggability, and signatures. We found that only approximately 30% of all mutations were clonal and that only 61% of the known TCGA gastric cancer drivers harbored clonal mutations. Multiple clonal mutations were found in new candidate gastric cancer drivers such as EYS, FAT4, PCDHA1, RAD50, EXO1, RECQL4, and FSIP2. The genomically stable (GS) molecular subtype, which has the worse prognosis, was identified in 48% of our Latino patients, a fraction that was >2.3-fold higher than in TCGA Asian and White patients. Only a third of all tumors harbored clonal pathogenic mutations in druggable genes, with most (93%) GS tumors lacking actionable clonal mutations. Mutation signature analyses revealed that, in microsatellite-stable (MSS) tumors, DNA repair mutations were common for both tumor initiation and progression, while tobacco, POLE, and inflammation signatures likely initiate carcinogenesis. MSS tumor progression was likely driven by aging- and aflatoxin-associated mutations, as these latter changes were usually nonclonal. In microsatellite-unstable tumors, nonclonal tobacco-associated mutations were common. Our study, therefore, contributed to advancing gastric cancer molecular diagnostics and suggests clonal status is important to understanding gastric tumorigenesis. Our findings of a higher frequency of a poor prognosis associated molecular subtype in Latinos and a possible new aflatoxin gastric cancer etiology also advance cancer disparities research. Significance: Our study contributes to advancing our knowledge of gastric carcinogenesis, diagnostics, and cancer health disparities.

Existen muy pocos estudios que hacen énfasis en las complicaciones macrovascularesy microvasculares de la DM, lo que justifica la realización de esta revisión bibliográfica para garantizar un abordaje total. Este estudio tiene como objetivo conocer la condición de la diabetes mellitus a nivel global, considerando datos epidemiológicos,clínicos, complicaciones macrovasculares y microvasculares asociadas a la edad al momento del diagnóstico.Método: Los datos se obtuvieron de Scopus, Scielo y Sciencedirect, incluyendo artículos actualizados desde el 2017.Se seleccionaron artículos científicos que investigaban el efecto de la edad de los pacientes relacionada a un diagnóstico temprano o tardío de diabetes, que repercute en las complicaciones macrovasculares y microvasculares en adultos con diabetes tipo 2, y artículos que comparaban la eficacia del tratamiento farmacológico con grados de evidencia.Se incluyeron datos de 15 estudios observacionales que comprendían 8131 personas de 8 países, el riesgo de padecer diabetes se incrementa con la edad, pero disminuye al aumentar el grado de escolaridad.La diabetes mellitus es una problemática mundial creciente cuya etiología se basa en la deficiencia de insulina en distinto grado, este estado hiperglucémico crónico produce complicaciones microvasculares y macrovasculares de no tratarse adecuadamente, las guías proporcionadas por la ADA y ALAD son una gran herramienta para ofrecer un tratamiento oportuno y eficiente al paciente diabético.

Melanoma is the deadliest form of skin cancer. Due to its high mutation rates, melanoma is a convenient model to study antitumor immune responses. Dendritic cells (DCs) play a key role in activating cytotoxic CD8+ T lymphocytes and directing them to kill tumor cells. Although there is evidence that DCs infiltrate melanomas, information about the profile of these cells, their activity states, and potential antitumor function remains unclear, particularly for conventional DCs type 1 (cDC1). Approaches to profiling tumor-infiltrating DCs are hindered by their diversity and the high number of signals that can affect their state of activation. Multiplexed immunofluorescence (mIF) allows the simultaneous analysis of multiple markers, but image-based analysis is time-consuming and often inconsistent among analysts. In this work, we evaluated several machine learning (ML) algorithms and established a workflow of nine-parameter image analysis that allowed us to study cDC1s in a reproducible and accessible manner. Using this workflow, we compared melanoma samples between disease-free and metastatic patients at diagnosis. We observed that cDC1s are more abundant in the tumor infiltrate of the former. Furthermore, cDC1s in disease-free patients exhibit an expression profile more congruent with an activator function: CD40highPD-L1low CD86+IL-12+. Although disease-free patients were also enriched with CD40−PD-L1+ cDC1s, these cells were also more compatible with an activator phenotype. The opposite was true for metastatic patients at diagnosis who were enriched for cDC1s with a more tolerogenic phenotype (CD40lowPD-L1highCD86−IL-12−IDO+). ML-based workflows like the one developed here can be used to analyze complex phenotypes of other immune cells and can be brought to laboratories with standard expertise and computer capacity.

La realidad extendida es un conjunto de tecnologías cuyo uso se está incrementando rápidamente, especialmente con el auge de las tecnologías 4.0, para el aprendizaje y entrenamiento de procedimientos complejos. El objetivo de este trabajo es identificar las características y atributos de una interfaz gráfica de usuario para dichos entornos virtuales, y su influencia en el desempeño, la atención y la carga cognitiva del usuario. Para lograr dicho objetivo, se siguió una metodología de revisión sistemática de la literatura. Los resultados mostraron la influencia de atributos como el color, la forma, la separación visual y la contigüidad espacial, espacialmente para la señalización visual. Se discutieron los resultados y su posible impacto en el diseño de interfaces gráficas para entornos de realidad extendida.

Head and neck squamous cell carcinomas (HNSCC) show a variety of biological and clinical characteristics that could depend on the association with the human papillomavirus (HPV). Biological and clinical characterization is essential to stratify patients based on prognostic and predictive factors. Reports on HNSCC are scarce in Mexico. Herein, we analyzed 414 Mexican patients with HNSCC, including oropharynx (OPSCC), larynx (LASCC), and oral cavity (OCSCC), and identified HPV DNA and p16 expression. Global gene expression profiles were analyzed in 25 HPV+/p16+ vs. HPV−/p16− cases. We found 32.3% p16+ and 22.3% HPV+ samples, HPV 16, 18, 39, 52, and 31 being the most frequent genotypes. For OPSCC, LASCC and OCSCC, 39.2, 14.7, and 9.6% were HPV+/p16+, respectively. High expression of SLIRP, KLF10, AREG, and LIMA was associated with poor survival, in contrast, high expression of MYB and SYCP2 correlated with better survival. In HPV+ cases, high expression of SLC25A39 and GJB2 was associated with poor survival. Likewise, EGFR, IL-1, IL-6, JAK-STAT, WNT, NOTCH, and ESR1 signaling pathways were downregulated in HPV+ cases. CSF1R, MYC, and SRC genes were identified as key hubs and therapeutic targets. Our study offers information regarding the molecular and clinical characteristics of HNSCC in Mexican patients.

Los laboratorios son herramientas fundamentales para el proceso de aprendizaje y la enseñanza en todas las ramas del conocimiento, particularmente, en las áreas STEM. Con ellos se busca que los estudiantes adquieran

Introduction: Tuberculosis is an infectious disease which is caused by bacilli from the M. tuberculosis complex. The Mycobacterium bovis Bacillus Calmette-Guérin vaccine is currently available as a prophylactic tool for preventing the disease; it has been shown to be efficient in preventing disseminated forms of tuberculosis during early ages; however, its efficiency is limited in areas where individuals have had prior exposure to environmental mycobacteria, and its efficacy decreases with a host’s age. Areas covered: Following a comprehensive search of the available literature, this review describes some of the most frequently used animal models, the most frequently used methods for evaluating efficacy in animal models and some in vitro strategies as alternatives for evaluating vaccines. Expert opinion: Identifying the animal models used up to now for evaluating vaccines during their development stages, their characteristics and limitations, as well as knowledge regarding strategies for evaluating promising vaccine candidate efficacy, will ensure more efficient, reliable and reproducible pre-clinical trials. Although much of the knowledge accrued to date concerning vaccine effectiveness against tuberculosis has been based on animal models, it is clear that large questions still need to be resolved and that extrapolation of such efficacy to humans has yet to be achieved. © 2019, © 2019 Informa UK Limited, trading as Taylor and Francis Group.

Objective: Mediastinal schwannomas sometimes can be confused with other neoplasms in the initial radiological studies, especially when there is a history of cancer in another site and that require a more accurate analysis by computed tomography (CT) or even magnetic resonance (MRI). Our study was aimed to perform a retrospective analysis of the clinical and imaging features in a series of patients with mediastinal schwannomas that were confirmed by histology and immunohistochemistry.Results: We found eight patients, five man and three women with an average age of 51 years. The main signs and symptoms at time of diagnosis were chest pain, dyspnea, cough and dysphagia. CT showed that the tumor was located in the posterior compartment of the chest in 7/8 cases. Tumors >10 cm were more heterogeneous and showed cystic changes. All cases underwent posterolateral thoracotomy and radiological follow-up showed no evidence of recurrence. Histological analysis was the gold standard to confirm diagnosis in addition to at least one neurogenic IHC marker. In conclusion, mediastinal schwannomas are benign encapsulated tumors. By CT, schwannomas >10 cm showed cystic degeneration more frequently. Posterolateral thoracotomy allows complete resection and is considered the surgical approach of choice.

Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8+ T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1+ PD-1+ CD8+ Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8+ Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy.

BackgroundApproximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency.ObjectiveTo evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters.MethodsFor HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively.ResultsSixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16.ConclusionsHPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Background Similarities between the pathologic progression of cancer and the physiologic process of placentation have been recognized for many years proposing that both present similar mechanisms and processes. Cervical cancer (CC) is one of the most frequent neoplasia among Mexican women turning it into an important health problem. Objective The aim of this study was to determine the degree of the involvement of pregnancy related genes and in cancer progression by in-silico analysis and validated in CC samples. Results The data mining analysis resulted in the identification of genes expressed in term placenta, first trimester placenta and normal cervical tissues. Finally, we selected KISS1 for the involvement of pregnancy related gene and also in cancer process. In order to explore KISS1 in CC, we analyzed Copy Number Variation (CNV) and gene expression using microarray experiments. KISS1 showed 20% genomic gain in 1q32.1 on CC samples. Furthermore, microarray analysis showed KISS1 as up-regulated genes. Results were validated showing an overexpression of 85% of KISS1 in CC samples. Conclusions Data suggest KISS1 as a great candidate for CC molecular markers or as a therapeutic target for CC. Also, HPV presence does not seem to alter the KISS1 expression in CC.

Evaluar la presencia de IgG contra C. trachomatis en mujeres entre 18 a 30 años con diagnóstico de artritis de la ciudad de Bogotá D.C. Métodos. Los grupos de estudio están compuestos por un grupo de casos AR (mujeres con diagnóstico de artritis reumatoide y reactiva) y un grupo control. Se obtuvieron muestras de suero y se realizó la determinación cuantitativa de IgG contra C. trachomatis, la determinación PCR (proteína C reactiva) y FR (factor reumatoide). Resultados. Las variables de talla y peso descritas en la población de estudio, muestran un comportamiento homogéneo, por lo cual no interfieren en los resultados obtenidos. Las medias se compararon por los test Mann Whitney y t test no pareado. El porcentaje de resultados positivos en la determinación cualitativa de PCR fueron de: 36,6% para el grupo de casos y 14,5% para el grupo control. En la determinación cualitativa de FR el porcentaje de resultados positivos fueron: 48,8% para el grupo de casos y 5,3% para el grupo control. Finalmente, el porcentaje de resultados positivos en la determinación de anticuerpos IgG específicos contra C trachomatis fue de 2,4% para el grupo de casos y 22,4% para el grupo de controles. Las variables de PCR y FR mostraron mayor frecuencia de resultados positivos en el grupo de casos, en comparación con el grupo control, lo cual se correlaciona con la existencia de procesos inflamatorios propios del desarrollo de artritis. Sin embargo el grupo control presentó mayor frecuencia de anticuerpos IgG específicos contra C. trachomatis en comparación con el grupo de casos. Estos resultados hacen necesario evaluar a futuro, el comportamiento de las pacientes del grupo control con resultados positivos de IgG contra C. trichomatis que permitirían observar una posible aparición de síntomas relacionados con artritis.

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-β) 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-β expression but not with ER-α expression. In the normal cervical epithelium, ER-α and ER-β were expressed but the BORIS protein was not detected. In the LSIL samples, BORIS, ER-α and ER-β were expressed; however, in the HSIL samples, only the BORIS and ER-β expressions were detected, but ER-α expression was minimal or null. In the SC, only BORIS and ER-β were detected. In summary, the results show that the expressions of BORIS and ER-β increase while the expression of ER-α decreases according to the severity of the lesions. These results suggest synergistic roles for BORIS and ER-β 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.

ResumenIntroducciónLa fluorescencia ha sido utilizada exitosamente como pesquisa del cáncer oral, adicional al examen oral convencional, identifica áreas con cambios histológicos que son desapercibidas con luz blanca.ObjetivoSaber si la resección guiada por fluorescencia se asocia a márgenes quirúrgicos negativos en pacientes con cáncer de lengua.Material y métodosSe incluyó a pacientes con carcinoma invasivo de lengua candidatos a resección. Se evaluaron con examen oral convencional y con fluorescencia determinándose si el límite de la lesión coincidía en ambos exámenes, se marcaron los límites quirúrgicos analizándose histológicamente.ResultadosFueron 30 pacientes con carcinoma epidermoide invasivo; 10 T1, 15 T2 y 5 T3; 18 mujeres y 12 hombres. El borde de la lesión neoplásica evaluado con el examen oral convencional coincidió con la evaluación con fluorescencia en 17 (56%) y en 13 (44%) la lesión fue mayor. Los márgenes de quirúrgicos fueron negativos en 27 (90%) y positivos en 3 (10%), los positivos lo fueron en el espesor lingual, todos fueron cT3.ConclusionesLa fluorescencia identifica lesiones mayores a las diagnosticadas con el examen oral convencional en el 44% de los pacientes, favorece resección quirúrgica con márgenes negativos en el 90%, la infiltración submucosa y muscular no puede ser detectada por este método.AbstractBackgroundFluorescence has been successfully used as screening method of oral cavity cancer. In addition to the conventional oral examination, it identifies areas with histological changes that are not identified with conventional white light.ObjectiveTo determine whether fluorescence facilitates resection with negative margins in patients diagnosed with squamous cell carcinoma of the tongue.Material and methodsPatients diagnosed with invasive tongue squamous cell carcinoma were evaluated with a conventional oral examination and fluorescence. To determine whether the threshold of injury coincided in both tests, the limits of section were identified and histologically evaluated.ResultsThe study included 30 patients, 18 women and 12 men; 10 T1, 15 T2, and 5 patients with T3. The neoplastic margin evaluated with conventional light coincided with fluorescence in 17 patients (56%), and in 13 (44%) fluorescence identified a larger tumour. Surgical margins were negative in 27 (90%), and 3 (10%) positives that were all in the tongue thickness and with bulky tumours (T3).ConclusionsFluorescence identifies larger tumours than those identified with conventional oral examination in 44% of patients, and ensures a longer surgical resection with free surgical margins in 90% of cases. Submucosal and muscular invasion is not detected by this method.

Background The goal of conservative surgical treatment of laryngeal cancer is to obtain oncological control with preservation of laryngeal function. The concept of laryngeal function preservation should be understood as the preservation of the patient's ability to breathe normally with neither tracheostomy nor aspiration, and maintaining intelligible speech. This can be achieved by a balance between two fundamental aspects, proper patient selection (based on tumour extension and preoperative laryngeal function), and an adequate histopathological analysis of the surgical specimen. Supracricoid subtotal laryngectomy is the voice conservative surgical technique that offers the best possibility of control in patients with locally advanced laryngeal cancer. The proper histopathological analysis allows staging and selecting patients for adjuvant therapy, avoiding unnecessary ones as well as designing monitoring and surveillance programs based on risk factors. Objective To highlight key points in the histopathological evaluation of the surgical specimen of a subtotal laryngectomy. Conclusion The proper communication between the surgeon and pathologist, offering complete information on preoperative clinical evaluation and the knowledge of the key points in the evaluation of the surgical specimen (sites of tumour leakage and surgical resection margins) are fundamental parameters to achieve a proper histopathological evaluation of the surgical specimen.

ResumenIntroducciónLa finalidad del tratamiento quirúrgico conservador del cáncer laríngeo es obtener control oncológico con preservación de la función laríngea; a su vez, la preservación de la función debe entenderse como la conservación de la capacidad del paciente para ventilar por vía normal sin traqueotomía y sin aspiración, manteniendo habla inteligible. Este propósito se logra manteniendo el balance entre 2 aspectos fundamentales: la adecuada selección del paciente (con base en la extensión tumoral y la función laríngea preoperatoria) y un adecuado análisis histopatológico de la pieza quirúrgica. La laringectomía subtotal supracricoidea es la técnica quirúrgica conservadora de la voz que oncológicamente ofrece la mejor posibilidad de control en pacientes con cáncer localmente avanzado de laringe; su adecuado análisis histopatológico permite estadificar y seleccionar a los pacientes candidatos a tratamiento adyuvante, evitando terapias innecesarias, y permite diseñar un programa de seguimiento y vigilancia con base en los factores de riesgo.ObjetivoSeñalar los puntos clave en la evaluación histopatológica de la pieza de laringectomía subtotal.ConclusionesLa adecuada comunicación entre el cirujano y el patólogo, el ofrecer información completa de la evaluación preoperatoria clínica y el conocimiento de los puntos clave en la evaluación de la pieza (sitios de probable fuga tumoral y márgenes de sección quirúrgica) son parámetros fundamentales para lograr la adecuada evaluación histopatológica del espécimen quirúrgico.AbstractIntroductionThe goal of conservative surgical treatment of laryngeal cancer is to obtain oncological control with preservation of laryngeal function. The concept of laryngeal function preservation should be understood as the preservation of the patient's ability to breathe normally with neither tracheostomy nor aspiration, and maintaining intelligible speech. This can be achieved by a balance between two fundamental aspects, proper patient selection (based on tumour extension and preoperative laryngeal function), and an adequate histopathological analysis of the surgical specimen. Supracricoid subtotal laryngectomy is the voice conservative surgical technique that offers the best possibility of control in patients with locally advanced laryngeal cancer. The proper histopathological analysis allows staging and selecting patients for adjuvant therapy, avoiding unnecessary ones as well as designing monitoring and surveillance programs based on risk factors.ObjectiveTo highlight key points in the histopathological evaluation of the surgical specimen of a subtotal laryngectomy.ConclusionThe proper communication between the surgeon and pathologist, offering complete information on preoperative clinical evaluation and the knowledge of the key points in the evaluation of the surgical specimen (sites of tumour leakage and surgical resection margins) are fundamental parameters to achieve a proper histopathological evaluation of the surgical specimen.

ResumenAntecedentesEl tratamiento de referencia de tipo conservador no quirúrgico para el cáncer de laringe en etapa avanzada es combinado (quimio-radioterapia). Sin embargo, las complicaciones que se presentan con dicho tratamiento no son pocas, principalmente en lo que se refiere a la deglución. La cirugía conservadora de laringe sigue siendo una alternativa eficaz para el control oncológico sin las complicaciones asociadas a la quimio-radioterapia.Material y métodosEstudio retrospectivo que incluyó a pacientes con cáncer laríngeo cT3, cN0 con infiltración paraglótica, fijación cordal, pero movilidad aritenoidea normal y sin infiltración subglótica que fueron tratados con laringectomía subtotal supracricoidea. Se evaluaron complicaciones, secuelas del tratamiento y recurrencia. La aspiración bronquial fue estudiada con gammagrafía de tránsito esofágico.ResultadosFueron intervenidos 25 pacientes; los márgenes de sección fueron negativos en 22; en uno, los márgenes mostraron contacto con el tumor, y en dos resultaron positivos. Dos pacientes recibieron radioterapia posoperatoria. La media del tiempo hasta la decanulación fue de 15 días, en tanto que para el retiro de la sonda nasogástrica fue de 25 días. La media del seguimiento fue de 26 meses. Ninguno de los pacientes ha presentado recurrencia tumoral, ni conversión a laringectomía total. Todos los pacientes presentan deglución normal y ninguno ha requerido traqueotomía permanente, en tanto que la voz es considerada inteligible en todos ellos. Los estudios de gammagrafía del tránsito esofágico mostraron aspiración en 15/25 pacientes, ninguno con repercusión clínica. Cinco pacientes experimentaron complicaciones posoperatorias, cuatro requirieron re-intervención, pero ninguno requirió conversión a laringectomía total.ConclusiónLa cirugía conservadora es una alternativa eficaz a la asociación quimio-radioterapéutica, que ofrece un control oncológico con complicaciones aceptables y secuelas mínimas. Aunque la mayoría de los pacientes experimenta aspiración, ésta no repercute en el estado funcional.AbstractBackgroundThe non-surgical organ-preserving standard of care for advanced-stage laryngeal cancer is combined treatment (chemo-radiotherapy). However, complications occurring with this treatment are not few, and mainly with regards to swallowing. Conservative laryngeal surgery remains an effective alternative for cancer control without the complications associated with chemo-radiotherapy.Material and methodsRetrospective study that included patients with cT3, cN0 laryngeal cancer with paraglottic infiltration, vocal cord fixation, but with normal arytenoid mobility, and without subglottic infiltration, who were treated with supracricoid subtotal laryngectomy. Complications, treatment sequels, and recurrence were assessed. Bronchial aspiration was studied with swallowing scintigraphy.ResultsTwenty-five patients underwent the intervention. Surgical margins were negative in 22, and in one, they were in contact with the tumour, and in 2 they were positive. Two patients received post-operative radiotherapy. Mean time to de-cannulation was 15 days, and 25 days to nasogastric tube removal. Mean follow-up was 26 months. None of the patients has had tumour recurrence or has required conversion to total laryngectomy. In all patients, swallowing has been normal and no one has required permanent tracheotomy. The voice is considered to be intelligible in all patients. Swallowing scintigraphy showed aspiration in 15/25 patients, which was not clinically relevant. Five patients had post-operative complications, with 4 patients requiring re-intervention, but no one required conversion to total laryngectomy.ConclusionConservative surgery is an effective alternative to chemo-radiotherapy that offers cancer control with acceptable complications and minimal sequels. Although most patients experience aspiration, this does not affect the functional status.

Background: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. Materials and Methods: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. Results: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. Conclusions: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Cervical cancer (CC) as other cancer types, presents molecular deregulations, such as the alterations of transcription factors. Kruppel-like factors (KLF) are a family of transcriptional regulators. They are involved in diverse cellular processes, such as proliferation, apoptosis, and angiogenesis among others. Here, we analyzed the expression of all 17 KLF members at messenger RNA (mRNA) level, and protein expression of the two most commonly altered KLF5 and KLF6 in cervical tissues. Fifty-nine cervical tissues ranging from normal tissue to CC were evaluated for KLF1–17 mRNA expression by end-point RT-PCR and KLF5 by qRT-PCR. For KLF5 and KLF6 protein analysis, a tissue microarray was constructed containing the 59 cases and subjected for immunohistochemistry assay and KLF6 IVS1-27G>A single nucleotide polymorphism by direct DNA sequencing. KLF2–16 expressions were present in normal tissue, whereas all 17 were present in Low-Grade Squamous Intraepithelial Lesion, High-Grade-SIL and CC, unrelated to presence of human papillomavirus (HPV). KLF5 mRNA expression gradually increased throughout the subgroups and overexpressed in CC (p = 0.01). KLF5 and KLF6 proteins were immunodetected in all samples. For the KLF6 SNP analysis, 80 % of the CC population analyzed presented GG genotype and the remaining 20 % presented GA genotype (p = 0.491). Our present data show that KLFs expression could not be related to HPV presence, at least at transcriptional level, and KLF5 mRNA overexpression could represent a potential molecular marker for CC; KLF6 SNP has no relation to increased risk of CC.

Este artículo presenta un análisis sobre la utilización del control directo de potencia en sistemas fotovoltaicos conectados a la red de distribución. Esta técnica es utilizada para regular directamente las potencias instantáneas activa y reactiva intercambiadas entre el sistema fotovoltaico y la red de distribución trifásica, eliminando los lazos de control de corriente utilizados por las estrategias de control tradicionales. El funcionamiento del control directo de potencia en sistemas fotovoltaicos es evaluado mediante simulaciones en PSIM, lo cual muestra su buen desempeño para este tipo de aplicaciones. Finalmente, se realiza un análisis comparativo entre este controlador y una técnica tradicional utilizada en sistemas fotovoltaicos conocida como control orientado a tensión.

Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

Mechanistic studies of tumorigenesis point towards stem cells (SCs) being the cell of origin in prostate cancer initiation, suggesting stem pathways have a crucial role in the early stages of cancer development (Gu et al, 2007; Goldstein et al, 2010; Lawson et al, 2010). Furthermore, known stem pathways have been seen to be aberrantly expressed as the prostate cancer progresses (Linn et al, 2010; Jia et al, 2011; Kregel et al, 2013). Characterisation of the genes at play within prostate SCs, and characterising these same markers in the malignant setting may identify unique therapeutic opportunities for the treatment of prostate cancer. We have recently demonstrated the presence of the androgen receptor (AR) within normal human prostate SCs (Williamson et al, 2012), so identification of specific novel AR pathway processes within these cells will be of particular importance. Such mechanisms may explain the maintenance of androgen ‘addiction' in the malignant setting during cancer progression despite androgen deprivation, as it is established that the AR pathway has diverse roles depending on the degree of prostate differentiation (Gregory et al, 1998; Buchanan et al, 2001; Mousses et al, 2001; Chen et al, 2004; Taplin and Balk, 2004; Attard et al, 2009; Bonkhoff and Berges, 2010; Lee et al, 2012). Human prostate SCs can be enriched by their expressions of α2β1-integrins and CD133 (Richardson et al, 2004). In this work, we describe gene expression signatures associated with SCs (α2β1HI CD133+VE), transiently amplifying (TAP) cells (α2β1HI CD133−VE) and terminally differentiated (TD) cells (α2β1LOW CD133−VE) following the intuitive pathway analysis of transcriptome characterisation of human prostates. Within normal prostate SCs, we discovered a deficiency in class 1 UDP (uridine 5′-diphospho)-glucuronosyltransferase; UGT) enzymes (UGTA1), which are regulators of androgen catabolism. Our functional in vitro models of prostate cancer demonstrated that UGT1A knock down leads to upregulation of prostate-specific antigen (PSA) along with increased cell survival. Furthermore, reduced UGT1A expression was shown to be a feature of clinical prostate cancer that was associated with a poorer prognosis.

The androgen receptor (AR) is a key molecule involved in prostate cancer (PC) development and progression. Post-translational modification of the AR by co-regulator proteins can modulate its transcriptional activity. To identify which demethylases might be involved in AR regulation, an siRNA screen was performed to reveal that the demethylase, KDM4B, may be an important co-regulator protein. KDM4B enzymatic activity is required to enhance AR transcriptional activity; however, independently of this activity, KDM4B can enhance AR protein stability via inhibition of AR ubiquitination. Importantly, knockdown of KDM4B in multiple cell lines results in almost complete depletion of AR protein levels. For the first time, we have identified KDM4B to be an androgen-regulated demethylase enzyme, which can influence AR transcriptional activity not only via demethylation activity but also via modulation of ubiquitination. Together, these findings demonstrate the close functional relationship between AR and KDM4B, which work together to amplify the androgen response. Furthermore, KDM4B expression in clinical PC specimens positively correlates with increasing cancer grade (P < 0.001). Consequently, KDM4B is a viable therapeutic target in PC.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer. Fil: Sahasrabudhe, Ruta. University of California at Davis; Estados Unidos Fil: Lott, Paul. University of California at Davis; Estados Unidos Fil: Bohorquez, Mabel. Universidad del Tolima; Colombia Fil: Toal, Ted. University of California at Davis; Estados Unidos Fil: Estrada, Ana P.. Universidad del Tolima; Colombia Fil: Suarez, John J.. Universidad del Tolima; Colombia Fil: Brea Fernández, Alejandro. Ciber Enfermedades Raras; España Fil: Cameselle Teijeiro, José. Complejo Hospitalario Universitario de Santiago; España Fil: Pinto, Carla. Instituto Portugues de Oncologia de Francisco Gentil Porto; Portugal Fil: Ramos, Irma. Instituto Mexicano del Seguro Social; México Fil: Mantilla, Alejandra. Departamento de Patologia la Unidad Medica Alta Especialidad Oncologia; México Fil: Prieto, Rodrigo. Universidad del Tolima; Colombia Fil: Corvalan, Alejandro. Pontificia Universidad Católica de Chile; Chile Fil: Norero, Enrique. Pontificia Universidad Católica de Chile; Chile Fil: Alvarez, Carolina. Universidad Católica de Chile; Chile Fil: Tapia, Teresa. Pontificia Universidad Católica de Chile; Chile Fil: Carvallo, Pilar. Pontificia Universidad Católica de Chile; Chile Fil: Gonzalez, Luz M.. Instituto de Cancerologia, Las Americas; Colombia Fil: Cock-Rada, Alicia. Instituto de Cancerologia, Las Americas; Colombia Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educaciones Médicas e Investigación Clínica ; Argentina. Universidad de Buenos Aires; Argentina Fil: Neffa, Florencia. Laboratorio Genia; Uruguay Fil: Della Valle, Adriana. Laboratorio Genia; Uruguay Fil: Yau, Chris. University of Oxford; Reino Unido Fil: Soares, Gabriela. Centro Hospitalar Do Porto; Portugal Fil: Borowsky, Alexander. University of California at Davis; Estados Unidos Fil: Hu, Nan. National Cancer Institute; Estados Unidos Fil: He, Li-Ji. Yangcheng Cancer Hospital; China Fil: Han, Xiao-You. Shanxi Cancer Hospital; China Fil: Taylor, Philip R.. National Institutes of Health; Estados Unidos Fil: Goldstein, Alisa M.. National Institutes of Health; Estados Unidos Fil: Torres, Javier. Instituto Mexicano del Seguro Social; México Fil: Echeverry, Magdalena. Universidad del Tolima; Colombia Fil: Ruiz-Ponte, Clara. Centro de Investigación Biomédica en Red de Enfermedades Raras; España Fil: Teixeira, Manuel R.. Universidad de Porto; Portugal Fil: Carvajal Carmona, Luis G.. University of California at Davis; Estados Unidos

En este artículo se propone un algoritmo basado en filtros sintonizados para extraer las componentes instantáneas de secuencia positiva, negativa y cero (+,-,0) de señales de tensión y/o corrientes desequilibradas y distorsionadas. El trabajo se encuentra justificado en la necesidad de disponer de nuevos algoritmos que puedan ser utilizados en la medición de parámetros que afectan a la calidad de la energía eléctrica con el fin de diagnosticar y compensar las perturbaciones presentes en las señales de tensión y/o corriente. El desempeño del algoritmo es evaluado mediante simulaciones en Matlab/Simulink y por medio de su implementación en tiempo real en la tarjeta de desarrollo dSPACE 1104. Los resultados obtenidos muestran la eficacia del algoritmo propuesto.