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BACKGROUND: Cancer treatment has many side effects; therefore, more efficient treatments are needed. Mesenchymal stem cells (MSC) have immunoregulatory properties, tumor site migration and can be genetically modified. Some proteins, such as soluble TRAIL (sTRAIL) and interleukin-12 (IL-12), have shown antitumoral potential, thus its combination in solid tumors could increase their activity. MATERIALS AND METHODS: Lentiviral transduction of bone marrow MSC with green fluorescent protein (GFP) and transgenes (sTRAIL and IL-12) was confirmed by fluorescence microscopy and Western blot. Soluble TRAIL levels were quantified by ELISA. Lymphoma L5178Y cells express a reporter gene (GFP/mCherry), and TRAIL receptor (DR5). RESULTS: An in vivo model showed that combined treatment with MSC expressing sTRAIL+IL-12 or IL-12 alone significantly reduced tumor volume and increased survival in BALB/c mice (p < 0.05) with only one application. However, at the histological level, only MSC expressing IL-12 reduced tumor cell infiltration significantly in the right gastrocnemius compared with the control group (p < 0.05). It presented less tissue dysplasia confirmed by fluorescence and hematoxylin-eosin dye; nevertheless, treatment not inhibited hepatic metastasis. CONCLUSIONS: MSC expressing IL-12, is or combination with BM-MSC expressing sTRAIL represents an antitumor strategy for lymphoma tumors since they increase survival and reduce tumor development. However, the combination did not show significative additive effect. The localized application did not inhibit metastasis but reduced morphological alterations of tissue associated with liver metastasis.

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As the understanding of cancer grows, new therapies have been proposed to improve the well-known limitations of current therapies, whose efficiency relies mostly on early detection, surgery and chemotherapy. Mesenchymal stem cells (MSCs) have been introduced as a promissory and effective therapy. This fact is due to several useful features of MSCs, such as their accessibility and easy culture and expansion in vitro, and their remarkable ability for 'homing' towards tumors, allowing MSCs to exert their anticancer effects directly into tumors. Additionally, MSCs offer the practicability of being genetically engineered to carry anticancer genes, increasing their specificity and efficacy for fighting tumors. In the present study, the antitumoral efficacy and post-implant survival of mice bearing lymphomas implanted intratumorally were determined using mouse bone marrow-derived (BM)-MSCs transduced with soluble TRAIL (sTRAIL), full length TRAIL (flTRAIL), or interferon ß (IFNß), naïve BM-MSCs, or combinations of these. The percentage of surviving mice was determined once all not-implanted mice succumbed. It was found that the percentage of surviving mice implanted with the combination of MSCs-sTRAIL and MSCs-IFN-ß was 62.5%. Lymphoma model achieved 100% fatality in the non-treated group by day 41. On the other hand, the percentage of surviving mice implanted with MSCs-sTRAIL was 50% and with MSCs-INFß 25%. All the aforementioned differences were statistically significant (P<0.05). In conclusion, all implants exhibited tumor size reduction, growth delay, or apparent tumor clearance. MSCs proved to be effective anti-lymphoma agents; additionally, the combination of soluble TRAIL and IFN-ß resulted in the most effective antitumor and life enlarging treatment, showing an additive antitumoral effect compared with individual treatments.

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INTRODUCTION: The iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs. METHODS: We compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT). RESULTS: All sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted. CONCLUSIONS: Xenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair.

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ABSTRACT: Covid-19 is a viral disease that has spread throughout the world, becoming a pandemic. Dysgeusia and anosmia are some of its most frequent symptoms. The aim of the study was to determine the frequent signs and symptoms associated with COVID-19 patients. A cross-secional study from 370 patients with acute respiratory illness admitted by emergenc y services of a hospital in Acapulco. An institutional survey was applied to all patients as a data collection instrument, and a SARS-CoV-2 test, by RT-PCR processed by a certified laboratory. Statistical analysis was performed using the STATA V13 program. The numerical variables without normality were reported in medians, 25th and 75th percentiles, and the Mann W ithney U test was performed for differences between groups. The categorical variables were presented in percentages and differences between groups with Chi-square test. A generalized linear models (GLM) analysis was carried out to determine the most frequent symptoms and signs associated with COVID-19. Clinical signs and symptoms associated to COVID-19 in the bivariate análysis were dysgeusia, odynophagia, anosmia, arthralgia, myalgia, conjunctivitis, and age older than 40 years. In the final multivariate model only age older than 40 years (OR) 2.2; CI 95 % 1.3,3.8) and dysgeusia (OR 2.1; CI95 % 1.2,3.6) kept significance. Dysgeusia, odynophagia, anosmia, arthralgia, myalgia and conjunctivitis are clinical signs and symptoms that can appear in the early stages of the disease, so they could be important for an early diagnosis.

RESUMEN: El Covid-19 es una enfermedad viral que se ha extendido por todo el mundo, convirtiéndose en una pandemia. La disgeusia y la anosmia son algunos de sus síntomas más frecuentes. El objetivo del estudio fue determinar los signos y síntomas frecuentes asociados con los pacientes con COVID-19. Estudio transversal de 370 pacientes con enfermedad respiratoria aguda ingresados por los servicios de emergencia de un hospital de Acapulco. A todos los pacientes se les aplicó una encuesta institucional como instrumento de recolección de datos, y una prueba de SARS-CoV-2, por RT-PCR procesada por un laboratorio certificado. El análisis estadístico se realizó utilizando el programa STATA V13. Las variables numéricas sin normalidad se reportaron en medianas, percentiles 25 y 75, y se realizó la prueba U de Mann Withney para diferencias entre grupos. Las variables categóricas se presentaron en porcentajes y diferencias entre grupos con la prueba de Chi-cuadrado. Se realizó un análisis de modelos lineales generalizados (GLM) para determinar los síntomas y signos más frecuentes asociados a la COVID-19. Los signos y síntomas clínicos asociados a COVID-19 en el análisis bivariado fueron disgeusia, odinofagia, anosmia, artralgia, mialgia, conjuntivitis y edad mayor de 40 años. En el modelo multivariado final solo la edad mayor de 40 años (OR) 2,2; IC 95 % 1,3,3,8) y la disgeusia (OR 2,1; IC95 % 1,2,3,6) mantuvieron significanca estadística. Disgeusia, odinofagia, anosmia, artralgias, mialgias y conjuntivitis son signos y síntomas clínicos que pueden aparecer en etapas tempranas de la enfermedad, por lo que podrían ser importantes para un diagnóstico precoz.

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The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis.

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Colorectal cancer (CRC) is one of the main causes of mortality. Recent studies suggest that cancer stem cells (CSCs) can survive after chemotherapy and promote tumor invasiveness and aggression. According to a higher hierarchy complexity of CSC, different protocols for isolation, expansion, and characterization have been used; however, there are no available resistance biomarkers that allow predicting the clinical response of treatment 5­fluorouracil (5FU) and oxaliplatin. Therefore, the primary aim of the present study was to analyze the expression of gene resistance on tumors and CSC­derived isolates from patients CRC. In the present study, adenocarcinomas of the colon and rectum (CRAC) were classified based on an in vitro adenosine triphosphate­based chemotherapy response assay, as sensitive and resistant and the percentage of CD24 and CD44 markers are evaluated by immunohistochemistry. To isolate resistant colon­CSC, adenocarcinoma tissues resistant to 5FU and oxaliplatin were evaluated. Finally, all samples were sequenced using a custom assay with chemoresistance­associated genes to find a candidate gene on resistance colon­CSC. Results showed that 59% of the CRC tissue analyzed was resistant and had a higher percentage of CD44 and CD24 markers. An association was found in the expression of some genes between the tumor­resistant tissue and CSC. Overall, isolates of the CSC population CD44+ resistant to 5FU and oxaliplatin demonstrated different expression profiles; however, the present study was able to identify overexpression of the KRT­18 gene, in most of the isolates. In conclusion, the results of the present study showed overexpression of KRT­18 in CD44+ cells is associated with chemoresistance to 5FU and oxaliplatin in CRAC.

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Tsantsas are shrunken human heads originally made for ceremonial purposes by Amazonian indigenous groups of the Shuar and Achuar family, previously called Jivaroan tribes. A significant demand of these objects during the first half of the 20th century led to the manufacture of counterfeit shrunken heads for commercial purposes. For museums where these collections are held, as well as for the indigenous groups who claim their ownership, it is important to identify the origin and authenticity of these tsantsas. We hypothesized that a collection of 14 tsantsas from 3 different museum collections in Ecuador are human and aimed to characterize their sex and potential origin. We amplified the amelogenin gene and performed a high resolution melting analysis to determine their human origin and characterize their sex. We also analyzed a fragment (16209-16402) from the HVR-1 region to identify the mtDNA haplogroups present in the tsantsa collection. Our exploratory results show that all the tsantsas are human and that the collection is comprised of 13 males and 1 female. A total of seven mtDNA haplogroups were found among the tsantsa collection using the mtDNA EMPOP database. These results show a predominance of the Amerindian mtDNA haplogroups B, C and D. Additional principal component analysis, genetic distance tree and haplotype network analyses suggest a relationship between the tsantsa specimens and Native American groups.

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RESUMEN Objetivos: Determinar en pacientes trasplantados renales la prevalencia de enfermedad arterial periférica y la validez de las manifestaciones clínicas de claudicación intermitente para su diagnóstico. Material y métodos: Ámbito y período: Servicio de Nefrología del Complejo Hospitalario Universitario A Coruña, 2013-2017. Criterios inclusión: pacientes trasplantados renales con injerto funcionante que consientan participar en el estudio. Justificación del tamaño muestral: n=371 pacientes (seguridad= 95% y precisión= ± 4,25%). Mediciones: edad, edad al trasplante, sexo, dislipemia, índice de masa corporal, tabaquismo, diabetes, signo de Godet, edema perimaleolar, índice tobillo-brazo y cuestionario Edimburgo. El riesgo cardiovascular se midió mediante los scores Framingham-Wilson, Regicor, SCORE y Dorica. Resultados: La edad media al trasplante fue de 47,86 ± 12,62 años, 65,5% hombres. El 8,7% de los pacientes presentan un índice tobillo-brazo <0,90. El 16,2% de los pacientes manifiestan claudicación intermitente según el cuestionario Edimburgo. La concordancia entre ambas pruebas diagnósticas es débil (índice de Kappa=0,34). El cuestionario de Edimburgo mostró sensibilidad del 59,38% para predecir índice tobillo-brazo <0,90 y especificidad del 88,10%. Las variables asociadas a la presencia de arteriopatía son la edad al trasplante (OR=1,07) y el tabaquismo (OR=6,17), encontrándose la dislipemia en el límite de la significación estadística. Conclusiones: Una décima parte de los pacientes presentan arteriopatía periférica. La concordancia entre el cuestionario Edimburgo y el índice tobillo-brazo es débil. Por lo que debería usarse el índice tobillo-brazo como método diagnóstico. Las manifestaciones clínicas infraestiman la prevalencia de arteriopatía. La edad, el tabaquismo y la dislipemia incrementan su riesgo. Los pacientes con arteriopatía presentan riesgo cardiovascular más elevado.

ABSTRACT Objectives: To assess the prevalence of peripheral artery disease in kidney transplant patients and the validity of intermittent claudication for its diagnosis. Methods: Setting and period: Nephrology Department of the University Hospital A. Coruña, 2013-2017. Inclusion criteria: transplant patients with functioning grafts who gave their consent to participate in the study. Sample size rationale: n=371 patients (confidence interval= 95%; precision= ± 4.25%). Measurements: age, age at the time of transplant, sex, dyslipemia, body mass index, smoking, diabetes, sign of Godet, perimalleolar edema, ankle-brachial index and the Edinburgh Questionnaire. Cardiovascular risk was measured with these scores: Framingham-Wilson, Regicore, SCORE and Dorica. Results: The mean age at the time of transplant was 47.86±12.62; 65.5% of patients were men and 8.7% of them had an ankle-brachial index of <0.90. When answering the Edinburgh Questionnaire, 16.2% of subjects reported suffering from intermittent claudication. Concordance between these two diagnostic tests is poor (kappa index= 0.34). The Edinburgh Questionnaire showed a sensitivity of 59.38% in predicting the ankle-brachial index (<0.90) and specificity (88.10%). The variables associated with the presence of artery disease are age at the time of transplant (OR=1.07) and smoking (OR=6.17), dyslipidemia being at the limit of statistical significance. Conclusions: A tenth part of the patients have peripheral artery disease. Concordance between the Edinburgh Questionnaire and the ankle-brachial index is poor; therefore, the latter should be used as diagnostic method. Clinical signs and symptoms underestimate the prevalence of artery disease. Age, smoking and dyslipidemia increase the risk of this disease. Artery disease patients have a higher cardiovascular risk.

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Vitiligo is a skin disorder characterized by depigmentation of the skin due to a lack of melanin. This condition affects men and woman of all ages and its incidence is not restricted by ethnicity or region. Vitiligo is a multifactorial disease, in which melanocytes, which serve important functions in skin pigmentation and immune processes, are impaired. There is sufficient evidence that immunological and genetic factors are primarily responsible for the destruction and dysfunction of melanocytes. Therefore, genetic DNA sequence variants that participate in skin homeostasis, pigmentation and immune response regulation, as well as altered expression patterns, may contribute to the risk of developing vitiligo. The current review presented an overview of the mechanism of pigmentation and of currently known factors involved in depigmentation, as well as the classification, epidemiology, associated comorbidities, risk factors, immunopathogenesis and several genetic and molecular changes associated with vitiligo.

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ABSTRACT This study aims to estimate job satisfaction levels in graduated of dental school of Autonomous University of Guerrero, México, and determine which factors influence such satisfaction levels. A cross-sectional study was carried out in 144 dentists graduated from the dental school of Autonomous University of Guerrero through a validated survey. Logistic regression analysis was performed to obtain OR, p-value and confidence intervals (95% CI) in the STATA13 statistical program. The overall percentage of job satisfaction was 92%, while the variables that explained the model were, the role of the dentist (Owner or employed) (OR = 2.2 , p = 0.03 95% CI 1.1-4.4), and the level of satisfaction of the knowledge acquired within their academic dental school training (OR = 19.2, p = 0.00 95%CI 3.1-118). The professional satisfaction of a dentist is of great importance, because it impacts their performance at work, and is closely related to overall satisfaction of life, since both contribute reciprocally to the happiness of a person, as well as the general welfare in the community.

RESUMO Este estudo tem como objetivo estimar os níveis de satisfação no trabalho de graduados da Faculdade de Odontologia da Universidade Autônoma de Guerrero, México, e determinar quais fatores influenciam esses níveis de satisfação. Foi realizado um estudo transversal com 144 dentistas formados pela Faculdade de Odontologia da Universidade Autônoma de Guerrero por meio de um questionário validado. Uma análise de regressão logística foi realizada para obter OR, valor de p e intervalos de confiança (IC95%) no programa estatístico STATA13. O percentual geral de satisfação no trabalho foi de 92%, enquanto as variáveis que explicaram o modelo foram a função do dentista (proprietário ou funcionário) (OR = 2,2 , p = 0,03 IC 95% 1,1-4, 4) e o nível de satisfação com o conhecimento adquirido na formação acadêmica em odontologia (OR = 19,2 , p = 0,00 IC95% 3,1-118).. A satisfação profissional do dentista é de grande importância, pois impacta no seu desempenho no trabalho, e está intimamente relacionada à satisfação geral de vida, uma vez que ambas contribuem para a felicidade da pessoa, bem como para o bem-estar geral da comunidade.

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The objective of this study is to show the distribution of periodontal disease, risk factors, and importance of primary healthcare, for the improvement of clinical parameters. Two phases study transversal and nonrandomized trial (before - after), with educational intervention and conservative treatment, were carried out at Dental School of the Universidad Autónoma de Guerrero México, in 161 subjects who met the inclusion criteria. Oral healthcare education was carried out as well as conservative periodontal treatment, with six months follow up. Clinical measurements were performed with a Williams probe, O'Leary plaque index, calculus index and dental mobility Miller method. Periodontal disease was found on 82 % of all participants. Multinomial logistic regression analysis showed an odds ratio of 14.3 (95 % CI: 2.5, 82.1), 13.4 (95 % CI: 1.7, 103.5), 29.2 (95 % CI: 3.2, 260.9) and 68 (95 % CI: 6.6, 711.0) plaque in gingivitis, mild, moderate and severe chronic periodontitis, respectively. The longitudinal panel data analysis showed a significant effect (p <0.001) in the mean decrease of the clinical parameters after intervention, probing depth 0.4 mm (95 % CI: -0.5, -0.3), pockets depth 1.1 mm (95 % CI: -1.3, -0.9), amount of pockets 4.5 (95 % CI: -5.2, -3.7), bleeding 5.2 (95 % CI: -5.9, -4.5) and dental mobility 0.6 degrees (95 % CI: -0.7, -0.5). Primary healthcare is still the best option to improve the periodontal health in population who do not have access to specialty services. Dentists can achieve significant clinical improvement at very low cost, if they are aware of primary health care.

El objetivo del estudio fue mostrar la distribución de la enfermedad periodontal, los factores de riesgo y la importancia de la atención primaria de salud, para la mejora de los parámetros clínicos. Material y método: Estudio de dos fases transversal y no aleatorizado (antes - después), con intervención educativa y tratamiento conservador, realizado en la Facultad de Odontología de la Universidad Autónoma de Guerrero México, en 161 sujetos que cumplieron con los criterios de inclusión. Se llevó a cabo una educación sanitaria oral, así como un tratamiento periodontal conservador, con un seguimiento de seis meses. Las mediciones clínicas se realizaron con una sonda Williams, el índice de placa O'Leary, el índice de cálculo y el método Miller de movilidad dental. Resultados: se encontró enfermedad periodontal en el 82 % de todos los participantes. El análisis de regresión logística multinomial mostró un odds ratio de 14.3 (IC 95 %: 2.5, 82.1), 13.4 (IC 95 %: 1.7, 103.5), 29.2 (IC 95 %: 3.2, 260.9) y 68 (IC 95 %: 6.6, 711.0) placa en gingivitis, periodontitis crónica leve, moderada y grave, respectivamente. El análisis de datos del panel longitudinal mostró un efecto significativo (p <0.001) en la disminución media de los parámetros clínicos después de la intervención, profundidad de sondeo 0.4 mm (IC 95 %: -0.5, -0.3), profundidad de bolsillos 1.1 mm (IC 95 %: -1.3, -0.9), cantidad de bolsillos 4.5 (IC 95 %: -5.2, -3.7), hemorragia 5.2 (IC 95 %: -5.9, -4.5) y movilidad dental 0.6 grados (IC 95 %: -0.7, - 0.5). Conclusiones: la atención primaria de salud sigue siendo la mejor opción para mejorar la salud periodontal en la población que no tiene acceso a servicios especializados. Relevancia clínica: los dentistas pueden lograr una mejora clínica significativa a un costo muy bajo, si conocen la atención primaria de salud.

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Periodontitis is modulated by a complex dysbiotic microbiota, these species stimulate upward the production of pro-inflammatory cytokines such as TNF-α, which, in turn, upregulates the production of bone resorption molecules. Enzymes such as MMP-8 and 9 have been associated with the destructive disease. This study evaluated the composition of periodontal microbiota with the checkerboard hybridization technique and its correlation with TNF-α, MMP-8, and MMP-9 evaluated with ELISA, of 80 patients (45 healthy, and 35 with chronic periodontitis). The frequency of the 18 species evaluated was higher in patients with bone loss compared with control group. TNF-α in gingival crevicular fluid was significantly higher in bone loss group (p < 0.01); MMP-8 (p = 0.34) by MMP-9 (p < 0.05) in bone loss group obtained lower values than in control group. Positive correlation of TNF-α was obtained with Aggregatibacter actinomycetemcomitans (rho = 0.38; p < 0.01), Fusobacterium nucleatum (rho = 0.25; p < 0.05) and Porphyromonas gingivalis (rho = 0.26; p < 0.05); negative correlation of MMP-8 with A. actinomycetemcomitans (rho = 0.26; p < 0.01), Capnocytophaga sputigena (rho = 0.33; p < 0.01), and F. nucleatum (rho = 0.21; p < 0.05); also negative correlation of MMP-9 with F. nucleatum (rho = 0.23; p < 0.05), P. gingivalis (rho = 0.23; p < 0.05), and Tannerella forsythia (rho = 0.26; p < 0.01). TNF-α increased due to the increase in each count of A. actinomycetemcomitans (ß = 0.57; p = 0.00). The presence of A. actinomycetemcomitans (ß = 1.88; p = 0.00), Campylobacter rectus (ß = 0.78; p = 0.01), F. nucleatum (ß = 0.65; p = 0.04), and P. gingivalis (ß = 0.65; p = 0.04) significantly increases TNF-α levels. TNF-α in gingival crevicular fluid, despite the minimal amounts collected, is a good biomarker of periodontal disease; since levels of TNF-α increases with the increase of the most harmful species to the periodontium.

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OBJECTIVE: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes. MATERIALS AND METHODS: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development. RESULTS: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them. CONCLUSIONS: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients.

OBJETIVO: El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. MATERIAL Y MÉTODOS: Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tec- nológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Ins- tituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. RESULTADOS: Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. C. CONCLUSIONES: Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.

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The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have in vitro models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated. The results indicated that in the chemical model, the effect of hypoxia appeared in an early form at 6 h; whereas in the gas chamber the effect was slow and gradual and at 72 h there was an overexpression of erythropoietin (EPO), vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1α (HIF1α). In addition to the genes analyzed by reverse transcription-quantitative polymerase chain reaction, the global expression analysis between both models revealed the 9 most affected genes in common. The present study additionally identified 3 potential genes (lysyl oxidase, ankyrin repeat domain 37, B-cell lymphoma 2 interacting protein 3 like) previously identified in other studies, which may be considered as universal hypoxia genes along with HIF1α, EPO, VEGF, glucose transporter 1 (GLUT1), CA9, and LDH. To the best of the author's knowledge, this is the first time that both hypoxia models have been compared, and it was demonstrated that the effect of hypoxia induction was time sensitive in each model. These observations must be considered prior to selecting one of these models to identify selective hypoxia genes and their effects in cancer.

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PURPOSE: Advanced cancer is a catastrophic medical condition that is generally treated with surgery and conventional anticancer drugs, which are very toxic and often fail. A promising alternative is using genetically engineered mesenchymal stem cells. A popular method for genetically engineering mesenchymal stem cells (MSCs) is by employing transfection reagents. Nevertheless, a serious limitation of this procedure is its consistently low transfection efficiency. Therefore, the utility of transfection reagents in regenerative medicine - including cancer treatment - might increase strikingly by increasing their transfection efficiency and maintaining, to the greatest extent possible, cell viability and transgene expression levels. The purpose of this study was to analyze various effects on gene expression level, transfection efficiency, and cell viability by increasing the volume of transfection reagents and the plasmid DNA mass. METHODS: Mouse bone marrow MSCs were transfected with trademarked Xfect®, Turbofect® or Lipofectamine 3000® and the plasmid pTracer-EF-His-A® expressing the green fluorescent protein (GFP). Additionally, we tested a protocol modification recommended by the Xfect manufacturer. The GFP expression level, transfection efficiency, and cell viability were evaluated together using a performance index. RESULTS: By doubling the quantities recommended by the manufacturers (reagent volume), plasmid DNA mass or both variables and by following a modified Xfect method, the transfection efficiency improved to 70%, the cell viability did not diminish, and the performance index increased to 47.7% with respect to the values determined using the original Xfect protocol. CONCLUSION: Transgene expression levels, transfection efficiency, and cell viability may be strikingly improved, by increasing the volume of the transfectant agent, the plasmid DNA mass or both, beyond those recommended by transfection kit manufacturers.

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OBJECTIVES: to determine the quality of life and anxiety in patients with breast cancer and the changes they experience after treatments. METHOD: prospective study. Breast cancer statistics (n=339, confidence=95%, accuracy= ± 5.32%). The quality of life questionnaires (QLQ) used were QLQ C-30 and QLQ Br23, and the State-Trait Anxiety Inventory (STAI) was used for anxiety. A multivariate analysis was performed to identify variables associated with baseline quality of life and anxiety as well as pre- and post-treatment differences. Authorization was obtained from the Ethics Committee, and informed consent was provided by all patients. RESULTS: the baseline quality of life dimensions with the lowest score were future prospects (46.0/100) and sexual enjoyment (55.7/100). The dimensions with the highest score were body image (94.2/100) and role (93.3/100). The most disturbing symptoms were insomnia, fatigue and concern about hair loss. After treatment, the dimensions of physical function, role, body image, financial concerns and symptomatology worsened, whereas emotional function and future prospects improved. Severe anxiety presented as a state (48.6%) and as a trait (18.2%). The highest baseline state anxiety was associated with married-widowed status and anxiolytic medication. The greatest trait anxiety was associated with an inactive work situation, anxiolytic medication, breast swelling and advanced stage at diagnosis. After treatment, anxiety significantly decreased. CONCLUSIONS: After treatment, the quality of life score was positively modified, while state and trait anxiety decreased.

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The implantation of adult mesenchymal stem cells (MSCs) has become a promising alternative in cancer treatments. Accordingly, in this article we revised the ultimate advances in the knowledge on the MSC-homing mechanism, the cancer cell and MSCs interactions and the microvesicles and exosomes used by malignant cells to transport and deliver pro-cancer cytokines or microRNA (miRNA), or by MSCs to favor or fight cancer progression. In addition, we analyzed the current knowledge generated by ongoing or terminated preclinical and clinical trials, using naive MSCs as natural anti-cancer living factors or gene-engineered MSCs as cytokine delivering vehicles, where anti-cancer cytokines were chosen and the pro-cancer factors were avoided. Finally, we present some concerns about the implantation of MSCs and anti-cancer therapies and hypothesize the MSC implantation combines with conventional or new therapies to treat cancer.

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PURPOSE: To determine in vitro, the efficacy and safety window of not-front-line and first-line anti-colorectal (CRC) drug combinations. METHODS: The adenocarcinoma cell line Colo 320DM and normal human mesenchymal stem cells derived from adipose tissue were used respectively to determine the anti-CRC efficacy (% of Colo 320DM cell death [CD]) and safety window [SW] - % Colo 320DM percent cancer death (PCD)/% of mesenchymal stem cell's death) of drug combinations, using the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: First-line anti-CRC drug combinations (5-fluorouracil [5FU]/oxaliplatin [oxa] and 5-FU/Oxa /leucovorin [Leuco]) produced 57.7% and 52.4% CD, and 1.38 and 2.44 SW, respectively. Combinations of 5-FU/Oxa and 1 to 3 non-front line drugs led to 56.3-99.8% CD and to 0.96-2.2 SW. The highest safety window corresponded to 5FU/Oxa/ carboplatin [Carbo] (93% CD and 1.4 SW) and to 5-FU/ Oxa/cisplatin [Cispl] (93.5% CD and 1.4 SW). In contrast, non-front line drugs led to 89.8-97.4% CD and to 1.1-78.2 SW. Outstandingly, those combinations containing Carbo/ Cispl/3,3'-diindolylmethane (DIM), aspirin (Asp), or 3,3'- DIM/ Asp showed a very high CD (91.9-96.9% [39.2-39.5 times higher than first-line-combined drugs]) and very wide SW (57.8-81.56 [66.6-40 times higher than the first-line drug combinations]). CONCLUSIONS: Human mesenchymal stem cells could be an excellent alternative to laboratory animals, when testing the safety profiles of drugs. The most promising combinations of non-frontline drugs to treat CRC are Carbo/Cispl/ Asp and Carbo/Cispl/DIM.

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