Search

The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or their combination on three adenocarcinoma lung cancer cell lines with different EGFRmutation status. A549, H1975, and HCC827 cell lines were treated with afatinib, metformin, and their combination for 72 h. Afterwards, several parameters were assessed including cytotoxicity, interactions, apoptosis, and EGFR protein levels at the cell membrane and several glycolytic, oxidative phosphorylation (OXPHOS), and EMT expression markers. All cell lines showed additive to synergic interactions for the induction of cytotoxicity caused by the tested combination, as well as an improved pro-apoptotic effect. This effect was accompanied by downregulation of glycolytic, EMT markers, a significant decrease in glucose uptake, extracellular lactate, and a tendency towards increased OXPHOS subunits expression. Interestingly, we observed a better response to the combined therapy in lung cancer cell lines A549 and H1975, which normally have low affinity for TKI treatment. Findings from this study suggest a sensitization to afatinib therapy by metformin in TKI-resistant lung cancer cells, as well as a reduction in cellular glycolytic phenotype.

BackgroundProgrammed death ligand-1 (PD-L1) expression is a predictive biomarker in patients with lung cancer, but its role in malignant pleural mesothelioma (MPM) remains unclear. Evidence suggests that higher PD-L1 expression is correlated with worse survival. CALGB is the main scoring system used to predict the benefit of chemotherapy treatment. This study aimed to determine the prognostic value of PD-L1 expression and its addition to CALGB scoring system in patients with MPM.MethodsIn this retrospective analysis, we evaluated samples with confirmed locally advanced or metastatic MPM. PD-L1 Tumor Proportional Score (TPS) was determined by immunohistochemistry at diagnosis.Results73 patients were included in this study. A cutoff value of 15 was set for a high or low PD-L1 TPS. In total, 71.2% (n=52) and 28.8% (n=21) of individuals harbored low or high PD-L1 expression, respectively. PD-L1High was associated with worse median progression-free Survival (mPFS) [4.9 vs. 10.8 months; HR 2.724, 95% CI (1.44-5.14); p = 0.002] and Overall Survival (OS) [6.0 vs. 20.9 months; HR 6.87, 95% CI (3.4-8.7); p

Introducción: Constituye hecho relevante en el ejercicio de la medicina, individual o poblacional, conocer precozmente la instauración de las enfermedades, y por ello se tratan de realizar los diagnósticos clínicos precozmente. Sin embargo, un grupo de enfermedades, infecciosaso no infecciosas, agudas o crónicas, se caracterizan por escasas manifestaciones clínicas, por loque el conocimiento de su existencia es de vital importancia, por ejemplo, la hipertensión arterial o la diabetes mellitus, cuyas expresiones sintomáticas pueden aparecer tardíamente. En igual medida, la actual pandemia por SARS-CoV-2, ha proliferado rápidamente debido al gran número de personas infectadas que no expresan síntomas.Objetivo: Caracterizar aspectos clínicos relevantes sobre las enfermedades asintomáticas y la importancia de los diagnósticos clínicos obiotecnológicos incipientes, individuales y poblacionales.Métodos: Se realizaron búsquedas bibliográficas de los últimos cinco añosen libros clásicos de Medicina Interna, se analizaron artículospublicados en revistas nacionales e internacionales, específicamente en revistas de alto impacto como Lancet y The New England Journal of Medicine.Se consideraron bases de datos de la Organización Mundial de la Salud, así como lo expuesto en Infomed; además se utilizó Google Académico, con los descriptores de interés al respecto.Conclusiones: Por el momento siempre serán parciales, pues se enfatiza en las recomendaciones de la Organización Mundial de la Salud sobre la actual pandemia, para la identificación y control del SARS-CoV-2; se acentúa en la importancia de los métodos clínicos y epidemiológicos, así como en el desarrollo de la biotecnología para el conocimiento de las enfermedades.

Immune dysregulation and cancer treatment may affect SARS-CoV-2 vaccination protection. Antibody production by B-cells play a vital role in the control and clearance of the SARS-CoV-2 virus. This study prospectively explores B-cell seroconversion following SARS-CoV-2 immunization in healthy individuals and non-small cell lung cancer (NSCLC) patients undergoing oncological treatment. 92 NSCLC patients and 27 healthy individuals’ blood samples were collected after receiving any COVID-19 vaccine. Serum and mononuclear cells were isolated, and a serum surrogate virus neutralization test kit evaluated SARS-CoV-2 antibodies. B-cell subpopulations on mononuclear cells were characterized by flow cytometry. Patients were compared based on vaccination specifications and target mutation oncological treatment. A higher percentage of healthy individuals developed more SARS-CoV-2 neutralizing antibodies than NSCLC patients (63% vs. 54.3%; p = 0.03). NSCLC patients receiving chemotherapy (CTX) or tyrosine kinase inhibitors (TKIs) developed antibodies in 45.2% and 53.7%, of cases, respectively, showing an impaired antibody generation. CTX patients exhibited trends towards lower median antibody production than TKIs (1.0, IQR 83 vs. 38.23, IQR 89.22; p = 0.069). Patients receiving immunotherapy did not generate antibodies. A sub-analysis revealed that those with ALK mutations exhibited non-significant trends towards higher antibody titers (63.02, IQR 76.58 vs. 21.78, IQR 93.5; p = 0.1742) and B-cells quantification (10.80, IQR 7.52 vs. 7.22, IQR 3.32; p = 0.1382) against the SARS-CoV-2 spike protein than EGFR patients; nonetheless, these differences were not statistically significant. This study shows that antibodies against SARS-CoV-2 may be impaired in patients with NSCLC secondary to EGFR-targeted TKIs compared to ALK-directed treatment.

Fundamento: es necesario profundizar en los contenidos, formas y métodos de la labor educativa desde el consultorio médico de familia con los estudiantes de las ciencias médicas. Objetivo: caracterizar la concepción de la labor educativa asumida desde el consultorio médico de familia en el enfrentamiento a la COVID-19. Métodos: se realizó una investigación acción participativa, de corte transversal, en el período de marzo de 2020 a septiembre del 2021. El trabajo de campo se hizo con estudiantes de las carreras de Medicina, Enfermería y Estomatología, vinculados a los consultorios 17-17 y 17-37 pertenecientes al policlínico universitario “Chiqui Gómez-Lubián. Los métodos teóricos empleados fueron: analítico-sintético, inductivo-deductivo, histórico-lógico y enfoque de sistema; empíricos: análisis de documentos, observación de tipo participante, entrevista en profundidad y semiestructurada y análisis del producto de la actividad. Resultados: la concepción de la labor educativa empleada facilitó el trabajo de enfrentamiento a la pandemia de la COVID-19 desde el consultorio médico, la formación integral de los estudiantes y contribuyó al trabajo comunitario integrado. Conclusiones: el enfrentamiento a la COVID-19 favoreció desplegar un sistema de acciones en la formación de los estudiantes que permitieron conformar una concepción acerca de la labor educativa desde el consultorio médico de familia.

Cryptorchidism (CO) or undescended testicle is an abnormality of male gonadal development that can generate long-term repercussions in men, such as infertility and germ cell neoplasia in situ (GCNIS). The origin of these alterations in humans is not completely clear, due to the absence of an animal model with similar testicular development as in humans with CO. This work intends to describe the testicular histological development of dogs with congenital CO, and determine whether the species could adequately serve as a study model for this pathology in humans. The study was carried out with 36 dogs, equally distributed in two groups: healthy control (CTRL) and CO groups. The contralateral testis to the undescended one in CO group of the animals was considered and analyzed. Each group was subdivided in three stages of development: (1) peripubertal stage (6–8 months), (2) young adult (9–48 months) and (3) senile (49–130 months). Histological development, the presence of cells with gonocyte morphology, cell proliferation, testicular lipoperoxidation and hormonal concentrations of testosterone, estradiol, FSH and LH were evaluated and described. In the cryptorchid testes, the first histological alterations appeared from the first stage of development and were maintained until the senile stage. A pronounced testicular lipoperoxidation occurred only in the second stage of development. The histological alterations due to CO were markedly evident in the young adult stage. Testosterone concentrations witnessed a decrease starting from in the second stage and kept on until the last stage. The contralateral testes of the CO animals showed alterations that positioned them between the control and CO testes. Testicular development of dogs with CO is similar to that of humans. The results of the study suggest that this species could serve as a suitable model for the study of CO in humans.

Abstract Objective CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non‐Small Cell Lung Cancer (NSCLC) has not been completely understood. Materials and Methods In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H‐score) with clinicopathological characteristics and survival outcomes was evaluated. Results CD47 protein was detected in 84% of patients with a median expression of 80% (0‐100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0‐300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression‐free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively. Conclusions CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

Objective. Targeted next-generation sequencing (t-NGS) has revolutionized clinical diagnosis allowing multiplexed de­tection of genomic alterations. This study evaluated the profile of somatic mutations by t-NGS in Mexican patients with non-small cell lung cancer (NSCLC). Materials and methods. Genomic DNA was extracted from 90 lung adenocarcinomas and sequences were generated for a panel of 48 cancer ge­nes. Epidermal Growth Factor Receptor (EGFR) mutations were detected in parallel by quantitative PCR. Results. The mutational profile of NSCLC revealed alterations in 27 genes, where TP53 (47.8%) and EGFR (36.7%) exhibited the highest mutation rates. EGFR Q787 mutations were present in 14 cases (15.6%), 10 cases had exon 19 deletions (11.1%), seven cases had L858R (7.8%). The mutational frequency for genes like EGFR, MET, HNF1A, HER2 and GUSB was different compared to caucasian population. Conclusion. t-NGS improved NSCLC treatments efficacy due to its sensitivity and specificity. A distinct pattern of somatic mutations was found in Mexican population.

Background. Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear. Methods. We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival. Results. A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki‐67>40%), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS. Conclusion. Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki‐67≥40%. This “paradox” remains to be confirmed and explained by larger studies.

Metformin has been under basic and clinical study as an oncological repurposing pharmacological agent for several years, stemming from observational studies which consistently evidenced that subjects who were treated with metformin had a reduced risk for development of cancer throughout their lives, as well as improved survival outcomes when diagnosed with neoplastic diseases. As a result, several basic science studies have attempted to dissect the relationship between metformin’s metabolic mechanism of action and antineoplastic cellular signaling pathways. Evidence in this regard was compelling enough that a myriad of randomized clinical trials was planned and conducted in order to establish the effect of metformin treatment for patients with diverse neoplasms, including lung cancer. As with most novel antineoplastic agents, early results from these studies have been mostly discouraging, though a recent analysis that incorporated body mass index may provide significant information regarding which patient subgroups might derive the most benefit from the addition of metformin to their anticancer treatment. Much in line with the current pipeline for anticancer agents, it appears that the benefit of metformin may be circumscribed to a specific patient subgroup. If so, addition of metformin to antineoplastic agents could prove one of the most cost-effective interventions proposed in the context of precision oncology. Currently published reviews mostly rely on a widely questioned mechanism of action by metformin, which fails to consider the differential effects of the drug in lean vs. obese subjects. In this review, we analyze the pre-clinical and clinical information available to date regarding the use of metformin in various subtypes of lung cancer and, further, we present evidence as to the differential metabolic effects of metformin in lean and obese subjects where, paradoxically, the obese subjects have reported more benefit with the addition of metformin treatment. The novel mechanisms of action described for this biguanide may explain the different results observed in clinical trials published in the last decade. Lastly, we present novel hypothesis regarding potential biomarkers to identify who might reap benefit from this intervention, including the role of prolyl hydroxylase domain 3 (PHD3) expression to modify metabolic phenotypes in malignant diseases.

En el presente trabajo se ha aplicado la estadística robusta para la identificación de valores “outliers” en la determinación del factor recobrado en el análisis de residuos de clorpirifos en maní por cromatografía de gases con detector ECD. Para ello fue elaborado un programa en lenguaje HP-BASIC, basado en la estadística robusta y específicamente en el algoritmo de Huber y el cual fue editado en la calculadora gráfica de última generación HP PRIME Graphing Calculator. El programa fue ejecutado ingresando los datos obtenidos de los resultados de la evaluación del factor de recobrado para el método de análisis de clorpirifos en una muestra de referencia interna de maní, obteniéndose como resultado un estimado de los parámetros de la población y la identificación de 3 “outliers”. Este programa fue validado con uno de referencia elaborado en Excel por el Comité de Métodos Analíticos de la Royal Society of Chemistry, observándose que la desviación de los parámetros de la población (m,s) fueron menores que la precisión iterativa, lo que indica que no hubo diferencias significativas entre los dos programas. Por otro lado, estos resultados se compararon con los obtenidos por las pruebas clásicas de Dixon y de Grubbs, concluyendo que el método de Huber es el más sensible. El menos sensible es el test de Dixon, dado que su aplicación no detectó ningún outlier, mientras que el test de Grubbs identificó los dos valores más pequeños.

Mexico is a highly diverse country where ticks and tick-borne diseases (TBD) directly impact the health of humans and domestic and wild animals. Ticks of the genera Rhipicephalus spp., Amblyomma spp., and Ixodes spp. represent the most important species in terms of host parasitism and geographical distribution in the country, although information on other genera is either limited or null. In addition, information regarding the influence of global warming on the increase in tick populations is scarce or nonexistent, despite climate conditions being the most important factors that determine tick distribution. In order to aid in the management of ticks and the risks of TBD in humans and domestic animals in Mexico, an analysis was conducted of the gaps in information on ticks with the purpose of updating the available knowledge of these ectoparasites and adapting the existing diagnostic tools for potential distribution analysis of TBD in wildlife. These tools will help to determine the epidemiological role of wildlife in the human–domestic animal interface in anthropized environments in Mexico.

The Constitution of the 2008 in Ecuador with the objective of improving the quality of its population's life, settled down to the popular and solidary economy (EPS) as the fourth economic sector of the country. Studies carried out by the National Institute of Popular and Solidary Economy (IEPS) from the 2009, they show problems in the development and progress of this economic sector, fundamentally in the logistics areas, marketing, production and managerial organization. This article determines the problems that are manifested in the supply of the inputs and the delivery from the products to the final consumer, of the nutritious services of the catering companies in the EPS of the canton Riobamba. It was obtained results of quantitative type through a market study, which concludes with alternatives that look for to solve the problems generated in this key sector of the Ecuadorian economy.

Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775) and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC) were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico) Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013–2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species), mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission.

Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

La fibrosis quística es una enfermedad genética hereditaria crónica, multisistémica y potencialmente letal que se caracteriza por afección pulmonar con infecciones sobreañadidas y recurrentes, insuficiencia pancreática que origina trastornos nutricionales y un fallo en el crecimiento. Presentamos un caso portador de fibrosis quística, homocigótico para la mutación mayor (pruebas genéticas moleculares) Df508 / Df508, el cual no mostró las manifestaciones comunes de esta afección, ya que presentó a los 49 d de nacido una anemia severa refractaria a tratamiento, lo que motivó su hospitalización, estudio y tratamiento hasta sus conclusiones.