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Resumen Introducción: La endarterectomía carotídea se emplea para el tratamiento de pacientes con estenosis severa (> 70 %) o síntomas cerebrovasculares por enfermedad de la carótida interna. La escala Eagle ha sido usada como predictor de eventos cardiacos luego de una cirugía mayor. Este estudio busca determinar el uso de la escala Eagle como predictor de eventos mayores luego de endarterectomía carotídea. Materiales y métodos: En este estudio observacional retrospectivo de corte transversal, se revisaron historias clínicas de pacientes sometidos a endarterectomía carótida entre los años 2017 y 2021, donde la escala Eagle se realizó durante la visita prequirúrgica, para evaluar el riesgo de complicaciones mayores luego de una endarterectomía carotídea hasta finalizar la hospitalización. Discusión: Un total de 19 pacientes fueron evaluados prequirúrgicamente con el puntaje de la escala de Eagle y fueron tratados con endarterectomía carotídea, con un promedio de edad de 77 años. El procedimiento quirúrgico se realizó con mayor frecuencia en pacientes sintomáticos (89,40 %), incluyendo 10 (59 %) con antecedentes de ataque isquémico transitorio (AIT) y 7 (41 %) con ataque cerebrovascular. Las imágenes diagnósticas indicaron estenosis severa de la arteria carótida en 18 pacientes (94,7 %) y la mayoría de los pacientes presentaron riesgo moderado (68,42 %) según la escala Eagle, además, 5 presentaron complicaciones menores y ninguno presentó complicaciones mayores. Conclusiones: Un puntaje moderado en la escala de Eagle indica riesgo de desarrollar complicaciones cardiovasculares menores luego de endarterectomía carotídea, pero se requieren estudios con mayor tamaño de muestra para dilucidar el papel del puntaje Eagle como predictor de complicaciones cardiovasculares mayores luego de una endarterectomía carotídea.
Abstract Introduction: Carotid endarterectomy is used for treating patients with severe stenosis (>70%) or cerebrovascular symptoms secondary to internal carotid disease. Eagle score has been used as a predictor of cardiovascular events after major surgery. This study aims to assess the use of Eagle Score as a predictor of major cardiovascular events after carotid endarterectomy. Materials and methods: A retrospective observational cross-sectional study was conducted. Medical records of patients who underwent carotid endarterectomy between 2017 and 2021 were reviewed. The EAGLE scale was performed pre-surgically to assess the risk of the risk of major complications after carotid endarterectomy from surgery to the last day of hospitalization. Discussion: A total of 19 patients were assessed pre-surgically using the Eagle scale score and subsequently underwent carotid endarterectomy (Mean age of 77 years-old). The surgical procedure was predominantly performed on symptomatic patients (89.4%), including 10 patients (59%) with a history of transient ischemic attack (TIA) and 7 patients (41%) with a cerebrovascular attack. Previous diagnostic imaging indicated severe carotid artery stenosis in 18 patients (94.7%). According to the EAGLE Scale, the majority presented a moderate risk (68.42%), among whom 5 patients experienced minor complications, and none experienced major complications. Conclusions: Patients with minor cardiovascular complications after carotid endarterectomy were most commonly adjudicated as moderate risk according to the Eagle score. Further studies with large sample sizes are required to elucidate the role of Eagle Score as predictor of major cardiovascular events after carotid endarterectomy.
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BACKGROUND: The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and controls energy balance. Recently, a cluster of neurons was identified as responsive to the orexigenic effect of ghrelin and fasting. However, the signaling pathway by which ghrelin and fasting induce feeding is unknown. AMP-activated protein kinase (AMPK) is a cellular energy sensor, and its Thr172 phosphorylation (AMPKThr172) in the mediobasal hypothalamus regulates food intake. However, whether the expression and activation of AMPK in CeA could be one of the intracellular signaling activated in response to ghrelin and fasting eliciting food intake is unknown. AIM: To evaluate the activation of AMPK into CeA in response to ghrelin, fasting, and 2-deoxy-D-glucose (2DG) and whether feeding accompanied these changes. In addition, to investigate whether the inhibition of AMPK into CeA could decrease food intake. METHODS: On a chow diet, eight-week-old Wistar male rats were stereotaxically implanted with a cannula in the CeA to inject several modulators of AMPKα1/2Thr172 phosphorylation, and we performed physiological and molecular assays. KEY FINDINGS: Fasting increased, and refeeding reduced AMPKThr172 in the CeA. Intra-CeA glucose injection decreased feeding, whereas injection of 2DG, a glucoprivation inductor, in the CeA, increased food intake and blood glucose, despite faint increases in AMPKThr172. Intra-CeA ghrelin injection increased food intake and AMPKThr172. To further confirm the role of AMPK in the CeA, chronic injection of Melanotan II (MTII) in CeA reduced body mass and food intake over seven days together with a slight decrease in AMPKThr172. SIGNIFICANCE: Our findings identified that AMPK might be part of the signaling machinery in the CeA, which responds to nutrients and hormones contributing to feeding control. The results can contribute to understanding the pathophysiological mechanisms of altered feeding behavior/consumption, such as binge eating of caloric-dense, palatable food.
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Proteínas Quinases Ativadas por AMP , Núcleo Central da Amígdala , Ingestão de Alimentos , Jejum , Grelina , Ratos Wistar , Animais , Masculino , Grelina/metabolismo , Grelina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Fosforilação/efeitos dos fármacos , Núcleo Central da Amígdala/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Desoxiglucose/farmacologia , Desoxiglucose/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Glucose/metabolismoRESUMO
The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.
A carga nacional de HCV aumentou significativamente ao longo das últimas décadas, colocando o Paquistão na pior colocação da segunda maior carga de HCV globalmente. Pela primeira vez no Paquistão, examinamos a correlação clínica de potenciais biomarcadores com HCV. Um estudo nacional foi realizado com 13.348 pacientes suspeitos de HCV de 2018 a 2022. Durante a era pré-COVID-19 de 2018 a 2019, a prevalência do HCV permaneceu em 30%. Durante 2018, entre pacientes positivos para HCV, 91% de ALT, 63% de AST, 67% de GGT, 28% de Bili T, 62% de HB, 15% de HBA1C, 25% de CREAT, 15% de PT, 15% de aPTT e 64% de AFP eram anormais. Durante 2019, entre os infectados pelo HCV, 74,47% de ALT, 63,54% de AST, 70,24% de GGT, 24,71% de Bili T, 8,77% de HB e 75% de AFP foram elevados. A TC/TAC revelou 4,65% de complicações hepáticas (leve 13,04%, moderada 30,43% e grave 56,52%). Durante 2020, a prevalência do HCV permaneceu em 25%. 65,17% de ALT, 64,20% de AST, 68,75% de GGT, 31,25% de Bili T, 20,97% de HB, 4,65% de CREAT e 73,68% de AFP estavam elevados. A análise de TAC revelou complicações hepáticas em 4,41% (14,81% leves, 40,74% moderadas e 44,44% graves). 85,71% dos participantes o diabetes estava fora de controle. Durante 2021, a prevalência de HCV permaneceu em 27,1%. Os níveis de ALT (73,86%), AST (50,6%), GGT (67,95%), Bili T (28,21%), HB (20%), CREAT (5,8%) e AFP (82,14%) estavam anormais. Durante 2022, os níveis de ALT (56,06%), AST (56,36%), GGT (56,6%), Bili T (19,23%), HB (43,48%), HBA1C (14,81), CREAT (18,92%), AFP (93,75%) eram anormais. A análise de TAC revelou 7,46% de complicações hepáticas (25% leves, 30,36% moderadas e 42,86% severas). Durante 2021 e 2022, 83,33% do diabetes do sujeito não foi controlado.
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Biomarcadores Tumorais , Tomografia Computadorizada por Raios X , Hepacivirus , COVID-19 , PaquistãoRESUMO
En los últimos años aumentaron las investigaciones sobre co-ocurrencia de trastorno del espectro autista (TEA) y disforia de género (DG) secundario a la necesidad de una mayor comprensión de este fenómeno clínico emergente. Objetivos: Caracterizar los estudios en torno a la co-ocurrencia entre TEA y DG en adolescentes. Metodología: Se realizó una revisión sistemática bibliográfica. Se seleccionaron los estudios que mencionaron esta correlación e incluyeron población adolescente. Resultados: La búsqueda inicial arrojó un total de 97 publicaciones. Finalmente, de acuerdo a los criterios de elegibilidad, se incluyeron 35 artículos. Existen escasos estudios enfocados sólo en adolescentes, amplios rangos de prevalencia de esta relación y heterogeneidad en los instrumentos utilizados. Conclusiones: Al evaluar individuos con DG se debiese llevar a cabo un screening de TEA, y viceversa, para no pasar por alto esta co-ocurrencia. Cabe destacar que quienes presentan TEA tienen particularidades relacionadas con el pensamiento y planificación a futuro que hay que considerar al momento de realizar cualquier tipo de tratamiento afirmativo irreversible, enmarcado dentro de un proceso terapéutico multidimensional. Palabras claves: Adolescentes, Disforia de género, Trastorno de Espectro Autista (TEA), Condición de Espectro Autista (CEA), Autismo.
Research on co-occurrence of autism spectrum disorder (ASD) and gender dysphoria (GD) increased in recent years driven by the need for greater understanding of this emerging clinical phenomenon. Objective. To characterize studies on the co-occurrence of ASD and GD in adolescents. Methodology. A systematic literature review was conducted. Studies mentioning this correlation and including adolescent population were selected. Results. The initial search showed a total of 97 publications. 35 articles were included in the review that met the eligibility criteria. There are few studies focused only on adolescents, there is a wide range of prevalence of this relationship and heterogeneity in the instruments used. Conclusions. When evaluating individuals with GD, an ASD screening should be conducted,and vice versa, to avoid overlooking this cooccurrence. It is important to note that those with ASD have particularities related to cognitive development that need to be considered when undergoing any type of irreversible affirmative treatment, within a multidimensional therapeutic process. Keywords. Adolescents, Gender dysphoria, Autism Spectrum Disorder (ASD), Autism.
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Humanos , Criança , Adolescente , Adulto , Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/epidemiologia , Disforia de Gênero/psicologia , Disforia de Gênero/epidemiologia , Comorbidade , PrevalênciaRESUMO
BACKGROUND: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent. METHODS: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS). RESULTS: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031). CONCLUSIONS: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.
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Antígeno Carcinoembrionário , Neoplasias do Colo , Humanos , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Prognóstico , Intervalo Livre de Doença , Biomarcadores Tumorais , Estadiamento de NeoplasiasRESUMO
Patterns of drug ingestion may have a dissimilar impact on the brain, and therefore also the development of drug addiction. One pattern is binge intoxication that refers to the ingestion of a high amount of drug on a single occasion followed by an abstinence period of variable duration. In this study, our goal was to contrast the effect of continuous low amounts with intermittent higher amounts of Arachidonyl-chloro-ethylamide (ACEA), a CB1R agonist, on amphetamine seeking and ingestion, and describe the effects on the expression of CB1R and CRFR1 in the central nucleus of the amygdala (CeA) and in the nucleus accumbens shell (NAcS). Adult male Wistar rats were treated with a daily administration of vehicle or 20 µg of ACEA, or four days of vehicle followed by 100 µg of ACEA on the fifth day, for a total of 30 days. Upon completion of this treatment, the CB1R and CRFR1 expression in the CeA and NAcS was evaluated by immunofluorescence. Additional groups of rats were evaluated for their anxiety levels (elevated plus maze, EPM), amphetamine (AMPH) self-administration (ASA) and breakpoint (A-BP), as well as AMPH-induced conditioned place preference (A-CPP). Results indicated that ACEA induced changes in the CB1R and CRFR1 expression in both the NAcS and CeA. An increase in anxiety-like behavior, ASA, A-BP and A-CPP was also observed. Since the intermittent administration of 100 µg of ACEA induced the most evident changes in most of the parameters studied, we concluded that binge-like ingestion of drugs induces changes in the brain that may make the subject more vulnerable to developing drug addiction.
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Anfetamina , Núcleo Accumbens , Ratos , Masculino , Animais , Núcleo Accumbens/metabolismo , Anfetamina/farmacologia , Ratos Wistar , Tonsila do Cerebelo , Condicionamento ClássicoRESUMO
Gallbladder cancer (GBC) is commonly diagnosed at late stages when conventional treatments achieve only modest clinical benefit. Therefore, effective treatments for advanced GBC are needed. In this context, the administration of T cells genetically engineered with chimeric antigen receptors (CAR) has shown remarkable results in hematological cancers and is being extensively studied for solid tumors. Interestingly, GBC tumors express canonical tumor-associated antigens, including the carcinoembryonic antigen (CEA). However, the potential of CEA as a relevant antigen in GBC to be targeted by CAR-T cell-based immunotherapy has not been addressed. Here we show that CEA was expressed in 88% of GBC tumors, with higher levels associated with advanced disease stages. CAR-T cells specifically recognized plate-bound CEA as evidenced by up-regulation of 4-1BB, CD69 and PD-1, and production of effector cytokines IFN-γ and TNF-α. In addition, CD8+ CAR-T cells up-regulated the cytotoxic molecules granzyme B and perforin. Interestingly, CAR-T cell activation occurred even in the presence of PD-L1. Consistent with these results, CAR-T cells efficiently recognized GBC cell lines expressing CEA and PD-L1, but not a CEA-negative cell line. Furthermore, CAR-T cells exhibited in vitro cytotoxicity and reduced in vivo tumor growth of GB-d1 cells. In summary, we demonstrate that CEA represents a relevant antigen for GBC that can be targeted by CAR-T cells at the preclinical level. This study warrants further development of the adoptive transfer of CEA-specific CAR-T cells as a potential immunotherapy for GBC.
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Neoplasias da Vesícula Biliar , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Antígeno Carcinoembrionário/genética , Imunoterapia Adotiva/métodos , Antígeno B7-H1 , Neoplasias da Vesícula Biliar/terapia , Imunoterapia , Linfócitos TRESUMO
INTRODUCTION: This study aimed to develop a prognostic nomogram for patients with gastric cancer (GC) based on the levels of programmed death 1 ligand 1 (PDL1) and carcinoembryonic antigen (CEA). METHODS: The nomogram was developed using data from a primary cohort of 247 patients who had been clinicopathologically diagnosed with GC, as well as a validation cohort of 63 patients. Furthermore, the nomogram divided the patients into three different risk groups for overall survival (OS)-the low-risk, middle-risk, and high-risk groups. Univariate and multivariate Cox hazard analyses were used to determine all of the factors included in the model. Decision curve analysis and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram. RESULTS: The Kaplan-Meier survival analysis revealed that metastasis stage, clinical stage, and CEA and PDL1 levels were predictors for progress-free survival (PFS) and OS of patients with GC. Metastasis stage, clinical stage, and CEA and PDL1 levels were found to be independent risk factors for the PFS and OS of patients with GC in a multivariate analysis, and the nomogram was based on these factors. The concordance index of the nomogram was 0.763 [95% confidence interval (CI) 0.740-0.787]. The area under the concentration-time curve of the nomogram model was 0.81 (95% CI 0.780-0.900). According to the decision curve analysis and ROC curves, the nomogram model had a higher overall net efficiency in forecasting OS than clinical stage, CEA and PDL1 levels. CONCLUSION: In conclusion, we proposed a novel nomogram that integrated PDL1 and CEA, and the proposed nomogram provided more accurate and useful prognostic predictions for patients with GC.
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Nomogramas , Neoplasias Gástricas , Humanos , Antígeno Carcinoembrionário , Ligantes , PrognósticoRESUMO
Purpose. Adipose tissue in overweight and obesity shows metabolic imbalance in the function of adipocytes and macrophages, this leads to altered regulation of hunger, lipid storage, and chronic inflammation possibly related to the development of breast cancer. Methods. The study was retrospective of 653 breast cancer patients treated at a tertiary care hospital. Histopathology, hormone receptors, grade, clinical stage, clinical biometry analysis, CEA and CA 15-3 antigens were analyzed. The analyses were performed at diagnosis and at the end of oncological treatments. Results. Mexican women studied and treated for breast cancer have an BMI of 29 from diagnosis and at the end of their cancer treatments. The average age was 52 ± 12 years, 54% in women older than 55 years. Cancer recurrence occurs in any molecular type; however, the common factor was overweight and obesity with 73% vs. 21% in normal weight patients. The most frequent tumor tissue in the population was positive hormone receptors of the luminal type (65%), HER2 (15%), and NT (15%). The analyses of macrophages/lymphocytes (M/L), CEA, and CA 15-3 antigens evaluated in women >55 and <55 years, with and without recurrence are elevated at the end of oncological treatments. Conclusions. The analysis of Mexican women with breast cancer showed a predominance of overweight and obesity at diagnosis and at the end of treatment. A relationship between obesity and cancer recurrence with a low response to treatment due to elevation in Ag CEA and CA 15-3 is suggested. The L/M ratio could be an indicator of inflammation related to adipose tissue since diagnosis.
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Neoplasias da Mama , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Antígeno Carcinoembrionário , Feminino , Hormônios/uso terapêutico , Humanos , Inflamação/complicações , Lipídeos/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Clear cell carcinoma arising from the malignant transformation of endometriosis is a rare but aggressive cancer often diagnosed in perimenopausal women. Malignant transformation constitutes a rare complication of endometriosis, with only a few cases reported in the medical literature. Clear cell carcinoma and endometrioid carcinoma are the two most common histological subtypes associated with malignant endometriosis. Case Presentation: A 61-year-old Afro-Trinidadian woman underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a degenerated uterine leiomyoma. Histopathology demonstrated an isolated finding of clear cell carcinoma occurring within an endometriotic cyst on the uterine serosa. Subsequent surgical staging demonstrated early-stage disease associated with a high-risk histological subtype and the patient was referred for adjuvant chemoradiotherapy. Conclusion: This case highlights the clinical manifestations and treatment modalities employed for an early-stage high-risk subtype of endometriosis-associated cancer. In light of the few publications on this clinical entity, we hope to raise awareness of this unique complication of endometriosis and contribute evidence to the development of standardized treatment protocols.
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The orexin peptides promote hedonic intake and other reward behaviors through different brain sites. The opioid dynorphin peptides are co-released with orexin peptides but block their effects on reward in the ventral tegmental area (VTA). We previously showed that in the paraventricular hypothalamic nucleus (PVN), dynorphin and not orexin peptides enhance hedonic intake, suggesting they have brain-site-specific effects. Obesity alters the expression of orexin and dynorphin receptors, but whether their expression across different brain sites is important to hedonic intake is unclear. We hypothesized that hedonic intake is regulated by orexin and dynorphin peptides in PVN and that hedonic intake in obesity correlates with expression of their receptors. Here we show that in mice, injection of DYN-A1-13 (an opioid dynorphin peptide) in the PVN enhanced hedonic intake, whereas in the VTA, injection of OXA (orexin-A, an orexin peptide) enhanced hedonic intake. In PVN, OXA blunted the increase in hedonic intake caused by DYN-A1-13. In PVN, injection of norBNI (opioid receptor antagonist) reduced hedonic intake but a subsequent OXA injection failed to increase hedonic intake, suggesting that OXA activity in PVN is not influenced by endogenous opioid activity. In the PVN, DYN-A1-13 increased the intake of the less-preferred food in a two-food choice task. In obese mice fed a cafeteria diet, orexin 1 receptor mRNA across brain sites involved in hedonic intake correlated with fat preference but not caloric intake. Together, these data support that orexin and dynorphin peptides regulate hedonic intake in an opposing manner with brain-site-specific effects.
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Dinorfinas , Núcleo Hipotalâmico Paraventricular , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacologia , Animais , Encéfalo/metabolismo , Dinorfinas/metabolismo , Dinorfinas/farmacologia , Camundongos , Obesidade/metabolismo , Orexinas/metabolismoRESUMO
BACKGROUND: Non-small cell lung cancer elevates serum carcinoembryonic antigen (CEA). CEA determinations are not recommended currently. This study aims to identify the correlation between reducing serum CEA levels with progression-free survival (PFS) and overall survival. METHODS: This study assessed at baseline and in every scheduled visit serum CEA levels throughout first-line therapy. A sensitivity and specificity analysis identified the best cut-off point and correlated it with progression-free survival and overall survival. Multivariate Cox proportional hazard models were conducted. RESULTS: We assessed 748 patients with elevated serum CEA levels at diagnosis. A ≥20% decrease from baseline was associated with a 2-fold median survival compared with patients with lower decreases (20.5 months vs 9.1 months; hazard ratio, 0.53; 95% confidence interval, 0.44 to -0.64; P < .001). CEA sensitivity and specificity to predict survival was 79.8% and 59.8%, respectively. A ≥10% decrease in CEA concentrations was associated with longer progression-free survival (7.7 months vs 5.9 months; hazard ratio, 0.71; 95% confidence interval, 0.57 to -0.88; P = .001) in those treated with chemotherapy, and in patients under tyrosine kinase inhibitors (11.9 months vs 7.3 months; hazard ratio, 0.63; 95% confidence interval, 0.47 to -0.83; P = .0001) and a ≥20% decrease. CONCLUSION: In patients with metastatic non-small cell lung cancer with an elevated baseline CEA level, the percentage decrease of CEA concentrations above the threshold during the first-line therapy was associated with more prolonged survival and progression-free intervals. Serum CEA determinations are a feasible, noninvasive option for monitoring and prognosis.
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Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Intervalo Livre de Progressão , Idoso , Feminino , Humanos , Masculino , Auditoria Médica , México , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Interleukin-1ß (IL-1ß) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1ß is released by glial cells in regions associated with pain processing during neuropathic pain. It also has important roles in neuroinflammation and in regulating NMDA receptor activity required for learning and memory. The modulation of glycine-mediated inhibitory activity via IL-1ß may play a critical role in the perception of different levels of pain. The central nucleus of the amygdala (CeA) participates in receiving and processing pain information. Interestingly, this nucleus is enriched in the regulatory auxiliary glycine receptor (GlyR) ß subunit (ßGlyR); however, no studies have evaluated the effect of IL-1ß on glycinergic neurotransmission in the brain. Hence, we hypothesized that IL-1ß may modulate GlyR-mediated inhibitory activity via interactions with the ßGlyR subunit. Our results show that the application of IL-1ß (10 ng/ml) to CeA brain slices has a biphasic effect; transiently increases and then reduces sIPSC amplitude of CeA glycinergic currents. Additionally, we performed molecular docking, site-directed mutagenesis, and whole-cell voltage-clamp electrophysiological experiments in HEK cells transfected with GlyRs containing different GlyR subunits. These data indicate that IL-1ß modulates GlyR activity by establishing hydrogen bonds with at least one key amino acid residue located in the back of the loop C at the ECD domain of the ßGlyR subunit. The present results suggest that IL-1ß in the CeA controls glycinergic neurotransmission, possibly via interactions with the ßGlyR subunit. This effect could be relevant for understanding how IL-1ß released by glia modulates central processing of pain, learning and memory, and is involved in neuroinflammation.
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BACKGROUND: This systematic review summarizes results of studies that evaluated the expression of microRNAs (miRs) in prediabetes or type 2 diabetes (T2D). METHODS: The information was obtained from PubMed, EMBL-EBI, Wanfang, Trip Database, Lilacs, CINAHL, Human microRNA Disease Database (HMDD) v3.0, and Google. A qualitative synthesis of the results was performed and miRs frequency was graphically represented. From 1893 identified studies, only 55 fulfilled the inclusion criteria. These 55 studies analyzed miRs in T2D, and of them, 13 also described data of prediabetes. RESULTS: In diabetics, 122 miRs were reported and 35 miRs for prediabetics. However, we identified that five miRs (-122-5p, 144-3p, 210, 375, and -126b) were reported more often in diabetics and four (144-3p, -192, 29a, and -30d) in prediabetics. CONCLUSIONS: Circulating miRs could be used as biomarkers of T2D. However, it is necessary to validate these microRNAs in prospective and multicenter studies with different population subgroups, considering age, gender, and risk factors.
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Biomarcadores/sangue , MicroRNA Circulante/sangue , Diabetes Mellitus Tipo 2/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangueRESUMO
OBJECTIVE: The aim of the study was to demonstrate the clinical and economic impact of two PD-L1 IHC assays, SP142 versus 22C3, to identify the eligibility of the patients with advanced triple negative breast cancer (aTNBC) to the treatment with atezolizumab plus nab-paclitaxel in the Brazilian private healthcare system (BPHS). METHODS: The study performed a cost-effectiveness analysis based on a partitioned-survival model with three mutually exclusive health states: progression-free (PF), progression, and death. Data of progression-free survival and overall survival were extracted from a retrospective exploratory analysis of IMpassion130, an analytical harmonization of PD-L1 IHC assays. The analyses included only direct costs (drug acquisition and management of adverse events) that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED PF18% (Câmara de Regulação do Mercado de Medicamentos) tables. A probabilistic sensitivity analysis was performed as a second-order Monte Carlo Simulation in order to evaluate the uncertainties of the model. RESULTS: The SP142 assay has the potential to improve PFS and generate savings to the BPHS. The incremental cost-effectiveness ratio (ICER) was -USD 4,119.43 per month of progression-free survival. CONCLUSIONS: The SP142 assay demonstrated to be a dominant alternative compared to 22C3 to guide the treatment with atezolizumab plus nab-paclitaxel in patients with aTNBC.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/análise , Técnicas e Procedimentos Diagnósticos/economia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brasil , Feminino , Humanos , Modelos Econométricos , Intervalo Livre de ProgressãoRESUMO
This study aimed at evaluating the behaviour and understanding the diagnostic value of the carcinoembryonic antigen (CEA) in bitches with mammary carcinoma as a tool for monitoring and prognosis of canine cancer patients. Serum samples from 77 bitches were divided into four groups, G1 (n = 21), control group (healthy/neoplasia free bitches); G2 (n = 31), bitches with non-metastatic mammary carcinoma less than 3 cm; G3 (n = 12), bitches with non-metastatic mammary carcinoma greater than 3 cm; and, G4 (n = 13) bitches with mammary carcinoma and lymph node metastasis. The marker was dosed once in G1, whereas in G2, G3 and G4, CEA levels were determined before (M0) and 15 days after (M1) mastectomy, using the ELISA kit for humans while reading used ELISYS ONE human. A group of 11 bitches was followed up 45 days after mastectomy (M2). The results for the concentration of markers in blood serum samples at the evaluated times and their relationship with neoplasia biological behaviour and observed clinicopathological changes were evaluated by the Tukey test at 5% significance. The ROC curve was established to find the cut-off value and calculate the test sensitivity and specificity, the multivariate matching analysis was performed to confirm the association between CEA values and clinicopathological variables. CEA values increased significantly in bitches with mammary carcinoma, metastatic tumours with a diameter larger than 3.0 cm and high grade, compared with healthy ones. In addition, mastectomy reduced the CEA concentration in the blood (P < .05) whereas high CEA levels were associated with unfavourable prognostic factors (P < .05). The biomarker presented good diagnostic value, especially for more aggressive tumours. In conclusion, CEA serum concentrations allowed to follow efficiently the evolution of mammary tumours in bitches, since CEA values increased in bitches with mammary gland tumour and decreased after mastectomy while correlating with prognostic factors such as tumour size, nodal metastasis and histological grade. Further studies are still needed to confirm its diagnostic value for follow-up of relapse and early metastasis.
Assuntos
Antígeno Carcinoembrionário/sangue , Doenças do Cão/sangue , Neoplasias Mamárias Animais/sangue , Animais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/veterinária , Doenças do Cão/diagnóstico , Cães , Feminino , Neoplasias Mamárias Animais/diagnóstico , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/veterinária , Prognóstico , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To study the clinical significance of serum epidermal growth factor receptor (EGFR) gene mutation and serum tumor markers in the prediction of tyrosine kinase inhibitor (TKI) efficacy in patients with lung adenocarcinoma. METHODS: Ninety patients with pathologically diagnosed lung adenocarcinoma were enrolled. Further, 51 out of 90 patients received the EGFR-TKI therapy, oral gefitinib. The correlations among serum EGFR gene mutations in exons 18-21, serum tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), carbohydrate antigen 125, carbohydrate antigen 15-3 as well as carbohydrate antigen 19-9 (CA19-9) levels, and EGFR-TKI efficacy were determined. RESULTS: There was a high consistency of EGFR gene mutation rate between serum and tissue samples. The serum EGFR gene mutation rate in female patients or non-smokers was significantly higher than that in male patients or smokers, respectively. Serum CA19-9, CA24-2, and CEA levels were significantly correlated with serum EGFR mutation. After receiving gefitinib, the progression-free survivals (PFSs) of patients with high serum CEA level, high serum CA19-9 level, or serum EGFR gene mutation were significantly higher than those of normal patients, respectively. The PFSs were significantly prolonged in patients with EGFR gene mutation and high serum CEA level or patients with EGFR gene mutation and high serum CA19-9 level compared with those in patients with one abnormal biomarker and normal patients. CONCLUSION: Combined detection of EGFR gene mutations as well as CA19-9 and CEA levels in peripheral blood can predict the efficacy of EGFR-TKI in the treatment of patients with lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Receptores ErbB/sangue , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Taxa de SobrevidaRESUMO
BACKGROUND: Carcinoembryonic Antigen (CEA) is a recommended prognostic marker in Colorectal Cancer (CRC) for tumor diagnosis and monitoring response to therapy. High CEA levels are specifically associated with CRC progression and increased levels of the marker are expected to fall following surgical treatment. Due to its role in CRC, CEA has also been explored as a target for cancer therapy and diagnosis approaches. OBJECTIVE: The goal of this work is to highlight the role of CEA in CRC progression and liver metastasis as well as its potential as a biomarker for clinical and biotechnological approaches. METHOD: A literature search of electronic medical and patent databases Pubmed, Scopus, and Science Direct, Google patents, Esp@cenet and United States Patent and Trademark Office (USPTO), was performed. Information was collected in recent publications, including 81 articles besides 13 patents related to different CEA targeting biotechnological approaches for CRC therapy and diagnosis. RESULTS: CEA enhances CRC metastatic potential through many ways. CEA protects metastatic cells from death, changes the microenvironment of sinusoids, promoting the expression of adhesion molecule and malignant cell survival, besides being considered a proangiogenic molecule. Furthermore CEA has also been evaluated as a target in drug delivery systems, photodynamic therapy, radioimmunotherapy, cancer imaging and nanotechnological devices, leading to many patents concerning to development of anti-CEA antibodies or their fragments with potential to target colorectal cancer and liver metastasis cells. CONCLUSION: CEA is already clinically used to monitor CRC patients, and it is a very promising targeting biomarker for multiple biotechnological applications. As far as we know this is the first report on CEA that addresses patents database.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Hepáticas/diagnóstico , Animais , Biotecnologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/secundário , Patentes como AssuntoRESUMO
Resumen:El porocarcinoma ecrino es un tipo muy poco frecuente de cáncer de piel, originado en la porción epidérmica de las glándulas sudoríparas ecrinas. Representa no más del 0.01% de los tumores cutáneos. El 20% de los porocarcinomas ecrinos son recurrentes y el 20% producen metástasis a ganglios linfáticos. Se ha reportado escasos casos de metástasis a distancia. Tiene un índice de mortalidad del 67% de los pacientes con metástasis.El diagnóstico es basado en los hallazgos histopatológicos y los estudios complementarios de inmunohistoquímica, a veces necesarios para el diagnóstico diferencial con otros tipos más frecuentes de cáncer de piel.No existen pruebas de que este tipo de carcinoma responda a la quimioterapia ni la radioterapia. Se considera que el manejo principal debe ser la resección quirúrgica y la electroquimioterapia.
Abstract:Eccrine porocarcinoma is a rare type of skin cáncer arising from the intraepidermal portion of eccrine sweat glands, representing no more tan 0.01% of all cutaneous tumors. 20% of the Eccrine porocarcinoma will recur and 20% will metastasize to regional lymph nodes. Few cases of distant metastases has been reported . There is a mortality rate of 67% in patients with metastases. The diagnosis is primarily based on histopathologic findings and complementary immunohistochemistry for differential diagnosis mainly with more frequent skin cáncer.Neither chemotherapy nor radiation therapy has been proven to be of clinical benefit in treating this type of carcinoma. It is considered that the management should be based on surgical resection and electrochemotherapy.
Assuntos
Humanos , Neoplasias das Glândulas Sudoríparas , Glândulas Sudoríparas , Poroma , Porocarcinoma ÉcrinoRESUMO
BACKGROUND: The new proposed classification for pancreaticobiliary cytology has advocated the use of carcinoembryonic antigen (CEA) analysis of cyst fluid as an ancillary diagnostic tool for the determination of mucinous neoplasms in pancreatic cyst aspirates. We aimed to investigate the effect of CEA cyst fluid analysis on cases primarily called negative or nondiagnostic and on the sensitivity and specificity of the method. METHODS: We retrospectively identified and collected all pancreatic cyst aspirates from 2010 to 2014 at Mayo Clinic, Jacksonville, Florida, along with available corresponding surgical diagnoses. Cases primarily classified as nondiagnostic or negative but that had a cyst CEA level of 192 ng mL-1 or higher were reclassified as mucinous neoplasms. Cytohistologic correlation was assessed whenever possible. RESULTS: We retrieved pancreatic cyst aspirates from 255 patients who had a corresponding CEA level measurement. Median patient age was 70 years (range, 25-100 years). Among all samples, 129 (50.6%) had been classified as negative and 42 (16.4%) as nondiagnostic. Applying the new criteria, the number of samples previously classified as negative and nondiagnostic decreased considerably, with a statistically significant difference among negative cases. Fifty-four cases (21.2%) had an available corresponding surgical diagnosis, and complete agreement was achieved in 95.4% of the cases. Use of the new cutoff for CEA levels increased the sensitivity and negative predictive value, compared with the original diagnoses. CONCLUSIONS: The incorporation of the new proposed terminology and CEA fluid analysis has significantly decreased the number of samples primarily classified as negative and nondiagnostic, along with improved test characteristics. Diagn. Cytopathol. 2017;45:101-106. © 2016 Wiley Periodicals, Inc.