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1.
Respirar (Ciudad Autón. B. Aires) ; 16(1): 31-43, Marzo 2024.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1551189

ABSTRACT

Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.


Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.


Subject(s)
Humans , Health Programs and Plans , Early Detection of Cancer , Lung Neoplasms/diagnosis , Patient Care Team/organization & administration , Preventive Health Services/organization & administration , Tomography/methods , Incidence , Mortality , Education, Professional , Health Policy , Latin America
2.
Respirar (Ciudad Autón. B. Aires) ; 16(1): 23-30, Marzo 2024.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1551185

ABSTRACT

Introducción: La EBUS ha sido el foco de numerosos estudios destinados a evaluar su utilidad y rendimiento diagnóstico en diversas patologías. Objetivo principal: Identificación de las características ganglionares evaluadas en el procedimiento de Ultrasonido Endobronquial (EBUS) y su relación con el diagnóstico de malignidad en pacientes del Instituto Nacional del Cáncer de Colombia del 1 de enero de 2017 al 31 de marzo de 2021.Métodos: Estudio analítico observacional transversal. La recopilación de datos implicó un muestreo de casos consecutivos no probabilísticos entre individuos que cumplían los criterios de inclusión.Resultados: Un total de 75 pacientes fueron sometidos a EBUS. Se identificaron 6 características ecográficas de los ganglios de la biopsia asociadas a malignidad destacándose los ganglios mayores de 1 cm, márgenes mal definidos, ecogenicidad heterogénea, ausencia de una estructura hiliar central, presencia de signos de necrosis o coagulación y presencia de conglomerado ganglionar. Conclusión: Este estudio caracterizó la frecuencia de los hallazgos en la ultrasonografía endobronquial destacando algunas características ecográficas de los ganglios mediastínicos que podrían predecir patología maligna.


Introduction: The EBUS has been the focus of numerous studies aiming to evaluate its utility and diagnostic performance across various pathologies. Objective: Identification of the node characteristics evaluated in the Endobronchial Ultrasound (EBUS) procedure and their relationship with malignancy diagnosis in patients at the National Cancer Institute of Colombia from January 1st, 2017, to March 31st, 2021. Methods: Observational cross-sectional analytical study. Data collection involved non-probabilistic consecutive case sampling among individuals meeting the inclusion criteria.Results: A total of 75 patients underwent the EBUS procedure. Our findings revealed six predictors of malignancy based on sonographic features of biopsy nodes, including nodes larger than 1 cm, poorly defined margins, heterogeneous echogenicity, absence of a central hilar structure, presence of signs indicating necrosis or coagulation, and the presence of a ganglion conglomerate. Conclusions: This study showed that endobronchial ultrasonography has several sonographic characteristics at the time of evaluating mediastinal nodes that could predict malignant and benign pathology.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Lymphadenopathy/pathology , Lung Neoplasms/diagnosis , Lymph Nodes/diagnostic imaging , Mediastinal Neoplasms/diagnosis , Biopsy/methods , Ultrasonography/methods , Colombia , Neoplasm Staging/methods
3.
Respirar (Ciudad Autón. B. Aires) ; 15(4): 279-284, Diciembre 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1518697

ABSTRACT

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.


Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula


Subject(s)
Humans , Male , Aged , Pleural Effusion/complications , Bile , Empyema, Pleural/drug therapy , Liver Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Surgical Procedures, Operative , Biliary Tract , Biopsy , Tomography , Pleural Cavity , Neoplasm Metastasis/diagnosis
4.
Rev. Ciênc. Méd. Biol. (Impr.) ; 22(2): 181-187, set 2023. tab
Article in Portuguese | LILACS | ID: biblio-1516183

ABSTRACT

Introdução: o câncer é um grave problema de saúde pública, considerado a segunda causa de óbitos no Brasil. Devido à sua relevância, é indispensável um controle eficiente dos casos através do acompanhamento da taxa de mortalidade. Dessa forma, o trabalho analisou a evolução da mortalidade por câncer para as localizações primárias mais frequentes, segundo sexo, durante o período de 2010 a 2020. Metodologia: trata-se de um estudo observacional descritivo, no qual os dados foram obtidos através do Atlas On-line de Mortalidade por Câncer. Os dados colhidos correspondem ao número de óbitos estratificados por tipo de câncer mais frequente, por ano estudado e por sexo, além das taxas de mortalidade específica bruta e a taxa de mortalidade ajustada por idade para o sexo masculino e feminino, para cada tipo de câncer em estudo, considerando a população padrão mundial, sendo avaliado por regressão linear a significância da tendência temporal. Resultados: no Brasil, no período de 2010 a 2020, as neoplasias mais frequentes em mulheres foram câncer de mama, câncer nos brônquios e pulmões, câncer no colo do útero, câncer no cólon e no pâncreas e em homens foram brônquios e pulmões, câncer de próstata, câncer de estômago, de esôfago e no fígado e vias biliares, sendo observado uma tendência crescente na taxa de mortalidade em mulheres e decrescente na taxa de mortalidade em homens. Conclusão: os resultados demonstram um possível comprometimento com a notificação durante o período de pandemia por Covid-19 e um possível rastreamento ainda deficiente de câncer na população masculina.


Introduction: cancer is a severe public health problem, considered the second cause of death in Brazil. Due to its relevance, efficient control of cases by monitoring the mortality rate is essential. Thus, the work analysed the evolution of cancer mortality for the most frequent primary locations, according to sex, from 2010 to 2020. Methodology: this is a descriptive observational study in which data were obtained through the Atlas Online Cancer Mortality Report. The data collected correspond to the number of deaths stratified by the most frequent type of cancer, by year studied and by sex, in addition to the crude specific mortality rates and the age-adjusted mortality rate for males and females, for each type of cancer. Understudy, considering the standard world population, the significance of the temporal trend is evaluated by linear regression. Results: in Brazil, from 2010 to 2020, the most frequent neoplasms in women were breast cancer, bronchial and lung cancer, cervical cancer, colon and pancreas cancer and in men, they were bronchial and lung cancer, cancer prostate, stomach, oesophagal and liver and biliary tract cancer, with an increasing trend in the mortality rate in women and a decreasing trend in the mortality rate in men. Conclusion: the results demonstrate a possible compromise with notification during the Covid-19 pandemic and a possible still poor screening of cancer in the male population.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Death , Neoplasms , Pancreatic Neoplasms , Prostatic Neoplasms , Stomach Neoplasms , Breast Neoplasms , Esophageal Neoplasms , Uterine Cervical Neoplasms , Epidemiology, Descriptive , Liver Neoplasms , Lung Neoplasms
5.
Respirar (Ciudad Autón. B. Aires) ; 15(3): [211-216], sept. 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1510804

ABSTRACT

En Colombia, para 2020, el cáncer de pulmón se reportó como la segunda neoplasia con mayor incidencia y la primera con mayor tasa de mortalidad según las cifras del minis-terio de salud de Colombia. El compromiso peritoneal en el cáncer de pulmón es algo extremadamente raro, se considera <1%. A continuación, exponemos un caso de car-cinomatosis peritoneal en cáncer de pulmón en un hospital en la ciudad de Bogotá. Se incorpora una posterior revisión descriptiva de la literatura de los casos clínicos de car-cinomatosis peritoneal en cáncer de pulmón reportados en la literatura mundial en los últimos 20 años, con el objetivo de resumir las principales características de estos pa-cientes que permiten plantear hipótesis de su enfoque terapéutico y pronóstico


In Colombia for 2020, lung cancer was reported as the fifth neoplasm with the highest incidence and the second with the highest mortality rate. Peritoneal involvement in lung cancer is extremely rare, it is considered <1%. Next, we present a case of peritoneal car-cinomatosis in lung cancer in Bogotá, with a subsequent literature review of the litera-ture of clinical cases of peritoneal carcinomatosis in lung cancer reported in the world li-terature in the last 20 years. The aim is to summarize the main characteristics of these patients that allow to hypothesize their prognostic and therapeutic approach


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Peritoneal Neoplasms/therapy , Lung Neoplasms/therapy , Neoplasm Metastasis , Case Reports , Incidence , Mortality
6.
Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 139-142, sept. 2023.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1517906

ABSTRACT

Introducción: la medicina basada en el valor ha logrado mejorar la calidad de atención del paciente y/o la satisfacción de las personas, reduciendo costos y obteniendo mejores resultados. Se apoya sobre tres pilares básicos: la medicina basada en la evidencia, la atención centralizada en el paciente, y la sustentabilidad. Sin embargo, existen pocas publicaciones sobre la estrategia de personas navegadoras para pacientes con cáncer de pulmón, que podrían ser una herramienta clave para brindar apoyo, asegurando que tengan acceso al conocimiento y los recursos necesarios a fin de completar la vía de atención clínica recomendada. Estado del arte: se trata de una intervención en salud cuyo objetivo principal es lograr vencer las barreras relacionadas con la atención (p. ej., logísticas, burocrático-administrativas, de comunicación y financieras) para poder mejorar la calidad y el acceso a la salud en el marco de la atención del cáncer. Estas personas cumplen un papel de guía para pacientes durante el proceso de diagnóstico y tratamiento activo. Su labor consiste en vincular al paciente con los proveedores clínicos, brindar un sistema de apoyo, asegurar un acompañamiento individualizado, garantizar que tengan acceso al conocimiento y a los recursos necesarios para completar el seguimiento y/o tratamiento adecuado. Discusión/Conclusión: indudablemente, es un elemento cada vez más reconocido en los programas de cáncer, centrado en el paciente y de alta calidad. Su implementación será de especial interés en la Unidad de Práctica Integrada para personas con cáncer de pulmón. (AU)


Introduction: Value-based medicine has succeeded in improving the quality of patient care and or patient satisfaction, reducing costs, and obtaining better outcomes. It rests on three fundamental pillars: evidence-based medicine, patient-centered care, and sustainability. However, there are few publications on the people navigator strategy for lung cancer patients, which could be a crucial tool for providing support, ensuring that they have access to the knowledge and resources needed to complete the recommended clinical care pathway. State of the art: It is a health intervention whose main objective is to overcome care-related barriers (e.g., logistical, bureaucratic-administrative, communication, and financial) to improve quality and access to health in the context of cancer care. These individuals play a guiding role for patients during the diagnostic and active treatment process. Their job is to link the patient with clinical providers, provide a support system, ensure individualized accompaniment, and guarantee that they get access to the knowledge and resources necessary to complete the appropriate follow-up and, or treatment. Discussion/Conclusion: Undoubtedly, patient navigators represent an increasingly recognized element of high-quality, patient-centered cancer programs. Its implementation will be of specific interest in the Integrated Practice Unit for people with lung cancer. (AU)


Subject(s)
Humans , Patient Navigation/organization & administration , Lung Neoplasms , Patient Care Team , Patient Satisfaction , Patient-Centered Care/methods , Access to Information , Quality Improvement , Patient Navigation/history , Patient Outcome Assessment , Patient Reported Outcome Measures , Health Services Accessibility/trends
7.
Arch. argent. pediatr ; 121(3): e202202714, jun. 2023. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1436134

ABSTRACT

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo


Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.


Subject(s)
Humans , Male , Child , Pneumothorax/complications , Pneumothorax/etiology , Sarcoma, Synovial/complications , Sarcoma, Synovial/diagnosis , Sarcoma, Synovial/pathology , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Cough , Lung/pathology
8.
Medicentro (Villa Clara) ; 27(2)jun. 2023.
Article in Spanish | LILACS | ID: biblio-1440537

ABSTRACT

Introducción: La Organización Mundial de la Salud declaró el COVID-19 como una pandemia el 11 de marzo de 2020. El antecedente de cáncer es considerado un factor de riesgo de mortalidad para múltiples padecimientos; la evolución de los pacientes con enfermedades neoplásicas puede verse influida por afecciones sobreañadidas como fue el caso del COVID-19. Objetivo: Caracterizar, desde el punto de vista clínico, a los pacientes oncológicos que ingresaron con COVID-19. Métodos: Se realizó una investigación descriptiva y transversal en pacientes con diagnóstico de enfermedad oncológica ingresados por COVID-19, en el Hospital Universitario Dr. Celestino Hernández Robau, Villa Clara, en el período de enero-diciembre 2021. Se incluyeron en el estudio 78 pacientes con diagnóstico de neoplasia de 5 años o menos de evolución. Resultados: Predominó el sexo masculino y los mayores de 60 años de edad. El 39,7 % de los pacientes presentó cáncer de pulmón o de laringe seguido por cáncer de mama, hemolinfopoyético y colorrectal. El 46,2 % se encontraba en estadio estable y el 29,5 % en paliativo. El 34,6 % de los pacientes recibía tratamiento con quimioterapia en el momento del ingreso. Los fármacos más utilizados fueron: esteroides (85,9 %), interferón alfa (73,1 %) y heparina sódica (55,1 %). Conclusiones: En los pacientes oncológicos hospitalizados con COVID-19, los tumores de pulmón y laringe fueron los más frecuentes, aunque el de mama, próstata y colorrectal, en ese orden, se relacionaron con mayor mortalidad. Los pacientes que se encontraban en progresión de la enfermedad y los que recibían tratamiento con quimioterapia presentaron mayor probabilidad de morir.


Introduction: the World Health Organization declared COVID-19 as a pandemic on March 11, 2020. A history of cancer is considered a mortality risk factor for multiple diseases; the evolution in patients with neoplastic diseases can be influenced due to superadded conditions such as the case of COVID-19. Objective: to characterize, from a clinical point of view, cancer patients admitted with COVID-19. Methods: a descriptive and cross-sectional research was carried out in cancer patients admitted with COVID-19 at "Dr. Celestino Hernández Robau" University Hospital in Villa Clara from January to December 2021. A number of 78 cancer patients with 5 years or less of evolution was included in the study. Results: male gender and those over 60 years of age predominated. The 39.7% of the patients had lung or laryngeal cancer followed by breast, hemolymphopoietic and colorectal cancers. The 46.2% were in a stable state and 29.5% in palliative care. The 34.6% of them were receiving chemotherapy treatment at the time of admission. Steroids (85.9%), alpha interferon (73.1%) and sodium heparin (55.1%) were the most used drugs. Conclusions: lung and laryngeal tumours were the most common malignancy in cancer patients hospitalized with COVID-19, although breast, prostate, and colorectal tumours, in that order, were associated with higher mortality. Patients with disease progression and those receiving chemotherapy were more likely to die.


Subject(s)
Patient-Centered Care , Lung Neoplasms , Neoplasms , COVID-19
9.
Int. j. morphol ; 41(1): 118-133, feb. 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1430508

ABSTRACT

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.


Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.


Subject(s)
Humans , Chloride Channels/metabolism , Adenocarcinoma of Lung/diagnosis , Lung Neoplasms/diagnosis , Prognosis , RNA, Messenger , Lymphocytes , Biomarkers, Tumor , Chloride Channels/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/metabolism , Lung Neoplasms/immunology , Lung Neoplasms/metabolism
10.
Rio de Janeiro; s.n; 2023. 163 f p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1532941

ABSTRACT

O câncer de pulmão é reconhecidamente um dos mais agressivos dentre os tumores, com alta letalidade. A detecção precoce do câncer de pulmão com tomografia computadorizada de baixa dose tem sido avaliada em diversos países e implementada em alguns. Entretanto, a implementação do rastreamento com uso dessa tecnologia para detecção precoce de novos casos, permanece questionado no mundo, e no Brasil não está recomendado. Por esse motivo, foi elaborada uma avaliação de custo-efetividade do uso da tomografia computadorizada de baixa dose como estratégia de rastreamento para detecção precoce do câncer de pulmão em população de risco sob a perspectiva do Sistema Único de Saúde como órgão financiador. Inicialmente uma revisão sistemática foi elaborada e descrita uma síntese das diferentes abordagens disponíveis nas avaliações econômicas. Os 30 estudos selecionados e incluídos na revisão mostraram qualidade global, com bom padrão metodológico, que atendeu a mais de 80% dos critérios estabelecidos pelo formulário (Consensus Health Economic Criteria list). A análise da eficiência comparativa entre duas alternativas (anual e bianual) para o diagnóstico precoce de câncer de pulmão, considerando a estratégia de rastreamento com tomografia computadorizada de baixa dose e a conduta clínica sem rastreio, como cenário de referência, teve por base uma coorte hipotética de 100.000 indivíduos assintomáticos, e tabagistas de alto risco. O horizonte temporal considerou a expectativa de vida dos indivíduos, e a perspectiva foi o Sistema Único de Saúde como financiador da assistência à saúde. Apenas os custos médicos diretos dos itens relacionados ao processo de diagnóstico e tratamento foram estimados. O desfecho foi medido em anos de vida ganhos. O desconto de 5% foi aplicado aos custos e benefícios. E realizadas análises de sensibilidade determinística univariada e probabilística. A razão de custo-efetividade incremental da estratégia de rastreamento anual com a tomografia computadorizada de baixa dose para a detecção precoce de câncer de pulmão foi estimada em R$ 97.583,52 por cada ano de vida ganho e de R$ 56.642,20 por ano de vida ganho, com o rastreio a cada dois anos. A análise determinística mostrou que o impacto da redução da incidência de câncer de pulmão, em ambas as alternativas (anual e bianual), chega a gerar quase o triplo dos gastos estimados para a razão de custo-efetividade incremental. Para o anual esse aumento chega a R$ 176.834,47, fora do limiar de R$105.000,00, enquanto o rastreamento bianual, mesmo dobrando os gastos, ainda se manteria dentro do limiar de custo-efetividade atualmente definido para o país. Os demais parâmetros de relevância (sensibilidade do rastreamento para detecção de câncer e a proporção de diagnósticos em estadio I/II com o rastreamento) não impactaram nos resultados finais. A análise probabilística das alternativas de rastreamento mostrou para o rastreamento anual 52% das simulações dentro do limiar estabelecido e 94,2% referente ao bianual. O resultado do modelo econômico mostrou resultados favoráveis com a adoção da estratégia de rastreamento de câncer de pulmão com uso de tomografia computadorizada de baixa dose comparada a condução clínica, realizada a cada dois anos em população de alto risco, sob a perspectiva do SUS. (AU)


Lung cancer is one of the most aggressive tumors, with high lethality. Early detection of lung cancer with low-dose computed tomography has been evaluated in several countries and implemented in some. However, the implementation of screening using this technology for early detection of new cases remains questioned worldwide, but in Brazil, it has not been recommended. Thus, a cost-effectiveness assessment of a screening strategy with low-dose computed tomography for early lung cancer detection in a high-risk population under the Unified Health System perspective as a funding body. First, a systematic review was performed and synthesized the different approaches available in economic evaluations. Thirty studies selected and included in the review showed overall quality, with a well-designed methodological standard, which met more than 80% of the criteria established by the Consensus Health Economic Criteria (CHEC) list form. The analysis of the comparative efficiency between two alternatives (annual and biannual) for the early diagnosis of lung cancer, considering the screening strategy with low-dose computed tomography and the clinical management, without screening, as a reference scenario, was based on a cohort hypothetical 100,000 asymptomatic individuals, and high-risk smokers. The time horizon considered the individuals' life expectancy, and the perspective was the Brazilian Unified Health System as the funder of health care. Only the direct medical costs of items related to the diagnosis and treatment process were estimated. The outcome measure was life years gained. A discount of 5% has been applied to costs and benefits. A deterministic and probabilistic sensitivity analysis has been performed. The incremental cost-effectiveness ratio of the annual screening strategy for early lung cancer detection has been estimated at BRL 97,583.52 for each life-year gained and BRL 56,642.20 per year of life gained, with screening every two years. The deterministic analysis showed that the impact of reducing the incidence of lung cancer, in both alternatives (annual and biannual) generated almost three times the estimated expenses for the incremental cost-effectiveness ratio. For the annual survey, this increase reaches BRL 176,834.47, outside the BRL 105,000.00 threshold, while biannual screening, even doubling the expenses, would remain within the cost-effectiveness threshold currently defined for the country. The other relevant parameters (screening sensitivity for cancer detection and the proportion of stage I/II diagnoses with screening) have no impact on the final results. The probabilistic analysis showed that 52% of simulations within the established threshold correspond to the annual screening, and 94.2% to the biannual. The economic model designed to evaluate the cost-effectiveness of lung cancer screening using low-dose computed tomography compared to clinical care showed favorable results from the strategy performed every two years in a high-risk population, under the SUS perspective. (AU)


Subject(s)
Humans , Unified Health System , Tomography, X-Ray Computed , Mass Screening , Early Detection of Cancer , Lung Neoplasms , Brazil , Cost-Effectiveness Analysis
11.
Rev. guatemalteca cir ; 28(1): 3-11, 2023. tab
Article in Spanish | LILACS, LIGCSA | ID: biblio-1413410

ABSTRACT

El cáncer pulmonar se establece como la segunda causa de muerte en países desarrollados y en algunos en vías de desarrollo. Su diagnóstico es tardío, sus opciones de resección y su curación aun con terapias adyuvantes son limitadas, lo que incide en la pobre sobrevida a 5 años, es por ello que se necesitan mayores esfuerzos para combatir el hábito del tabaco, principal agente etiológico. Material y Métodos: Se trata de un estudio descriptivo transversal en pacientes adultos atendidos de 01 de enero del 2011 al 31 de diciembre del 2021, ingresados al servicio de cirugía del Hospital San Vicente de Guatemala, con diagnósticos de cáncer pulmonar, masa pulmonar, derrame pleural o nódulo pulmonar solitario. Resultados: Se atendieron 202 pacientes con diagnósticos presuntivos de cáncer pulmonar, no encontrando diferencias significativas en relación al sexo. La edad mayormente afectada se estableció entre los 50 y 70 años. Prevalecieron los estadíos IIIA, IIIB y IV basados en los hallazgos clínicos, tomográficos y transoperatorios y solo al 10% se le sometió a una cirugía de resección pulmonar mayor. Los cánceres de células no pequeñas NSCLC fueron reportados en el 68.7% y el adenocarcinoma fue la variedad más frecuente con el 54.95% sobre el 7.29% del epidermoide. La mortalidad a los treinta días se estableció en 2.97%. Conclusión: El adenocarcinoma pulmonar ocupa el primer lugar en la incidencia de los cánceres pulmonares, desplazando así al carcinoma epidermoide popularizado desde la mitad del siglo pasado. Esta tendencia en el cambio histológico está firmemente asociado a las modificaciones en los hábitos del fumar (AU)


Lung cancer is established as the second cause of death in developed countries and in some developing ones. Its diagnosis is late, its resection options and its cure even with adjuvant therapies are limited, which affects the poor survival at 5 years, which is why greater efforts are needed to combat the tobacco habit, the main etiological agent. Material and Methods: This is a cross-sectional descriptive study in adult patients treated from January 1, 2011 to December 31, 2021, admitted to the surgery service of the Hospital San Vicente de Guatemala, with diagnoses of lung cancer, lung mass, effusion pleural or solitary pulmonary nodule. Results: 202 patients with presumptive diagnoses of lung cancer were treated, finding no significant differences in relation to sex and the most affected age was established between 50 and 70 years. Stages IIIA, IIIB, and IV prevailed based on clinical, tomographic, and intraoperative findings, and only 10% underwent major lung resection surgery. NSCLC non-small cell cancers were reported in 68.7% and adenocarcinoma was the most frequent variety with 54.95% over 7.29% of epidermoid. Thirty-day mortality was established at 2.97%. Conclusion: Pulmonary adenocarcinoma occupies the first place in the incidence of lung cancers, thus displacing squamous cell carcinoma popularized since the middle of the last century. This trend in histological change is strongly associated with changes in smoking habits.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Adenocarcinoma of Lung/epidemiology , Histology/classification , Lung Neoplasms/diagnosis , Pleural Effusion/complications , Bronchoscopy/instrumentation , Diagnostic Techniques and Procedures , Multiple Pulmonary Nodules/diagnostic imaging
12.
Oncología (Guayaquil) ; 33(3): [266-272], 2023.
Article in English, Spanish | LILACS | ID: biblio-1531956

ABSTRACT

Introducción:La inmunoterapia con pembrolizumab ha mejorado el pronóstico del cáncer de pulmón metastásico. En el presente caso se presenta la supervivencia extendidad y evolución de un paciente específico.Caso clínico:Hombre de 66 años, fumador. Diagnosticado de masa pulmonar en lóbulo infe-rior izquierdo de dimensiones 9 x 8 cm, con metástasis supra e infratentoriales intraaxiliares. Taller diagnóstico: Establecida como neoplasia de pulmón en estadio IVc, se comprobó el estado de PDL1 que positivo en un 80 % de la muestra de masa pulmonar. Debuta con me-tástasis cerebrales.Evolución: Se inció inmunoterapia con Pembrolizumab, el cual se mantubo hasta la presencia de un efecto secundario atribuido al pembrolizumab, cumpliendo 30meses de supervivencia hasta el cierre de esta observación no se reportó la muerte del paciente.Conclusiones:En el presente reporte, la determinación del biomarcador histológico PDL1 po-sitivo en cáncer de pulmón ayudo a prescribir un tratamiento con inmunoterpia dirigida, lo que demostró aumentar la supervivencia más allá que el tratamiento convencional con quimiote-rapia


Introduction: Immunotherapy with pembrolizumab has improved the prognosis of metastatic lung cancer. A specific patient's extended survival and evolution is presented in the present case.Clinical case: 66-year-old man, smoker. Diagnosed with a lung mass in the left lower lobe measuring 9 x 8 cm, with supra and infratentorial intra-axial metastases.Diagnostic workshop: To establisha stage IVc lung neoplasm, 80% of the lung mass sample was confirmed to be positive for PDL1.Evolution: Immunotherapy was started with Pembrolizumab, which was maintained until the presence of a side effect attributed to pembrolizumab, completing 30 months of survival until the closure of this observation, the patient's death was not reported.Conclusions: In the present report, the determination of the positive histological biomarker PDL1 in lung cancer helped prescribe treatment with targeted immunotherapy, which was shown to increase survival beyond conventional treatment with chemotherapy


Subject(s)
Humans , Male , Aged , Immunotherapy , Lung Neoplasms , Lung Diseases
13.
Oncología (Guayaquil) ; 33(3): [254-265], 2023.
Article in English, Spanish | LILACS | ID: biblio-1531949

ABSTRACT

Introducción:El cáncer representa un extraordinario problema para la Salud Pública mundial, suponiendo la primera causa de mortalidad global. El cáncer de pulmón es el más frecuente. El número de defunciones se ha ordenado de acuerdo a la Clasificación de Bertillon. El objetivo del estudio fue analizar las causas de mortalidad por cáncer; determinar que grupos de edad presentan más muertes y que estaciones; calcular las tasas de mortalidad.Materiales y métodos:mediante la lectura de los Libros de Defunción del Archivo Parroquial de la ciudad (APJC), se han obtenido 26.203 difuntos, 18.538 de los cuales tienen anotado el motivo de su muerte, los cuales son utilizados para su análisis posterior.Resultados:Se registraron 182 defuncionespor cáncer(1% del total), la gran mayoría adultos, 165 (90.7%), siendo las mujeres casi el doble, 121 (66.5%). La mayor mortalidad se da entre los 45 y los 74 años, 122 difuntos (67.0%). El cáncer más frecuente es el del apartado de otros órganos, con 50 defunciones (40.6%). El mes con más muertos es marzo.las papeletas de defunción solían presentar errores ortográficos o de transcripción. Estudios similares en otras poblaciones arrojan cifras dispares según el periodo analizado y la cifra de muertos. Existe una estrecha relación entre cáncer y edad.Conclusión:El cáncer de otros órganos es el más numeroso. La mortalidad difiere entre las distintas poblaciones comparadas. El número de difuntos es muy inferior al actual, debido a la falta de medios diagnósticos y conocimientos de la época y la posible existencia de un subregistro


Introduction: Cancer represents an extraordinary problem for Global Public Health and is the leading cause of global mortality. Lung cancer is the most common cancer. The number of deaths was ordered according to the Bertillon Classification. The objective of the study was to analyze the causes of mortality due to cancer, determine which age groups have the most deaths and which seasons, and calculate mortality rates.Materials and methods: By reading the Death Books of the city's Parish Archive (APJC), 26,203 deceased persons were obtained, 18,538 of whom were diagnosed with COVID-19, and these individuals were used for subsequent analysis.Results: A total of 182deaths due to cancer were recorded (1% of the total);the vast majority wereadults (165,90.7%), with nearlytwice as manywomen (121, 66.5%). The highest mortal-ity occurredbetween 45 and 74 years of age, with 122 deaths (67.0%). The most common cancer wasthat of other organs, accounting for50 deaths (40.6%). The month with the most deaths wasMarch. Death certificates often had spelling or transcription errors. Similar studies in other populations show different figures depending on the period analyzed and the number of deaths. There is a close relationship between cancer incidence and age.Conclusion: Cancer of other organs is the most common cancer. Mortality differs between the different populations compared. The number of deaths is much lower than the current numberdue to the lack of diagnostic methods, knowledge of the time,and the possibility of underrecording


Subject(s)
Humans , Male , Female , Adult , Aged , Lung Neoplasms , Neoplasms
14.
Rev. colomb. cancerol ; 27(1): 76-79, 2023.
Article in Spanish | LILACS, COLNAL | ID: biblio-1451945

ABSTRACT

En el día a día de la atención en salud vemos cómo el cáncer de pulmón sigue siendo una de las patologías oncológicas con peor pronóstico: su tasa global de sobrevida de solo el 20,0 %. Esto se debe, en parte, a que en la mayoría de los casos su diagnóstico se hace en estadios avanzados, cuando ya no hay muchas opciones de tratamiento, más allá de medidas paliativas. A diferencia de otros tipos de cáncer ­como el de cuello uterino, el de mama o el de próstata­, en los cuales existen estrategias de tamizaje y prevención asequibles y que favorecen un mejor pronóstico, en el de pulmón no ha sido posible implementar a gran escala tales intervenciones, lo cual ha favorecido el pobre pronóstico de la enfermedad y ha contribuido a que siga siendo la principal causa de muerte por cáncer en el mundo (1).


In the day-to-day health care we see how lung cancer continues to be one of the oncological pathologies with the worst prognosis: its overall survival rate of only 20.0%. This is due, in part, to the fact that in most cases its diagnosis is made in advanced stages, when there are no longer many treatment options, beyond palliative measures. Unlike other types of cancer ­such as cervical, breast or prostate cancer­, in which there are affordable screening and prevention strategies that favor a better prognosis, in lung cancer it has not been possible to implement such interventions on a large scale, which has favored the poor prognosis of the disease and has contributed to its continuing to be the leading cause of death from cancer in the world (1).


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Lung Neoplasms , Lung Neoplasms/complications , Lung Neoplasms/therapy , Neoplasms
15.
Braz. J. Anesth. (Impr.) ; 73(4): 441-445, 2023. graf
Article in English | LILACS | ID: biblio-1447632

ABSTRACT

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.


Subject(s)
Animals , Male , Rats , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Melanoma/pathology , Morphinum/pharmacology , Toll-Like Receptor 4
16.
Article in Spanish | LILACS, BDENF, CUMED | ID: biblio-1508162

ABSTRACT

Introducción: El cáncer de pulmón constituye un problema sanitario a nivel mundial, a pesar de los avances tecnológicos y terapéuticas en oncología, hay un alto porcentaje de personas que se diagnostican en estadios avanzados de la enfermedad, las cuales tienen una mayor demanda de cuidados continuos. Objetivo: Identificar la necesidad de cuidados continuos en personas con cáncer de pulmón avanzado. Métodos: Revisión sistemática realizada durante enero a julio del 2021. Se realizó análisis de contenido de documentos, que incluyó artículos originales y de revisión publicados desde 2010 hasta 2021 en las bases de datos SciELO, Google Scholar y Elsevier. Se elaboró la pregunta guía a través del acrónimo PICo. La estrategia de búsqueda se realizó mediante los descriptores en Ciencias de la Salud (DeCS) "Personal de enfermería", "Neoplasia de pulmón" y "cuidados de enfermería" y el operador booleano AND. Se utilizó el diagrama de flujo (PRISMA) para la formulación de la estrategia de búsqueda, se identificaron y revisaron 77 artículos, de los que fueron útiles 12 de la evolución de la categoría. Conclusiones: El análisis realizado referido a la necesidad de los cuidados continuos en personas con cáncer de pulmón avanzado permitió definición operativa de esta categoría, a partir de las características de esta entidad y la demanda que enfrentan los servicios de hospitalización y los profesionales de enfermería en correspondencia con la satisfacción de necesidades de estas personas, y permitió establecer un acercamiento en los referentes teóricos que sustentan el tema(AU)


Introduction: Lung cancer is a worldwide health problem; despite technological and therapeutic advances in oncology, there is a high percentage of people diagnosed in advanced stages of the disease, which have a greater demand for continuous care. Objective: To identify the need for continuous care in people with advanced lung cancer. Methods: A systematic review was conducted from January to July 2021. Document content analysis was performed, including original and review articles published from 2010 to 2021 in the SciELO, Google Scholar and Elsevier databases. The guiding question was elaborated using the acronym PICo. The search strategy was performed using the Health Sciences Descriptors (DeCS) Personal de enfermería [nursing personnel], Neoplasia de pulmón [lung neoplasia], and cuidados de enfermería [nursing care], together with the Boolean operator AND. The PRISMA flowchart was used for the formulation of the search strategy; 77 articles were identified and reviewed, of which 12 from the category evolution. Conclusions: The carried out analysis regarding the need for continuous care in people with advanced lung cancer allowed the operational definition of this category, based on the characteristics of this entity or the demand faced by hospitalization services and nursing professionals in correspondence with the satisfaction of needs of these people, as well as it allowed establishing an approach within the theoretical references that support the topic(AU)


Subject(s)
Humans , Lung Neoplasms/diagnosis , Review Literature as Topic , Databases, Bibliographic
17.
Frontiers of Medicine ; (4): 18-42, 2023.
Article in English | WPRIM | ID: wpr-971635

ABSTRACT

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Tumor Microenvironment/genetics
18.
Frontiers of Medicine ; (4): 105-118, 2023.
Article in English | WPRIM | ID: wpr-971622

ABSTRACT

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.


Subject(s)
Humans , Mice , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Acrylamides/pharmacology , ErbB Receptors/metabolism , Cell Line, Tumor , CD47 Antigen/therapeutic use
19.
Protein & Cell ; (12): 123-136, 2023.
Article in English | WPRIM | ID: wpr-971616

ABSTRACT

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Carrier Proteins/metabolism , Cell Line , Cell Proliferation , Exosomes/metabolism , Lung Neoplasms/genetics , Membrane Proteins/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism
20.
Journal of Southern Medical University ; (12): 242-250, 2023.
Article in Chinese | WPRIM | ID: wpr-971521

ABSTRACT

OBJECTIVE@#To screen the differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) cells with acquired resistance to osimertinib and explore their roles in drug resistance of the cells.@*METHODS@#The cell lines H1975_OR and HCC827_OR with acquired osimertinib resistance were derived from their osimertinib-sensitive parental NSCLC cell lines H1975 and HCC827, respectively, and their sensitivity to osimertinib was assessed with CCK-8 assay, clone formation assay and flow cytometry. RNA sequencing (RNA-seq) and real-time quantitative PCR (qPCR) were used to screen the differentially expressed lncRNAs in osimertinib-resistant cells. The role of the identified lncRNA in osimertinib resistance was explored using CCK-8, clone formation and Transwell assays, and its subcellular localization and downstream targets were analyzed by nucleoplasmic separation, bioinformatics analysis and qPCR.@*RESULTS@#The resistance index of H1975_OR and HCC827_OR cells to osimertinib was 598.70 and 428.82, respectively (P < 0.001), and the two cell lines showed significantly increased proliferation and colony-forming abilities with decreased apoptosis (P < 0.01). RNA-seq identified 34 differentially expressed lncRNAs in osimertinib-resistant cells, and among them lnc-TMEM132D-AS1 showed the highest increase of expression after acquired osimertinib resistance (P < 0.01). Analysis of the TCGA database suggested that the level of lnc-TMEM132D-AS1 was significantly higher in NSCLC than in adjacent tissues (P < 0.001), and its high expression was associated with a poor prognosis of the patients. In osimertinib-sensitive cells, overexpression of Lnc-TMEM132D-AS1 obviously promoted cell proliferation, colony formation and migration (P < 0.05), while Lnc-TMEM132D-AS1 knockdown partially restored osimertinib sensitivity of the resistant cells (P < 0.01). Lnc-TMEM132D-AS1 was localized mainly in the cytoplasm, and bioinformatics analysis suggested that hsa-miR-766-5p was its candidate target, and their expression levels were inversely correlated. The target mRNAs of hsa-miR-766-5p were mainly enriched in the Ras signaling pathway.@*CONCLUSION@#The expression of lnc-TMEM132D-AS1 is significantly upregulated in NSCLC cells with acquired osimertinib resistance, and may serve as a potential biomarker and therapeutic target for osimertinibresistant NSCLC.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/genetics , RNA, Long Noncoding/metabolism , Sincalide/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Movement , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism
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