Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico / Hypertensive Emergency as the Debut of Paraneoplastic Cushing Syndrome

Presentamos el caso de un paciente con antecedentes de hipertensión arterial vasculorrenal tratada un año antes, que acude a urgencias por emergencia hipertensiva (HTA) y disnea. Descartada primera sospecha de reestenosis de arteria renal con angiografía por tomografía computarizada (angioTC), se completa el estudio confirmándose diagnóstico de cáncer de pulmón mediante prueba de imagen y anatomía patológica. En el estudio de hipertensión se detecta elevación de hormona adrenocorticótropa (ACTH), hipercortisolismo y datos analíticos de hiperaldosteronismo. Con el diagnóstico final de síndrome de Cushing secundario a producción ectópica de ACTH se inicia tratamiento médico, sin llegar a recibir nada más por fallecimiento del paciente a los pocos días.(AU)

We present the case of a patient with a history of renal-vascular hypertension treated with stent one year previously, who attended the emergency room due to hypertensive emergency and dyspnea. Once the first suspicion of renal artery restenosis was ruled out with CT angiography, the study was completed, confirming the diagnosis of lung cancer through imaging and pathological anatomy. In the hormonal study, elevation of ACTH, hypercortisolism and analytical data of hyperaldosteronism were detected. With the final diagnosis of Cushing's syndrome secondary to ectopic production of ACTH, medical treatment was started, without being able to receive anything else due to the death of the patient after a few days.(AU)

Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data.

PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed. RESULTS: In all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival. CONCLUSION: A high number of concurrent medications was associated with poor clinical outcomes.

The characteristics and prognosis of different disease patterns of multiple primary lung cancers categorized according to the 8th edition lung cancer staging system.

INTRODUCTION: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. METHOD: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. RESULTS: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. CONCLUSIONS: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.

The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study.

PURPOSE: We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). METHODS: The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). RESULTS: 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6-19.8) in combined therapy and 8.2 months (95% CI, 5.7-10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1-5 BMs (HR = 1.808, P = 0.012). CONCLUSIONS: Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1-5 BMs reduce the risk of extracranial recurrence.

Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus/enterocytes for effective oral absorption of shikonin and gefitinib.

The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy.

Placental metastasis from maternal NUT carcinoma: diagnostic pitfalls and challenges.

We report a young pregnant woman with large midline thoracic mass and markedly elevated serum alpha-fetoprotein (AFP) levels. Initially suspected as a germ cell tumour (GCT) due to age, site, and high AFP levels, a biopsy unveiled a high-grade malignant tumour characterised by undifferentiated monotonous cells. Although tumour cells exhibited positive AFP, the overall immunoprofile did not provide additional evidence to support GCT. Further work-up showed positive for NUT (nuclear protein in testis) immunostaining and the presence of BRD4-NUT1 fusion, confirming the diagnosis of NUT carcinoma. On radiology, there were extensive metastases to lungs, liver, vertebrae, and placenta. Despite aggressive chemotherapy, radiotherapy and immunotherapy, she did not respond to the therapies. Fortunately, her child was not affected by the carcinoma. This is the first case highlighting that thoracic lung primary NUT carcinoma can spread to the placenta and manifest with elevated serum AFP levels, potentially leading to misdiagnosis as GCT both clinically and pathologically.

A combined model of serum neutrophil extracellular traps, CD8+ T cells, and tumor proportion score provides better prediction of PD-1 inhibitor efficacy in patients with NSCLC.

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors. Serum myeloperoxidase (MPO)-double-stranded DNA (dsDNA) was detected as a marker of NET serum concentration. T cells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression-free survival after PD-1 inhibitor treatment was associated with higher levels of CD3+ T cells, a lower neutrophil : CD3+-T-cell ratio (NEU/CD3+) and lower neutrophil : CD8+-T-cell ratio (NEU/CD8+) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune-related adverse events (IrAEs) as well as higher NEU/CD3+ and NEU/CD8+. The combined model of serum NETs, CD8+ T cells, and tumor proportion score (TPS) significantly improved the prediction of PD-1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD-1 inhibitor response and reflect the tissue neutrophil-to-lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8+ T cells, and TPS is a powerful tool for predicting the efficacy of PD-1 inhibitor treatment in patients with NSCLC.

Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study.

OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

[18F]fluorodeoxyglucose positron emission tomography/computed tomography in combination with clinical data in predicting overall survival in non-small-cell lung cancer patients: A retrospective study.

INTRODUCTION: Positron emission tomography/computed tomography (PET/CT) has an established role in evaluating patients with lung cancer. The aim of this work was to assess the predictive capability of [18F]Fluorodeoxyglucose ([18F]FDG) PET/CT parameters on overall survival (OS) in lung cancer patients using an artificial neural network (ANN) in parallel with conventional statistical analysis. METHODS: Retrospective analysis was performed on a group of 165 lung cancer patients (98M, 67F). PET features associated with the primary tumor: maximum and mean standardized uptake value (SUVmax, SUVmean), total lesion glycolysis (TLG) metabolic tumor volume (MTV) and area under the curve-cumulative SUV histogram (AUC-CSH) and metastatic lesions (SUVmaxtotal, SUVmeantotal, TLGtotal, and MTVtotal) were evaluated. In parallel with conventional statistical analysis (Chi-Square analysis for nominal data, Student's t test for continuous data), the data was evaluated using an ANN. There were 97 input variables in 165 patients using a binary classification of either below, or greater than/equal to median survival post primary diagnosis. Additionally, phantom study was performed to assess the most optimal contouring method. RESULTS: Males had statistically higher SUVmax (mean: 10.7 vs 8.9; p = 0.020), MTV (mean: 66.5 cm3 vs. 21.5 cm3; p = 0.001), TLG (mean 404.7 vs. 115.0; p = 0.003), TLGtotal (mean: 946.7 vs. 433.3; p = 0.014) and MTVtotal (mean: 242.0 cm3 vs. 103.7 cm3; p = 0.027) than females. The ANN after training and validation was optimised with a final architecture of 4 scaling layer inputs (TLGtotal, SUVmaxtotal, SUVmeantotal and disease stage) and receiving operator characteristic (ROC) analysis demonstrated an AUC of 0.764 (sensitivity of 92.3%, specificity of 57.1%). CONCLUSION: Conventional statistical analysis and the ANN provided concordant findings in relation to variables that predict decreased survival. The ANN provided a weighted algorithm of the 4 key features to predict decreased survival. IMPLICATION FOR PRACTICE: Identification of parameters which can predict survival in lung cancer patients might be helpful in choosing the group of patients who require closer look during the follow-up.

Incidental diagnosis of lung cancer on chest CT scan performed for suspected or documented COVID-19 infection.

CONTEXT: Recent studies have shown a benefit of chest computed tomography (CT scan) in lung cancer screening. The COVID-19 pandemic has led to many chest CT scan performed on a large population. The objective of this study was to describe the incidence and characteristics of lung cancer detected on chest CT scan, outside the framework of a clinical trial, for a suspected or documented COVID-19 infection. METHODS: We conducted a multicenter study, carried out from the analysis of data from the prospective COVID-19 database of the Clinical Data Warehouse of the Greater Paris University Hospitals (AP-HP). We identified the patients who had been diagnosed with a lung cancer, due to a chest CT scan done for a suspected or confirmed COVID-19 infection. The study period was limited to the first two epidemic lockdowns: (03/01/20 - 05/31/20) and (10/10/20 - 11/30/20). RESULTS: Over the study period, 24 390 patients had at least one chest CT scan. Among them, 72 lung cancer diagnoses were made (incidence 0.30 %; median age 67.4 years old, 50.0 % current smokers, 55.6 % adenocarcinoma). Half of the lung cancer patients (n = 36) did not meet the National Lung Screening Trial inclusion criteria. Twenty-six patients (36.1 %) were diagnosed at an early stage, 25 (34.7 %) of whom received radical curative treatment. Twenty-six patients died during the follow-up (36.1 %) but none in early stages. The median overall survival in lung cancer patients was 693 days [532 - NA]. CONCLUSIONS: A large-scale chest CT scan strategy for suspected or documented COVID-19 infection has allowed a significant proportion of early-stage lung cancer diagnosis, all of which have benefited from curative treatment.

Quantum-Enhanced Hybrid Feature Engineering in Thoracic CT Image Analysis for State-of-the-Art Nodule Classification: An Advanced Lung Cancer Assessment.

The intricate nature of lung cancer treatment poses considerable challenges upon diagnosis. Early detection plays a pivotal role in mitigating its escalating global mortality rates. Consequently, there are pressing demands for robust and dependable early detection and diagnostic systems. However, the technological limitations and complexity of the disease make it challenging to implement an efficient lung cancer screening system. AI-based CT image analysis techniques are showing significant contributions to the development of computer-assisted detection (CAD) systems for lung cancer screening. Various existing research groups are working on implementing CT image analysis systems for assessing and classifying lung cancer. However, the complexity of different structures inside the CT image is high and comprehension of significant information inherited by them is more complex even after applying advanced feature extraction and feature selection techniques. Traditional and classical feature selection techniques may struggle to capture complex interdependencies between features. They may get stuck in local optima and sometimes require additional exploration strategies. When applied to a prominent feature space, traditional techniques may also struggle with combinatorial optimization problems. This paper proposed a methodology to overcome the existing challenges by applying feature extraction using Vision Transformer (FexViT) and Feature selection using the Quadratic unconstrained binary optimization (FSelQUBO) technique. This algorithm shows better performance when compared with other existing techniques. The proposed methodology showed better performance as compared to other existing techniques when evaluated by applying necessary output measures, such as accuracy, Area under roc (receiver operating characteristics) curve, precision, sensitivity, and specificity, obtained as 94.28%, 99.10%, 96.17%, 90.16% and 97.46%. The further advancement of CAD systems is essential to meet the demand for more reliable detection and diagnosis of cancer, which can be addressed by leading the proposed quantum computation and growing AI-based technology ahead. .

Screening of lung cancer serum biomarkers based on Boruta-shap and RFC-RFECV algorithms.

OBJECTIVE: This study aimed to identify a set of serum miRNAs as potential biomarkers for lung cancer diagnosis using algorithmic approaches. METHODS: Serum miRNA expression data from lung cancer patients and non-tumor controls were obtained. The top six miRNAs were selected using Boruta-shap and RFC-RFECV algorithms. A Gaussian Naive Bayes (NB) classifier was trained and evaluated using cross-validation, ROC curve analysis, and evaluation metrics. RESULTS: Six miRNAs (hsa-miRNA-144, hsa-miRNA-107, hsa-miRNA-484, hsa-miRNA-103, hsa-miRNA-26b, and hsa-miRNA-641) were identified as feature genes. The NB classifier achieved an area under curve (AUC) of 0.8966 and a mean AUC of 0.88 in cross-validation. Accuracy, recall, and F1 scores exhibited promising results, with an accuracy of 82%. In the validation set, the AUC values for the NB and SVC classifiers were 0.9345 and 0.9423, respectively, with a mean AUC of 0.95 in cross-validation. The classifiers demonstrated an accuracy of 89% in diagnosing lung cancer. CONCLUSION: This study identified a panel of six serum miRNAs with potential as non-invasive biomarkers for lung cancer diagnosis. These miRNAs show promise in providing sensitive and specific tools for detecting lung cancer. SIGNIFICANCE: Lung cancer is one of the top cancers worldwide, threatening the health and lives of tens of thousands of people. miRNA is a biomarker, which can be used as a potential clinical tool for diagnosis and prognosis of cancer patients. Therefore, the use of multiple miRNAs to construct diagnostic models may be one of the future methods of accurate diagnosis of lung cancer. In this study, we used the Boruta-shap and RFC-RFECV algorithms to automatically identify and extract characteristic miRNAs highly associated with lung cancer, thereby establishing an accurate classifier for the diagnosis of lung cancer with characteristic miRNAs.

Knockdown of heat shock protein family D member 1 (HSPD1) in lung cancer cell altered secretome profile and cancer-associated fibroblast induction.

The crosstalk between lung cancer cells and cancer-associated fibroblast (CAF) is pivotal in cancer progression. Heat shock protein family D member 1 (HSPD1) is a potential prognostic biomarker associated with the tumor microenvironment in lung adenocarcinoma (LUAD). However, the role of HSPD1 in CAF activation remains unclear. This study established stable HSPD1-knockdown A549 lung cancer cells using a lentivirus-mediated shRNA transduction. A targeted label-free proteomic analysis identified six significantly altered secretory proteins in the shHSPD1-A549 secretome compared to shControl-A549. Functional enrichment analysis highlighted their involvement in cell-to-cell communication and immune responses within the tumor microenvironment. Additionally, most altered proteins exhibited positive correlations and significant prognostic impacts on LUAD patient survival. Investigations on the effects of lung cancer secretomes on lung fibroblast WI-38 cells revealed that the shControl-A549 secretome stimulated fibroblast proliferation, migration, and CAF marker expression. These effects were reversed upon the knockdown of HSPD1 in A549 cells. Altogether, our findings illustrate the role of HSPD1 in mediating CAF induction through secretory proteins, potentially contributing to the progression and aggressiveness of lung cancer.

Effects of reprogrammed splenic CD8+ T-cells in vitro and in mice with spontaneous metastatic Lewis lung carcinoma.

BACKGROUND: Metastatic disease is a major and difficult-to-treat complication of lung cancer. Considering insufficient effectiveness of existing therapies and taking into account the current problem of lung cancer chemoresistance, it is necessary to continue the development of new treatments. METHODS: Previously, we have demonstrated the antitumor effects of reprogrammed CD8+ T-cells (rCD8+ T-cells) from the spleen in mice with orthotopic lung carcinoma. Reprogramming was conducted by inhibiting the MAPK/ERK signalling pathway through MEKi and the immune checkpoint PD-1/PD-L1. Concurrently, CD8+ T-cells were trained in Lewis lung carcinoma (LLC) cells. We suggested that rCD8+ T-cells isolated from the spleen might impede the development of metastatic disease. RESULTS: The present study has indicated that the reprogramming procedure enhances the survival and cytotoxicity of splenic CD8+ T-cells in LLC culture. In an LLC model of spontaneous metastasis, splenic rCD8 + T-cell therapy augmented the numbers of CD8+ T-cells and CD4+ T-cells in the lungs of mice. These changes can account for the partial reduction of tumors in the lungs and the mitigation of metastatic activity. CONCLUSIONS: Our proposed reprogramming method enhances the antitumor activity of CD8+ T-cells isolated from the spleen and could be valuable in formulating an approach to treating metastatic disease in patients with lung cancer.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer.

BACKGROUND: CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). MATERIALS AND METHODS: Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. RESULTS: Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. CONCLUSIONS: This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.

Tumor-associated macrophages affect the treatment of lung cancer.

As one of the most common malignant tumors in the world, lung cancer has limited benefits for patients despite its diverse treatment methods due to factors such as personalized medicine targeting histological type, immune checkpoint expression, and driver gene mutations. The high mortality rate of lung cancer is partly due to the immune-suppressive which limits the effectiveness of anti-cancer drugs and induces tumor cell resistance. The currently widely recognized TAM phenotypes include the anti-tumor M1 and pro-tumor M2 phenotypes. M2 macrophages promote the formation of an immune-suppressive microenvironment and hinder immune cell infiltration, thereby inhibiting activation of the anti-tumor immune system and aiding tumor cells in resisting treatment. Analyzing the relationship between different treatment methods and macrophages in the TME can help us better understand the impact of TAMs on lung cancer and confirm the feasibility of targeted TAM therapy. Targeting TAMs to reduce the M2/M1 ratio and reverse the immune-suppressive microenvironment can improve the clinical efficacy of conventional treatment methods and potentially open up more efficient combination treatment strategies, maximizing the benefit for lung cancer patients.

Effective treatment of steroid-resistant immune checkpoint inhibitor pneumonitis with mycophenolate mofetil.

Insufficient evidence is available for treating steroid-resistant immune checkpoint inhibitor pneumonitis (CIP). Although guidelines recommend the use of immunosuppressants, the efficacy of mycophenolate mofetil (MMF) has not been sufficiently verified. We report two cases of steroid-resistant CIP treated with MMF. Both patients responded to initial treatment with prednisolone (PSL), but the CIP flared up repeatedly as the steroids were gradually tapered off. Upon receiving MMF in addition to PSL, their subjective symptoms improved, and the shadows gradually disappeared, allowing for a reduction in the steroid dose. Ultimately, no CIP recurrence was observed despite discontinuing PSL and MMF. Both cases were completely resolved by treatment with MMF. This indicates that MMF may be effective in treating steroid-resistant CIP. In the future, the effects and safety of MMF should be investigated in large-scale clinical trials targeting patients with steroid-resistant CIP.

A2AR-mediated CXCL5 upregulation on macrophages promotes NSCLC progression via NETosis.

Tumor-associated macrophages (TAMs) are abundant in tumors and interact with tumor cells, leading to the formation of an immunosuppressive microenvironment and tumor progression. Although many studies have explored the mechanisms underlying TAM polarization and its immunosuppressive functions, understanding of its progression remains limited. TAMs promote tumor progression by secreting cytokines, which subsequently recruit immunosuppressive cells to suppress the antitumor immunity. In this study, we established an in vitro model of macrophage and non-small cell lung cancer (NSCLC) cell co-culture to explore the mechanisms of cell-cell crosstalk. We observed that in NSCLC, the C-X-C motif chemokine ligand 5 (CXCL5) was upregulated in macrophages because of the stimulation of A2AR by adenosine. Adenosine was catalyzed by CD39 and CD73 in macrophages and tumor cells, respectively. Nuclear factor kappa B (NFκB) mediated the A2AR stimulation of CXCL5 upregulation in macrophages. Additionally, CXCL5 stimulated NETosis in neutrophils. Neutrophil extracellular traps (NETs)-treated CD8+ T cells exhibited upregulation of exhaustion-related and cytosolic DNA sensing pathways and downregulation of effector-related genes. However, A2AR inhibition significantly downregulated CXCL5 expression and reduced neutrophil infiltration, consequently alleviating CD8+ T cell dysfunction. Our findings suggest a complex interaction between tumor and immune cells and its potential as therapeutic target.