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The SUMMIT Study Utilising a written Next Steps information booklet to prepare participants for potential lung cancer screening results and follow-up.

Low-Dose Computed Tomography (LDCT) screening for lung cancer can result in several potential outcomes of varying significance. Communication methods used in Lung Cancer Screening (LCS) programmes must, therefore, ensure that participants are prepared for the range of possible results and follow-up. Here, we assess perceptions of a written preparatory information booklet provided to participants in a large LCS cohort designed to convey this information. All participants in the SUMMIT Study (NCT03934866) were provided with a results preparation information booklet, entitled The SUMMIT Study Next Steps at their baseline appointment which outlined potential results, their significance, and timelines for follow up. Results from the LDCT scan and Lung Health Check were subsequently sent by letter. Perceptions of this booklet were assessed among participants with indeterminate pulmonary findings when they attended a face-to-face appointment immediately before their three-month interval scan. Specifically, questions assessed the perceived usefulness of the booklet and the amount of information contained in it. 70.1% (n 1,4122,014) participants remembered receiving the booklet at their appointment. Of these participants, 72.0% (n 1,0171,412) found it quite or very useful and 68.0% (n 9601,412) reported that it contained the right amount of information. Older participants, those from the least deprived socioeconomic quintile and those of Black ethnicity were less likely to report finding the booklet either quite or very useful, or that it contained the right amount of information. Participants who remembered receiving the booklet were more likely to be satisfied with the process of results communication by letter. Providing written information that prepares participants for possible LDCT results and their significance appears to be a useful resource and a helpful adjunct to a written method of results communication for large scale LCS programmes.

Radiogenomics in lung cancer Where are we

Huge technological and biomedical advances have improved the survival and quality of life of lung cancer patients treated with radiotherapy. However, during treatment planning, a probability that the patient will experience adverse effects is assumed. Radiotoxicity is a complex entity that is largely dose-dependent but also has important intrinsic factors. One of the most studied is the genetic variants that may be associated with susceptibility to the development of adverse effects of radiotherapy. This review aims to present the current status of radiogenomics in lung cancer, integrating results obtained in association studies of SNPs (single nucleotide polymorphisms) related to radiotherapy toxicities. We conclude that despite numerous publications in this field, methodologies and endpoints vary greatly, making comparisons between studies difficult. Analyzing SNPs from the candidate gene approach, together with the study in cohorts limited by the sample size, has complicated the possibility of having validated results. All this delays the incorporation of genetic biomarkers in predictive models for clinical application. Thus, from all analysed SNPs, only 12 have great potential as esophagitis genetic risk factors and deserve further exploration. This review highlights the efforts that have been made to date in the radiogenomic study of radiotoxicity in lung cancer.

PLAGL2 promotes the stemness and is upregulated by transcription factor E2F1 in human lung cancer.

This study mainly focuses on revealing the role of PLAGL2 in lung cancer stemness. In vitro and in vivo experiments were performed to evaluate the effects of PLAGL2 on lung cancer cell stemness. Mechanistic analysis using luciferase reporter and ChIP assays were implemented to reveal the underlying mechanisms. The transcriptional factor E2F1 transcriptionally activated PLAGL2 expression via directly binding to PLAGL2 promoter in lung cancer cells. Moreover, PLAGL2 promoted the stemness of lung cancer cells dependent on E2F1-mediated transcriptional activation. This study provides a potential target for lung cancer progression.

Real-life experience of patients with sarcomatoid renal cell carcinoma a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates > 50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPKYAP pathway.

Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study was to investigate the mechanism of Sestrin2 on the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Human embryonic lung fibroblasts, NSCLC cell lines, and nude mice were experimental subjects in this study. qRT-PCR and western blot were performed to evaluate the mRNA and protein expression of genes. CCK-8 and EdU assay were conducted to detect cell proliferation. The scratch test and Transwell assay were applied to examine cell migration and invasion. The bioinformatics analysis and Co-IP assay were employed to predict and consolidate the interaction between YAP and TEAD. We found the expression of Sestrin2 was declined but the expression of YAP was elevated in NSCLC cells. Sestrin2 sufficiency or YAP silencing could effectively impair cell growth and metastasis. Mechanistically, YAP interacted with TEAD to enhance FOXM1 expression. Additionally, the elevation of FOXM1 abolished the inhibitory influences of Sestrin2 sufficiency on NSCLC cell growth, invasion, and EMT process. Eventually, Sestrin2 elevation attenuated tumor growth in mice via modulation of the AMPKYAPFOXM1 axis, which was reversed by FOXM1 overexpression. Our consequences suggested Sestrin2 could inhibit the activation of YAP via prompting AMPK phosphorylation and then suppress FOXM1 expression through the interplay between YAP and TEAD to impair the capacities of NSCLC cell proliferation, migration, invasion, and EMT. This study provided a novel mechanism of Sestrin2 in NSCLC.

Case report Rare intrapulmonary malignant mesothelioma complicated with myositis.

Malignant pleural mesothelioma is an uncommon aggressive tumor. Its incidence is even lower when the lung parenchyma is the primary site. Myositis is a common paraneoplastic syndrome, but it rarely presents with malignant pleural mesothelioma. This report presents a rare intrapulmonary malignant mesothelioma complicated by cancer-associated myositis. The patient presented with limb muscle weakness as the first symptom and was diagnosed with intrapulmonary malignant mesothelioma complicated by cancer-associated myositis on the basis of clinical, histological, immunohistochemical, and radiological findings. The patient responded poorly to conventional hormone therapy and died of respiratory failure within 2 months after the first presence of limb muscle weakness.

Case report

Cyclin-dependent kinase 46 inhibitor (CDK46i) has become the commonest first-line treatment of hormonal receptor positive and human epidermal growth factor receptor 2 negative (HRHER2-) metastatic breast cancer (MBC). However, therapy is quite individualized after progression of disease (PD) when CDK46i fails. Estrogen receptor (ER) status of metastatic lesions of bone, lung or liver might be different from the primary tumor and biopsy of metastatic lesions was invasive and not always available. Prediction of treatment response after PD of CDK46i remains unsolved. A 70-year-old woman with Parkinsons disease, osteoporosis and cardiovascular co-morbidity was diagnosed with HRHER2- breast cancer (pT2N2M0, stage IIIa). Three years later, she developed metastases in right lung and pleura with pleural effusion and received palbociclib letrozole. After 8 months the disease progressed, and This case demonstrated that

Role of cuproptosis-related gene in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD. An integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by In this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. Whats more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature. A new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and

Identifying diagnostic markers and constructing a prognostic model for small-cell lung cancer based on blood exosome-related genes and machine-learning methods.

Small-cell lung cancer (SCLC) usually presents as an extensive disease with a poor prognosis at the time of diagnosis. Exosomes are rich in biological information and have a powerful impact on tumor progression and metastasis. Therefore, this study aimed to screen for diagnostic markers of blood exosomes in SCLC patients and to build a prognostic model. We identified blood exosome differentially expressed (DE) RNAs in the exoRBase cohort and identified feature RNAs by the LASSO, Random Forest, and SVM-REF three algorithms. Then, we identified DE genes (DEGs) between SCLC tissues and normal lung tissues in the GEO cohort and obtained exosome-associated DEGs (EDEGs) by intersection with exosomal DEmRNAs. Finally, we performed univariate Cox, LASSO, and multivariate Cox regression analyses on EDEGs to construct the model. We then compared the patients overall survival (OS) between the two risk groups and assessed the independent prognostic value of the model using receiver operating characteristic (ROC) curve analysis. We identified 952 DEmRNAs, 210 DElncRNAs, and 190 DEcircRNAs in exosomes and identified 13 feature RNAs with good diagnostic value. Then, we obtained 274 EDEGs and constructed a risk model containing 7 genes (TBX21, ZFHX2, HIST2H2BE, LTBP1, SIAE, HIST1H2AL, and TSPAN9). Low-risk patients had a longer OS time than high-risk patients. The risk model can independently predict the prognosis of SCLC patients with the areas under the ROC curve (AUCs) of 0.820 at 1 year, 0.952 at 3 years, and 0.989 at 5 years. We identified 13 valuable diagnostic markers in the exosomes of SCLC patients and constructed a new promising prognostic model for SCLC.

Knowledge mapping visualization of the pulmonary ground-glass opacity published in the web of science.

With low-dose computed tomography(CT) lung cancer screening, many studies with an increasing number of patients with ground-glass opacity (GGO) are published. Hence, the present study aimed to analyze the published studies on GGO using bibliometric analysis. The findings could provide a basis for future research in GGO and for understanding past advances and trends in the field. Published studies on GGO were obtained from the Web of Science Core Collection. A bibliometric analysis was conducted using the R package and VOSviewer for countries, institutions, journals, authors, keywords, and articles relevant to GGO. In addition, a bibliometric map was created to visualize the relationship. The number of publications on GGO has been increasing since 2011. China is ranked as the most prolific country however, Japan has the highest number of citations for its published articles. Seoul National University and Professor Jin Mo Goo from Korea had the highest publications. Most top 10 journals specialized in the field of lung diseases. Radiology is a comprehensive journal with the greatest number of citations and highest H-index than other journals. Using bibliometric analysis, research topics on prognosis and diagnosis, artificial intelligence, treatment, preoperative positioning and minimally invasive surgery, and pathology of GGO were identified. Artificial intelligence diagnosis and minimally invasive treatment may be the future of GGO. In addition, most top 10 literatures in this field were guidelines for lung cancer and pulmonary nodules. The publication volume of GGO has increased rapidly. The top three countries with the highest number of published articles were China, Japan, and the United States. Japan had the most significant number of citations for published articles. Most key journals specialized in the field of lung diseases. Artificial intelligence diagnosis and minimally invasive treatment may be the future of GGO.

Immunoregulatory framework and the role of miRNA in the pathogenesis of NSCLC - A systematic review.

With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has drawn attention. Numerous variables, such as disrupted signaling caused by somatic mutations in the EGFR-mediated RASRAFMAPK, PI3KAKT, JAKSTAT signaling cascade, supports tumour survival in one way or another. Here, the tumour microenvironment significantly contributes to the development of cancer by thwarting the immune response. MicroRNAs (miRNAs) are critical regulators of gene expression that can function as oncogenes or oncosuppressors. They have a major influence on the occurrence and prognosis of NSCLC. Though, a myriad number of therapies are available and many are being clinically tested, still the drug resistance, its adverse effect and toxicity leading towards fatality cannot be ruled out. In this review, we tried to ascertain the missing links in between perturbed EGFR signaling, miRNAs favouring tumorigenesis and the autophagy mechanism. While connecting all the aforementioned points multiple associations were set, which can be targeted in order to combat NSCLC. Here, we tried illuminating designing synthetically engineered circuits with the toggle switches that might lay a prototype for better therapeutic paradigm.

Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma.

The most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD. This particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program. We detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs). In conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.

Successful treatment of extensive-stage small cell lung cancer with concurrent pleural and pericardial effusions Case report.

It is unclear whether pleuralpericardial drainage and pleurodesispericardiodesis should be performed before or after initiating chemotherapy in patients with chemotherapy-sensitive small-cell lung cancer. A 76-year-old woman presented to the emergency department with progressive dyspnea on exertion for a week. Chest computed tomography showed a mass shadow anterior to the left upper lobe, bilateral pleural effusions, and a circumferential pericardial effusion surrounding the heart. We diagnosed extensive-stage small-cell lung cancer based on the clinical course and pathological findings. We first performed pleurodesis and pericardial drainage and successfully initiated immune checkpoint inhibitor combined chemotherapy, with improved performance status. This case highlights the importance of aggressive drainage and pleurodesispericardiodesis, and suggests that drainage and pleurodesispericardiodesis should be considered before systemic chemotherapy in patients with concurrent pericardial or pleural effusions, even in patients with small-cell lung cancer that is sensitive to chemotherapy.

Development of a novel nomogram-based model incorporating 3D radiomic signatures and lung CT radiological features for differentiating invasive adenocarcinoma from adenocarcinoma in situ and minimally invasive adenocarcinoma.

Lung cancer is one of the most serious cancers in the world. Subtypes of lung adenocarcinoma can be quickly distinguished by analyzing 3D radiomic signatures and radiological features. This study included 493 patients from 3 hospitals with a total of 506 lesions confirmed as minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), or invasive adenocarcinoma (IAC). After segmenting the lesion area, 3D radiomic signatures were extracted using the PyRadiomics package v. 3.0.1 implemented in Python (httpspyradiomics.readthedocs.ioenlatestindex.html), and the corresponding radiological features were collected. Subsequently, the top 100 features were identified by feature screening methods, including the Spearman rank correlation and minimum redundancy maximum relevance (mRMR) feature selection, and the top 10 features were determined by the least absolute shrinkage and selection operator (LASSO) classifier. Multivariable logistic regression analysis was used to develop a nomogram incorporating 3D radiomic signatures and radiological features in the prediction system. The nomogram was evaluated from multiple perspectives and tested on the validation cohort. The model combined 3 radiological features and seven 3D radiomic signatures. The area under the curve (AUC) of the model was 0.877 (95% CI 0.829-0.925) in the training cohort, 0.864 (95% CI 0.789-0.940) in the testing cohort, and 0.836 (95% CI 0.749-0.924) in the validation cohort. The nomogram applied in all 3 cohorts showed reliable accuracy and calibration. The decision curve also demonstrated the clinical effectiveness of the nomogram. In this study, a nomogram-based model combining 3D radiomic signatures and radiological features was developed. Its performance in identifying IAC and MIAAIS was satisfactory and had clinical value.

Standard treatment-refractoryineligible small cell lung cancer treated with drug-eluting beads bronchial arterial chemoembolization a retrospective cohort study.

Patients with small cell lung cancer (SCLC) are prone to developing refractoriness to standard treatment, and some patients are ineligible for systemic therapy owing to comorbidities or poor pulmonary function. The prognosis of patient with standard treatment-refractoryineligible (STRI)-SCLC remains poor. This retrospective cohort study aimed to investigate the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for the treatment of SRTI-SCLC and to identify the predictors of overall survival (OS). A total of 18 patients with STRI-SCLC who received DEB-BACE were included. Treatment response, adverse events, progression-free survival (PFS), and OS were evaluated. Further molecular targeted therapy or immunotherapy was administered as a second-line treatment or beyond for those patients who had not received these regimens previously. Univariate and multivariate Cox analyses were used to explore the predictors of OS for STRI-SCLC treated with DEB-BACE. The overall disease control rate at 3 months after DEB-BACE was 77.8% (1418) of these patients who experienced disease control, partial response and stable disease were achieved in 2 patients (11.1%) and 12 patients (66.7%), respectively. There were 7 patients (38.9%) who received anlotinib after DEB-BACE. No severe DEB-BACE-related or anlotinib-related adverse events were observed. The median PFS was 5.0 months the 6- and 12-month PFS rates were 55.6% (1018) and 11.1% (218), respectively. The median OS was 9.0 months the 6- and 12-month OS rates were 77.8% (1418) and 33.3% (618), respectively. Postoperative anlotinib hazard ratio 0.302 95% confidence interval (CI) 0.098-0.930 P0.037 was identified as the predictor of OS in patients with STRI-SCLC treated with DEB-BACE. DEB-BACE is an effective and well-tolerated approach for patients with STRI-SCLC. Postoperative anlotinib is the predictor of OS and may indicate a better prognosis for patients with STRI-SCLC.

Rapid Response to Sotorasib of a Patient With

The efficacy of sotorasib for patients with

An unusual case of interstitial lung disease Revisiting peribronchiolar metaplasia interstitial lung disease (PBM-ILD).

Peribronchiolar metaplasia (PBM) is a histological finding of uncertain significance commonly seen in interstitial lung disease (ILD). PBM is thought to be secondary to small airway injury from insults such as tobacco smoke and other environmental exposures. The term PBM-ILD has been proposed for patients with ILD where PBM is the major histologic finding, however a lack of radiographic changes supportive of ILD in previously reported cases has limited recognition of the diagnosis. We present a rare case of welding-associated ILD with clinical, radiographic, and histologic evidence consistent with the proposed definition of PBM-ILD. We outline an approach to its consideration as a diagnosis based on our experience through multidisciplinary discussion.

Retracted Effects of Afatinib on Development of Non-Small-Cell Lung Cancer by Regulating Activity of Wnt

This retracts the article DOI 10.115520225213016..

The correlation between dysfunctional intestinal flora and pathology feature of patients with pulmonary tuberculosis.

Recent studies have provided insights into the important contribution of gut microbiota in the development of Pulmonary Tuberculosis (PTB). As a chronic consumptive infectious disease, PTB involves many pathological characteristics. At present, research on intestinal flora and clinical pathological Index of PTB is still rare. We performed a cross-sectional study in 63 healthy controls (HCs) and 69 patients with untreated active PTB to assess the differences in their microbiota in feces via 16S rRNA gene sequencing. Significant alteration of microbial taxonomic and functional capacity was observed in PTB as compared to the HCs. The results showed that the alpha diversity indexes of the PTB patients were lower than the HCs (P<0.05). Beta diversity showed differences between the two groups (P<0.05). At the genus level, the relative abundance of Bacteroides, Parabacteroides and Veillonella increased, while Faecalibacterium, Bifidobacterium, Agathobacter and CAG-352 decreased significantly in the PTB group, when compared with the HCs. The six combined genera, including Lactobacillus, Faecalibacterium, Roseburia, Dorea, Monnoglobus and Eubacteriumventriosumgroup might be a set of diagnostic biomarkers for PTB (AUC0.90). Besides, the predicted bacterial functional pathway had a significant difference between the two groups (P<0.05), which was mainly related to the nutrient metabolism pathway. Significant alterations in the biochemical index were associated with changes in the relative abundance of specific bacteria, the short chain fatty acid (SCFA)-producing bacteria enriched in HCs had a positively correlated with most of the biochemical indexes. Our study indicated that the gut microbiota in PTB patients was significantly different from HCs as characterized by the composition and metabolic pathway, which related to the change of biochemical indexes in the PTB group. It was hypothesized that the abovementioned changes in the gut microbiota could exert an impact on the clinical characteristics of PTB through the regulation of the nutrient utilization pathway of the host by way of the gut-lung axis.

Development and validation of a nomogram for predicting survival time and making treatment decisions for clinical stage IA NSCLC based on the SEER database.

The aim of this study was to establish and validate a nomogram model for accurate prediction of patients survival with T1aN0M0 none small cell lung cancer (NSCLC). The patients, diagnosed with the stage IA NSCLC from 2004-2015, were identified from the Surveillance, Epidemiology and End Results (SEER) database. The variables with a Eight variables, including treatment, age, sex, race, marriage, tumor size, histology, and grade were selected to develop the nomogram model by univariate and multivariate cox regression. The C-index was 0.704 (95% CI, 0.694-0.714) in the training set and 0.713 (95% CI, 0.697-0.728) in the test set, which performed significantly better than 8th edition AJCC TNM stage system (0.550, 95% CI, 0.408-0.683, We established and validated a prognostic nomogram to predict 3-years and 5-years overall survival in stage IA NSCLC.

From targeted therapy to a novel way Immunogenic cell death in lung cancer.

Lung cancer (LC) is one of the most incident malignancies and a leading cause of cancer mortality worldwide. Common tumorigenic drivers of LC mainly include genetic alterations of EGFR, ALK, KRAS, BRAF, ROS1, and MET. Small inhibitory molecules and antibodies selectively targeting these alterations orand their downstream signaling pathways have been approved for treatment of LC. Unfortunately, following initial positive responses to these targeted therapies, a large number of patients show dismal prognosis due to the occurrence of resistance mechanisms, such as novel mutations of these genes and activation of alternative signaling pathways. Over the past decade, it has become clear that there is no possible cure for LC unless potent antitumor immune responses are induced by therapeutic intervention. Immunogenic cell death (ICD) is a newly emerged concept, a form of regulated cell death that is sufficient to activate adaptive immune responses against tumor cells. It transforms dying cancer cells into a therapeutic vaccine and stimulates long-lasting protective antitumor immunity. In this review, we discuss the key targetable genetic aberrations and the underlying mechanism of ICD in LC. Various agents inducing ICD are summarized and the possibility of harnessing ICD in LC immunotherapy is further explored.

Validation of skeletal muscle and adipose tissue measurements using a fully automated body composition analysis neural network versus a semi-automatic reference program with human correction in patients with lung cancer.

To validate skeletal muscle and adipose tissues cross sectional area (CSA) and densities between a fully automated neural network (test program) and a semi-automated program requiring human correction (reference program) for lumbar 1 (L1) and lumbar 2 (L2) CT scans in patients with lung cancer. Agreement between the reference and test programs was measured using Dice-similarity coefficient (DSC) and Bland-Altman plots with limits of agreement within 1.96 standard deviation. A total of 49 L1 and 47 L2 images were analyzed from patients with lung cancer (mean age 70.51 ± 9.48 years mean BMI 27.45 ± 6.06 kgm The use of a fully automated neural network to analyze body composition at L1 and L2 in patients with lung cancer is valid for measuring skeletal muscle and adipose tissue CSA and densities when compared to a reference program. Further validation in a more diverse sample and in different disease and health states is warranted to increase the generalizability of the test program at L1 and L2.

Emerging trends and hot spots on electrical impedance tomography extrapulmonary applications.

Electrical impedance tomography (EIT) develops rapidly in technology and applications. Nowadays EIT is used in multiple clinical and experimental scenarios including pulmonary, brain, and tissue monitoring, etc. The present study explores the research trends and hotspots on EIT extrapulmonary application research by bibliometrics analysis. Publications on EIT extrapulmonary applications between 1987 and 2021 were retrieved from the Web of Science Core Collection database. For precise screening, search strategy electrical impedance tomography plus hemodynamic or brain or nerve or cancer or venous or vessel or tumor or veterinary or tissue or cell or wearable or application and excluding lung, ventilation respiratory, pulmonary, algorithm, current, voltage or electrode were used. CiteSpace and VOSviewer were used to analyze the publication features, collaboration, keywords co-occurrence, and co-cited reference. A total of 506 articles were finally identified. The global publication numbers on extrapulmonary applications gradually increased yearly in the past 30 years. The US, UK, and China contributed most three publications concerning EIT extrapulmonary applications. tissues, conductivity, model were research hotspots, and cutaneous melanoma, microstructure, diagnosis were recent topics (Portions of this research have previously been presented in poster form). Overall, EIT extrapulmonary applications bibliometrics analysis provides a unique insight into research focus, current trends, and future directions.

Gefitinib conjugated PEG passivated graphene quantum dots incorporated PLA microspheres for targeted anticancer drug delivery.

In the present study, polyethylene Glycol passivated Graphene Quantum Dots (PEG-GQDs) were successfully synthesized via the hydrothermal method. Furthermore, for the synthesis of anticancer drug loaded GQD embedded microspheres, the anticancer drug was mixed with synthesized PEG-GQD. As prepared, Gefitinib-PEG-GQDs were incorporated into poly-lactic acid (PLA) microspheres using poly-vinyl-acetate (PVA) as surfactant via solvent evaporation technique and single emulsification method. The successful synthesis of anticancer drug loaded microspheres was confirmed by several characterization techniques, including Field-Emission Scanning Electron Microscopy (FE-SEM), which shows the morphology of microspheres, Fourier Transform Infrared Spectroscopy (FTIR) analysis gives an idea about functional group present in the microspheres. X-ray diffraction (XRD) provides information about the crystallinity of the samples respectively. The drug release characteristics were determined by UV-Vis spectrophotometric analysis. Moreover, the

An evaluation of KIF20A as a prognostic factor and therapeutic target for lung adenocarcinoma using integrated bioinformatics analysis.

The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses,

In Vitro and In Vivo Analysis of Extracellular Vesicle-Mediated Metastasis Using a Bright, Red-Shifted Bioluminescent Reporter Protein.

Cancer cells produce heterogeneous extracellular vesicles (EVs) as mediators of intercellular communication. This study focuses on a novel method to image EV subtypes and their biodistribution in vivo. A red-shifted bioluminescence resonance energy transfer (BRET) EV reporter is developed, called PalmReNL, which allows for highly sensitive EV tracking in vitro and in vivo. PalmReNL enables the authors to study the common surface molecules across EV subtypes that determine EV organotropism and their functional differences in cancer progression. Regardless of injection routes, whether retro-orbital or intraperitoneal, PalmReNL positive EVs, isolated from murine mammary carcinoma cells, localized to the lungs. The early appearance of metastatic foci in the lungs of mammary tumor-bearing mice following multiple intraperitoneal injections of the medium and large EV (mlEV)-enriched fraction derived from mammary carcinoma cells is demonstrated. In addition, the results presented here show that tumor cell-derived mlEVs act on distant tissues through upregulating LC3 expression within the lung.

Prognostic and Immune Infiltration Value of Proteasome Assembly Chaperone (PSMG) Family Genes in Lung Adenocarcinoma.

The complexity of lung adenocarcinoma (LUAD) including many interacting biological processes makes it difficult to find therapeutic biomarkers for treatment. Previous studies demonstrated that

Therapeutic Outcomes of

This study aimed to evaluate the therapeutic outcomes of All post-therapeutic scans were collected retrospectively from patients treated with 100-200 mCi Out of 36 patients (aged 67±8.8 years), 23 underwent at least two treatment cycles. Nineteen patients (82.6%) had bone metastases, 12 (52.2%) had nodal metastases, 5 (21.7%) had liver metastases, and 3 (13.0%) had lung metastases. Eleven patients (47.8%) were considered responsive in the post-therapeutic scans, two of which experienced complete eradication of the metastatic sites. Three patients (13%) were categorized as progressive, and 9 (39.1%) patients remained stable. Regarding mortality, nine patients died during the late follow-up (median of 24 months). In the surviving population, 65% reported no or mild pain in the final follow-up, based on a 5-point scale pain assessment. The treatment of mCRPC patients with

Immunotherapy strategies and prospects for acute lung injury Focus on immune cells and cytokines.

Acute lung injuryacute respiratory distress syndrome (ALIARDS) is a disastrous condition, which can be caused by a wide range of diseases, such as pneumonia, sepsis, traumas, and the most recent, COVID-19. Even though we have gained an improved understanding of acute lung injuryacute respiratory distress syndrome pathogenesis and treatment mechanism, there is still no effective treatment for acute lung injuryacute respiratory distress syndrome, which is partly responsible for the unacceptable mortality rate. In the pathogenesis of acute lung injury, the inflammatory storm is the main pathological feature. More and more evidences show that immune cells and cytokines secreted by immune cells play an irreplaceable role in the pathogenesis of acute lung injury. Therefore, here we mainly reviewed the role of various immune cells in acute lung injury from the perspective of immunotherapy, and elaborated the crosstalk of immune cells and cytokines, aiming to provide novel ideas and targets for the treatment of acute lung injury.

Emerging therapies for non-small cell lung cancer harboring EGFR exon 20 insertion mutations narrative review.

Epidermal growth factor receptor ( Searches were conducted in PubMed and supplemented with recent conference proceedings in November 30th, 2021. Several novel emerging therapies showed favorable safety profile and promising anti-tumor activity in NSCLC patients with EGFR ex20ins in recent several clinical trials. There is still room for improvement in the treatment results of NSCLC harboring EGFR ex20ins. Future research should focus on the molecular heterogeneity in the size and location of distinct EGFR ex20ins, the mechanisms of acquired resistance to novel EGFR inhibitors, effective treatment that have good central nervous system penetrance, and the potential role of combination strategy.

Non-small cell lung cancer with MET exon 14 skip mutation case report.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up 80-85% of all lung malignancies. It can be further subdivided into different types. The three main subtypes are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Traditionally, NSCLCs have been treated with a combination of chemotherapy, surgery, andor radiation therapy. However, with the advent of genotype subtype analysis and targeted therapy it has become possible to have individualized treatment options for patients with NSCLC. We present a case report of a 68-year-old female with NSCLC. Patient initially only received radiation therapy due to her not being a surgical candidate. While initial treatment was responsive, later imaging showed metastasis of disease. Subsequent genotype analysis of the patients tumor indicated a MET exon 14 skipping mutation which qualified her for treatment with Capmatinib (Tabrecta). Patients on Capmatinib have minimal side effects and better efficacy than traditional chemotherapy. Patients with MET exon 14 skipping mutations should be considered for Capmatinib therapy.

Development and validation of a random forest model for predicting radiation pneumonitis in lung cancer patients receiving moderately hypofractionated radiotherapy a retrospective cohort study.

Radiation pneumonitis (RP) is a type of toxicity commonly associated with thoracic radiation therapy. We sought to establish a random forest (RF) model and evaluate its ability to predict RP in patients with non-small cell lung cancer (NSCLC) receiving moderately hypofractionated radiotherapy (hypo-RT). A total of 106 patients with stage II-IVa NSCLC who received moderately hypofractionated helical tomotherapy (2.3-3.0 Gyfraction) at Zhongshan Hospital were included. All enrolled patients were divided chronologically into the training (67 patients) and validation (39 patients) groups. Higher than or equal to grade 2 RP was defined as the end point. Logistic regression and RF models were established and compared using the receiver operating characteristic (ROC) and a confusion matrix in the training and validation groups. The cumulative incidence of the end point was 25.4% and 17.9% in the training and validation groups, respectively. Logistic regression models were constructed by dosage parameters of total lungs, ipsilateral or contralateral lungs, respectively. ROC analysis revealed that the dosimetric factors of total lungs yielded a superior classification performance than did that of the ipsilateral or contralateral lungs area under the curve (AUC) 0.920, AUC 0.701, and AUC 0.661, respectively. Furthermore, the RF model yielded a better prediction capacity than did the traditional logistic model based on the dosimetric factors of the total lungs (accuracy 88.06% precision 84.62% sensitivity 64.71% specificity 96.00%). Moreover, the RF identified mean lung dose MLD mean decrease gini (MDG) 5.74, V20 (MDG 4.62), and V35 (MDG 3.08) of total lungs as the most common primary differentiators of RP. Our RF model established based on the dosimetric parameters of the total lungs could accurately predict the RP risk in patients with NSCLC treated with moderately hypofractionated tomotherapy.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial.

Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV Fifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV The current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV

Sex differences in the association of phase angle and lung cancer mortality.

Lung cancer is a lethal malignant tumor that is common worldwide and is associated with a high incidence of malnutrition. Phase angle (PA) is a simple, objective, and non-invasive indicator of body composition that has increasingly attracted attention as an indicator of the nutritional status and prognosis of patients with malignant tumors. This study aimed to investigate the association between the PA and overall survival in patients with lung cancer. This study prospectively analyzed 804 lung cancer patients in the Investigation on Nutrition Status and its Clinical Outcome of Common Cancers (INSCOC) project from 40 hospitals in China. We used a restricted cubic spline to analyze the sex-specific association between PA and mortality in men and women with lung cancer. Cox regression analysis was used to evaluate the independent association between PA and mortality in men and women. Sensitivity analysis was performed. The Kaplan-Meier method was used to evaluate the survival of patients with high and low PA values. There was an L-shaped association between PA and survival in both men and women with lung cancer ( Phase angle is an independent risk factor for the mortality of male lung cancer patients. However, its role in predicting the mortality of female lung cancer patients seems to be limited.

Comparative study of differentiating human pluripotent stem cells into vascular smooth muscle cells in hydrogel-based culture methods.

Vascular smooth muscle cells (VSMCs), which provides structural integrity and regulates the diameter of vasculature, are of great potential for modeling vascular-associated diseases and tissue engineering. Here, we presented a detailed comparison of differentiating human pluripotent stem cells (hPSCs) into VSMCs (hPSCs-VSMCs) in four different culture methods, including 2-dimensional (2D) culture, 3-dimensional (3D) PNIPAAm-PEG hydrogel culture, 3-dimensional (3D) alginate hydrogel culture, and transferring 3-dimensional alginate hydrogel culture to 2-dimensional (2D) culture. Both hydrogel-based culture methods could mimic

Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics.

Cancer is a heterogeneous disease characterized by various genetic and phenotypic aberrations. Cancer cells undergo genetic modifications that promote their proliferation, survival, and dissemination as the disease progresses. The unabated proliferation of cancer cells incurs an enormous energy demand that is supplied by metabolic reprogramming. Cancer cells undergo metabolic alterations to provide for increased energy and metabolite requirement these alterations also help drive the tumor progression. Dysregulation in glucose uptake and increased lactate production

CHI3L1 enhances melanoma lung metastasis

ICOSICOSL and CD28B7-1B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.

Evaluation of Methylation Panel in the Promoter Region of

Lung cancer is the most common cause of cancer death in the world. Effective early detection and appropriate medications can help treat this deadly cancer. Therefore, early detection of lung cancer is of utmost importance, especially in screening high-risk populations (such as smokers) with an urgent need to identify new biomarkers. The present study aimed to demonstrate the potential of using the panel of DNA methylation as a biomarker for the early diagnosis of lung cancer from sputum samples. The methylated promoter of

A case series of malignant pericardial effusion.

The most common primary malignancies that affect the pericardium are lung cancers. Typically, pericardial involvement stays undiagnosed, with almost 1-20% of all tumor-related autopsies revealing invasion of the pericardium. Pericardial effusions are seldom the first location of metastasis and presentation of a primary malignancy. Malignant pericardial effusions are usually silent, although they cause dyspnea, chest discomfort, arrhythmias, cough, and, in rare cases, pericardial tamponade. In a patient with tamponade, a high index of tumor-related suspicion is crucial to rule out cancer. Emergency pericardiocentesis is indicated based on the clinical presentation, however, the patient frequently has a bad prognosis regardless of whether treatment is administered or not. In this case series, we report five cases of non-small cell lung cancer (NSCLC) with pericardial effusion as an initial presentation.

Cavitary Lung Metastases in Prostate Cancer.

Single-Cell Transcriptome Identifies Drug-Resistance Signature and Immunosuppressive Microenvironment in Metastatic Small Cell Lung Cancer (Advanced Genetics 203).

Single-Cell RNA Sequencing This cover illustrates the work of Xujun Wang, Xianmin Zhu, Peng Zhang, and co-workers in article number 2100060 which reveals the drug-resistance signature and immunosuppressive microenvironment in small cell lung cancer (SCLC) by single-cell RNA-sequencing. Wu Song Fought the Tiger comes from the famous Chinese novel Outlaws of the Marsh. In the cover, the warrior Wu Song stands for the doctors and researchers. The tiger bearing SCLC on its face is dangerous for its sharp teeth and claws (early metastasis and drug resistance) and the surrounding water bubbles (immune infiltration). In addition, 2022 is the Year of the Tiger.

Single-Cell Transcriptome Identifies Drug-Resistance Signature and Immunosuppressive Microenvironment in Metastatic Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a deadly neuroendocrine malignancy with high metastasis. However, the heterogeneity of metastatic SCLC at the single-cell level remains elusive. The single-cell transcriptome of a total of 24 081 cells in metastatic lymph node samples from seven SCLC patients via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is examined. Genomic alterations are also examined by whole exome sequencing (WES) and the immune infiltration between SCLC and non-SCLC (NSCLC) is compared using public single-cell RNA sequencing (scRNA-seq) data. It is identified that malignant cells in lymph-node metastatic SCLC have inter-patient and intra-tumor heterogeneity characterized by distinct

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy framework, docking and molecular dynamic simulations of (

In this work, a novel crystal, (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (

Sintilimab combined with chemotherapy successfully treated a patient with advanced submandibular gland tumor.

Primary submandibular gland tumors are relatively rare. Due to its low incidence and broad spectrum phenotypic, biological and clinical heterogeneity types, a wide range of options have been developed to treat this tumor. To date, however, efficacious standard treatment regimens are lacking. Here, the authors present a case of a patient with an advanced submandibular gland tumor. Histological and imaging results diagnosed the case as stage IV submandibular gland adenocarcinoma with multiple metastases. The patient was subjected to systemic platinum-based chemotherapy combined with sintilimab. A primary lesion complete response was observed after six cycles of treatment. This case affirms the efficacy of the PD-1 inhibitor sintilimab combined with platinum-based chemotherapy as a first-line treatment for advanced submandibular gland tumors. Primary submandibular gland tumors are very uncommon. There is a lack of standard treatment plans due to the low incidence and diverse clinical situations. The authors report a case of an advanced submandibular gland tumor patient who received platinum-based chemotherapy combined with sintilimab as the initial treatment plan. The tumor and multiple lung metastases significantly shrank after six cycles of treatment. This case indicates the regimen is effective for advanced submandibular gland tumor patients.

Pharmacokinetics of Afatinib after Intravenous and Oral Administrations in Rats Using Validated UPLC MSMS Assay.

Afatinib is designated as the first-line management therapy for patients with advanced non-small cell lung cancer, and metastatic head and neck cancer. LC coupled to MSMS can be utilised in therapeutic drug monitoring to ensure optimal use of Afatinib with the reduction of its possible adverse reactions. The aim of this investigation was to determine the pharmacokinetics of Afatinib in rats after single IV (2 mgkg) and oral (8 mgkg) doses. Therefore, a selective, sensitive and precise UPLC MSMS assay thru electrospray ionisation basis with positive ionisation approach was established to measure Afatinib concentrations in the rat. The precision and accuracy of the developed assay method in the concentration range of 10-1000 ngml show no significant difference among inter- and-intra-day analysis (P > 0.05). Linearity was detected over the studied range with correlation coefficient, r > 0.995 (n 6day). The pharmacokinetics of Afatinib in the rat after a single IV dose showed a mean terminal half-life of 4.6 ± 0.97 h, and a mean clearance 480 ± 80 mlhkg. After PO administration, a short absorption phase with a mean Tmax of 1.3 ± 0.6 h with the highest concentration of 513.9 ± 281.1 ngml, and the lowest concentration detected after 24 h was 18.8 ± 10.7 ngml.

Hybrids of thiazolidinone with 1,2,3-triazole derivatives design, synthesis, biological evaluation,

A new series of thiazolidinone linked 1,2,3-triazole hybrids

Research progress in immune microenvironment and immunotherapy of brain metastasis in non-small cell lung cancer.

In recent years, the rise of immunotherapy has comprehensively changed the treatment pattern of advanced non-small cell lung cancer(NSCLC). With the understanding of the immune microenvironment in brain metastasis, patients with advanced lung cancer with brain metastasis, who usually were previously excluded from clinical studies, gradually gained attention from researchers. The development from immune monotherapy to combination with chemotherapy significantly improved the survival prognosis of patients with brain metastases from lung cancer. This review aimed to briefly elucidate the mechanism of the immune microenvironment, and summarized the latest research progress of immunotherapy for NSCLC patients with brain metastasis. 近年来，免疫治疗的兴起全面改变了晚期非小细胞肺癌的治疗格局。随着对肿瘤免疫微环境的研究渐深，常被临床研究排除在外的肺癌晚期脑转移患者逐渐被研究者们关注，从免疫单药治疗发展到免疫联合治疗，极大程度改善了脑转移肺癌患者的生存预后。本文旨在阐述转移灶的免疫微环境基础，同时回顾并总结近年来非小细胞肺癌脑转移免疫治疗的最新研究进展。.

Treatment of oligoprogression to immunotherapy resistance in advanced non-small cell lung cancer.

In recent years, the incidence of lung cancer has been increasing year by year. Traditional treatments have limited clinical effects in advanced, driver-gene-negative non-small cell lung cancer. Immune checkpoint inhibitors (ICI) have dramatically changed the treatment landscape of advanced non-small cell lung cancer. However, most patients are suffered from primary and acquired resistance inevitably. Oligoprogression is one of the main progression patterns of acquired resistance. Therefore, it is essential to further understand treatment of oligoprogression to immunotherapy resistance. This article aimed to conduct a systematic review of the treatment of oligoprogression to immunotherapy resistance. 近年来，肺癌的发病率逐年上升，驱动基因阴性的晚期非小细胞肺癌传统治疗临床效果较为有限，免疫检查点抑制剂（immune checkpoint inhibitor，ICI）的临床应用极大地改变了晚期非小细胞肺癌患者的治疗格局，然而多数患者仍不可避免地出现原发性耐药或获得性耐药，寡进展是获得性耐药的主要进展模式之一。因此，进一步认识免疫治疗耐药后寡进展的治疗措施至关重要，本文旨在对免疫治疗出现寡进展之后的治疗进行系统性的综述。.

Scimitar syndrome with pulmonary sequestration containing carcinoma a case report.

We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment. 报道1例弯刀综合征、肺隔离症合并癌变的患者临床表现、辅助检查及诊疗经过的资料，并对2022年1月之前的相关文献进行检索、复习，总结弯刀综合征合并肺隔离症、肺隔离症合并癌变的临床特征。弯刀综合征可伴随同侧肺隔离症，隔离肺有发生癌变的风险，临床上应重视并进行筛查，从而早诊断早治疗。.

Chinese expert consensus on diagnosis of early lung cancer (2023 Edition).

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in our country, seriously endangering peoples lives and health. The treatment of lung cancer has made great progress in the past 10 years, and the 5-year survival rate of lung cancer in China has also increased from 16.1% to 19.7%, but about 75% of patients are still in advanced stages of lung cancer at the time of diagnosis, missing the best time for radical surgery. Early diagnosis can significantly improve the prognosis and survival of lung cancer patients. From the 5-year survival rate of lung cancer patients, it can be seen that the 5-year survival rate of stage Ⅰ patients was 77%-92%, while that of stage ⅢA-ⅣA patients was only 10%-36%, and there was a significant difference in the 5-year survival rate. Studies have shown that early-diagnosed and completely resected lung adenocarcinoma 肺癌在我国居恶性肿瘤发病与死亡之首，严重危害到人民生命健康。近年来肺癌治疗取得了较大的进展，我国肺癌的5年生存率也从16.1%提高到19.7%，但仍有约75%的患者在诊断时处于肺癌晚期，错过了最佳根治性手术治疗时机。早期诊断可显著提高肺癌患者预后生存，从肺癌患者术后5年生存率可以看出，Ⅰ期患者术后5年生存率在77%92%，而ⅢAⅣA期患者仅为10%36%，5年生存率存在显著差异。研究显示早期诊断并完全切除的肺原位腺癌（AIS）及微浸润腺癌（MIA）术后5年疾病特异性生存率分别为100%和100%。早期诊断是提高肺癌预后的关键，为进一步提高我国早期肺癌诊断水平，尤其是肺结节暨早期肺癌诊断、评估中的准确性、规范性，中华医学会呼吸病学分会肺癌学组的专家针对国内肺癌早诊领域实际情况，参考国内外最新研究数据和相关指南，制定了《早期肺癌诊断中国专家共识（2023年版）》，共识围绕早期肺癌筛查人群、无创检查、有创检查、人工智能与大数据及机器人技术、物联网及多学科合作等在早期肺癌诊断中的应用、疑诊早期肺癌的肺结节管理及随访策略等7个方面分别给出推荐意见，为临床医生在早期肺癌诊断方面提供参考，以进一步推动我国早期肺癌诊断工作。.

Low grade adenosarcoma with sex cord differentiation with lung metastasis report of a case.

子宫腺肉瘤是女性生殖道罕见的恶性肿瘤，约占子宫肉瘤的5%，腺肉瘤通常具有较低的恶性潜能，约25%的病例表现为局部复发，不到5%的病例发生远处转移。伴性索样分化的子宫腺肉瘤更为罕见，本文报道1例低级别伴性索分化的子宫腺肉瘤肺转移病例，结合国内外文献，就子宫腺肉瘤伴性索样分化的临床病理学特征、免疫表型、诊断及鉴别诊断进行探讨。.

TTF1 and p40 co-expression in the same tumor cells in a non-small cell lung carcinoma a clinicopathological analysis of three cases.

The impact of HIV on the risk of COVID-19 death among hospitalized patients.

Little is known about the association between Human Immunodeficiency Virus (HIV) infection and risk of death among hospitalized COVID-19 patients. We aimed to investigate this association using a multicenter study. This multicenter study was conducted using the registry database of Coronavirus Control Operations Headquarter from March 21, 2021 to January 18, 2020 in the province of Tehran, Iran. The interest outcome was COVID-19 death among hospitalized patients living with and without HIV. The Cox regression models with robust standard error were used to estimate the association between HIV infection and risk of COVID-19 death. The subgroup and interaction analysis were also performed in this study. 326052 patients with COVID-19 were included in the study, of whom 127 (0.04%) were living with HIV. COVID-19 patients with HIV were more likely to be female, older, and to have symptoms such as fever, muscular pain, dyspnea and cough. The death proportion due to COVID-19 was 18 (14.17%) and 21595 (6.63%) among HIV and non-HIV patients, respectively. Patients living with HIV had lower mean survival time compared to those without HIV (26.49 vs. 15.31 days, P-value 0.047). Crude risk of COVID-19 death was higher among HIV patients than in non-HIV group (hazard ratioHR 1.60, 1.08-2.37). Compared to those without HIV, higher risk of COVID-19 death was observed among patients with HIV after adjusting for sex (1.60, 1.08-2.36), comorbidities (1.49, 1.01-2.19), cancer (1.59, 1.08-2.33), and PO2 (1.68, 1.12-2.50). However, the risk of COVID-19 death was similar in patients with and without HIV after adjusting for age (1.46, 0.98-2.16) and ward (1.30, 0.89-1.89). We found no strong evidence of association between HIV infection and higher risk of COVID-19 death among hospitalized patients. To determine the true impact of HIV on the risk of COVID-19 death, factors such as age, comorbidities, hospital ward, viral load, CD4 count, and antiretroviral treatment should be considered.

BiRPN-YOLOvX A weighted bidirectional recursive feature pyramid algorithm for lung nodule detection.

Lung cancer has the second highest cancer mortality rate in the world today. Although lung cancer screening using CT images is a common way for early lung cancer detection, accurately detecting lung nodules remains a challenged issue in clinical practice. This study aims to develop a new weighted bidirectional recursive pyramid algorithm to address the problems of small size of lung nodules, large proportion of background region, and complex lung structures in lung nodule detection of CT images. First, the weighted bidirectional recursive feature pyramid network (BiPRN) is proposed, which can increase the ability of network model to extract feature information and achieve multi-scale fusion information. Second, a CBAMCSPDarknet53 structure is developed to incorporate an attention mechanism as a feature extraction module, which can aggregate both spatial information and channel information of the feature map. Third, the weighted BiRPN and CBAMCSPDarknet53 are applied to the YOLOvX model for lung nodule detection experiments, named BiRPN-YOLOvX, where YOLOvX represents different versions of YOLO. To verify the effectiveness of our weighted BiRPN and CBAM CSPDarknet53 algorithm, they are fused with different models of YOLOv3, YOLOv4 and YOLOv5, and extensive experiments are carried out using the publicly available lung nodule datasets LUNA16 and LIDC-IDRI. The training set of LUNA16 contains 949 images, and the validation and testing sets each contain 118 images. There are 1987, 248 and 248 images in LIDC-IDRIs training, validation and testing sets, respectively. The sensitivity of lung nodule detection using BiRPN-YOLOv5 reaches 98.7% on LUNA16 and 96.2% on LIDC-IDRI, respectively. This study demonstrates that the proposed new method has potential to help improve the sensitivity of lung nodule detection in future clinical practice.

Predictive value of p53 and AXL immunostaining for the efficacy of immune checkpoint inhibitor-based therapy after osimertinib treatment in patients with epidermal growth factor-mutant non-small cell lung cancer.

Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear. We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations other mutations were defined as uncommon mutations. A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test p 0.04 and p 0.02, respectively). The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastaticrecurrent NSCLC patients with EGFR mutation from a phase IIIa study.

Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase IIIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastaticrecurrent EGFR mutated non-small cell lung cancer (NSCLC). Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI 69.3-93.2%). The median DoR was 19.3 (95% CI 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI 13.8-24.8) months and 22.0 (95% CI 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastaticrecurrent NSCLC patients with EGFR mutation in the first-line setting. ClinicalTrials.gov, NCT03386955.

Research Progress of Relationship between Pleural Deformation and Visceral Pleural Invasion in Lung Cancer Manifesting as Ground-glass Opacity.

Visceral pleural invasion (VPI) is one of the negative prognostic factors of non-small cell lung cancer (NSCLC). With the popularization of computed tomography (CT) screening for lung cancer, more and more ground-glass nodule (GGN) have been found. However, it remains unclear whether the relationship between the pleural deformation of lung cancer manifesting as ground-glass opacity (GGO) and VPI affects the effect of sub-lobectomy, which is reviewed in this paper. . 【中文题目：磨玻璃结节型肺癌胸膜改变与脏层胸膜侵犯的相关性研究进展】 【中文摘要：脏层胸膜侵犯（visceral pleural invasion, VPI）是非小细胞肺癌（non-small cell lung cancer, NSCLC）预后的不良影响因素之一。随着计算机断层扫描（computed tomography, CT）肺癌筛查的普及，肺磨玻璃结节（ground-glass nodule, GGN）的发现越来越多，但是磨玻璃影（ground-glass opacity, GGO）型肺癌的胸膜改变与 VPI之间的关系是否影响亚肺叶切除的疗效尚不明确，本文对此进行了梳理。 】 【中文关键词：肺肿瘤；磨玻璃结节；胸膜改变；脏层胸膜侵犯】.

Research Progress of Treatment for NSCLC in Young Patients.

Non-small cell lung cancer (NSCLC) young patients (≤45 years old), despite their low prevalence, have unique clinical and pathological features. Its morbidity has been on the rise in recent years. With the concept of individualized lung cancer treatment, related researches are gradually gaining attention. In addition, the treatment response and prognosis in NSCLC young patients are different from older patients, so the study of NSCLC young patients is of great clinical significance. This article reviews the clinical manifestations, treatment and prognosis of NSCLC young patients. . 【中文题目：青年型非小细胞肺癌治疗研究进展】 【中文摘要：青年型非小细胞肺癌（non-small cell lung cancer, NSCLC）患者（≤45岁）尽管占比较低，但其有独特的临床病理特征，近年来患病率有上升的趋势。随着肺癌个体化治疗观念的提出，其研究也逐渐受到重视。另外，青年型NSCLC患者在治疗反应和预后等方面与老年肺癌患者有所不同，因此对青年型NSCLC进行研究极具临床意义。本文就青年型NSCLC患者的临床表现、治疗手段和预后等特点作一综述。 】 【中文关键词：肺肿瘤；综合治疗；青年患者；临床特点；预后】.

Research Progresses in the Treatment of NSCLC with MET Gene Variants A Riview.

Mesenchymal-epithelial transition factor (MET) has long been considered as the most crucial and promising driver gene in the occurrence and development of non-small cell lung cancer (NSCLC), except for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ROS oncogene 1 receptor tyrosine kinase (ROS1). In recent years, therapeutic drugs targeting MET have been continuously developed and applied in clinical practice. First, the curative effect of NSCLC patients with MET exon 14 skipping mutations has been further improved. In addition, when MET amplification occurs after resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR-mutant NSCLC, the combination of MET-TKIs and EGFR-TKIs has brought significant survival benefits and many other advances. This article reviews the treatment progress of NSCLC patients with different types of MET variants under different circumstances, which provides reference for the selection of clinical treatment strategies. . 【中文题目：合并MET基因变异的非小细胞肺癌治疗 研究进展】 【中文摘要：间质-上皮细胞转化因子（mesenchymal-epithelial transition factor, MET）长期以来被认为是非小细胞肺癌（non-small cell lung cancer, NSCLC）发生发展过程中除表皮生长因子受体（epidermal growth factor receptor, EGFR）、间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）、原癌基因酪氨酸蛋白激酶（c-ros oncogene 1 receptor tyrosine kinase, ROS1）之外最重要和最有前景的驱动基因。近年来，靶向MET的治疗药物不断被研发并应用于临床。首先是合并MET外显子14跳跃突变的NSCLC患者疗效得到进一步的提高。另外，晚期EGFR突变型NSCLC患者EGFR酪氨酸激酶受体抑制剂（EGFR tyrosine kinase inhibitors, EGFR-TKIs）耐药后继发MET扩增时，联合MET-TKIs和EGFR-TKIs的方案带来了明显的生存获益等诸多进展。本文综述了在不同情况下，NSCLC患者合并MET不同变异类型的治疗进展，为临床治疗策略的选择提供参考。 】 【中文关键词：肺肿瘤；MET扩增；跳跃突变；MET酪氨酸激酶抑制剂】.

Review for N2 Sub-staging in Non-small Cell Lung Cancer.

Patients with N2 non-small cell lung cancer (NSCLC) were heterogeneous groups and required further stratification. The International Society for the Study of Lung Cancer (IASLC) divided N2 into three sub-stages N2 at a single station without N1 involvement (N2a1), N2 at a single station with N1 involvement (N2a2), and N2 at multiple stations (N2b). These new descriptors significantly distinguished the overall survival (OS), disease-free survival (DFS), and recurrence pattern of patients with different N2 sub-stages. The OS and DFS of N2a1 were not sufficiently distinguished from N1 at multiple stations (N1b). The OS and DFS of N2a2 were intermediate between those of N2a1 and N2b. Current evidence did not support the further subdivision of the N2b. The main recurrence pattern of N2a1, N2a2 and N2b were distant metastasis, and the risks of distant metastasis increased successively. N2a1 patients were at low risk of locoregional recurrence, which could not be reduced by postoperative radiotherapy (PORT). N2a2 and N2b patients had a similar higher risk of locoregional recurrence, which could be reduced to a similar level of N2a1 patients by PORT. . 【中文题目：非小细胞肺癌N2亚分期研究进展】 【中文摘要：N2期非小细胞肺癌的异质性较大，国际肺癌研究学会根据预后差异将其划分为三个亚分期，即N1淋巴结阴性的单站N2淋巴结转移（N2a1）、N1淋巴结阳性的单站N2淋巴结转移（N2a2）以及多站N2淋巴结转移（N2b）。目前的证据显示，N2亚分期可以更好地区分非小细胞肺癌的总生存期（overall survival, OS）、无病生存期（disease-free survival, DFS）及复发模式。N2a1人群的OS及DFS更接近多站N1淋巴结转移（N1b）；N2a2人群的OS及DFS介于N2a1及N2b之间；N2b人群的OS及DFS较差，目前的证据尚不支持将N2b期进一步细分。尽管危险度不同，但N2a1、N2a2及N2b三个亚分期的主要复发模式均为远处转移，且远处转移的风险依次升高。N2a1人群的局部区域复发风险较低，术后放疗不能改善其局部区域复发；而N2a2和N2b人群的局部区域复发风险相似，术后放疗可以显著改善这两个人群的局部区域复发，使之降低至与N2a1人群相近的水平。 】 【中文关键词：肺肿瘤；N2；亚分期；总生存期；无病生存期；复发模式】.

Advances in the Study of Tissue-resident Memory T Cells in Lung Cancer.

Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of lung cancer, but the benefit population is limited and there is a lack of effective predictive markers of efficacy. Tissue-resident memory T cells (TRM) reside in tissues and exert anti-tumor effects by expressing the integrins CD103, CD49a or C-type lectin CD69 and immune checkpoint receptors. TRM expressing programmed cell death 1 (PD-1) is enriched with transcriptional products associated with cytotoxicity and enhances T cell (antigen) receptor (TCR)-mediated cytotoxicity. TRM is a promising biomarker for predicting the efficacy and prognosis of immunotherapy in lung cancer patients. This review will describe the progress of TRM research in lung cancer. . 【中文题目：组织驻留记忆T细胞在肺癌中的研究进展】 【中文摘要：免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）虽然广泛用于肺癌的治疗，但获益人群有限，且缺乏有效的疗效预测标志物。组织驻留记忆T细胞（tissue-resident memory T cell, TRM）通过表达整合素CD103、CD49a或C型凝集素CD69和免疫检查点受体，使其在组织中驻留，并发挥抗肿瘤作用。表达程序性死亡受体1（programmed cell death 1, PD-1）的TRM富含与细胞毒性相关的转录产物，增强了T细胞（抗原）受体（T cell receptor, TCR）介导的细胞毒作用。TRM可以预测肺癌患者免疫治疗疗效和预后，是具有前景的生物标志物。本综述将阐述TRM在肺癌中的研究进展。 】 【中文关键词：组织驻留记忆T细胞；肺肿瘤；免疫治疗】.

Correlation Analysis of Ki67 Expression and EGFR Mutation on the Risk of Recurrence and Metastasis in Postoperative Patients with Stage I Lung Adenocarcinoma.

The prognosis of stage I non-small cell lung cancer (NSCLC) is generally good. However, some of the stage I NSCLC patients still may have early recurrence and metastasis, and there is no standard method to screen this part of the population. The aim of this study is to investigate the relationship between Ki67 expression as well as epidermal growth factor receptor (EGFR) mutation and the risk of recurrence in postoperative patients with stage I lung adenocarcinoma. We retrospectively enrolled 118 postoperative patients with stage I lung adenocarcinoma. EGFR mutation was tested using amplification refractory mutation system polymerase chain reaction (ARMS-PCR) , and Ki67 level was detected by immunohistochemistry (IHC), followed by the collection of the patients clinical characteristics. Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model were used for the prognostic statistical analysis. Among the 118 patients, the rate of high Ki67 expression was 43.22% (51118), which is related to gender, smoking status, surgical method, differentiation degree, and postoperative stage (P<0.05). Meanwhile, EGFR mutation rate was 61.02% (72118), of which EGFR exon 19 deletion mutation rate was 19.49% (23118), and the EGFR exon 21 L858R mutation rate was 41.53% (49118). However, Ki67 expression was not associated with EGFR mutation status (χ21.412, P0.235). Survival analysis showed that high Ki67 expression was inversely associated with disease-free survival (DFS) and overall survival (OS) in stage I lung adenocarcinoma (P<0.05), but EGFR mutation status was not significantly associated with DFS and OS (P>0.05). In the subgroup analysis, the DFS of the EGFR exon 19 deletion group was significantly decreased compared with the EGFR exon 21 L858R mutation group (P0.031), but there was no significant difference in OS (P0.308). Multivariate analysis showed that there was statistical significance between Ki67 expression (P0.001) and DFS in stage I lung adenocarcinoma Ki67 expression (P0.03) and gender (P0.015) were associated with OS in stage I lung adenocarcinoma. Ki67 expression is an independent influencing factor for postoperative recurrence and OS of stage I lung adenocarcinoma and it is not significantly associated with EGFR mutation. There is no significant difference between EGFR mutation status and the prognostis of stage I lung adenocarcinoma. However, the prognosis differed in EGFR mutation types the patients with EGFR exon 19 deletion are at higher risk of recurrence than EGFR exon 21 L858R mutation. 【中文题目：Ki67表达及EGFR突变对I期肺腺癌患者 术后复发转移风险的相关分析】 【中文摘要：背景与目的 尽管多数I期非小细胞肺癌（non-small cell lung cancer, NSCLC）术后患者的预后良好，但仍有部分可能早期复发转移，目前临床尚无标准方法筛选这部分人群。本研究探讨了I期肺腺癌术后患者Ki67的表达及表皮生长因子受体（epidermal growth factor receptor, EGFR）突变状态与其复发风险的关系。方法 对118例I期肺腺癌患者进行回顾性调查，将患者术后标本用免疫组化法（immunohistochemistry, IHC）检测Ki67的表达水平，扩增阻滞突变系统-链式聚合酶反应法（amplification refractory mutation system polymerase chain reaction, ARMS-PCR）或直接测序法检测EGFR基因突变状态，并收集一般临床资料。采用Kaplan-Meier法、Log-rank检验、Cox比例风险回归模型进行预后统计分析。结果 118例患者中，Ki67高表达率为43.22%（51118），与性别、是否吸烟、手术方式、分化程度、术后分期相关（P<0.05）；EGFR突变率61.02%（72118），其中EGFR外显子19缺失突变率19.49%（23118），EGFR外显子21 L858R突变率41.53%（49118），女性、非吸烟者更容易出现EGFR突变（P<0.05）。Ki67表达与EGFR突变状态无显著相关（χ21.412, P0.235）。生存分析提示Ki67高表达与I期肺腺癌术后无病生存期（disease-free survival, DFS）及总生存期（overall survival, OS）呈负相关（P<0.05）；EGFR突变状态与I期肺腺癌术后DFS、OS无显著相关（P>0.05），而亚组分析显示，相较于EGFR外显子21 L858R突变组，EGFR外显子19缺失组的5年DFS显著降低，差异有统计学意义（P0.031），但在OS上并无统计学差异（P0.308）。多因素分析发现Ki67表达（P0.001）对I期肺腺癌术后DFS影响具有统计学意义，Ki67表达（P0.03）、性别（P0.015）对I期肺腺癌术后OS影响具有统计学意义。结论 Ki67表达是I期肺腺癌术后复发及OS的独立影响因素，与EGFR突变无明显相关；本研究中，EGFR突变状态与I期肺腺癌预后未见显著相关，但不同EGFR突变类型预后不同，相较于EGFR外显子21 L858R突变，EGFR外显子19缺失患者的术后复发风险更高。 】 【中文关键词：Ki67；表皮生长因子受体；肺肿瘤；预后】.

Efficacy of Osimertinib Combined with Bevacizumab in Advanced Non-small Cell Lung Cancer Patients with Acquired EGFR T790M Mutation.

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation. A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed. The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P0.045) and OS (P0.023). Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation. 【中文题目：奥希替尼联合贝伐珠单抗在获得性EGFR T790M突变晚期非小细胞肺癌的疗效分析】 【中文摘要：背景与目的 奥希替尼是对表皮生长因子受体（epidermal growth factor receptor, EGFR）T790M突变非小细胞肺癌（non-small cell lung cancer, NSCLC）有效的第三代靶向药物。尽管第一代EGFR酪氨酸激酶抑制剂（EGFR-tyrosine kinase inhibitors, EGFR-TKIs）联合贝伐珠单抗治疗可延长无进展生存期（progression-free survival, PFS），但奥希替尼联合贝伐珠单抗的后线疗效在II期研究WJOG8715L中并未得到肯定，目前该联合模式在中国人群中的数据仍非常有限。本研究旨在分析真实世界中奥希替尼联合贝伐珠单抗二线治疗的疗效，评价奥希替尼联合抗血管治疗模式在EGFR T790M获得性耐药突变NSCLC中的二线治疗价值。方法 收集2020年1月-2021年8月收治的第一、二代EGFR-TKIs治疗后伴EGFR T790M突变NSCLC患者共42例。16例接受二线奥希替尼联合贝伐珠单抗治疗，另26例接受二线奥希替尼单药治疗。分析患者的治疗效果。结果 联合组和单药组客观缓解率（objective response rate, ORR）相当（43.8% vs 50.0%, P0.694）。两组中位PFS（14.0个月 vs 13.0个月，P0.797）和总生存期（overall survival, OS）（29.0个月 vs 26.0个月，P0.544）均未见统计学差异。Cox回归模型显示前线联合贝伐珠单抗治疗是奥希替尼后线单药或联合治疗PFS（P0.045）及OS（P0.023）更短的独立预测因素。结论 奥希替尼联合贝伐珠单抗二线治疗相比靶向单药治疗未见更好的疗效。 】 【中文关键词：肺肿瘤；表皮生长因子受体；血管内皮生长因子；奥希替尼；贝伐珠单抗】.

Exosomal miR-10b Promotes Invasion and Epithelial-mesenchymal Transformation of Lung Adenocarcinoma A549 Cells by Regulating Macrophage M2 Polarization.

Metastasis is the main cause of death in patients with lung cancer. Macrophages are innate immune cells that play important roles in cancer metastasis. Exosomes could play an important role of communication between tumor cells and macrophages. This study investigated the effect of miR-10b on cell growth invasion and epithelial mesenchymal transition (EMT) in lung adenocarcinoma A549 cell exosomes. Exosomes were isolated from A549 cells and identified by transmission electron microscopy (TEM) and Western blot. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis. Cell migration and invasion were detected by Transwell assay. The expression of mRNA and protein were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot, respectively. The expression of miR-10b was up-regulated in non-small cell lung cancer, and miR-10b inhibitor could inhibit the proliferation of A549 cell. Meanwhile, the tumor cell-derived exosome miR-10b promoted the invasion of A549 cell and EMT by promoting the M2 polarization of macrophages. Tumor cell-derived exosome miR-10b promotes A549 cell invasion and EMT through M2 macrophage polarization. 【中文题目：外泌体miR-10b通过调控巨噬细胞M2极化 促进肺腺癌A549细胞的侵袭和上皮间质转化】 【中文摘要：背景与目的 肺癌转移是引起死亡的主要原因。先天免疫细胞特别是巨噬细胞在肿瘤转移中扮演非常重要的角色。外泌体在肿瘤细胞与巨噬细胞间的通讯非常重要，因此本研究探讨肺腺癌A549细胞外泌体中的miR-10b对其细胞生长侵袭及上皮间质转化（epithelial mesenchymal transition, EMT）的影响。方法 从A549细胞中分离外泌体，通过透射电镜及蛋白质印迹法对外泌体进行鉴定。采用CCK-8试剂盒和流式细胞术检测A549细胞的增殖和凋亡。Transwell法检测细胞侵袭以及通过定量逆转录聚合酶链式反应（quantitative reverse transcription polymerase chain reaction, RT-qPCR）和Western blot分别检测A549细胞中mRNA和蛋白的表达。结果 miR-10b在非小细胞肺癌（A549、NCI-H1650和NCI-H1299）中表达上调，miR-10b inhibitor可抑制非小细胞肺癌的增殖。同时，外泌体miR-10b通过促进巨噬细胞M2极化，进而促进A549细胞的侵袭和EMT。结论 外泌体miR-10b通过M2巨噬细胞极化促进A549细胞的侵袭和EMT。 】 【中文关键词：A549；M2型巨噬细胞极化；外泌体；miR-10b；侵袭；上皮间质转化】.

The expression of HER2neu in patients with lung cancer and its associated factors.

Lung cancer is the most common cause of cancer-related death worldwide in both sexes. Evidence suggests the role of genetic factors in lung cancer. Studying of such factors can help understand the cancer prognosis. Overexpression of the human epidermal growth factor receptor-2 (HER2neu) protein is considered an important prognostic factor in breast cancer, but its role has not been confirmed in lung cancer. Therefore, the present study aimed to investigate the role of its expression in patients with lung cancer. In this cross-sectional study, patients aged >18 years who were referred to Afzalipoor Hospital, Kerman, Iran, from 2016 to 2017, and were diagnosed with lung cancer were enrolled into the study if they had a pathological sample of their cancerous lung. Their demographics were recorded, and the sample was sectioned and stained to measure HER2neu gene expression according to DAKO instructions using heat-induced antigen retrieval (HIER) enzyme marker. The samples of 100 patients with lung cancer were evaluated (84% men and 16% women) with a mean age of 61.34 years (standard deviation of 12.51 years). HER2neu expression was significantly associated with the type of cancer and was highest in adenocarcinoma and zero in small cell carcinoma (P < 0.001), but not with patients sex, age, smoking status and family history of cancer (P > 0.05). These results emphasized the overexpression of HER2neu in different types of lung cancer, which can be used further for therapeutic purposes. The results showed that HER2neu was overexpressed not only in adenocarcinoma but also in other types, like squamous cell carcinoma. Therefore, all subtypes of non-small cell lung carcinoma should be considered for anti-HER2 therapies, and further research is required for small cell lung carcinoma.

The antibiofilm, antibacterial, antioxidant, and anticancer activities of the methanolic extract of

Dose and organ displacement comparisons with breast conservative radiotherapy using abdominal and thoracic deep-inspiration breath-holds A comparative dosimetric study.

Deep-inspiration breath-hold (DIBH) reduces the radiation dose to the heart and lungs during breast radiotherapy in cancer. However, there is not enough discussion about suitable breathing methods for DIBH. Therefore, we investigated the radiation doses and organ and body surface displacement in abdominal DIBH (A-DIBH) and thoracic DIBH (T-DIBH). Free-breathing, A-DIBH, and T-DIBH computed tomography images of 100 patients were used. After contouring the targets, heart, and lungs, radiotherapy plans were created. We investigated the heart and lung doses, the associations between the heart and left lung displacements, and the thorax and abdominal surface displacements. No significant differences were observed in the target dose indices. However, the heart and lung doses were significantly lower in A-DIBH than in T-DIBH for all the indices the mean heart and lung doses were 1.69 and 3.48 Gy, and 1.91 and 3.55 Gy in A-DIBH and T-DIBH, respectively. The inferior displacement of the heart and the left lung was more significant in A-DIBH. Therefore, inferior expansion of the heart and lungs may be responsible for the respective dose reductions. The abdominal surface displaced more than the thoracic surface in both A-DIBH and T-DIBH, and thoracic surface displacement was greater in T-DIBH than in A-DIBH. Moreover, A-DIBH can be identified because abdominal surface displacement was greater in A-DIBH than in T-DIBH. In conclusion, A-DIBH and T-DIBH could be distinguished by comparing the abdominal and thoracic surfaces of A-DIBH and T-DIBH, thereby ensuring the implementation of A-DIBH and reducing the heart and lung doses.

Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking in wedge resection for fluoroscopically invisible small lung lesions.

We developed a novel wireless localization technique after electromagnetic navigation bronchoscopy-guided radiofrequency identification marker placement for fluoroscopically invisible small lung lesions. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared 2 marking approaches with or without cone-beam computed tomography (CBCT). Consecutive patients from January 2021 to March 2022 in our institution were enrolled. Markers were placed central to the lesions either in a bronchoscopic suite under intravenous anaesthesia or a hybrid operation theatre with CBCT under general anaesthesia. The efficacy of the 2 marking methods was compared using an inverse probability of treatment weighting adjusted analysis. Totally 80 markers were placed (45 under CBCT and 35 under fluoroscopy) for 74 patients with 80 lesions mean size 6.9 mm (interquartile range 5.1-8.4) at a median depth from the pleura of 14.0 mm (interquartile range 8.5-19.5). The median distance from marker to lesion was 9.1 mm, with a pleural depth of 15.5 mm. The tumour resection rate was 97.5% (7880) with the median surgical margin of 10.0 mm (interquartile range 8.0-11.0). Although the bronchoscopy time was longer using CBCT because of the need for 2.8 scans per lesion, the distance from the marker to the lesion was shorter for marking using CBCT than marking using fluoroscopy (adjusted difference -4.56, 95% confidence interval -6.51 to -2.61, P < 0.001). Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking provided a high tumour resection rate with sufficient surgical margins.

Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles Radiosensitizing Properties.

Among the plethora of nanosystems used in the field of theranostics, iron oxide nanoparticles (IONPs) occupy a central place because of their biocompatibility and magnetic properties. In this study, we highlight the radiosensitizing effect of two IONPs formulations (namely 7 nm carboxylated IONPs and PEG

The Cytotoxic Effectiveness of Thiourea-Reduced Graphene Oxide on Human Lung Cancer Cells and Fungi.

This study demonstrated the effective reduction of graphene oxide (GO) by employing thiourea as a reducing and stabilizing agent. Two fungi (

Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice.

Nicotinamide mononucleotide (NMN) is a natural antioxidant approved as a nutritional supplement and food ingredient, but its protective role in silicosis characterized by oxidative damage remains unknown. In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes

Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients.

Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLCMSMS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC 0.765, Sig 0.017, CI 0.58-0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer.

Gefitinib (GEF) is utilized in clinical settings for the treatment of metastatic lung cancer. However, premature drug release from nanoparticles in vivo increases the exposure of systemic organs to GEF. Herein, nanostructured lipid carriers (NLC) were utilized not only to avoid premature drug release but also due to their inherent lymphatic tropism. Therefore, the present study aimed to develop a GEF-NLC as a lymphatic drug delivery system with low drug release. Design of experiments was utilized to develop a stable GEF-NLC as a lymphatic drug delivery system for the treatment of metastatic lung cancer. The in vitro drug release of GEF from the prepared GEF-NLC formulations was studied to select the optimum formulation. MTT assay was utilized to study the cytotoxic activity of GEF-NLC compared to free GEF. The optimized GEF-NLC formulation showed favorable physicochemical properties lt300 nm PS, lt0.2 PDI, lt-20 ZP values with gt90% entrapment efficiency. Interestingly, the prepared formulation was able to retain GEF with only ≈57% drug release within 24 h. Furthermore, GEF-NLC reduced the sudden exposure of cultured cells to GEF and produced the required cytotoxic effect after 48 and 72 h incubation time. Consequently, optimized formulation offers a promising approach to improve GEFs therapeutic outcomes with reduced systemic toxicity in treating metastatic lung cancer.

Phytochemical Analysis and Antiproliferative Activity of

The genus

Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH

A Natural CHI3L1-Targeting Compound, Ebractenoid F, Inhibits Lung Cancer Cell Growth and Migration and Induces Apoptosis by Blocking CHI3L1AKT Signals.

Our previous big data analyses reported a strong association between CHI3L1 expression and lung tumor development. In this present study, we investigated whether a CHI3L1-inhibiting natural compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis. Ebractenoid F concentration-dependently (0, 17, 35, 70 µM) and significantly inhibited the proliferation and migration of A549 and H460 lung cancer cells and induced apoptosis. In the mechanism study, we found that ebractenoid F bound to CHI3L1 and suppressed CHI3L1-associated AKT signaling. Combined treatment with an AKT inhibitor, LY294002, and ebractenoid F synergistically decreased the expression of CHI3L1. Moreover, the combination treatment further inhibited the growth and migration of lung cancer cells and further induced apoptosis, as well as the expression levels of apoptosis-related proteins. Thus, our data demonstrate that ebractenoid F may serve as a potential anti-lung cancer compound targeting CHI3L1-associated AKT signaling.

Design, Synthesis and Antiproliferative Evaluation of Bis-Indole Derivatives with a Phenyl Linker Focus on Autophagy.

This work deals with the study of the synthesis of new bis-indole analogues with a phenyl linker derived from indole phytoalexins. Synthesis of target bis-indole thiourea linked by a phenyl linker was achieved by the reaction of 1-(tert-butoxycarbonyl)indol-3-ylmethyl isothiocyanate with p-phenylenediamine. By replacing the sulfur of the thiocarbonyl group in bis-indole thiourea with oxygen using mesityl nitrile oxide, a bis-indole homodimer with a urea group was obtained. A cyclization protocol utilizing bis-indole thiourea and methyl bromoacetate was applied to synthesize a bis-indole homodimer with a thiazolidin-4-one moiety. Bis-indole homodimers derived from 1-methoxyspirobrassinol methyl ether were prepared by bromospirocyclization methodology. Among the synthesized analogues, compound 49 was selected for further study. To evaluate the mode of the mechanism of action, we used flow cytometry, Western blot, and spectroscopic analyses. Compound 49 significantly inhibited the proliferation of lung cancer cell line A549 with minimal effects on the non-cancer cells. We also demonstrated that compound 49 induced autophagy through the upregulation of Beclin-1, LC3AB, Atg7 and AMPK and ULK1. Furthermore, chloroquine (CQ an autophagy inhibitor) in combination with compound 49 decreased cell proliferation and induced G1 cell cycle arrest and apoptosis. Compound 49 also caused GSH depletion and significantly potentiated the antiproliferative effect of cis-platin.

Immunoregulatory Role of the Mechanosensitive Ion Channel Piezo1 in Inflammation and Cancer.

Piezo1 was originally identified as a mechanically activated, nonselective cation ion channel, with significant permeability to calcium ions, is evolutionally conserved, and is involved in the proliferation and development of various types of cells, in the context of various types of mechanical or innate stimuli. Recently, our study and work by others have reported that Piezo1 from all kinds of immune cells is involved in regulating many diseases, including infectious inflammation and cancer. This review summarizes the recent progress made in understanding the immunoregulatory role and mechanisms of the mechanical receptor Piezo1 in inflammation and cancer and provides new insight into the biological significance of Piezo1 in regulating immunity and tumors.

The Synthesis, Characterization and Anti-Tumor Activity of a Cu-MOF Based on Flavone-6,2-dicarboxylic Acid.

A novel two-dimensional copper(II) framework (LDU-1), formulated as Cu

Design of Novel Coumarin Derivatives as NUDT5 Antagonists That Act by Restricting ATP Synthesis in Breast Cancer Cells.

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2

Response to Immune Checkpoint Inhibitors Is Affected by Deregulations in the Antigen Presentation Machinery A Systematic Review and Meta-Analysis.

Immune checkpoint inhibitors (ICI) targeting programmed death 1 (PD-1), its ligand (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have shown promising results against multiple cancers, where they reactivate exhausted T cells primed to eliminate tumor cells. ICI therapies have been particularly successful in hypermutated cancers infiltrated with lymphocytes. However, resistance may appear in tumors evading the immune system through alternative mechanisms than the PD-1PD-L1 or CTLA-4 pathways. A systematic pan-cancer literature search was conducted to examine the association between alternative immune evasion mechanisms via the antigen presentation machinery (APM) and resistance towards ICI treatments targeting PD-1 (pembrolizumab and nivolumab), PD-L1 (durvalumab, avelumab, and atezolizumab), and CTLA-4 (ipilimumab). The APM proteins included the human leucocyte antigen (HLA) class I, its subunit beta-2 microglobulin (B2M), the transporter associated with antigen processing (TAP) 1, TAP2, and the NOD-like receptor family CARD domain containing 5 (NLRC5). In total, 18 cohort studies (including 21 original study cohorts) containing 966 eligible patients and 9 case studies including 12 patients were reviewed. Defects in the APM significantly predicted poor clinical benefit with an odds ratio (OR) of 0.39 (95% CI 0.24-0.63,

Impact of Type 2 Diabetes Mellitus on the Prognosis of Non-Small Cell Lung Cancer.

Type 2 diabetes mellitus (T2DM) is the most common metabolic disease and is characterized by sustained hyperglycemia. The impact of T2DM on the survival of lung cancer patients remains controversial. The aim of this study was to investigate the associations of type 2 diabetes with lung cancer mortality. From January 2019 to January 2020, 228 patients with non-small cell lung cancer (NSCLC) staging earlier than IIIA were included. In our study, we found that the overall survival (OS) and progression-free survival (PFS) of lung cancer patients with diabetes was longer than non-diabetes group. Diagnosed T2DM was associated with the prognosis of lung cancer after adjusting for age and covariates. The association between T2DM and OS was influenced by age, stage of cancer and cancer treatment, as well as whether taking metformin was associated with the OS of lung cancer. However, with the adjustment for age and covariates, the relation trended to lose statistical significance. T2DM is an independent prognostic factor for patients with NSCLC staging before IIIA. The patients with both NSCLC and T2DM trended to having a longer OS, possibly due to metformin.

Role of Radiomics Features and Machine Learning for the Histological Classification of Stage I and Stage II NSCLC at

The aim of this study was to compare two different PETCT tomographs for the evaluation of the role of radiomics features (RaF) and machine learning (ML) in the prediction of the histological classification of stage I and II non-small-cell lung cancer (NSCLC) at baseline

Landscape and Predictive Significance of the Structural Classification of

Reactivation of Hepatitis B Virus in Lung Cancer Patients Receiving Tyrosine Kinase Inhibitor Treatment.

(1) Background We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods In this retrospective hospital-based cohort study, we screened all lung cancer patients with positive hepatitis B core antibodies (anti-HBc) receiving systemic antineoplastic treatment during the period from January 2011 to December 2020. Cumulative incidences of HBV reactivation, and their hazard ratios (HRs), were evaluated after adjusting patient mortality as a competing risk. (3) Results Among 1960 anti-HBc-positive patients receiving systemic therapy, 366 were HBsAg-positive and 1594 were HBsAg-negative. In HBsAg-positive patients without prophylactic NUC, 3-year cumulative incidences of HBV reactivation were similar between patients receiving chemotherapy and patients receiving TKI (15.0%, 95% confidence interval (CI) 0-31.2% vs. 21.2%, 95% CI 10.8-31.7%

Targeting Copper in Cancer Imaging and Therapy A New Theragnostic Agent.

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (

Long-Term Survival after Extended Sleeve Lobectomy (ESL) for Central Non-Small Cell Lung Cancer (NSCLC) A Meta-Analysis with Reconstructed Time-to-Event Data.

We conducted a thorough literature search on patients with central non-small cell lung cancer (NSCLC) undergoing either extended sleeve lobectomy (ESL) or pneumonectomy (PN). We identified all original research studies that compared the long-term survival of ESL versus PN from 1990 to 2022. The primary endpoints were the median overall survival (OS) and disease-free survival (DFS). Complications, operative mortality, and the reoperation rate were the secondary endpoints. Regarding the primary endpoints, independent patient data were extracted from the included studies, and pooled Kaplan-Meier curves were constructed. A sensitivity analysis was performed using the leave-one-out method. Nine studies were included in the qualitative and seven in the quantitative synthesis, including 431 patients. Patients in the ESL group demonstrated a significantly higher OS compared with the PN group (HR, 0.63 95% CI, 0.46-0.87 The present meta-analysis indicates that ESL is associated with enhanced survival outcomes compared to PN for patients with central NSCLC. Further randomized controlled trials are necessary to validate our findings.

Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer.

Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people. We aimed to examine the impact of the results of the TTF-1 immunostaining of tumor cells on the therapeutic effect of chemotherapy in Japanese patients with nonsq NSCLC. We examined the results of TTF-1 immunostaining and the clinical background of Japanese patients with nonsq NSCLC who received platinum-doublet chemotherapy at our hospital, from April 2009 to April 2021, and the correlation between regimens with or without pemetrexed in progression-free survival (PFS) and overall survival (OS). The efficacy of each regimen was then compared between TTF-1-positive and TTF-1-negative tumors. TTF-1 immunostaining was performed in 145 patients during the study period 92 were positive, and 53 were negative. A total of 24 patients presented with EGFRALK gene abnormality (16.6%). The PFS and OS of patients who were TTF-1-positive tended to be longer than those of the patients who were TTF-1-negative under either regimen. In other words, patients who were TTF-1-negative were frequently resistant to numerous chemotherapy drugs and experienced a poor prognosis under both regimens. The OS of patients who were TTF-1-positive and treated with the pemetrexed regimen was significantly longer than those on regimens without pemetrexed (963 vs. 412 days, HR 0.73 95% CI 0.55-0.96, The positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who have advanced nonsq NSCLC. Our analysis examined the possibility of a pemetrexed regimen leading to a longer prognosis in Asian patients who were TTF-1-positive for nonsq NSCLC, as shown in previous studies.

Mobocertinib (TAK-788) in

Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for

Survival and Functional Outcomes after Surgical Treatment for Spinal Metastasis in Patients with a Short Life Expectancy.

This study aimed to analyze the survival and functional outcome after surgery in spinal metastasis patients with a short life expectancy and to compare the baseline characteristics based on 3-month survival. A total of 492 surgical treatment cases with a preoperative revised Tokuhashi score

Surgical and Oncological Outcomes of En-Bloc Resection for Malignancies Invading the Thoracic Spine.

There is still limited data in the literature concerning the survival of patients with tumors of the thoracic spine. In this study, we analyzed clinical features, perioperative and long-term outcomes in patients who underwent vertebrectomy for cancer. Furthermore, we evaluated the survival and surgical complications. We retrospectively reviewed all cases of thoracic spinal tumors treated by the same team between 1998 and 2018. We divided them into three groups according to type of tumor (primary vertebral, primary lung and metastases) and compared outcomes. For each patient, Overall Survival (OS) and Cumulative Incidence of Relapse (CIR) were estimated. Complications and survival were analyzed using a logistic model. Seventy-two patients underwent thoracic spine surgery (40 in group 1, 16 in each group 2 and 3). Thirty patients died at the end of the observation at a mean follow up time of 60 months (41%). The 5-year overall survival was 72% (95% CI 0.52-0.84), 20% (95% CI 0.05-0.43) and 27% (95% CI 0.05-0.56) for each group, respectively. CIR of group 3 was higher (HR 2.57, 95% CI 1.22-5.45, Although the cohort size was limited, primary vertebral tumors displayed the best 5-y-OS with an acceptable complications rate. The indication of surgery should be advised by a multidisciplinary team and only for selected cases. Finally, the use of a combined approach does not increase the risk of complications.

α4-α5 Helices on Surface of KRAS Can Accommodate Small Compounds That Increase KRAS Signaling While Inducing CRC Cell Death.

KRAS is the most frequently mutated oncogene associated with the genesis and progress of pancreatic, lung and colorectal (CRC) tumors. KRAS has always been considered as a therapeutic target in cancer but until now only two compounds that inhibit one specific KRAS mutation have been approved for clinical use. In this work, by molecular dynamics and a docking process, we describe a new compound (P14B) that stably binds to a druggable pocket near the α4-α5 helices of the allosteric domain of KRAS. This region had previously been identified as the binding site for calmodulin (CaM). Using surface plasmon resonance and pulldown analyses, we prove that P14B binds directly to oncogenic KRAS thus competing with CaM. Interestingly, P14B favors oncogenic KRAS interaction with BRAF and phosphorylated C-RAF, and increases downstream Ras signaling in CRC cells expressing oncogenic KRAS. The viability of these cells, but not that of the normal cells, is impaired by P14B treatment. These data support the significance of the α4-α5 helices region of KRAS in the regulation of oncogenic KRAS signaling, and demonstrate that drugs interacting with this site may destine CRC cells to death by increasing oncogenic KRAS downstream signaling.

Drug Repurposing against KRAS Mutant G12C A Machine Learning, Molecular Docking, and Molecular Dynamics Study.

The Kirsten rat sarcoma viral G12C (KRAS

Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations A Case Report.

Epidermal growth factor receptor (

Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer.

Tumor cells have evolved to express immunosuppressive molecules allowing their evasion from the hosts immune system. These molecules include programmed death ligands 1 and 2 (PD-L1 and PD-L2). Cancer cells can also produce acetylcholine (ACh), which plays a role in tumor development. Moreover, tumor innervation can stimulate vascularization leading to tumor growth and metastasis. The effects of atropine and muscarinic receptor 3 (M3R) blocker, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), on cancer growth and spread were evaluated in vitro using murine colon cancer cell line, CT-26, and in vivo in an orthotopic mouse model of colorectal cancer. In the in vitro model, atropine and 4-DAMP significantly inhibited CT-26 cell proliferation in a dose dependent manner and induced apoptosis. Atropine attenuated immunosuppressive markers and M3R via inhibition of EGFRAKTERK signaling pathways. However, 4-DAMP showed no effect on the expression of PD-L1, PD-L2, and choline acetyltransferase (ChAT) on CT-26 cells but attenuated M3R by suppressing the phosphorylation of AKT and ERK. Blocking of M3R in vivo decreased tumor growth and expression of immunosuppressive, cholinergic, and angiogenic markers through inhibition of AKT and ERK, leading to an improved immune response against cancer. The expression of immunosuppressive and cholinergic markers may hold potential in determining prognosis and treatment regimens for colorectal cancer patients. This studys results demonstrate that blocking M3R has pronounced antitumor effects via several mechanisms, including inhibition of immunosuppressive molecules, enhancement of antitumor immune response, and suppression of tumor angiogenesis via suppression of the AKTERK signaling pathway. These findings suggest a crosstalk between the cholinergic and immune systems during cancer development. In addition, the cholinergic system influences cancer evasion from the hosts immunity.

Dosimetry Effects Due to the Presence of Fe Nanoparticles for Potential Combination of Hyperthermic Cancer Treatment with MRI-Based Image-Guided Radiotherapy.

Nanoparticles have proven to be biocompatible and suitable for many biomedical applications. Currently, hyperthermia cancer treatments based on Fe nanoparticle infusion excited by alternating magnetic fields are commonly used. In addition to this, MRI-based image-guided radiotherapy represents, nowadays, one of the most promising accurate radiotherapy modalities. Hence, assessing the feasibility of combining both techniques requires preliminary characterization of the corresponding dosimetry effects. The present work reports on a theoretical and numerical simulation feasibility study aimed at pointing out preliminary dosimetry issues. Spatial dose distributions incorporating magnetic nanoparticles in MRI-based image-guided radiotherapy have been obtained by Monte Carlo simulation approaches accounting for all relevant radiation interaction properties as well as charged particles coupling with strong external magnetic fields, which are representative of typical MRI-LINAC devices. Two main effects have been evidenced local dose enhancement (up to 60% at local level) within the infused volume, and non-negligible changes in the dose distribution at the interfaces between different tissues, developing to over 70% for low-density anatomical cavities. Moreover, cellular uptakes up to 10% have been modeled by means of considering different Fe nanoparticle concentrations. A theoretical temperature-dependent model for the thermal enhancement ratio (

Invadosome Formation by Lung Fibroblasts in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by abnormal fibroblast accumulation in the lung leading to extracellular matrix deposition and remodeling that compromise lung function. However, the mechanisms of interstitial invasion and remodeling by lung fibroblasts remain poorly understood. The invadosomes, initially described in cancer cells, consist of actin-based adhesive structures that coordinate with numerous other proteins to form a membrane protrusion capable of degrading the extracellular matrix to promote their invasive phenotype. In this regard, we hypothesized that invadosome formation may be increased in lung fibroblasts from patients with IPF. Public RNAseq datasets from control and IPF lung tissues were used to identify differentially expressed genes associated with invadosomes. Lung fibroblasts isolated from bleomycin-exposed mice and IPF patients were seeded with and without the two approved drugs for treating IPF, nintedanib or pirfenidone on fluorescent gelatin-coated coverslips for invadosome assays. Several matrix and invadosome-associated genes were increased in IPF tissues and in IPF fibroblastic foci. Invadosome formation was significantly increased in lung fibroblasts isolated from bleomycin-exposed mice and IPF patients. The degree of lung fibrosis found in IPF tissues correlated strongly with invadosome production by neighboring cells. Nintedanib suppressed IPF and PDGF-activated lung fibroblast invadosome formation, an event associated with inhibition of the PDGFRPI3KAkt pathway and TKS5 expression. Fibroblasts derived from IPF lung tissues express a pro-invadosomal phenotype, which correlates with the severity of fibrosis and is responsive to antifibrotic treatment.

Single-Cell Transcriptomics Unveils the Dedifferentiation Mechanism of Lung Adenocarcinoma Stem Cells.

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its prognosis is still poor due to therapy resistance, metastasis, and recurrence. In recent years, increasing evidence has shown that the existence of lung cancer stem cells is responsible for the propagation, metastasis, therapy resistance, and recurrence of the tumor. During their transition to cancer stem cells, tumor cells need to inhibit cell differentiation and acquire invasive characteristics. However, our understanding of the property and role of such lung cancer stem cells is still limited. In this study, lung adenocarcinoma cancer stem cells (LCSCs) were enriched from the PC-9 cell line in a serum-free condition. PC-9 cells grew into spheres and showed higher survival rates when exposed to gefitinib the drug used for the treatment of LUAD. Additionally, we found that the canonical stemness marker protein

Ladinin 1 Shortens Survival via Promoting Proliferation and Enhancing Invasiveness in Lung Adenocarcinoma.

Lung cancer is one of the deadliest cancers worldwide, including in Taiwan. The poor prognosis of the advanced lung cancer lies in delayed diagnosis and non-druggable targets. It is worth paying more attention to these ongoing issues. Public databases and an in-house cohort were used for validation. The KM plotter was utilized to discover the clinical significance. GSEA and GSVA were adopted for a functional pathway survey. Molecular biological methods, including proliferation, migration, and the EMT methods, were used for verification. Based on public databases, the increased expression of Ladinin 1 (LAD1) was presented in tumor and metastatic sites. Furthermore, an in-house cohort revealed a higher intensity of LAD1 in tumor rather than in normal parts. The greater the expression of LAD1 was, the shorter the duration of lung adenocarcinoma (LUAD) patient survival. Moreover, the association of B3GNT3 with LAD1 affected the survival of LUAD patients. Functional analyses using GSEA and GSVA revealed the associations with survival, migration, invasion, and EMT. Biologic functions supported the roles of LAD1 in proliferation via the cell cycle and migration in EMT. This study reveals that LAD1 plays a major role in regulating proliferation and migration in lung cancer and impacts survival in LUAD. It is worth investing in further studies and in the development of drugs targeting LAD1.

Prognostic and Immunological Implications of FAM72A in Pan-Cancer and Functional Validations.

The family with sequence similarity 72 Member A (FAM72A) is overexpressed in several types of cancer. However, its contributions to tumorigenesis remain largely unknown. Based on The Cancer Genome Atlas (TCGA) database, FAM72A was upregulated across 33 types of cancer. Accordingly, high levels of FAM72A predicted inferior outcomes in half of the cancer types using survival analysis (the Kaplan-Meier curve and univariate Cox regression model). Receiver operating characteristic (ROC) analysis demonstrated that FAM72A showed high accuracy in distinguishing cancerous tissues from normal ones. FAM72A was correlated with immune and stromal scores and immune cell infiltrations in various tumors. Moreover, FAM72A was also associated with tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes. Immunophenoscore (IPS) further validated that the FAM72A