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Medical image instance segmentation from candidate region to no candidate region.

In recent years, the task of object detection and segmentation in medical image is the research hotspot and difficulty in the field of image processing. Instance segmentation provides instance-level labels for different objects belonging to the same class, so it is widely used in the field of medical image processing. In this paper, medical image instance segmentation was summarized from the following aspects First, the basic principle of instance segmentation was described, the instance segmentation models were classified into three categories, the development context of the instance segmentation algorithm was displayed in two-dimensional space, and six classic model diagrams of instance segmentation were given. Second, from the perspective of the three models of two-stage instance segmentation, single-stage instance segmentation and three-dimensional (3D) instance segmentation, we summarized the ideas of the three types of models, discussed the advantages and disadvantages, and sorted out the latest developments. Third, the application status of instance segmentation in six medical images such as colon tissue image, cervical image, bone imaging image, pathological section image of gastric cancer, computed tomography (CT) image of lung nodule and X-ray image of breast was summarized. Fourth, the main challenges in the field of medical image instance segmentation were discussed and the future development direction was prospected. In this paper, the principle, models and characteristics of instance segmentation are systematically summarized, as well as the application of instance segmentation in the field of medical image processing, which is of positive guiding significance to the study of instance segmentation. 医学图像中目标的检测和分割任务是近年来图像处理领域中的研究热点和难点。实例分割为属于同一类的不同对象提供实例级标签，因此广泛应用于医学图像处理领域。本文对医学图像实例分割从以下几个方面进行总结：第一，阐述实例分割的基本原理，将实例分割模型归纳为三类，并采用二维空间展示实例分割算法发展脉络，给出六个实例分割经典模型图；第二，从两阶段实例分割、单阶段实例分割以及三维（3D）实例分割三类模型的角度出发，分别总结三类模型的思想，探讨优缺点和梳理最新发展；第三，总结了实例分割在结肠组织图像、宫颈图像、骨显像图像、胃癌病理切片图像、肺结节计算机断层扫描图像和乳腺X线片图像等六种医学图像的应用现状；第四，讨论当前医学图像实例分割领域面对的主要挑战，并展望未来的发展方向。本文系统总结实例分割的原理、模型、特点，以及实例分割在医学图像处理领域中的应用，对实例分割的研究具有积极的指导意义。.

Circ0006220 Contributes to NSCLC Progression through miR-342-3pGOT2 Axis.

Dysregulated circular RNAs (circRNAs) have shown crucial modulatory functions in tumorigenesis, containing non-small cell lung cancer (NSCLC). The purpose of this study was to explore the biological functions and regulatory theory of circ0006220 in NSCLC. Reverse transcription-quantitative polymerase chain reaction and Western blot assay were conducted to measure RNA and protein expression, respectively. A total of 73 cases of NSCLC tumor samples were collected for expression analysis, and A-549 and NCI-H1299 cell lines were used for functional experiments. Cell proliferation was assessed by cell counting kit-8 assay, colony formation assay, 5-ethynyl-2-deoxyuridine assay, and flow cytometry. Cell apoptosis, motility, and angiogenesis ability were analyzed by flow cytometry, transwell assays, and capillary-like network formation assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the target relationships. Circ0006220 was highly expressed in NSCLC tissues and cell lines. Circ0006220 silencing inhibited the proliferation, migration, invasion, and angiogenesis but induced the apoptosis of NSCLC cells. Circ0006220 acted as a microRNA-342-3p (miR-342-3p) sponge, and circ0006220 knockdown-induced changes on the phenotypes of NSCLC cells were largely overturned by the knockdown of miR-342-3p. miR-342-3p interacted with the 3 untranslated region of glutamic-oxaloacetic transaminase 2 (GOT2), and GOT2 overexpression largely diminished miR-342-3p overexpression-mediated influences in NSCLC cells. Circ0006220 could up-regulate GOT2 expression by sponging miR-342-3p. Circ0006220 promoted the malignant behaviors of NSCLC cells through mediating the miR-342-3pGOT2 regulation cascade.

The ectonucleotidase CD39 identifies tumor-reactive CD8

Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8

Bioprosthetic heart valve structural degeneration associated with metabolic syndrome Mitigation with polyoxazoline modification.

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer.

Cancer is one of the most serious malignant diseases, and chemotherapy is cancers main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlics active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC

Molecular Pathways and Mechanisms of HER2 in Cancer Therapy.

The oncogene ERBB2 encoding the receptor tyrosine-protein kinase erbB-2 (HER2) is frequently overexpressed or amplified and occasionally mutated in a variety of human cancers. The early discovery of this oncogene, its established oncogenic relevance in diverse cancers, its substantial expression on surface of cancer cells, and its druggable catalytic activity have made it one of the most pursued targets in the history of cancer drug development. Initiatives targeting HER2 provided the early stimulus for several transformational pharmaceutical technologies including monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, and others. The seismic impact of these efforts has been felt in treatment of many cancers including breast, gastroesophageal, lung, colorectal and others. This impact continues to broaden with increasing indications on the horizon and a plethora of novel agents in development. However, implementation of these therapeutic strategies has been complex. The clinical translation of every one of these classes of agents has been notable for underperformance or overperformance characteristics that have informed new lines of research providing deeper insights into the mechanistic complexities and unrealized opportunities provided by this molecular target. Despite all the successes to date, the preponderance of scientific evidence indicates that the full potential of HER2 as a target for cancer therapeutics is far greater than currently realized and numerous lines of investigation are ongoing to deepen and broaden the scope of impact of HER2 as a signaling, homing, or immunologic target. In this review, we explore the existing data and evolving paradigms surrounding this remarkable target for cancer therapy.

Challenges in the Diagnosis of Epstein-Barr Virus-positive Inflammatory Follicular Dendritic Cell Sarcoma Extremely Wide Morphologic Spectrum and Immunophenotype.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. Here, we investigated the wide morphologic spectrum and immunophenotype of this tumor with the aim to help avoid misdiagnosis. Thirteen cases of EBV IFDCS were retrospectively analyzed, combined with a review of 70 cases reported in the literature. The median age of patients was 49 (range, 29 to 67 y). Six patients were male and 7 were female. Most cases (92.3%, 1213) occurred in the liver or spleen, and only 1 case affected an extra-hepatosplenic site (lung, 7.7%, 113). Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups classic type (53.8%, 713), lymphoma-like subtype (38.5%, 513), and hemangioma-like subtype (7.7%, 113). The classic type had distinct EBV-positive neoplastic cells with a fascicular or storiform growth pattern, variable lymphoplasmacytic infiltrates, and blood vessels. The lymphoma-like subtype had extremely prominent lymphoplasmacytic infiltrates (resembling marginal zone lymphoma with plasmacytoid differentiation) with singly dispersed distinct EBV-positive neoplastic cells, highlighted by in situ hybridization for EBV-encoded small RNA. The hemangioma-like subtype had extremely prominent blood vessels with hyaline andor fibrinoid degeneration, singly dispersed distinct EBV-positive neoplastic cells, and limited lymphoplasmacytic infiltrates. Immunohistochemically, the neoplastic cells showed variable staining for FDC markers (CD21, CD35, CD23, and SSTR2) and the fibroblastic marker SMA, with the staining ranging from very focal to extensive. The number of EBV-positive neoplastic cells ranged from 80 to 400HPF. All cases showed variable expression of PD-ligand 1 (PD-L1) (CPS 5-90). IgG4-positive cells ranged from rare up to 100HPF. Interestingly, 2 cases satisfied the criteria proposed in a previous study, mimicking IgG4-related disease. EBV IFDCS is an entity with an extremely wide morphologic spectrum and immunophenotype. Awareness of the spectrum of morphologic presentations of this rare tumor, specifically the lymphoma-like subtype and hemangioma-like subtype, is important for accurate diagnosis.

Dual-AND Logic Gate-Based Strip Assay for Amplified Detection of Four miRNAs and Diagnosis of Lung Cancer.

The detection of circulating tumor microRNAs (miRNAs) holds great promise for the noninvasive and early-stage diagnosis of cancer. However, the low abundance of lung cancer-related miRNAs and the false-positive results of single miRNA detection limited the development of strip-based point-of-care testing methods in clinic. We developed a duplex-specific nuclease (DSN)-mediated and dual-AND logic gate-based triple-line lateral flow strip detection system for the rapid and simultaneous detection of four miRNAs of lung cancer in a single strip test. This system combines DSN-mediated signal amplification with AND logic gate-based simple signal output. Meanwhile, the limit of detection of this platform was calculated to be 26.51 fM. Furthermore, this assay was used to detect lung cancer-related miRNAs from serum in a homogeneous and separation-free format, which could discriminate lung cancer patients from healthy individuals with an accuracy of 100%. Our approach provides a simple and easy-to-handle method for the diagnosis of lung cancer in clinic.

Tetrakis(4-pyridylphenyl)ethylene-based Zinc Metal-Organic Framework with Aggregation-Induced Chemiluminescence Emission on a Paper Platform for Formaldehyde Detection in Breath.

Volatile formaldehyde (FA) in exhaled breath (EB) is considered as a biomarker for lung cancer (LC). On-the-spot selective and sensitive detection of gaseous FA is rather important for LC screening and diagnosis. Herein, a tetrakis(4-pyridylphenyl)ethylene (Py-TPE)-based zinc metal-organic framework (MOF) with excellent aggregation-induced emission (AIE) property was utilized for absorption and selective detection of FA in EB. The porous Zn-Py-TPE served as a gaseous confinement cavity for the adsorption of FA in EB. Interestingly, Zn-Py-TPE was aggregated on paper, and then aggregation-induced chemiluminescence (CL) emission can be triggered by only adding bis(2,4,6-trichlorophenyl)oxalate (TCPO). Though without H

Receipt of follow-up care plans on colorectal cancer screening among breast, prostate, and lung cancer survivors.

Our study aimed to examine whether receipt of follow-up care plans is associated with greater guideline-concordant CRC screening stratified by breast, prostate, and lung cancer survivors. We used data from years 2016, 2018, and 2020 of the Behavioral Risk Factor Surveillance System on 3339 eligible treatment-utilizing cancer survivors with complete treatment. We performed descriptive statistics and multivariable logistic regression to examine the mentioned association. We observed that 83.9% of breast and 88.2% of prostate cancer survivors with follow-care plans received CRC screening (p-value < 0.001). The lowest CRC screening use was observed among lung cancer (70.8%). In multivariable analysis, receipt of follow-up care plans was strongly associated with greater odds of receiving CRC screening in breast (OR, 2.67 95% CI 1.71-4.16) and prostate (OR, 3.81 95% CI 2.30-6.31) cancer survivors. Regardless of provider type, 84 to 88% reduced likelihood of receipt of CRC screening when they received follow-up care plans among lung cancer survivors. Among those without follow-up care plans, breast (OR, 0.29 95% CI 0.09-0.92) and lung (OR, 0.05 95% CI 0.01-0.25) cancer survivors who received care from general practices were less likely to receive CRC screening compared to those who received care from non-general practices. Receipt of follow-up care plans was associated with greater CRC screening use in breast and prostate cancers. Lung cancer survivors demonstrated lower screening use despite receipt of follow-up care plans. Patient and provider communication regarding CRC screening recommendation should be included in their follow-up care plans.

Untargeted metabolomics and lipidomics identified four subtypes of small cell lung cancer.

Small cell lung cancer (SCLC) is a heterogeneous malignancy with dismal prognosis. However, few studies have conducted on the metabolic heterogeneity in SCLC. We therefore identify SCLC classifications using untargeted metabolomics and lipidomics. We also compared their survival and the immunotherapy responses. Liquid Chromatography-Mass SpectrometryMass Spectrometry (LC-MSMS) analysis was performed in 191 SCLC serum samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to identify metabolic pathways. The Kaplan-Meier and log-rank test were used to analyze the survival curves. The univariate and multivariate Cox proportional hazards regression models were used to evaluate prognostic factors for OS in patients with SCLC. Distinct subtypes of SCLC were identified by consensus clustering algorithm using partioning around medoids (pam) based on untargeted metabolomics and lipidomics. Four distinct subtypes of SCLC were identified, with distinct metabolic pathways. Subgroup 2 had the longest survival whereas Subgroup 1 had the shortest. Subtype 2 benefited most from immunotherapy in OS, as in contrast to Subtype 3 with shortest survival. Our study revealed the metabolic heterogeneity in SCLC and identified four subtypes with distinct metabolic features. It indicates promising therapeutic and prognostic value that may guide treatment for SCLC. The subtype-specific clinical trials may be designed and would be instructive for drug development.

circTAB2 inhibits lung cancer proliferation, migration and invasion by sponging miR-3142 to upregulate GLIS2.

Circular RNAs (circRNAs) are a specialized circular structure, are deregulated in cancers and play essential roles in biological processes involved in tumor progression. However, the mechanism by which circRNAs affect lung tumorigenesis and progression remains largely unexplored. To investigate the role of circRNA in lung cancer, circRNA expression profile was screened by bioinformatics analysis. The levels of circTAB2, miR-3142, and GLIS family zinc finger 2 (GLIS2) were measured by quantitate real-time (qRT-PCR) or western blot. Cell proliferation, apoptosis, migration and invasion were detected by EdU, flow cytometry, and transwell assays, respectively. Bioinformatics, western blot, RIP, pull down, dual luciferase reporter and rescue experiments were used to verify the direct relationship between miR-3142 and circTAB2 or GLIS2. The xenograft assays were used to assess the role of circTAB2 in vivo.CircTAB2 exhibited low expression in cancer tissues. Gain and loss-of-function assays indicated that circTAB2 could inhibit cell proliferation, migration and invasion. Functional studies revealed that circTAB2 acted as a miRNA sponge, directly interacted with miR-3142 and consequently regulated GLIS2 AKT. Taken together, circTAB2 serves as an inhibitory role in lung cancer through a novel circTAB2 miR-3142 GLIS2 AKT pathway and could be exploited a novel marker in lung cancer.

Establishing a metastasis-related diagnosis and prognosis model for lung adenocarcinoma through CRISPR library and TCGA database.

Existing biomarkers for diagnosing and predicting metastasis of lung adenocarcinoma (LUAD) may not meet the demands of clinical practice. Risk prediction models with multiple markers may provide better prognostic factors for accurate diagnosis and prediction of metastatic LUAD. An animal model of LUAD metastasis was constructed using CRISPR technology, and genes related to LUAD metastasis were screened by mRNA sequencing of normal and metastatic tissues. The immune characteristics of different subtypes were analyzed, and differentially expressed genes were subjected to survival and Cox regression analyses to identify the specific genes involved in metastasis for constructing a prediction model. The biological function of RFLNA was verified by analyzing CCK-8, migration, invasion, and apoptosis in LUAD cell lines. We identified 108 differentially expressed genes related to metastasis and classified LUAD samples into two subtypes according to gene expression. Subsequently, a prediction model composed of eight metastasis-related genes (RHOBTB2, KIAA1524, CENPW, DEPDC1, RFLNA, COL7A1, MMP12, and HOXB9) was constructed. The areas under the curves of the logistic regression and neural network were 0.946 and 0.856, respectively. The model effectively classified patients into low- and high-risk groups. The low-risk group had a better prognosis in both the training and test cohorts, indicating that the prediction model had good diagnostic and predictive power. Upregulation of RFLNA successfully promoted cell proliferation, migration, invasion, and attenuated apoptosis, suggesting that RFLNA plays a role in promoting LUAD development and metastasis. The model has important diagnostic and prognostic value for metastatic LUAD and may be useful in clinical applications.

More than conquerors a qualitative analysis of war metaphors for patients with cancer.

Meaning-making is fundamental to the cancer experience and communication within cancer care is saturated with metaphors. The objective of this study was to better understand the impact and function of war metaphors among patients with cancer. Patients at the Duke Cancer Center were purposively sampled for inclusion based on type and stage of their cancer. Each patient underwent a semi-structured interview to explore their use of metaphors in their lived experience with cancer. Qualitative interviews broadly explored two key areas of interest (1) frequency and use of metaphors to describe cancer diagnosis, treatment, or survivorship (2) function and impact of the war metaphor on the patient experience of cancer. Fifteen participants with either breast, lung, or colorectal cancer were interviewed. Most patients used metaphor themes of journey, war, and mystery to describe their cancer. All patients with non-metastatic disease used war metaphors and described how these metaphors facilitated meaning-making by promoting positivity and situating cancer within a larger life story. The few patients who did not use war metaphors had metastatic disease, and they explained that war metaphors were unhelpful due to feeling a lack of control over their metastatic disease and outcomes. The war metaphor should remain an integral part of cancer care. Disregarding war metaphors robs patients of an important framework for meaning-making-one that may promote strength, continuity, and resilience in navigating cancer.

A network-based dynamic criterion for identifying prediction and early diagnosis biomarkers of complex diseases.

Lung adenocarcinoma (LUAD) seriously threatens human health and generally results from dysfunction of relevant module molecules, which dynamically change with time and conditions, rather than that of an individual molecule. In this study, a novel network construction algorithm for identifying early warning network signals (IEWNS) is proposed for improving the performance of LUAD early diagnosis. To this end, we theoretically derived a dynamic criterion, namely, the relationship of variation (RV), to construct dynamic networks. RV infers correlation Formula see text statistics to measure dynamic changes in molecular relationships during the process of disease development. Based on the dynamic networks constructed by IEWNS, network warning signals used to represent the occurrence of LUAD deterioration can be defined without human intervention. IEWNS was employed to perform a comprehensive analysis of gene expression profiles of LUAD from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The experimental results suggest that the potential biomarkers selected by IEWNS can facilitate a better understanding of pathogenetic mechanisms and help to achieve effective early diagnosis of LUAD. In conclusion, IEWNS provides novel insight into the initiation and progression of LUAD and helps to define prospective biomarkers for assessing disease deterioration.

Barriers to Screening At-risk Populations in Canada.

Cancer screening is invaluable for early detection of disease, including for breast and lung cancer. Through early detection, cancer treatment can be commenced prior to the development of advanced stage disease, significantly reducing morbidity and mortality. However, eligible patients may face barriers when accessing screening services, and some groups may be more disproportionately affected than others. This review aims to describe some of the most prominent barriers that at-risk populations may face when accessing image-based cancer screening services in Canada. Characterizing these barriers would be helpful in determining the best strategies to increase uptake to these screening services and, consequently, improve health equity.

Lung cancer screening in primary care.

This article reviews the evidence supporting low-dose CT to screen for lung cancer, and the risks, costs, and challenges of implementing broad-based screening for eligible patients. Increased familiarity with lung cancer screening guidelines by primary care and specialty clinicians presents an opportunity to improve lung cancer screening rates and to save lives from the most common cause of cancer death in the United States.

Interpretation of Lung Cancer Plasma EGFR Mutation Tests in the Clinical Setting.

Comprehensive data synthesis of the clinical parameters that affect plasma EGFR mutation test results in non-small cell lung carcinoma is lacking. Although individual studies have suggested a variety of patient characteristics that can affect diagnostic accuracy, no unified conclusion has been reached. We analyzed 170 plasma EGFR mutation tests performed between 2015 and 2021 at our institution and carried out a systematic review and meta-analysis to identify clinical and imaging features that correlate with plasma EGFR mutation test sensitivity. Data synthesis from 14 studies of 2,576 patients revealed that patients with stage IV disease had a significantly lower false-negative rate than those with stage I through III disease. For our institutional cohort, which consisted of 75 paired plasma and tissue tests that were assessable for diagnostic accuracy, the overall sensitivity was 70.59% (95% confidence interval, 56.17%-82.51%). Patients who had distant metastases and more suspicious lymph nodes on imaging findings correlated with a low false-negative rate. While interpreting plasma EGFR mutation results, extra caution should be exercised for patients with early-stage, localized disease to accommodate the possibility of false-negative results. These meta-analyses and clinical data may enable clinicians to make evidence-based judgments for individual patients.

Comparing Thoracoscopic and Robotic Lobectomy Using a Nationally Representative Database.

Studies of robotic lobectomy (Robot-L) have been performed using data from high-volume, specialty centers which may not be generalizable. The purpose of this study was to compare mortality, length of stay (LOS), and cost between Robot-L and thoracoscopic lobectomy (VATS-L) using a nationally representative database hypothesizing they would be similar. The Premier Healthcare Database was used to identify patients receiving elective lobectomy for lung cancer from 2009 to 2019. Patients were categorized as receiving Robot-L or VATS-L using ICD-910 codes. Survey methodology and patient level weighting were used to correct for sampling error and estimation of a nationally representative sample. A propensity match analysis was performed to reduce bias between the groups. Primary outcome of interest was in-hospital mortality. Secondary outcomes were LOS and patient charges. Among 62 698 patients, 19 506 (31.1%) underwent Robot-L and 43 192 (68.9%) underwent VATS-L. Differences between the groups included age, race, comorbidities, and insurance type. A propensity matched cohort demonstrated similar in-hospital mortality for Robot-L and VATS-L (.9% vs .9%, respectively, In a nationally representative database, Robot-L and VATS-L had similar mortality. Although Robot-L was associated with shorter hospitalization, it was also associated with excess charges of almost $20,000. As Robot-L is now the most common approach for lobectomy in the U.S., further study into the cost and benefit of robotic surgery is warranted.

The Effect of Body Mass Index on Survival in Lung Cancer.

The prognostic significance of body mass index in lung cancer and the direction of this relationship are not yet clear. This study aimed to evaluate the relationship between BMI and overall survival time of advanced-stage lung cancer patients treated in a center in Turkey, a developing country. In this study, the data of 225 patients diagnosed with stage III or stage IV lung cancer between 2016 and 2020 were analyzed. The effects of BMI and other variables on survival were examined by Cox regression analysis for NSCLC and SCLC. For NSCLC and SCLC, being underweight compared to the normal group, being diagnosed at a more advanced stage, and having a worse performance score were associated with a significantly higher risk of death. Other variables significantly associated with survival were gender, type of radiotherapy for NSCLC, age group, and family history for SCLC. This study showed that being underweight relative to the normal group was associated with worse survival for NSCLC and SCLC but did not support the obesity paradox. Studies that are representative of all BMI categories and free of bias are needed to understand the BMI-lung cancer survival relationship clearly.

Circular RNA hsacirc0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.

The study aimed to explore the effect of circ0008003 on the progression of non-small-cell lung cancer (NSCLC) and its underlying regulation mechanism. Expression of hsacirc0008003, miRNA (miR)-548I and karyopherin subunit α 4 (KPNA4) was examined by quantitative real-time polymerase chain reaction. Cell viability and proliferation ability were detected by cell counting kit-8 assay and 5-ethynyl-2-deoxyuridine assay, respectively. Flow cytometry was performed to monitor cell apoptosis. Western blot assay was used to evaluate the protein levels of KPNA4, Bax, and Bcl-2. Cell migration and invasion were assessed by transwell assays. The targeted relationship between miR-548I and hsacirc0008003 or KPNA4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Furthermore, the role of hsacirc0008003 in vivo was investigated by xenograft assay. Circ0008003 expression was increased in NSCLC tissues and cell lines. Circ0008003 knockdown reduced cell viability, migration, invasion, angiogenesis, and caused apoptosis in NSCLC cells. Moreover, miR-548I was targeted by circ0008003, and miR-548I knockdown reversed the influence of circ0008003 silence on NSCLC progression. KPNA4 was targeted by miR-548I, and miR-548I overexpression suppressed cell viability, migration, invasion, angiogenesis, and promoted cell apoptosis via decreasing KPNA4. In addition, circ0008003 regulated KPNA4 expression via miR-548I. Circ0008003 knockdown decreased NSCLC cell growth in the xenograft model. Circular RNA hsacirc0008003 promoted progression in NSCLC by sponging miR-548I and regulating KPNA4 expression, hinting that circ0008003 participates in NSCLC pathogenesis.

Lung Cancer Screening Using Clinical Photon-Counting Detector Computed Tomography and Energy-Integrating-Detector Computed Tomography A Prospective Patient Study.

To evaluate the diagnostic quality of photon-counting detector (PCD) computed tomography (CT) in patients undergoing lung cancer screening compared with conventional energy-integrating detector (EID) CT in a prospective multireader study. Patients undergoing lung cancer screening with conventional EID-CT were prospectively enrolled and scanned on a PCD-CT system using similar automatic exposure control settings and reconstruction kernels. Three thoracic radiologists blinded to CT system compared PCD-CT and EID-CT images and scored examinations using a 5-point Likert comparison score (-2 left image is worse to 2 left image is better) for artifacts, sharpness, image noise, diagnostic image quality, emphysema visualization, and lung nodule evaluation focusing on the border. Post hoc correction of Likert scores was performed such that they reflected PCD-CT performance in comparison to EID-CT. A nonreader radiologist measured objective image noise. Thirty-three patients (mean, 66.9 ± 5.6 years 11 female body mass index 30.1 ± 5.1 kgm 2 ) were enrolled. Mean volume CT dose index for PCD-CT was lower (0.61 ± 0.21 vs 0.73 ± 0.22 P < 0.001). Pooled reader results showed significant differences between imaging modalities for all comparative rankings ( P < 0.001), with PCD-CT favored for sharpness, image noise, image quality, and emphysema visualization and lung nodule border, but not artifacts. Photon-counting detector CT had significantly lower image noise (74.4 ± 10.5 HU vs 80.1 ± 8.6 HU P 0.048). Photon-counting detector CT with similar acquisition and reconstruction settings demonstrated improved image quality and less noise despite lower radiation dose, with improved ability to depict pulmonary emphysema and lung nodule borders compared with EID-CT at low-dose lung cancer CT screening.

Commissioning and performance evaluation of commercially available mobile imager for image guided total body irradiation.

The setup of lung shield (LS) in total body irradiation (TBI) with the computed radiography (CR) system is a time-consuming task and has not been quantitatively evaluated. The TBI mobile imager (TBI-MI) can solve this problem through real-time monitoring. Therefore, this study aimed to perform commissioning and performance evaluation of TBI-MI to promote its use in clinical practice. The source-axis distance in TBI treatment, TBI-MI (CNERGY TBI, Cablon Medical B.V.), and the LS position were set to 400, 450, and 358 cm, respectively. The evaluation items were as follows accuracy of image scaling and measured displacement error of LS, image quality (linearity, signal-to-noise ratio, and modulation transfer function) using an EPID QC phantom, optimal thresholding to detect intra-fractional motion in the alert function, and the scatter radiation dose from TBI-MI. The accuracy of image scaling and the difference in measured displacement of the LS was <4 mm in any displacements and directions. The image quality of TBI imager was slightly inferior to the CR image but was visually acceptable in clinical practice. The signal-to-noise ratio was improved at high dose rate. The optimal thresholding value to detect a 10-mm body displacement was determined to be approximately 5.0%. The maximum fraction of scattering radiation to irradiated dose was 1.7% at patient surface. MI-TBI can quantitatively evaluate LS displacement with acceptable image quality. Furthermore, real-time monitoring with alert function to detect intrafraction patient displacement can contribute to safe TBI treatment.

Mitochondrial fusion and fission were identified to play key roles during multiple biology process. Thus, we aim to investigate the roles of OPA1 in mitochondria fusion and immune evasion of non-small cell lung cancer cells. The transcriptional activation of genes related to mitochondrial dynamics was determined by using multi-omics data in lung adenocarcinoma (LUAD). We elucidated the molecular mechanism and roles of OPA1 promoting lung cancer through single-cell sequencing and molecular biological experiments. Here, we found that copy number amplification of Our study demonstrated the high co-occurrence of copy number amplification and co-expression of

Pancancer Analysis of the Prognostic and Immunotherapeutic Value of Progestin and AdipoQ Receptor 4.

AdipoQ receptor 4 (PAQR4) belongs to the family of progestin and AdipoQ receptors. PAQR4 plays an oncogenic role in lung and breast cancer. However, systematic pancancer analyses of PAQR4 have not been performed. The purpose was to investigate the prognostic and immunological significance of PAQR4 across 31 tumor types. Data were obtained from the following sources TCGA, GEO, UALCAN, TIMER, GEPIA2, KM plotter, and TISIDB databases. The results proved that PAQR4 expression was significantly elevatory in most cancer types. We then explored the utility of PAQR4 as a prognostic indicator across all cancers. Using Cox proportional risk regression models, it has been demonstrated that PAQR4 is an independent risk factor in. High PAQR4 expression was not associated with other prognostic indicators, including overall survival, disease-free interval, disease-specific survival, and progression-free period. Subsequently, we explored the immunological value of PAQR4 and found that PAQR4 expression significantly correlated with tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoint genes in tumors. It also significantly negatively correlated with most tumors ESTIMATE scores, indicating that PAQR4 can influence the cellular composition of the tumor microenvironment. Our findings suggest the immunotherapeutic potential of PAQR4 in tumors. Finally, we explored the role of PAQR4 in tumor drug resistance and found that PAQR4 expression affected the sensitivity to multiple chemotherapeutic agents. A significant role for PAQR4 in tumor immunity is evident in these studies, as well as its potential role in cancer diagnosis, prognosis, and treatment precision.

Adult Pancreatoblastoma Report of 3 new Cases With Genetic Diversity and Autopsy Findings.

We report the histopathological, immunohistochemical (IHC), and molecular findings in 3 patients with adult pancreatoblastoma, including 2 with autopsy features. The tumors were located in the tail and body of the pancreas, and the 2 autopsy examinations revealed liver and lung metastases. Histopathologically the neoplasms were composed of solid epithelial elements with nested or trabecular growth patterns, fibrous stroma, and squamoid clusters. Keratin 19 was positive mainly in squamoid corpuscles, and trypsin or chymotrypsin was positive in the acinar component. Neuroendocrine differentiation was observed in all tumors, and nuclear β-catenin expression in 2 tumors. Despite nuclear β-catenin expression,

The Role of Myeloid-Derived Suppressor Cells in the Treatment of Pancreatic Cancer.

Pancreatic cancer has the highest mortality rate of all major cancers, with a 5-year survival rate of about 10%. Early warning signs and symptoms of pancreatic cancer are vague or nonexistent, and most patients are diagnosed in Stage IV, when surgery is not an option for about 80%-85% of patients. For patients with inoperable pancreatic cancer, current conventional treatment modalities such as chemotherapy and radiotherapy (RT) have suboptimal efficacy. Tumor progression is closely associated with the tumor microenvironment, which includes peripheral blood vessels, bone marrow-derived inflammatory cells, fibroblasts, immune cells, signaling molecules, and extracellular matrix. Tumor cells affect the microenvironment by releasing extracellular signaling molecules, inducing peripheral immune tolerance, and promoting tumor angiogenesis. In turn, the immune cells of the tumor affect the survival and proliferation of cancer cells. Myeloid-derived suppressor cells are key cellular components in the tumor microenvironment and exert immunosuppressive functions by producing cytokines, recognizing other immune cells, and promoting tumor growth and metastasis. Myeloid-derived suppressor cells are the main regulator of the tumor immune response and a key target for tumor treatments. Since the combination of RT and immunotherapy is the main strategy for the treatment of pancreatic cancer, it is very important to understand the immune mechanisms which lead to MDSCs generation and the failure of current therapies in order to develop new target-based therapies. This review summarizes the research advances on the role of Myeloid-derived suppressor cells in the progression of pancreatic cancer and its treatment application in recent years.

LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma.

Although many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear. TCGA, GEO, K-M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3. The expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance. LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD.

An overview of the role of selpercatinib and pralsetinib in RET-fusion-positive non-small cell lung cancer (NSCLC).

Selpercatinib and pralsetinib are new targeted therapies used to treat patients with non-small cell lung cancer (NSCLC) due to RET gene rearrangements. The objective of this article is to review selpercatinib and pralsetinib in the context of RET-fusion-positive NSCLC. The pivotal LIBRETTO-001 and ARROW trials were evaluated regarding the use of selpercatinib and pralsetinib as treatment for RET-fusion-positive NSCLC. Comparative studies, review articles and current studies on selpercatinib and pralsetinib in RET-fusion-positive NSCLC were searched on pubmed.org and scholar.google.com using selpercatinib, pralsetinib, and NSCLC as keywords. Product monographs were searched on google.ca and uptodate.com using the keywords selpercatinib, pralsetinib, andor monograph. Selpercatinib and pralsetinib are orally administered highly selective RET inhibitors approved by the FDA following the accelerated approvals granted due to the pivotal LIBRETTO-001 and ARROW trials which evaluated selpercatinib and pralsetinib, respectively. Both drugs have shown efficacy for brain metastases and are primarily metabolized by CYP3A4 through hepatic metabolism. The most common grade 3 or 4 adverse effects of selpercatinib were hypertension, increased ALT level, and increased AST level while for pralsetinib, it was neutropenia, hypertension, and anemia. The safety profile shows similarities in severity and tolerability but additional monitoring for QT prolongation in patients on selpercatinib is recommended, compared to the risks of interstitial lung disease or pneumonitis for patients on pralsetinib. Overall, the increased use of selpercatinib and pralsetinib has led to the implementation of these drugs in the clinical practice of healthcare professionals such as pharmacists.

Brain parenchymal and leptomeningeal metastasis in non-small cell lung cancer.

Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p < 0.0001). The median time to the onset of PM and LM from the diagnosis of advanced NSCLC was 0 months and 8.3 months, respectively. Patients with LM had a statistically shorter over survival (OS) compared to either No-BM or PM patients (p < 0.0001). Based on independent predictive variables, two nomogram models were constructed to predict the development of PM and LM in advanced NSCLC patients, and the C-indexes were 0.656 and 0.767, respectively. Although both considered as BM, PM and LM had different clinical characteristics. And the nomogram showed good performance in predicting LM development, but not PM.

3D collagen migration patterns reveal a SMAD3-dependent and TGF-β1-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma.

The TGF-β1 transcription factor SMAD3 is epigenetically repressed in tumour-associated fibroblasts (TAFs) from lung squamous cell carcinoma (SCC) but not adenocarcinoma (ADC) patients, which elicits a compensatory increase in SMAD2 that renders SCC-TAFs less fibrotic. Here we examined the effects of altered SMAD23 in fibroblast migration and its impact on the desmoplastic stroma formation in lung cancer. We used a microfluidic device to examine descriptors of early protrusions and subsequent migration in 3D collagen gels upon knocking down SMAD2 or SMAD3 by shRNA in control fibroblasts and TAFs. High SMAD3 conditions as in shSMAD2 fibroblasts and ADC-TAFs exhibited a migratory advantage in terms of protrusions (fewer and longer) and migration (faster and more directional) selectively without TGF-β1 along with Erk12 hyperactivation. This enhanced migration was abrogated by TGF-β1 as well as low glucose medium and the MEK inhibitor Trametinib. In contrast, high SMAD2 fibroblasts were poorly responsive to TGF-β1, high glucose and Trametinib, exhibiting impaired migration in all conditions. The basal migration advantage of high SMAD3 fibroblasts provides a straightforward mechanism underlying the larger accumulation of TAFs previously reported in ADC compared to SCC. Moreover, our results encourage using MEK inhibitors in ADC-TAFs but not SCC-TAFs.

A reverse phase protein array based phospho-antibody characterization approach and its applicability for clinical derived tissue specimens.

Systematic quantification of phosphoprotein within cell signaling networks in solid tissues remains challenging and precise quantification in large scale samples has great potential for biomarker identification and validation. We developed a reverse phase protein array (RPPA) based phosphor-antibody characterization approach by taking advantage of the lysis buffer compatible with alkaline phosphatase (AP) treatment that differs from the conventional RPPA antibody validation procedure and applied it onto fresh frozen (FF) and formalin-fixed and paraffin-embedded tissue (FFPE) to test its applicability. By screening 106 phospho-antibodies using RPPA, we demonstrated that AP treatment could serve as an independent factor to be adopted for rapid phospho-antibody selection. We also showed desirable reproducibility and specificity in clincical specimens indicating its potential for tissue-based phospho-protein profiling. Of further clinical significance, using the same approach, based on melanoma and lung cancer FFPE samples, we showed great interexperimental reproducibility and significant correlation with pathological markers in both tissues generating meaningful data that match clinical features. Our findings set a benchmark of an efficient workflow for phospho-antibody characterization that is compatible with high-plex clinical proteomics in precison oncology.

Artemisinin-isatin hybrids tethered via ethylene linker and their anti-lung cancer activity.

The synthesized 11 artemisinin-isatin hybrids 5a-c and 6a-h tethered via ethylene linker were assessed for their in vitro antiproliferative activity against A549 and H1299 nonsmall-cell lung cancer cell lines as well as their cytotoxicity towards BEAS-2B human normal lung epithelial cells. The preliminary results showed that hybrids 5a-c and 6a-h did not show any cytotoxicity (IC

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation.

Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT wasradiotherapy started within 30 days after the start of chemotherapy. Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n 1977) were treated with cCRT (median age 66 years) and 32.8% (n 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P .008), WHO ≥2 (P .006), and TNM IIIC (P .031). The multivariable analysis for acute toxicity was significant for cCRT (P .015), WHO ≥2 (P .001) and TNM IIIC (P .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.

Epidemiological Study to Assess the Prevalence of Lung Cancer in patients with smoking-associated atherosclerotic cardiovascular diseases PREVALUNG study protocol.

Eligibility criteria definition for a lung cancer screening (LCS) is an unmet need. We hypothesised that patients with a history of atheromatous cardiovascular disease (ACVD) associated with tobacco consumption are at risk of lung cancer (LC). The main objective is to assess LC prevalence among patients with ACVD and history of tobacco consumption by using low-dose chest CT scan. Secondary objectives include the evaluation LCS in this population and the constitution of a biological biobank to stratify risk of LC. We are performing a monocentric single-centre prospective study among patients followed up in adult cardiovascular programmes of vascular surgery, cardiology and cardiac surgery recruited from 18 November 2019 to 18 May 2021. The inclusion criteria are (1) age 45-75 years old, (2) history of ACVD and (3) history of daily tobacco consumption for 10 years prior to onset of ACVD. Exclusion criteria are symptoms of LC, existing follow-up for pulmonary nodule, fibrosis, pulmonary hypertension, resting dyspnoea and active pulmonary infectious disease. We targeted the inclusion of 500 patients. After inclusion (V0), patients are scheduled for a low-dose chest CT and blood and faeces harvesting within 7 months (V1). Each patient is scheduled for a follow-up by telephonic visits at month 3 (V2), month 6 (V3) and month 12 (V4) after V1. Each patient is followed up until 1 year after V1 (14 February 2023). We measure LC prevalence and quantify the National Lung Screening Trial and Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON) trial eligibility criteria, radiation, positive screening, false positivity, rate of localised LC diagnosis, quality of life with the Short Form 12 (SF-12) and anxiety with the Spielberger State-Trait Anxiety Inventory A and B (STAI-YA and STAI-YB, respectively), smoking cessation and onset of cardiovascular and oncological events within 1 year of follow-up. A case-control study nested in the cohort is performed to identify clinical or biological candidate biomarkers of LC. The study was approved according the French Jardé law the study is referenced at the French Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference ID RCB 2019-A00262-55) and registered on clinicaltrial.gov. The results of the study will be presented after the closure of the follow-up scheduled on 14 February 2023 and disseminated through peer-reviewed journals and national and international conferences. NCT03976804.

Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence.

Identification of hub genes associated with prognosis of lung cancer via integrated bioinformatics and

Lung cancer is a severe health problem that affects more men than women around the world. The goal of this study was to identify the biomarker hub genes for lung cancer in order to ascertain the biological pathway and protein- protein interaction networks. The microarray datasets GSE80796, GSE68571, GSE118370 and GSE43458 were retrieved from the GEO database and were analysed using GEO2R. STRING, Cytoscape, and cytoHubba were used to construct the PPI network and hub genes. GEPIA was used to obtain the overall survival and expression level in LUADLUSC and normal tissue. The MTT assay was used to examine antiproliferative activity. PI staining was used to determine the cell cycle arrest. qPCR was used to analyse gene expressions. The datasets revealed a total of 401 common DEGs, with 258 up-regulated genes and 143 down-regulated genes. Further,

Exosomes derived from lung cancer cells Isolation, characterization, and stability studies.

Recent advances in nanomedicine have paved the way for developing targeted drug delivery systems. Nanoscale exosomes are present in almost every body fluid and represent a novel mechanism of intercellular communication. Because of their membrane origin, they easily fuse with cells, acting as a natural delivery system and maintaining the bioactivity and immunotolerance of cells. To develop a reconstitutable exosome-based drug candidate for clinical applications, quality assurance by preserving its physical and biological properties during storage is necessary. Therefore, this study aimed to determine the best storage conditions for exosomes derived from lung cancer cells (A549). This study established that the phosphate-buffered saline buffer enriched with 25 mM trehalose is an optimal cryoprotectant for A549-derived exosomes stored at -80°C. Under these conditions, the concentration, size distribution, zeta potential, and total cargo protein levels of the preserved exosomes remained constant.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project Overview of Challenges and Opportunities in Revising the Nodal Classification of Lung Cancer.

The status of lymph node involvement is a major component of the TNM staging system. The N categories for lung cancer have remained unchanged since the fourth edition of the TNM staging system, partly because of differences in nodal mapping nomenclature, partly because of insufficient details to verify possible alternative approaches for staging. In preparation for the rigorous analysis of the International Association for the Study of Lung Cancer database necessary for the ninth edition TNM staging system, members of the N-Descriptors Subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee reviewed the evidence for alternative approaches to categorizing the extent of lymph node involvement with lung cancer, which is currently based solely on the anatomical location of lymph node metastasis. We reviewed the literature focusing on NSCLC to stimulate dialogue and mutual understanding among subcommittee members engaged in developing the ninth edition TNM staging system for lung cancer, which has been proposed for adoption by the American Joint Committee on Cancer and Union for International Cancer Control in 2024. The discussion of the range of possible revision options for the N categories, including the pros and cons of counting lymph nodes, lymph node stations, or lymph node zones, also provides transparency to the process, explaining why certain options may be discarded, others deferred for future consideration. Finally, we provide a preliminary discussion of the future directions that the N-Descriptors Subcommittee might consider for the 10th edition and beyond.

Signals transduced by Eph receptors and ephrin ligands converge on MAP kinase and AKT pathways in human cancers.

Eph receptors, the largest known family of receptor tyrosine kinases, and ephrin ligands have been implicated in a variety of human cancers. The novel bidirectional signaling events initiated by binding of Eph receptors to their cognate ephrin ligands modulate many cellular processes such as proliferation, metastasis, angiogenesis, invasion, and apoptosis. The relationships between the abundance of a unique subset of Eph receptors and ephrin ligands with associated cellular processes indicate a key role of these molecules in tumorigenesis. The combinatorial expression of these molecules converges on MAP kinase andor AKTmTOR signaling pathways. The intracellular target proteins of the initial signal may, however, vary in some cancers. Furthermore, we have also described the commonality of up- and down-regulation of individual receptors and ligands in various cancers. The current state of research in Eph receptors illustrates MAP kinase and mTOR pathways as plausible targets for therapeutic interventions in various cancers.

Nanocomplexes of doxorubicin and DNA fragments for efficient and safe cancer chemotherapy.

Cancer-targeted therapy by a chemotherapeutic agent formulated in a nanoscale platform has been challenged by complex and inefficient manufacturing, low drug loading, difficult characterization, and marginally improved therapeutic efficacy. This study investigated facile-to-produce nanocomplexes of doxorubicin (DOX), a widely used cancer drug, and clinically approved DNA fragments that are extracted from a natural source. DOX was found to self-assemble DNA fragments into relatively monodispersed nanocomplexes with a diameter of ∼70 nm at 14.3% (ww) drug loading by simple and scalable mixing. The resulting DOXDNA nanocomplexes showed sustained DOX release, unlike overly stable Doxil®, cellular uptake via multiple endocytosis pathways, and high hematological and immunological compatibility. DOXDNA nanocomplexes eradicated EL4 T lymphoma cells in a time-dependent manner, eventually surpassing free DOX. Extended circulation of DOXDNA nanocomplexes, while avoiding off-target accumulation in the lung and being cleared from the liver, resulted in rapid accumulation in tumor and lowered cardio toxicity. Finally, tumor growth of EL4-challenged C57BL6 mice (syngeneic model) and OPM2-challenged NSG mice (human xenograft model) were efficiently inhibited by DOXDNA nanocomplexes with enhanced overall survival, in comparison with free DOX and Doxil®, especially upon repeated administrations. DOXDNA nanocomplexes are a promising chemotherapeutics delivery platform for their ease of manufacturing, high biocompatibility, desired drug release and accumulation, efficient tumor eradication with improved safety, and further engineering versatility for extended therapeutic applications.

Percutaneous image-guided thermal ablation of lung cancer What is the evidence

Thermal ablation techniques have now been used for more than twenty years in the treatment of primary lung tumours, predominantly non-small cell lung cancer (NSCLC). Although primarily used for the treatment of early-stage disease in non-surgical patients, thermal ablation is now also being used in selected patients with oligometastatic and oligoprogressive disease. This review discusses the techniques available for thermal ablation, the evidence for use of thermal ablation in primary lung tumours in early- and advanced-stage disease and compares thermal ablation to alternative treatment strategies.

Single-cell transcriptional profiling uncovers the association between EOMES

Acquired resistance to tyrosine kinase inhibitors (TKIs) is reportedly inevitable in lung cancers harboring epidermal growth factor receptor (EGFR) mutations, emphasizing the need for novel approaches to predict EGFR-TKI resistance for clinical monitoring and patient management. This study identified a significant increase in eomesodermin (EOMES)

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors.

Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β trap) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy. In this expansion cohort of NCT02517398-a global, open-label, phase I trial-adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee) secondary endpoints included safety. Eighty-three eligible patients (62 74.7% treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8% 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 3.6%) and fatigue, eczema, and pruritus (2 each 2.4%). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa. Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy.

New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology and the Spanish Society of Medical Oncology have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.

Tremelimumab First Approval.

Tremelimumab (tremelimumab-actl IMJUDO

PEComa of the lung.

Clear cell sugar tumor of the lung is a rare benign tumor arising from perivascular epithelioid cells (PECs). They belong to a group of mesenchymal neoplasms called PEComas. Although widely presumed as benign, due to their rich vascular stroma they are usually avid for the different types of contrast agents used in imaging studies, mimicking a malignant lesion. We report the case of a 66-year-old man in whom a solitary pulmonary nodule was discovered during oncological staging for an adenocarcinoma of the prostate who underwent an anatomical pulmonary segmentectomy. The final pathology result was a perivascular epithelioid cell tumor (pulmonary PEComa or clear sugar cell tumor). Los tumores de células claras de azúcar (CCTL) son lesiones benignas muy infrecuentes. Forman parte de un grupo de neoplasias mesenquimales denominadas PEComas que se originan de las células epiteloides perivasculares. Por su rico estroma vascular, suelen tener avidez por los distintos tipos de contrastes utilizados en los estudios de diagnóstico por imágenes, simulando lesiones de estirpe maligna. Presentamos el caso de un paciente de 66 años con hallazgo de un nódulo pulmonar durante la estadificación oncológica por adenocarcinoma de próstata al que se le realizó una segmentectomía pulmonar anatómica. El resultado definitivo de anatomía patológica fue tumor de células epiteloides perivasculares (PEComa pulmonar o tumor de células claras de azúcar).

Tumour location predicts occult N1 nodal metastasis in clinical stage I non-small-cell lung cancer.

Pathological lymph node metastases are often observed in patients with clinical N0 lung cancer. Identifying preoperative predictors of occult hilar nodal metastasis (OHNM) is important in determining the surgical procedure in patients with clinical stage I non-small-cell lung cancer. This study aimed to determine the frequency and predictors of OHNM by tumour location in these patients. Between April 2007 and May 2019, data of patients who underwent lobectomy or segmentectomy for clinical stage I pure-solid non-small-cell lung cancer were retrospectively reviewed. The ratio of the distance from the pulmonary hilum to the proximal side of the tumour to the distance from the pulmonary hilum to the visceral pleural surface through the centre of the tumour, named distance ratio (DR), was calculated. The relationship of the DR with clinicopathological findings and prognosis was discussed. A total of 357 patients were enrolled. OHNM frequency was 14.6%. Patients were divided into 2 groups based on whether the DR was ≤0.67 (central type) or >0.67 (peripheral type). The frequency of OHNM was significantly higher in the DR ≤0.67 group (21.5% vs 7.4% P < 0.001). Multivariable analysis revealed that DR was the only independent preoperative predictor of OHNM (odds ratio, 3.63 95% confidence interval, 1.83-7.18 P < 0.001). The frequency of OHNM was significantly lower in peripheral-type lung cancer therefore, tumour location was the most important preoperative predictor of OHNM.

Long-term survival trends in solid cancers in the Nordic countries marking timing of improvements.

Survival studies are an important indicator of the success of cancer control. We analyzed the 5-year relative survival in 23 solid cancers in Denmark, Finland, Norway and Sweden over a 50-year period (1970-2019) at the NORDCAN database accessed from the International Agency for Research on Cancer website. We plotted survival curves in 5-year periods and showed 5-year periodic survival. The survival results were summarized in four groups (1) cancers with historically good survival (>50% in 1970-1974) which include melanoma and breast, endometrial and thyroid cancers (2) cancers which constantly improved survival at least 20% units over the 50 year period, including cancers of the stomach, colon, rectum, kidney, brain and ovary (3) cancer with increase in survival >20% units with changes taking place in a narrow time window, including oral, oropharyngeal, testicular and prostate cancers (4) the remaining cancers with <20% unit improvement in survival including lung, esophageal, liver, pancreatic, bladder, soft tissue, penile, cervical and vulvar cancers. For cancers in groups 1 and 2, the constant development implied multiple improvements in therapy, diagnosis and patient care. Cancers in group 3 included testicular cancers with known therapeutic improvements but for the others large incidence changes probably implied that cancer stage (prostate) or etiology (oropharynx) changed into a more tractable form. Group 4 cancers included those with dismal survival 50 years ago but a clear tendency upwards. In 17 cancers 5-year survival reached between 50% and 100% while in only six cancers it remained at below 50%.

Lymphangioleiomyomatosis a metastatic lung disease.

Lymphangioleiomyomatosis (LAM) is a rare disease affecting women, caused by somatic mutations in the TSC1 or TSC2 genes, and driven by estrogen. Similar to many cancers, it is metastatic, primarily to the lung. Despite its monogenetic nature, like many cancers, LAM is a heterogeneous disease. The cellular constituents of LAM are very diverse, including mesenchymal, epithelial, endothelial, and immune cells. LAM is characterized by dysregulation of many cell signaling pathways, distinct populations of LAM cells, and a rich microenvironment, in which the immune system appears to play an important role. This review delineates the heterogeneity of LAM and focuses on the metastatic features of LAM, the deregulated signaling mechanisms and the tumor microenvironment. Understanding the tumor-host interaction in LAM may provide insights into the development of new therapeutic strategies, which could be combinatorial or superlative to Sirolimus, the current U.S. Food and Drug Administration-approved treatment.

Limitations of phase-sorting based pencil beam scanned 4D proton dose calculations under irregular motion.

Chimeric RNA

Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we reported that high-expressed chimeric RNA

Varied Clinical Presentation and Management of Calvarial Metastases.

Calvarium and skull base can be affected by a variety of benign, tumor-like, and malignant processes. Skull metastases (SMs) may be located in any layer of the skull and may be incidental or present with neurological symptoms during the diagnostic workup. In the present study, we discuss the occurrence of SMs from various index malignancies and their myriad clinical presentation. This data-based study includes patients of bone metastases between June 2018 and July 2020. Patients with skull bone metastases were recognized, and location of primary site, their clinical presentation, and management strategy were noted. Ten patients with skull bone metastases were identified during this period. Four patients had skull base location with clinical manifestation as syndromes. Six patients had primary from breast cancer, three from Ewings sarcoma, and one from lung cancer. Management varied according to the primary site and symptoms of each patient. SM, though not rare, is often diagnosed incidentally but presents diagnostic and management challenges in the patient with cancer.

Outcome of Surgical Treatment for Metastatic Spinal Cord Compression A Single-Center Retrospective Study.

A rare lymphoplasmacyte-rich meningioma involving the dura of the skull base and cervical spinal cord A case report.

Lymphoplasmacyte-rich meningioma (LPRM) is a rare subtype of meningioma, the specific pathogenesis of which remains unclear. Herein, we report the case of a 48-year-old Asian man who experienced progressive deafness and limb weakness. Magnetic resonance imaging revealed extramedullary masses diffusely growing, wrapping, and compressing the cervical spinal cord. The dural lesion was partially excised by surgery, and postoperative pathological examination confirmed the diagnosis of LPRM. Diffuse LPRM is extremely rare, and its treatment is challenging owing to difficulties associated with surgery and the uncertain efficacy of traditional therapies. Therefore, further clinical practice and basic research are needed to improve the prognosis of diffuse LPRM.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study) primary analysis.

The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results. In treatment-naïve LA-NSCLC, cisplatin (60 mgm The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study. In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI 64.2-79.2%, 95% CI 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4% grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation. This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT. Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, httpsjrct.niph.go.jplatest-detailjRCTs031190127.

Dairy consumption and risk of esophagus cancer in the prostate, lung, colorectal, and ovarian cohort.

Epidemiological studies provide limited information on the relationship between dairy consumption and the incidence of esophagus cancer (EC). We examined whether eating dairy foods is associated with a lower risk of EC in an American population. In our study, we analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, which included 101,723 subjects. Dairy product consumption was assessed using a dietary history questionnaire. We used Cox regression and restricted cubic splines to assess whether dairy consumption is associated with EC incidence. A total of 154 EC cases were identified after a median follow-up of 12.2 years. After adjusting for confounders, we discovered no statistically significant correlation between total dairy product consumption and EC risk (HR with 95% CI for ≥1.79 servingsday vs. ≤0.6 servingsday 0.83, 0.50-1.38 We concluded that the findings of the PLCO cohort do not suggest dairy consumption reduces the risk of EC.

Overexpression of LINC00551 promotes autophagy-dependent ferroptosis of lung adenocarcinoma via upregulating DDIT4 by sponging miR-4328.

According to mounting evidence, long noncoding RNAs (lncRNAs) play a vital role in regulated cell death (RCD). A potential strategy for cancer therapy involves triggering ferroptosis, a novel form of RCD. Although it is thought to be an autophagy-dependent process, it is still unclear how the two processes interact. This study characterized a long intergenic noncoding RNA, LINC00551, expressed at a low level in lung adenocarcinoma (LUAD) and some other cancers. Overexpression of LINC00551 suppresses cell viability while promoting autophagy and RSL-3-induced ferroptosis in LUAD cells. LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes LUAD autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. This study provided an insight into the molecular mechanism regulating ferroptosis and highlighted LINC00551 as a potential therapeutic target for LUAD.

Immunogenic change after percutaneous microwave ablation in pulmonary malignancies Variation in immune cell subsets and cytokines in peripheral blood.

To investigate immunogenic changes after percutaneous microwave ablation (MWA) in pulmonary malignancies. Twenty-two consecutive patients with pulmonary malignancies who underwent percutaneous lung tumor MWA were prospectively enrolled in this study. Peripheral blood samples were collected on the day before (D0) and one month (M1) after MWA. Changes in immune cell subsets (CD3, CD4, and CD8 T cells, and B, natural killer, regulatory T (Treg), and CD3-CD20 cells) and cytokines (interleukin IL-2, 4, 6, 10, 17A, tumor necrosis factor TNF-α, and interferon-γ) were noted and compared. Progression-free survival (PFS) and potentially related factors were analyzed. The proportion of CD8 T cells increased from 22.95 ± 7.38% (D0) to 25.95 ± 9.16% (M1) ( Percutaneous MWA of pulmonary malignancies leads to immunogenic changes. The reduction in the proportion of Treg cells was independently associated with PFS.

PD-1PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer A real-world retrospective cohort study.

The aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer. In this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1PD-L1 inhibitors plus chemotherapy group (PC group), PD-1PD-L1 inhibitors plus anti-angiogenic agents group (PA group), PD-1PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Coxs proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis. The average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression HR 0.4, P0.005. Death HR 0.4, P0.024) and PAC group (Disease progression HR 0.3, P0.012. Death HR 0.3, P0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS7.5 vs.3.5, P0.00052. mOS33.1 vs.21.8, P0.093) and PAC group (mPFS5.1 vs.3.5, P0.075. mOS37.3 vs.21.8, P0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR96.3% vs.58.3%, P0.001) and PAC group (DCR100% vs.58.3%, P0.019) had a better disease control rate (DCR) than patients in PC group. PD-1PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

Patients with positive HER-2 amplification advanced gastroesophageal junction cancer achieved complete response with combined chemotherapy of AK104cadonilimab (PD-1CTLA-4 bispecific) A case report.

Human epidermal growth factor receptor 2 (HER2) is the most prominent therapeutic target for advanced gastric (G)GEJ cancer. However, targeted therapy did not significantly improve survival. Currently, there are no regimens for the treatment of HER-2 amplification that exclude targeted agents. A 42-year-old man was diagnosed with adenocarcinoma of GEJ (stage IV) with liver metastasis and lung metastasis. The patient was enrolled in a trial that excluded patients with known HER2-positivity AK104, a PD-1CTLA-4 bispecific antibody, combined with chemotherapy (mXELOX) as first-line therapy for advanced gastric GGEJ cancer (NCT03852251). After six cycles of AK104 combined with chemotherapy therapy, immune-related pulmonary toxicity was observed. We rechallenged AK104 after hormone therapy, and no further pulmonary toxicity was observed. Immune-related hepatitis occurred in the patient during immunotherapy combined with single-drug capecitabine therapy. After combining steroid therapy with mycophenolate mofetil, the patients immune hepatitis improved. Nevertheless, the patient was excluded from the clinical study due to the long-term absence of medication. Antitumor therapy was also discontinued in view of the patients adverse immune response. The patient did not receive subsequent immune antitumor therapy, and immune-related hepatitis still occurred intermittently, but the disease evaluation was maintained at PR. A complete response was confirmed by PETCT and the biopsy specimen from gastroscopy on 2020-06-10. Next generation sequencing of biopsy tissue was used to guide subsequent therapy at a recent follow-up visit. The results indicated that ERBB2 mutations occurred at copy number 58.4934 (HER-2), TMB 3.1, MSS. IHC EBV (-), PD-L1 CPS 3, HER-2 (3). Patients with HER-2-positive advanced GEJ cancer received PD-1CTLA-4 bispecific immunotherapy combined with chemotherapy and achieved complete remission. It offers a novel, highly specific, and highly potent therapeutic option for HER-2-positive patients. Its use should be considered as a new treatment when trastuzumab is not viable. Currently, we are working to overcome this resistance.

Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy.

This pilot study (NCT03958097 httpswww.clinicaltrials.govct2showNCT03958097) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIBIIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×10

Corrigendum Peripheral blood lymphocyte subsets predict the efficacy of immune checkpoint inhibitors in non- small cell lung cancer.

This corrects the article DOI 10.3389fimmu.2022.912180..

Diagnosis of pulmonary leiomyosarcoma extending into the main bronchus using repeated transbronchial cryobiopsy.

The diagnosis of pulmonary leiomyosarcoma using bronchoscopy is difficult, and surgical resection is often performed for definitive diagnosis and curative therapy. We report a case of pulmonary leiomyosarcoma, successfully diagnosed using repeated transbronchial cryobiopsy (TBCB). A 69-year-old-woman was found to have an oval mass in the left hilar region extending into the left main bronchus on computed tomography (CT). All transbronchial biopsy specimens were necrotic, but repeated TBCB removed the necrotic tissue from the tumour and finally led to the diagnosis of pulmonary leiomyosarcoma. Proton therapy was administered, which caused shrinkage of the tumour. Thus, TBCB is useful for definitive diagnosis of leiomyosarcoma without surgical biopsy. Repeated TBCB can reduce tumour volume, eliminate atelectasis, and reduce the extent of radiotherapy exposure.

Early-life farm exposures and eczema among adults in the Agricultural Lung Health Study.

Several studies conducted in Europe have suggested a protective association between early-life farming exposures and childhood eczema or atopic dermatitis few studies have examined associations in adults. To investigate associations between early-life exposures and eczema among 3217 adult farmers and farm spouses (mean age 62.8 years) in a case-control study nested within an US agricultural cohort. We used sampling-weighted logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for associations between early-life exposures and self-reported doctor-diagnosed eczema (273 cases) and polytomous logistic regression to estimate ORs (95%CIs) for a 4-level outcome combining information on eczema and atopy (specific IgE≥0.35). Additionally, we explored genetic and gene-environment associations with eczema. Although early-life farming exposures were not associated with eczema overall, several early-life exposures were associated with a reduced risk of having both eczema and atopy. Notably, results suggest stronger protective associations among individuals with both eczema and atopy than among those with either atopy alone or eczema alone. For example, ORs (95%CIs) for having a mother who did farm work while pregnant were 1.01 (0.60-1.69) for eczema alone and 0.80 (0.65-0.99) for atopy alone, but 0.54 (0.33-0.80) for having both eczema and atopy. A genetic risk score based on previously identified atopic dermatitis variants was strongly positively associated with eczema, and interaction testing suggested protective effects of several early-life farming exposures only in individuals at lower genetic risk.

Resveratrol regulates

Non-small cell lung cancer (NSCLC) is a common malignant subtype of lung cancer with high mortality. Resveratrol (RSV) is a natural molecule that regulates mitochondrial metabolism. Here, we explored the effect of RSV on NSCLC cell mitophagy and paclitaxel (PTX) resistance. LncRNA ZFAS1, miR-150-5p, and PTEN-induced putative kinase 1 (PINK1) expressions in NSCLC cells were analyzed by RT-qPCR. Levels of PINK1, Parkin and autophagy related molecules LC3I and LC3II were assessed by western blot. Mitophagy was demonstrated by transmission electron microscopy. Luciferase reporter assay revealed that miR-150-5p directly interacted with ZFAS1 or PINK1. MTT was performed to test the IC50 of NSCLC cells. Cell proliferation and apoptosis were measured with CCK-8, EdU, and TUNEL assays. A549PTX cells exhibited a higher mitophagy activity, and chemoresistance, whereas RSV suppressed PTX resistance and mitophagy in NSCLC cells. Furthermore, ZFAS1 was found to be a downstream effector of RSV in NSCLC cells. We next found ZFAS1 directly interacted with miR-150-5p and regulated the expression of a key mitophagy regulator PINK1. In addition, RSV modulated PTX resistance and mitophagy in NSCLC via ZFAS1miR-150-5pPINK1 axis. We validate that RSV influences mitophagy and PTX resistance in NSCLC via ZFAS1miR-150-5p mediated PINK1Parkin pathway. Combining these 2 drugs may be a new option of NSCLC therapy.

The critical roles and therapeutic implications of tuft cells in cancer.

Tuft cells are solitary chemosensory epithelial cells with microvilli at the top, which are found in hollow organs such as the gastrointestinal tract, pancreas, and lungs. Recently, an increasing number of studies have revealed the chemotactic abilities and immune function of the tuft cells, and numerous efforts have been devoted to uncovering the role of tuft cells in tumors. Notably, accumulating evidence has shown that the specific genes (POU2F3, DCLK1) expressed in tuft cells are involved in vital processes related with carcinogenesis and cancer development. However, the interaction between the tuft cells and cancer remains to be further elucidated. Here, based on an introduction of biological functions and specific markers of the tuft cells, we have summarized the functional roles and potential therapeutic implications of tuft cells in cancers, including pancreatic cancer, lung cancer, gastric cancer, colon cancer, and liver cancer, which is in the hope of inspiring the future research in validating tuft cells as novel strategies for cancer therapies.

A Comprehensive Survey on the Progress, Process, and Challenges of Lung Cancer Detection and Classification.

Lung cancer is the primary reason of cancer deaths worldwide, and the percentage of death rate is increasing step by step. There are chances of recovering from lung cancer by detecting it early. In any case, because the number of radiologists is limited and they have been working overtime, the increase in image data makes it hard for them to evaluate the images accurately. As a result, many researchers have come up with automated ways to predict the growth of cancer cells using medical imaging methods in a quick and accurate way. Previously, a lot of work was done on computer-aided detection (CADe) and computer-aided diagnosis (CADx) in computed tomography (CT) scan, magnetic resonance imaging (MRI), and X-ray with the goal of effective detection and segmentation of pulmonary nodule, as well as classifying nodules as malignant or benign. But still, no complete comprehensive review that includes all aspects of lung cancer has been done. In this paper, every aspect of lung cancer is discussed in detail, including datasets, image preprocessing, segmentation methods, optimal feature extraction and selection methods, evaluation measurement matrices, and classifiers. Finally, the study looks into several lung cancer-related issues with possible solutions.

Multidisciplinary treatment of a patient with severe immune checkpoint inhibitor-induced colitis A case report.

Immune checkpoint inhibitors (ICIs) are a new class of antitumor drugs that have been approved to treat a variety of malignant tumors. However, the occurrence of immune related adverse events (irAEs) has become an important reason for terminating treatment. ICIs sometimes lead to diarrhea and colitis, with severe enterocolitis potentially causing the hemorrhage of the lower gastrointestinal tract and colonic perforation. ICI-associated colitis is primarily treated with glucorticosteroids andor agents targeting tumor necrosis factor-α. Here, we describe a case of severe ICI-associated colitis due to anti-programmed cell death ligand 1 (PD-L1) (durvalumab) treatment for small cell lung cancer with liver metastasis. The patient exhibited a poor response to rescuable therapy, and eventually received a laparoscopic subtotal colectomy and ileostomy. The data presented here will contribute to optimizing current treatment strategies for patients with severe ICI-associated colitis. A 71-year-old man was admitted for a second course of anti-PD-L1 IP (durvalumab irinotecan cisplatin) treatment to manage lung cancer with liver metastasis, diagnosed 1 mo previously. Four days after the second dose, the patient developed abdominal pain and bloody diarrhea. Due to the anti-PD-L1 medication history and colonoscopy findings of the patient, he was diagnosed with a colitis associated with ICI treatment. After treatment with sufficient glucocorticoids and two courses of infliximab, the patient developed severe lower gastrointestinal bleeding. After adequate assessment, the patient was treated by laparoscopic surgery, and was discharged in stable condition. The early screening and hierarchical management of irAEs need the joint participation of a multidisciplinary team. For ICI-related colitis with ineffective medical treatment, timely surgical intervention could prevent the death of patients.

Lung squamous cell carcinoma presenting as rare clustered cystic lesions A case report and review of literature.

Lung cancer is the leading cause of cancer-related death. Early diagnosis is critical to improving a patients chance of survival. However, lung cancer associated with cystic airspaces is often misdiagnosed or underdiagnosed due to the absence of clinical symptoms, poor imaging specificity, and high risk of biopsy-related complications. We report an unusual case of cancer in a 55-year-old man, in which the lesion evolved from a small solitary thin-walled cyst to lung squamous cell carcinoma (SCC) with metastases in both lungs. The SCC manifested as rare clustered cystic lesions, detected on chest computed tomography. There were air-fluid levels, compartments, and bronchial arteries in the cystic lesions. Additionally, there was no clear extrathoracic metastasis. After chemotherapy, the patient achieved a partial response, type I respiratory failure was relieved, and the lung lesions became a clustered thin-walled cyst. Pulmonary cystic lesions require regular imaging follow-up. Lung SCC should be a diagnostic consideration in cases of thin-walled cysts as well as multiple clustered cystic lesions.

A machine learning-Based model to predict early death among bone metastatic breast cancer patients A large cohort of 16,189 patients.

A Hybrid Framework for Lung Cancer Classification.

Cancer is the second leading cause of death worldwide, and the death rate of lung cancer is much higher than other types of cancers. In recent years, numerous novel computer-aided diagnostic techniques with deep learning have been designed to detect lung cancer in early stages. However, deep learning models are easy to overfit, and the overfitting problem always causes lower performance. To solve this problem of lung cancer classification tasks, we proposed a hybrid framework called LCGANT. Specifically, our framework contains two main parts. The first part is a lung cancer deep convolutional GAN (LCGAN) to generate synthetic lung cancer images. The second part is a regularization enhanced transfer learning model called VGG-DF to classify lung cancer images into three classes. Our framework achieves a result of 99.84% ± 0.156% (accuracy), 99.84% ± 0.153% (precision), 99.84% ± 0.156% (sensitivity), and 99.84% ± 0.156% (F1-score). The result reaches the highest performance of the dataset for the lung cancer classification task. The proposed framework resolves the overfitting problem for lung cancer classification tasks, and it achieves better performance than other state-of-the-art methods.

Cost-effectiveness analysis of pembrolizumab vs. chemotherapy as second-line treatment for advanced esophageal carcinoma in the United States.

The national Comprehensive Cancer Network has suggested pembrolizumab as a second-line therapy for esophageal squamous cell carcinoma (ESCC) patients with a programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10. However, despite the increased survival rate associated with pembrolizumab in these patient population, the high cost of pembrolizumab may influence its antitumor effect. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared to chemotherapy as second-line treatments for esophageal carcinoma (EC) based on KEYNOTE-181 trial. A Markov model was constructed using TreeAge 2021 based on three different groups all intent-to-treat patients (ITT population), patients with ESCC (ESCC population), and patients with a PD-L1 CPS ≥10 (CPS ≥10 population). Incremental cost, Incremental effect, Life-years, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. Analyses were conducted on the setting of a willingness-to-pay threshold of $150,000 from the US perspective. The ICERs for pembrolizumab were $157,589.545 per QALY, $60,238.823 per QALY, and $100,114.929 per QALY compared with chemotherapy in the ITT, ESCC, and CPS≥10 populations, respectively. The ICER of the ITT population was higher than $150,000, suggesting that pembrolizumab was not a cost-effective treatment scheme in patients with a PD-L1 CPS ≤ 10 or esophageal adenocarcinoma. The ICER was < $150,000 in the ESCC and CPS≥10 populations, indicating that pembrolizumab was cost-effective in these two subgroups. The determining of pembrolizumab as a cost-effective second-line therapy for EC in the United States depends on the histologic type and PD-L1 expression.

Practice toward standardized performance testing of computer-aided detection algorithms for pulmonary nodule.

This study aimed at implementing practice to build a standardized protocol to test the performance of computer-aided detection (CAD) algorithms for pulmonary nodules. A test dataset was established according to a standardized procedure, including data collection, curation and annotation. Six types of pulmonary nodules were manually annotated as reference standard. Three specific rules to match algorithm output with reference standard were applied and compared. These rules included (1) center hit whether the center of algorithm highlighted region of interest (ROI) hit the ROI of reference standard (2) center distance (whether the distance between algorithm highlighted ROI center and reference standard center was below a certain threshold) (3) area overlap (whether the overlap between algorithm highlighted ROI and reference standard was above a certain threshold). Performance metrics were calculated and the results were compared among ten algorithms under test (AUTs). The test set currently consisted of CT sequences from 593 patients. Under center hit rule, the average recall rate, average precision, and average F

Overview of Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Targeted Therapy and Supportive Care for Lung Cancer.

Oral administration of ritonavir-boosted nirmatrelvir (Paxlovid) was found to be promising in the treatment of coronavirus disease 2019. The active antiviral component nirmatrelvir in Paxlovid is co-formulated with ritonavir, a strong cytochrome P450 (CYP) 3A4 inhibitor. Many oral targeted therapies indicated for lung cancer are known substrates of CYP 3A4, and concurrent use with Paxlovid may lead to potential drug-drug interaction (DDI). The purpose of this review is to evaluate the potential DDI between targeted therapies and supportive care for lung cancer and ritonavir-boosted nirmatrelvir. Drug database search in PubMed and the Food and Drug Administration was conducted to identify pharmacokinetic data on oral tyrosine kinase inhibitors (TKIs) used in NSCLC, both Food and Drug Administration approved and those in development. Metabolism pathways for various TKIs are extracted, and the impact of TKI area under the curves and maximum concentration by strong CYP 3A4 inducers and inhibitors is summarized. The most common toxicities and supportive care medications for the TKI were identified. Among EGFR and exon 20 insertion inhibitors, afatinib is least likely to be affected by CYP 3A4, followed by dacomitinib and osimertinib. Among ALK inhibitors, alectinib is the least susceptible to CYP 3A4. ROS1 inhibitors are affected by CYP 3A4 inhibition with the exception of crizotinib. Among MET inhibitors, capmatinib is substantially affected by CYP 3A4 inhibition. Drug exposure of RET inhibitors is expected to increase with CYP 3A4 inhibition, with selpercatinib being the least affected. Certain supportive care medications for lung cancer TKI may have relevant DDIs. The clinical impact of the DDI between lung cancer TKI and ritonavir-boosted nirmatrelvir varies largely on the basis of the susceptibility of CYP 3A4 inhibition caused by the antiviral. Close monitoring and medication adjustments (i.e., dose changes or alternative coronavirus disease 2019 therapy) can be used to overcome DDI to ensure patient safety.

Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases A case report.

Although the incidence of multiple primary malignancies (MPMs) is increasing, synchronous triple primary malignant tumours with prostate, bladder and lung is rarely reported. Gene mutation is thought to be a reason for MPMs, and severe cardiovascular diseases may interrupt the cancer treatment. Here we reported a 64-year-old male patient with synchronous triple primary malignant tumours of the bladder urothelial carcinoma, prostate adenocarcinoma, and non-small cell lung cancer (NSCLC) with mutations in TP53 and MEK1, all the three malignancies were diagnosed within 10 days. Although being interrupted by severe cardiovascular diseases (including myocardial infarction, venous thrombosis, and aneurism of the aortic root), he was successfully treated with radical cystoprostatectomy, chemotherapy plus pembrolizumab (a PD-1 antibody), and radiotherapy of the lung lesion, followed by maintenance monotherapy of pembrolizumab, overall survival was more than 26 months. In conclusion, a patient of synchronous triple primary malignant tumours with prostate, bladder, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases was treated successfully, which may suggest that comprehensive treatment, especially radical treatment such as operation and radiation, is very important for MPMs.

Impact of coronavirus disease 2019 on lung cancer patients A meta-analysis.

The coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the treatment of lung cancer patients. The PubMed, Embase, and Web of Science databases were searched for studies published before March 15, 2022, and Stata 14.0 software was used to perform a meta-analysis with a random-effects model. The odds ratio (OR) along with the corresponding 95% confidence interval (CI) was reported. Our meta-analysis included 80 articles with 318,352 patients involved. The proportion of lung cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 2.4% (95% CI 0.02-0.03) prior to the Omicron variant outbreak. Among COVID-19 patients, those with lung cancer showed a higher mortality rate than those with other types of malignant solid tumors (OR 1.82, 95% CI 1.61-2.06) and non-cancer patients (OR 4.67, 95% CI 3.61-6.05) however, no significant difference was observed in the mortality rate between patients with lung cancer and those with hematologic malignancies (OR 1.07, 95% CI 0.85-1.33). SARS-CoV-2 infection significantly increased the mortality rate in lung cancer patients (OR 8.94, 95% CI 6.50-12.31). By contrast, the all-cause mortality rate in lung cancer patients (OR 1.04, 95% CI 0.69-1.57) and the proportion of patients diagnosed with advanced lung cancer (OR 1.04, 95% CI 0.85-1.27) did not significantly change before and after the pandemic. More attention should be paid on improving the health of lung cancer patients during the COVID-19 pandemic.

Pan-cancer analysis identifies DDX56 as a prognostic biomarker associated with immune infiltration and drug sensitivity.

DDX56, a member of the RNA helicase family, is upregulated in colon adenocarcinoma, lung squamous cell carcinoma, and osteosarcoma. However, the relationships between DDX56 and other tumors are not clear, and the molecular mechanism of its action is not fully understood. Here, we explore the biological functions of DDX56 in 31 solid tumors and clarify that DDX56 can promote oncogenesis and progression in multiple tumor types based on multi-omics data. Bioinformatics analysis revealed that the cancer-promoting effects of DDX56 were achieved by facilitating tumor cell proliferation, inhibiting apoptosis, inducing drug resistance, and influencing immune cell infiltration. Furthermore, we found that copy number alterations and low DNA methylation of

Pan-cancer analysis reveals NAA50 as a cancer prognosis and immune infiltration-related biomarker.

Overall 5-year survival rate and disease-free survival after segmentectomy versus lobectomy in patients with non-small cell lung cancer.

Anatomical lobectomy has always been the standard operative treatment of early-stage non-small cell lung cancer. However, there have been emerging evidences suggesting that a subanatomical resection, such as segmentectomy, may yield the same treatment results, even in patients with higher-stage non-small cell lung cancer. This study aimed to compare overall 5-year survival rate and disease-free survival between lobectomy and segmentectomy in patients with non-small cell lung cancer. The retrospective study included 380 patients who underwent surgery for non-small cell lung cancer at Ramathibodi Hospital between 1st January 2016 and 31st December 2020. Of 380 patients, 307 patients underwent lobectomy, while the other 73 patients underwent segmentectomy. Operative, admission, and follow-up data were collected from electronic medical records. Missing data were collected by telephone calls to patients or their relatives in deceased cases. Overall and disease-free survival were analyzed. Median overall 5-year survival time after lobectomy and segmentectomy seemed to be different but not statistically significant (18.5 months versus 5.8 months, Lobectomy and segmentectomy result in similar overall 5-year survival rate and disease-free survival between these two comparison groups. Therefore, segmentectomy may be a potential alternative for operative treatment of non-small cell lung cancer. However, a larger and randomized-controlled trial may be needed to further validate these results.

Organoid technology and applications in lung diseases Models, mechanism research and therapy opportunities.

The prevalency of lung disease has increased worldwide, especially in the aging population. It is essential to develop novel disease models, that are superior to traditional models. Organoids are three-dimensional (3D)

Cancer overdiagnosis a challenge in the era of screening.

Screening is a search for preclinical, asymptomatic disease, including cancer. Widespread cancer screening has led to large increases in early-stage cancers and pre-cancers. Ubiquitous public messages emphasize the potential benefits to screening for these lesions based on the underlying assumption that treating cancer at early stages before spread to other organs should make it easier to treat and cure, using more tolerable interventions. The intuition is so strong that public campaigns are sometimes launched without conducting definitive trials directly comparing screening to usual care. An effective cancer screening test should not only increase the incidence of early-stage preclinical disease but should also decrease the incidence of advanced and metastatic cancer, as well as a subsequent decrease in cancer-related mortality. Otherwise, screening efforts may be uncovering a reservoir of non-progressive and very slowly progressive lesions that were not destined to cause symptoms or suffering during the persons remaining natural lifespan a phenomenon known as overdiagnosis. We provide here a qualitative review of cancer overdiagnosis and discuss specific examples due to extensive population-based screening, including neuroblastoma, prostate cancer, thyroid cancer, lung cancer, melanoma, and breast cancer. The harms of unnecessary diagnosis and cancer therapy call for a balanced presentation to people considering undergoing screening, even with a test of accepted benefit, with a goal of informed decision-making. We also discuss proposed strategies to mitigate the adverse sequelae of overdiagnosis.

Current and novel therapeutic strategies for optimizing immunotherapy outcomes in advanced non-small cell lung cancer.

During the past decade, immunotherapy has dramatically improved the outcomes of patients with non-small cell lung cancer (NSCLC). The development of specific antibodies against the programmed death (PD1) receptor and its ligand PD-L1 (programmed death ligand-1) has demonstrated substantial efficacy in advanced NSCLC either in the first or in the second line. However, the success of immune checkpoint inhibitors (ICIs) as monotherapy did not reach all patients and long-term responders still represent a small subset of cases. Under these circumstances, different strategies have been and are being tested to optimize clinical outcomes. Here, we reviewed the current evidence and the more promising perspectives of ICI combination approaches, such as the addition of chemotherapy, antiangiogenic agents, other co-inhibitory or co-stimulatory checkpoints, and targeted therapies.

The natural growth history of persistent pulmonary subsolid nodules Radiology, genetics, and clinical management.

The high detection rate of pulmonary subsolid nodules (SSN) is an increasingly crucial clinical issue due to the increased number of screening tests and the growing popularity of low-dose computed tomography (LDCT). The persistence of SSN strongly suggests the possibility of malignancy. Guidelines have been published over the past few years and guide the optimal management of SSNs, but many remain controversial and confusing for clinicians. Therefore, in-depth research on the natural growth history of persistent pulmonary SSN can help provide evidence-based medical recommendations for nodule management. In this review, we briefly describe the differential diagnosis, growth patterns and rates, genetic characteristics, and factors that influence the growth of persistent SSN. With the advancement of radiomics and artificial intelligence (AI) technology, individualized evaluation of SSN becomes possible. These technologies together with liquid biopsy, will promote the transformation of current diagnosis and follow-up strategies and provide significant progress in the precise management of subsolid nodules in the early stage of lung cancer.

Case report Recurrent lung infections following treatment with pralsetinib for an elderly patient with

Patients with

Changes in lung cancer-related serum tumor markers in patients with chronic kidney disease and determination of upper reference limit.

To investigate the changes in lung cancer-related serum tumor markers in patients with chronic kidney disease (CKD) and determine the upper reference limit for patients with different stages. Included inpatients diagnosed with CKD who did not receive dialysis temporarily in our hospital from March to September 2020. Changes in serum CA125, HE4, CYFRA21-1, SCCA, NSE and ProGRP in CKD patients were analyzed. The non-parametric method was used to estimate the upper reference limit of the above indicators in patients with CKD stages 2-5. The serum levels of HE4, CYFRA21-1, SCCA, and ProGRP in the CKD group were significantly higher than those in the healthy control group CA125 and NSE levels were not statistically different. The false positives of SCC, CYFRA21-1, ProGRP, and HE4 increased significantly with the CKD stage. Still, NSE and CA125 did not show a significant increasing trend. Both HE4 and ProGRP have independent upper reference limits from CKD2 to CKD5 stage, namely 220.8 pmoll and 101.4 pgml in the CKD2 stage, 496.7 pmoll and 168.63 pgml in CKD3 stage, 4592.4 pmoll and 272.8 pmoll for CKD4 stage, CKD5 stage was 4778.2 pmoll and 491.6 pmoll. This study preliminarily determined the upper reference limits of Lung cancer-related tumor markers in patients with different CKD stages and provided laboratory support for the rational use and interpretation of Lung cancer-related tumor markers in special populations.

Construction and validation of a novel web-based nomogram for patients with lung cancer with bone metastasis A real-world analysis based on the SEER database.

Patients with lung cancer with bone metastasis (LCBM) often have a very poor prognosis. The purpose of this study is to characterize the prevalence and associated factors and to develop a prognostic nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with LCBM using multicenter population-based data. Patients with LCBM at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database of the National Cancer Institute (NCI) from 2010 to 2015. Multivariable and univariate logistic regression analyses were performed to identify factors associated with all-cause mortality and lung cancer (LC)-specific mortality. The performance of the nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of patients with LCBM. We finally identified 26,367 patients with LCBM who were selected for survival analysis. Multivariate analysis demonstrated age, sex, T stage, N stage, grade, histology, radiation therapy, chemotherapy, primary site, primary surgery, liver metastasis, and brain metastasis as independent predictors for LCBM. The AUC values of the nomogram for the OS prediction were 0.755, 0.746, and 0.775 in the training cohort 0.757, 0.763, and 0.765 in the internal validation cohort and 0.769, 0.781, and 0.867 in the external validation cohort. For CSS, the values were 0.753, 0.753, and 0.757 in the training cohort 0.753, 0.753, and 0.757 in the internal validation cohort and 0.767, 0.774, and 0.872 in the external validation cohort. Our study constructs a new prognostic model and clearly presents the clinicopathological features and survival analysis of patients with LCBM. The result indicated that the nomograms had favorable discrimination, good consistency, and clinical benefits in patients. In addition, our constructed nomogram prediction models may assist physicians in evaluating individualized prognosis and deciding on treatment for patients.

Exosomes from cisplatin-induced dormant cancer cells facilitate the formation of premetastatic niche in bone marrow through activating glycolysis of BMSCs.

Lung cancer is the leading cause of cancer-related deaths worldwide. Chemotherapy kills most cancer cells however, residual cells enter a dormant state. The dormant cancer cells can be reactivated under specific circumstances. The premetastatic niche that is suitable for colonization of cancer cells is formed before the arrival of cancer cells. Tumor-derived exosomes are the main mediators of tumorigenesis. We are aiming to elucidate the roles of exosomes from cisplatin-induced dormant lung cancer cells in the formation of premetastatic niches in bone marrow. We performed differential proteomics in dormant A549 cell- and A549 cell-derived exosomes. Non-targeted metabolomics and RNA sequencing were performed to explore the molecular and metabolic reprogramming of bone marrow stromal cells (BMSCs). The growth and metastasis of A549 cells We found that Insulin-like growth factor 2 (IGF-2) and Insulin-like growth factor binding protein 2 (IGFBP2) were upregulated in dormant A549 cell-derived exosomes. BMSCs that took up exosomes from dormant A549 cells showed enhanced glycolysis and promoted the growth and metastasis of A549 cells possibly through Insulin-like growth factor 1 receptor (IGF-1R)-induced metabolic reprogramming. Inhibition of the production of lactate and IGF-1R signaling can suppress the growth and metastasis of A549 cells from bone marrow. Overall, we demonstrated that BMSCs formed a premetastatic niche upon taking up exosomes from cisplatin-induced dormant lung cancer cells. BMSCs promoted lung cancer cell growth and metastasis through the reverse Warburg effect.

Case Report Peripheral blood T cells and inflammatory molecules in lung cancer patients with immune checkpoint inhibitor-induced thyroid dysfunction Case studies and literature review.

Immunotherapy has changed the paradigm of cancer treatment, yet immune checkpoint inhibitors (ICIs) such as PD-1PD-L1 monoclonal antibodies may cause immune-related adverse events (irAEs) in some patients. In this report, two non-small cell lung cancer (NSCLC) patients treated with nivolumab presented with checkpoint inhibitor-induced thyroid dysfunction (CITD), followed by a second irAE of pneumonitis and intestinal perforation, respectively. Increases in peripheral CD8

Local therapy treatment conditions for oligometastatic non-small cell lung cancer.

Standard treatments for patients with metastatic non-small cell lung cancer (NSCLC) include palliative chemotherapy and radiotherapy, but with limited survival rates. With the development of improved immunotherapy and targeted therapy, NSCLC prognoses have significantly improved. In recent years, the concept of oligometastatic disease has been developed, with randomized trial data showing survival benefits from local ablation therapy (LAT) in patients with oligometastatic NSCLC (OM-NSCLC). LAT includes surgery, stereotactic ablation body radiation therapy, or thermal ablation, and is becoming an important treatment component for OM-NSCLC. However, controversy remains on specific management strategies for the condition. In this review, we gathered current randomized trial data to analyze prognostic factors affecting patient survival, and explored ideal treatment conditions for patients with OM-NSCLC with respect to long-term survival.

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer.

As a highly invasive thoracic malignancy with increasing prevalence, lung cancer is also the most lethal cancer worldwide due to the failure of effective early detection and the limitations of conventional therapeutic strategies for advanced-stage patients. Over the past few decades, nanotechnology has emerged as an important technique to obtain desired features by modifying and manipulating different objects on a molecular level and gained a lot of attention in many fields of medical applications. Studies have shown that in lung cancer, nanotechnology may be more effective and specific than traditional methods for detecting extracellular cancer biomarkers and cancer cells

Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer A case report.

Histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of mechanisms of the acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). However, SCLC transformation and tumor heterogeneity have never been reported in sequential targeted therapy and immunotherapy. Here, we described a patient with advanced EGFR-mutant NSCLC, who received erlotinib and underwent the resistance with EGFR T790M (-). The patient then received chemotherapy plus immunotherapy of programmed cell death 1 (PD-1) inhibitor, encountered progression with pathological transformation from NSCLC to SCLC that was overcome by chemotherapy of etoposide plus carboplatin (EC) with the main lesion significantly shrinking while metastatic nodules increasing. The pathology of the metastatic nodule showed NSCLC with EGFR T790M (). Based on the tumor heterogeneity, EC chemotherapy combined with osimertinib was used, and patients responded well. The patient experienced four lung biopsies in all, which helped to provide the patient with precise treatment. This case suggested that SCLC transformation and tumor heterogeneity should be paid attention to when disease progression occurred in advanced NSCLC whether receiving targeted therapy or immunotherapy.

Development of a web-based calculator to predict three-month mortality among patients with bone metastases from cancer of unknown primary An internally and externally validated study using machine-learning techniques.

Individualized therapeutic strategies can be carried out under the guidance of expected lifespan, hence survival prediction is important. Nonetheless, reliable survival estimation in individuals with bone metastases from cancer of unknown primary (CUP) is still scarce. The objective of the study is to construct a model as well as a web-based calculator to predict three-month mortality among bone metastasis patients with CUP using machine learning-based techniques. This study enrolled 1010 patients from a large oncological database, the Surveillance, Epidemiology, and End Results (SEER) database, in the United States between 2010 and 2018. The entire patient population was classified into two cohorts at random a training cohort (n600, 60%) and a validation cohort (410, 40%). Patients from the validation cohort were used to validate models after they had been developed using the four machine learning approaches of random forest, gradient boosting machine, decision tree, and eXGBoosting machine on patients from the training cohort. In addition, 101 patients from two large teaching hospital were served as an external validation cohort. To evaluate each models ability to predict the outcome, prediction measures such as area under the receiver operating characteristic (AUROC) curves, accuracy, and Youden index were generated. The studys risk stratification was done using the best cut-off value. The Streamlit software was used to establish a web-based calculator. The three-month mortality was 72.38% (7311010) in the entire cohort. The multivariate analysis revealed that older age (P0.031), lung metastasis (P0.012), and liver metastasis (P0.008) were risk contributors for three-month mortality, while radiation (P0.002) and chemotherapy (P<0.001) were protective factors. The random forest model showed the highest area under curve (AUC) value (0.796, 95% CI 0.746-0.847), the second-highest precision (0.876) and accuracy (0.778), and the highest Youden index (1.486), in comparison to the other three machine learning approaches. The AUC value was 0.748 (95% CI 0.653-0.843) and the accuracy was 0.745, according to the external validation cohort. Based on the random forest model, a web calculator was established httpsstarxueshu-codeok-main-8jv2ws.streamlitapp.com. When compared to patients in the low-risk groups, patients in the high-risk groups had a 1.99 times higher chance of dying within three months in the internal validation cohort and a 2.37 times higher chance in the external validation cohort (Both P<0.001). The random forest model has promising performance with favorable discrimination and calibration. This study suggests a web-based calculator based on the random forest model to estimate the three-month mortality among bone metastases from CUP, and it may be a helpful tool to direct clinical decision-making, inform patients about their prognosis, and facilitate therapeutic communication between patients and physicians.

Telemedicine in lung cancer during COVID-19 outbreak A scoping review.

The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the medical services, particularly cancer diagnosis and treatment, for vulnerable cancer patients. Although lung cancer has a high mortality rate, monitoring and following up of these patients can help to improve disease management during the pandemic. Telemedicine has proven to be an effective method of providing health care to these patients. As a result, the purpose of this study was to identify telemedicine applications in the management of lung cancer patients during the COVID-19 pandemic. In this scoping review, studies published in online scientific databases such as Web of Science, Scopus, and PubMed between January 1, 2020 and September 1, 2021 were systematically searched and screened. The studies were chosen using predetermined inclusion and exclusion criteria. The bibliometric information and technological aspects of included studies were collected using a data extraction form and the data was analyzed using the content analysis approach. A total of 68 articles were found, from which four articles were finally selected based on specific inclusionexclusion criteria. Real-time consultation was one of the most common applications of telemedicine to deliver health-care services to cancer patients. Health-care providers used applications such as Zoom, Facetime, WeChat, and e-mail, as well as devices including PCs, phones, and smartphones to provide real-time consultation to patients via videoconferencing, phone calls, and messaging, as well as store and forward consultation via e-mail. Telemedicine in the COVID-19 pandemic provides health-care services to lung cancer patients at their homes by enabling physicians and patients to communicate in real time. Several telemedicine services are still unavailable for patients with lung cancer. As a result, health experts, politicians, and entrepreneurs must pay special attention to this issue.

Prognostic Biomarkers after Radiotherapy for Nonsmall Cell Lung Cancer Based on Bioinformatics Analysis.

Radiotherapy is one of the main treatment modalities in nonsmall cell lung cancer (NSCLC). However, tumor radiosensitivity is influenced by intrinsic factors like genetic variations and extrinsic factors like tumor microenvironment. Consequently, we hope to develop novel biomarkers, so as to improve the response rate of radiotherapy and overcome resistance to radiotherapy in NSCLC. We investigate the difference genes of primary NSCLC patients before and after radiotherapy in GSE162945 dataset. Gene Ontology (GO), KEGG, Reactome, and GSEA were employed to represent the essential gene and biological function. It was found that most pathway genes clustered in extracellular matrix and ECM-receptor signal pathway. Additionally, TMT-based proteomics was used to survey the differential proteins present in the supernatant of H460 cells before or after irradiation with 2 Gy of

USP2 Inhibits Lung Cancer Pathogenesis by Reducing ARID2 Protein Degradation via Ubiquitination.

Ubiquitination is an important regulator in physiological and pathological conditions. Ubiquitin-specific protease 2 (USP2), as a member of the USP family, exhibits oncogenic effects in multiple malignancies. However, the exact role of USP2 has not been well clarified in lung cancer pathogenesis and progression. Therefore, we aimed to further investigate the regulatory roles of USP2 in lung cancer in this study. Firstly, immunoprecipitation-Mass Spectrometry (IP-MS), Co-immunoprecipitation (Co-IP), combined with immunofluorescent colocalization method, was conducted for USP2 protein interaction analysis in lung cancer cell lines. qRT-PCR, Western blot, and immunohistochemistry assays explored the USP2 expression pattern and USP2ARID2- (AT-rich interactive domain 2-) specific shRNAs and overexpression vectors. Co-IP assays were designed to validate USP2-ARID2 protein interaction. Further functional studies including CHX chase assay, transwell assay, and wound healing assay were subsequently applied to evaluate the impact of USP2 modulation on lung cancer cells. USP2 suppression was characteristic in lung cancer cell line models and lung cancer samples. USP2 and ARID2 demonstrated protein-protein interaction and overlapping localization in cancer cell models. Functional experiments suggested USP2 inhibited lung cancer cell invasion and migration by reducing ARID2 protein degradation. Subsequent ubiquitination assays indicated ARID2 protein degradation via the ubiquitination was significantly reduced by USP2 interaction. Our study provided novel insight that USP2 might suppress lung cancer by reducing ARID2 protein degradation via ubiquitination.

Avelumab-Induced Scleroderma in a Patient with Metastatic Squamous Cell Carcinoma of the Lung.

Immune checkpoint inhibitors are associated with a spectrum of cutaneous immune-related adverse events. While maculopapular eruptions are the most common cutaneous adverse event, scleroderma can rarely develop. Herein, we report a case of new-onset scleroderma associated with avelumab treatment in the setting of metastatic squamous cell carcinoma of the lung. The pathophysiology of immune checkpoint inhibitor-induced scleroderma is not completely understood. A proposed mechanism is discussed along with the clinical presentation of symptoms and associated therapeutic response in cancer treatment. This case contributes to the few existing reports of immune checkpoint inhibitor-induced scleroderma to better understand the implications in the management of cutaneous immune-related adverse events.

Is it necessary to define new diagnostic reference levels during pandemics like the Covid19-

This study intended to assess the dose length product (DLP), effective cumulative radiation dose (E.D.), and additional cancer risk (ACR) due to a chest CT scan to detect or follow up the Covid-19 disease in four university-affiliated hospitals that used different imaging protocols. Indeed, this study aimed to examine the differences in decision-making between different imaging centers in choosing chest CT imaging protocols during the pandemic, and to assess whether a new diagnostic reference level (DRL) is needed in pandemic situations. This retrospective study assessed the E.D. of all chest imagings for Covid-19 for six months in four different hospitals in our country. Imaging parameters and DLP (mGy.cm) were recorded. The E.D.s and ACRs from chest CT scans were calculated using an online calculator. Thousand-six hundred patients were included in the study. The mean cumulative dose due to chest CT was 3.97 mSv which might cause 2.59 × 10 The variety of mean E.D.s shows that different hospitals used different imaging protocols. Since there is no defined DRL in the pandemic, some centers use routine protocols, and others try to reduce the dose but insufficiently.In pandemics such as Covid-19, when CT scan is used for screening or follow-up, DLPs can be significantly lower than in normal situations. Therefore, international regularized organizations such as the international atomic energy agency (IAEA) or the international commission on radiological protection (IRCP) should provide new DRL ranges.

Circular RNA Sec61 subunit alpha isoform 1 by competitive absorption of microRNA-513a-5p mediates peroxisomal biogenesis factor 5 expression and promotes the malignant phenotype of non-small cell lung cancer.

Circular RNAs (circRNAs) are functional RNAs in the development and metabolism of non-small cell lung cancer (NSCLC). Therein, this paper particularly elucidated the circRNA SEC61 subunit alpha isoform 1 (circSEC61A1) in NSCLC has not been fully elucidated. Clinical analysis of circSEC61A1 expression was performed on specimens collected from 51 patients with primary NSCLC, together with patients survival. Cell experiments were performed after interfering with circSEC61A1, microRNA (miR)-513a-5p, and peroxisomal biogenesis factor 5 (PEX5) expression, respectively, and cell malignant phenotypes and aerobic glycolysis were evaluated, as well as epithelial-to-mesenchymal transition (EMT)-related markers and Wntβ-catenin pathway. Xenografts experiments studied the performance of circSEC61A1 in vivo. The downstream molecules of circSEC61A1 were searched. Our data demonstrated that circSEC61A1 was upregulated in NSCLC patients, showing an association with poorer survival outcomes. In cell experiments, circSEC61A1 overexpression promoted NSCLC malignant phenotypes, glycolysis, EMT, and Wntβ-catenin pathway activation, whereas circSEC61A1 underexpression did the opposite. Knockdown of circSEC61A1 limited tumor growth and metastasis. Furthermore, circSEC61A1 could regulate PEX5 expression through competitive absorption of miR-513a-5p. Generally, circSEC61A1 is a potential biomarker for NSCLC, and circSEC61A1 serves tumor-promoting action in the progression of NSCLC.

Lobectomy versus sublobar resection for stage I (T1-T2aN0M0) small cell lung cancer A SEER population-based propensity score matching analysis.

This study evaluated whether sublobar resection (sub-L) is non-inferior to lobectomy (L) for stage I (T1-T2aN0M0) small cell lung cancer (SCLC) regarding long-term overall survival (OS). Clinicopathological and prognostic data of patients with stage I (pT1-T2aN0M0) SCLC were retrieved. Kaplan-Meier curves and Breslow tests were performed for the assessment of OS. Propensity score matching (PSM) analysis was used to mediate the inherent bias of retrospective researches. A total of 188 patients with stage I SCLC were included in this study after PSM. For resected stage I SCLC, surgery plus adjuvant therapy was related to a better OS compared with surgery only (p 0.016). For resected stage I SCLC, no matter adjuvant therapy was performed or not, no significant difference was observed in long-term OS between the L and sub-L groups (p 0.181). Further subgroup analysis demonstrated that the OS disadvantage of sub-L over L was not statistically significant for stage I SCLC patients underwent surgery only (p 0.653), but also for the patients underwent surgery plus adjuvant therapy (p 0.069). Moreover, in the subgroup analyses according to TNM stage (IA and IB), sex (male and female), and age (≥70 and <70 years), OS did not differ between the L and sub-L groups except in female patients (p 0.008). Multivariate Cox regression analysis indicated that adjuvant therapy was positively associated with OS. Surgery plus adjuvant therapy confers a better survival benefit than surgery only for stage I SCLC patients. However, as far as the range of surgical resection is concerned, sublobar resection may be non-inferior to lobectomy regarding OS. Our study could conduce to the development of optimal therapeutic strategies for stage I SCLC patients. Further validation is warranted in larger retrospective and prospective cohort studies.