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Immune cells in mesothelioma microenvironment simplistic marker of response to nivolumab plus ipilimumab

Malignant pleural mesothelioma (MPM) is a malignant disease of the pleura which recently can be treated with immune checkpoint inhibitors (ICI). To optimize this treatment, a better understanding of the tumor micro environment is needed. We investigated subgroups of immune cells in subsequent tumor biopsies of patients treated with ICI. Biopsies from MPM patients included in two clinical ICI trials (nivolumab alone and an ipilimumabnivolumab combination) were examined. At baseline and after 6 weeks of treatment, pleural biopsies were taken to examine the tumor microenvironment (CD20, CD4, CD8, FoxP3 and PD-1 ). Cell density was defined as the number of marker positive cells per mm Thirty-four and 36 patients were included in the nivolumab and ipiliumumabnivolumab trial respectively. In the nivolumab trial, no significant differences in cell densities were seen in baseline biopsies of patients with partial response versus progressive disease. In contrast, in the ipilimumabnivolumab trial, a higher cell density of CD4, CD8, FoxP3 and PD-1 cells at baseline was significantly correlated with partial responses. On-treatment biopsies of both trials did not show significant changes when compared to baseline biopsies. Biopsies from patients responding to nivolumab plus ipilimumab treatment show a significant higher cell density of CD4, CD8, FoxP3 and PD-1 cells, without a change after 6 weeks of treatment. This observation is a first step in exploring the tumor microenvironment as predictor of response in ICI treatment in MPM.

Value of Geographical Information Systems in Analyzing Geographic Accessibility to Inform Radiotherapy Planning A Systematic Review.

Vulnerable populations face geographical barriers in accessing radiotherapy (RT) facilities, resulting in heterogeneity of care received and cancer burden faced. We aimed to explore the current use of Geographical Information Systems (GIS) in access to RT and use these findings to create sustainable solutions against barriers for access in low- and middle-income countries. A systematic review using the PRISMA search strategy was done for studies using GIS to explore outcomes among patients with cancer. Included studies were reviewed and classified into three umbrella categories of how GIS has been used in studying access to RT. Forty articles were included in the final review. Thirty-eight articles were set in high-income countries and two in upper-middle-income countries. Included studies were published from 2000 to 2020, and were comprised of patients with all-cancers combined, breast, colon, skin, lung, prostate, ovarian, and rectal carcinoma patients. Studies were categorized under three groups on the basis of how they used GIS in their analyses to describe geographic access to RT, to associate geographic access to RT with outcomes, and for RT planning. Most studies fell under multiple categories. Although this field is relative nascent, there is a wide array of functions possible through GIS for RT planning, including identifying high-risk populations, improving access in high-need areas, and providing valuable information for future resource allocation. GIS should be incorporated in future studies, especially set in low- and middle-income countries, which evaluate access to RT.

Selpercatinib in Patients With

Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with Patients were enrolled to LIBRETTO-001, a phase III, single-arm, open-label study of selpercatinib in patients with In treatment-naive patients, the ORR was 84% (95% CI, 73 to 92) 6% achieved complete responses (CRs). The median DoR was 20.2 months (95% CI, 13.0 to could not be evaluated) 40% of responses were ongoing at the data cutoff (median follow-up of 20.3 months). The median PFS was 22.0 months 35% of patients were alive and progression-free at the data cutoff (median follow-up of 21.9 months). In platinum-based chemotherapy pretreated patients, the ORR was 61% (95% CI, 55 to 67) 7% achieved CRs. The median DoR was 28.6 months (95% CI, 20.4 to could not be evaluated) 49% of responses were ongoing (median follow-up of 21.2 months). The median PFS was 24.9 months 38% of patients were alive and progression-free (median follow-up of 24.7 months). Of 26 patients with measurable baseline CNS metastasis by the independent review committee, the intracranial ORR was 85% (95% CI, 65 to 96) 27% were CRs. In the full safety population (n 796), the median treatment duration was 36.1 months. The safety profile of selpercatinib was consistent with previous reports. In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with

Effect of Continuous Infusion of Intravenous Nefopam on Postoperative Opioid Consumption After Video-assisted Thoracic Surgery A Double-blind Randomized Controlled Trial.

Although nefopam has been reported to have opioid-sparing and analgesic effects in postsurgical patients, its effectiveness in video-assisted thoracoscopic surgery (VATS) is unknown. This study aimed to investigate the opioid-sparing and analgesic effects of perioperative nefopam infusion for lung resection. Double-blinded randomized controlled trial. Operating room, postoperative recovery room, and ward at a single tertiary university hospital. Ninety patients scheduled for elective VATS for lung resection were randomized to either the nefopam (group N) or control group (group C). Group N received 20 mg nefopam over 30 minutes immediately after the induction of anesthesia. Nefopam was administered continuously for 24 hours postoperative, using a dual-channel elastomeric infusion pump combined with fentanyl-based intravenous patient-controlled analgesia. Group C received the same volume of normal saline as nefopam solution administered in the same manner. The primary outcome measure was fentanyl consumption for the first postoperative 24 hours. The secondary outcome measures were the cumulative fentanyl consumption during the first postoperative 48 hours, pain intensity at rest and during coughing evaluated using an 11-point numeric rating scale, quality of recovery at postoperative time points 24 hours and 48 hours, and the occurrence of analgesic-related side effects during the first postoperative 24 hours and postoperative 24 to 48 hour period. Variables related to chronic postsurgical pain (CPSP) were also investigated by telephone interviews with patients at 3 months postoperative. This prospective randomized trial was approved by the appropriate institutional review board and was registered in the ClinicalTrials.gov registry. A total of 83 patients were enrolled. Group N showed significantly lower fentanyl consumption during the first postoperative 24 hours and 48 hours (24 hours median difference -270 µg 95%CI, -400 to -150 µg, P < 0.001) 48 hours median difference -365 µg 95% CI -610 to -140 µg, P < 0.001). Group N also showed a significantly lower pain score during coughing at 24 hours postoperative (median difference, -1 corrected 95% CI -2.5 to 0, adjusted P 0.040). However, there were no significant between-group differences in the postoperative quality of recovery, occurrence of analgesic-related side effects, length of hospital stay, and occurrence of CPSP. Despite the significant opioid-sparing effect of perioperative nefopam infusion, it would have been difficult to observe significant improvements in other postoperative outcomes owing to the modest sample size. Perioperative nefopam infusion using a dual-channel elastomeric infusion pump has a significant opioid-sparing effect in patients undergoing VATS for lung resection. Therefore, it could be a feasible option for multimodal analgesia in these patients.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) Prevalence, clinicopathological characteristics and survival outcome in a cohort of 311 patients with well-differentiated lung neuroendocrine tumours.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS). We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020. Clinical data were collected from medical records. The relationship between baseline characteristics and TTP and OS was analysed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazards model. Of 311 patients with well-differentiated lung NETs, 61 (20%) had DIPNECH and were included in the study. Baseline demographics described 95% female, 59% never smokers and mean body mass index 34.4 kg m DIPNECH may be more prevalent in the lung NET population than previously appreciated, especially in women. Although our results confirm that DIPNECH is predominantly an indolent disease associated with TC, 23% developed AC and these patients may warrant closer observation.

Nanomaterials-Mediated Co-Stimulation of Toll-Like Receptors and CD40 for Antitumor Immunity.

Toll-like receptors (TLRs) and CD40-related signaling pathways represent critical bridges between innate and adaptive immune responses. Here, an immunotherapy regimen that enables co-stimulation of TLR78- and CD40-mediated pathways is developed. TLR78 agonist resiquimod (R848) derived amino lipids, RAL1 and RAL2, are synthesized and formulated into RAL-derived lipid nanoparticles (RAL-LNPs). The RAL2-LNPs show efficient CD40 mRNA delivery to DCs both in vitro (90.8 ± 2.7%) and in vivo (61.3 ± 16.4%). When combined with agonistic anti-CD40 antibody, this approach can produce effective antitumor activities in mouse melanoma tumor models, thereby suppressing tumor growth, prolonging mouse survival, and establishing antitumor memory immunity. Overall, RAL2-LNPs provide a novel platform toward cancer immunotherapy by integrating innate and adaptive immunity.

Antenatal Steroid Exposure Among Term Newborns.

This cross-sectional study evaluates the association between dissemination of the Antenatal Late Preterm Steroid trial and changes in steroid exposure among term newborns.

Validation of deep learning-based computer-aided detection software use for interpretation of pulmonary abnormalities on chest radiographs and examination of factors that influence readers performance and final diagnosis.

To evaluate the performance of a deep learning-based computer-aided detection (CAD) software for detecting pulmonary nodules, masses, and consolidation on chest radiographs (CRs) and to examine the effect of readers experience and data characteristics on the sensitivity and final diagnosis. The CRs of 453 patients were retrospectively selected from two institutions. Among these CRs, 60 images with abnormal findings (pulmonary nodules, masses, and consolidation) and 140 without abnormal findings were randomly selected for sequential observer-performance testing. In the test, 12 readers (three radiologists, three pulmonologists, three non-pulmonology physicians, and three junior residents) interpreted 200 images with and without CAD, and the findings were compared. Weighted alternative free-response receiver operating characteristic (wAFROC) figure of merit (FOM) was used to analyze observer performance. The lesions that readers initially missed but CAD detected were stratified by anatomic location and degree of subtlety, and the adoption rate was calculated. Fishers exact test was used for comparison. The mean wAFROC FOM score of the 12 readers significantly improved from 0.746 to 0.810 with software assistance (P 0.007). In the reader group with < 6 years of experience, the mean FOM score significantly improved from 0.680 to 0.779 (P 0.011), while that in the reader group with ≥ 6 years of experience increased from 0.811 to 0.841 (P 0.12). The sensitivity of the CAD software and the adoption rate for the lesions with subtlety level 2 or 3 (obscure) lesions were significantly lower than for level 4 or 5 (distinct) lesions (50% vs. 93%, P < 0.001 and 55% vs. 74%, P 0.04, respectively). CAD software use improved doctors performance in detecting nodulesmasses and consolidation on CRs, particularly for non-expert doctors, by preventing doctors from missing distinct lesions rather than helping them to detect obscure lesions.

Systemic Sclerosis Association with Malignancy.

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.

PLEK2 and IFI6, representing mesenchymal and immune-suppressive microenvironment, predicts resistance to neoadjuvant immunotherapy in esophageal squamous cell carcinoma.

Immunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated. Transcriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence. PLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort PLEK2 PLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment.

Socioeconomic and insurance-related disparities in disease-specific survival among patients with metastatic bone disease.

Approximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD. Patients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016). Kaplan-Meier and Cox Proportional Hazard models were used to evaluate survival, and prognostic factors for each cohort. Prognostic significance of socioeconomic status (SES) and insurance status were ascertained. The five most common anatomical-sites with MBD at presentation included lung (n 59 739), prostate (n 19 732), breast (n 16 244), renal and urothelium (n 7718) and colon (n 3068). Lower SES was an independent risk factor for worse disease-specific survival (DSS) for patients with MBD originating from lung, prostate, breast and colon. Lack of insurance was an independent risk factor for worse DSS for MBD patients with primary tumors in lung and breast. MBD patients from the five most common primary sites demonstrated SES and insurance-related disparities in disease-specific survival. This is the first and largest study to explore SES and insurance-related disparities among patients specifically afflicted with MBD. Our findings highlight vulnerability of patients with MBD across multiple primary sites to financial toxicity.

Anticancer Activity of ST101, A Novel Antagonist of CCAATEnhancer Binding Protein β.

CCAATenhancer binding protein β (CEBPβ) is a basic leucine zipper (bZIP) family transcription factor, which is upregulated or overactivated in many cancers, resulting in a gene expression profile that drives oncogenesis. CEBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously undruggable oncogenic target. Here we describe the mechanism of action and antitumor activity of ST101, a novel and selective peptide antagonist of CEBPβ that is currently in clinical evaluation in patients with advanced solid tumors. ST101 binds the leucine zipper domain of CEBPβ, preventing its dimerization and enhancing ubiquitin-proteasome dependent CEBPβ degradation. ST101 exposure attenuates transcription of CEBPβ target genes, including a significant decrease in expression of survival, transcription factors, and cell-cycle-related proteins. The result of ST101 exposure is potent, tumor-specific in vitro cytotoxic activity in cancer cell lines including glioblastoma, breast, melanoma, prostate, and lung cancer, whereas normal human immune and epithelial cells are not impacted. Further, in mouse xenograft models ST101 exposure results in potent tumor growth inhibition or regression, both as a single agent and in combination studies. These data provide the First Disclosure of ST101, and support continued clinical development of ST101 as a novel strategy for targeting CEBPβ-dependent cancers.

Guangsangon E triggers mitochondria dysfunction and mitophagy in triple-negative breast cancer and leads to non-apoptotic cell death.

Guangsangon E (GSE) is a natural product separated from Morus alba L. It has been reported to treat lung cancer through autophagy. However, whether GSE is effective in repressing triple-negative breast cancer (TNBC) cells is yet to be elucidated. In the present study, GSE inhibited cell growth of MDA-MB-231, MDA-MB-453, and MDA-MB-468 cells. Moreover, GSE induced mitochondrial dysfunction, including membrane potential loss, mitochondria fission, and reactive oxygen species accumulation, and finally led to mitophagy-related non-apoptotic cell death. In the xenograft tumor nude mice, GSE treatment significantly reduced the size and weight of MDA-MB-231 tumors. The tumor inhibition rates of GSE treatment were 49.68% (low-dose) and 48.73% (high-dose). In summary, GSE is a potential anticancer drug available for treating TNBC with apoptosis resistance.

Identification of the BolA Protein Reveals a Novel Virulence Factor in K. pneumoniae That Contributes to Survival in Host.

BolA has been characterized as an important transcriptional regulator, which is induced in the stationary phase of growth and is often associated with bacterial virulence. This study was initiated to elucidate the role of the BolA in the virulence of K. pneumoniae. Using a mouse infection model, we revealed

SOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling.

The balance between self-renewal and differentiation in human foetal lung epithelial progenitors controls the size and function of the adult organ. Moreover, progenitor cell gene regulation networks are employed by both regenerating and malignant lung cells, where modulators of their effects could potentially be of therapeutic value. Details of the molecular networks controlling human lung progenitor self-renewal remain unknown. We performed the first CRISPRi screen in primary human lung organoids to identify transcription factors controlling progenitor self-renewal. We show that SOX9 promotes proliferation of lung progenitors and inhibits precocious airway differentiation. Moreover, by identifying direct transcriptional targets using Targeted DamID, we place SOX9 at the centre of a transcriptional network, which amplifies WNT and RTK signalling to stabilise the progenitor cell state. In addition, the proof-of-principle CRISPRi screen and Targeted DamID tools establish a new workflow for using primary human organoids to elucidate detailed functional mechanisms underlying normal development and disease.

Advanced age is associated with changes in alveolar macrophages and their responses to the stress of traumatic injury.

Alveolar macrophages (AMs) are tissue-resident cells of the lower airways that perform many homeostatic functions critical for pulmonary health and protection against pathogens. However, little is known about the factors that shape AMs during healthy aging. In these studies, we sought to characterize age-related changes in AM phenotype, function, and responses to a physiologic stressor, that is, distal injury. Age was associated with a wide range of changes in cell surface receptor and gene expression by AMs, reflecting a unique alternatively activated phenotype. AMs from aged mice also exhibited markers of cellular senescence along with down-regulation of genes involved in growth and cell cycle pathways relative to young controls. Furthermore, AMs from aged mice showed a stunted transcriptional response to distal injury compared with AMs from young mice. Many changes were found to involve glucocorticoid-regulated genes, and corticosteroid treatment of primary AMs ex vivo revealed diminished transcriptional responses in cells from aged animals. These results demonstrate that there is a complex age-dependent AM phenotype associated with dysregulated stress hormone signaling that may interfere with AM responses to physiologic stressors and could contribute to AM dysfunction and the decline of pulmonary immunity during healthy aging.

Overcoming cisplatin resistance of human lung cancer by sinomenine through targeting the miR-200a-3p-GLS axis.

Lung cancer, a malignant disease, is one of the leading causes of patient death. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Currently, chemotherapeutic agents such as cisplatin are widely used against lung cancer. However, development of chemoresistance, which led to poor prognosis and low survival rate greatly limited the clinical applications of cisplatin. Sinomenine (SIN) is a bioactive component of sinomenium acutum. Accumulating evidence revealed SIN exhibits potential anti-tumor activities in various types of cancers. However, the precise molecular mechanisms for the sinomenine-induced anti-cancer effects have not been fully elucidated. Here, we assessed the effects of sinomenine on cisplatin sensitivity in NSCLC cells. The combination of SIN with cisplatin showed synergistically inhibitory effects on lung cancer cells by calculating the combination index (CI value) using the Calcusyn 2.0 software. Moreover, we detected that the glutamine metabolism was significantly suppressed by sinomenine treatments in lung cancer cells. Under low glutamine supply, A549 cells showed less sensitivity to sinomenine treatments. Meanwhile, miR-200a-3p was found to be significantly induced by SIN treatments. We demonstrated a suppressive role of miR-200a-3p on glutamine metabolism. Furthermore, miR-200a-3p was downregulated but the glutamine metabolism was significantly hyperactive in A549 cisplatin resistant cells compared with parental cells. Bioinformatical analysis and luciferase assay demonstrated the glutaminase (GLS), a key enzyme of glutamine metabolism, is the direct target of miR-200a-3p in lung cancer cells. Finally, rescue experiments demonstrated that recovery of GLS in miR-200a-3p overexpressing-cisplatin resistant cells successfully overrode the sinomenine-mediated cisplatin sensitization. In summary, this study revealed a new molecular mechanism for the sinomenine-promoted cisplatin sensitization, contributing to investigating the sinomenine-based therapeutic agents against chemoresistant NSCLC.

Neighborhood Deprivation, Hospital Quality and Mortality After Cancer Surgery.

To evaluate if receipt of complex cancer surgery at high quality hospitals is associated with a reduction in disparities between individuals living in the most and least deprived neighborhoods. The association between social risk factors and worse surgical outcomes for patients undergoing high-risk cancer operations is well documented. To what extent neighborhood socioeconomic deprivation as an isolated social risk factor known to be associated with worse outcomes can be mitigated by hospital quality is less known. Using 100% Medicare fee-for-service claims, we analyzed data on 212,962 Medicare beneficiaries >age 65 undergoing liver resection, rectal resection, lung resection, esophagectomy and pancreaticoduodenectomy for cancer between 2014 and 2018. Clinical risk-adjusted 30-day post-operative mortality rates were used to stratify hospitals into quintiles of quality. Beneficiaries were stratified into quintiles based on census tract Area Deprivation Index. The association of hospital quality and neighborhood deprivation with 30-day mortality was assessed using logistic regression. There were 212,962 patients in the cohort including 109,419(51.4%) men with mean (SD) age of 73.8(5.9) years old. At low-quality hospitals, patients living in the most deprived areas had significantly higher risk-adjusted mortality than those from the least deprived areas for all procedures esophagectomy 22.3% versus 20.7% P<0.003, liver resection 19.3% versus 16.4% P<0.001, pancreatic resection 15.9% versus 12.9% P<0.001, lung resection 8.3% versus 7.8% P<0.001, rectal resection 8.8% versus 8.1% P<0.001. Surgery at a high-quality hospitals was associated with no significant differences in mortality between individuals living in the most compared to least deprived neighborhoods for esophagectomy, rectal resection, liver resection and pancreatectomy. For example, the adjusted odds of mortality between individuals living in the most deprived compared to least deprived neighborhoods following esophagectomy at low quality hospitals (OR 1.22 95% CI 1.14-1.31 P<0.001) was higher than at high quality hospitals (OR 0.98, 95%CI 0.94-1.02 P0.03). Receipt of complex cancer surgery at a high-quality hospital was associated with no significant differences in mortality between individuals living in the most deprived neighborhoods compared to least deprived. Initiatives to increase access referrals to high quality hospitals for patients from high deprivation levels may improve outcomes and contribute to mitigating disparities.

CT-based radiomics signature to predict CD8 tumor infiltrating lymphocytes in non-small-cell lung cancer.

An abundance of CD8 tumor infiltrating lymphocytes (TILs) in the center of solid tumors is a reliable predictive biomarker for patients eligible for immunotherapy. To develop a computed tomography (CT)-based radiomics signature for a preoperative prediction of an abundance of CD8 TILs in non-small-cell lung cancer (NSCLC). In this retrospective study, 117 consecutive patients with pathologically confirmed NSCLC were included and randomly divided into training (n 77) and test sets (n 40). A total of 107 radiomics features were extracted from the three-dimensional volumes of interest of each patient. Least absolute shrinkage and selection operator (LASSO) regression was used to select the strongest features for abundance of CD8 TILs in NSCLC, and the radiomics score was constructed through a linear combination of these selected features. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the radiomics score. The radiomics score was associated with an abundance of CD8 TILs in NSCLC, which achieved an area under the curve (AUC) of 0.83 (95% CI0.73-0.92) and 0.68 (95% CI0.54-0.87) in the training and test sets, respectively. The difference was not statistically significant ( CT-based radiomics features have the ability to predict CD8 TILs expression levels of an abundance of CD8 TILs in NSCLC, which was shown to be a potential imaging biomarker for stratifying patients who may benefit from immunotherapy.

Precise quantitative evaluation of pharmacokinetics of cisplatin using a radio-platinum tracer in tumor-bearing mice.

The platinum-based antineoplastic drug cisplatin is commonly used for chemotherapy in clinics. This work aims to demonstrate a radio-platinum tracer is useful for precisely quantifying small amounts of platinum in pharmacokinetics studies. A cisplatin radiotracer (radio-cisplatin) was synthesized, and a comprehensive evaluation of cisplatin over 7 days after its intravenous injection into nude mice bearing a subcutaneous lung tumor (H460) was conducted. A biphasic retention curve in the whole body and blood was observed T12 (α) 1.14 h, T12 (β) 5.33 days for the whole body, and T12 (α) 23.9 min, T12 (β) 4.72 days for blood. The blood concentration decreased within 1 day after injection. Most of the intact cisplatin was excreted via the kidneys in the early time points, and a small part was distributed in tissues including tumors. The plasma protein binding rate of cisplatin increased rapidly after injection, and the protein-bound cisplatin remained in the blood longer than intact cisplatin. The peak uptake in H460 tumors was 4.7% injected dose per gram at 15 min after injection, and the area under the curve (AUC 0-7 days ) was approximately one-half to one-third of the AUC 0-7 days in the kidneys, liver, and bone, where some toxicity is observed in humans. The radio-platinum tracer revealed the highly quantitative biodistribution of cisplatin, providing insights into the properties of cisplatin, including its adverse effects. The tracer enables a precise evaluation of pharmacokinetics for platinum-based drugs with high sensitivity.

Endothelial activation and stress index (EASIX) as a predictive biomarker in small cell lung cancer.

Endothelial activation and insult may contribute to the aggressive clinical course of small-cell lung cancer (SCLC) however, no predictive biomarker for this pathogenesis has been identified. To evaluate the clinical impact of the endothelial activation and stress index (EASIX) in SCLC. In this retrospective study, the EASIX was calculated from measurements of serum lactate dehydrogenase, creatinine, and platelet levels. A total of 264 patients with SCLC treated with platinum-based chemotherapy were stratified into high and low EASIX groups. Complete and objective response rates in the limited-stage (LD) were 19.5% vs. 33.3% (P 0.050) and 85.4% vs. 97.9% (P 0.028) in the high and low EASIX groups, respectively. There was no significant difference in the response rate between the two groups in the extensive-stage (ED). The median overall survival was 9.8 vs. 40.5 months in LD (P< 0.001) and 7.2 vs. 11.9 months in ED (P< 0.001) in the high and low EASIX groups, respectively. In multivariate analyses, a high EASIX level was an independent prognostic factor for worse progression-free and overall survival irrespective of stage. EASIX may be a potential predictive biomarker of SCLC.

Clinical application of the optimized X-ray parameter model through analysis of disease risk and image quality when combining the ion chamber of automatic exposure control of digital radiography.

To present an optimized examination model by analyzing the risk of disease and image quality according to the combination of the ion chamber of automatic exposure control (AEC) with digital radiography (DR). The X-ray quality was analyzed by first calculating the percentage average error (PAE) of DR. After that, when using AEC, the combination of the ion chambers was the same as the left and centre and right, right and centre, left and centre, centre, right, and left, for a total of six. Accordingly, the entrance surface dose (ESD), risk of disease, and image quality were evaluated. ESD was obtained by attaching a semiconductor dosimeter to the L4 level of the lumbar spine, and then irradiating X-rays to dosimeter centre through average and standard deviation of radiation dose. The calculated ESD was input into the PCXMC 2.0 programme to evaluate disease risk caused by radiation. Meanwhile, image quality according to chamber combination was quantified as the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) through Image J. X-ray quality of DR used in the experiment was within the normal range of±10. ESD of six ion chamber combinations was 1.363mGy, 0.964mGy, 0.946mGy, 0.866mGy, 0.748mGy, 0.726mGy for lumbar anteroposterior (AP), and the lumbar lateral values were 1.126mGy, 0.209mGy, 0.830mGy, 0.662mGy, 0.111mGy, and 0.250mGy, respectively. Meanwhile, disease risk analyzed through PCXMC 2.0 was bone marrow, colon, liver, lung, stomach, urinary and other tissue cancer, and disease risk showed a tendency to increase in proportion to ESD. SNR and CNR recorded the lowest values when three chambers were combined and did not show proportionality with dose, while showed the highest values when two chambers were combined. In this study, combination of three ion chambers showed the highest disease risk and lowest image quality. Using one ion chamber showed the lowest disease risk, but lower image quality than two ion chambers. Therefore, if considering all above factors, combination of two ion chambers can optimally maintain the disease risk and image quality. Thus, it is considered an optimal X-ray examination parameter.

Histamine activates an intracellular Ca

Histamine is an inflammatory mediator that can be released from mast cells to induce airway remodeling and cause persistent airflow limitation in asthma. In addition to stimulating airway smooth muscle cell constriction and hyperplasia, histamine promotes pulmonary remodeling by inducing fibroblast proliferation, contraction, and migration. It has long been known that histamine receptor 1 (H1R) mediates the effects of histamine on human pulmonary fibroblasts through an increase in intracellular Ca

Corrigendum Negatively regulated by miR-29c-3p, MTFR1 promotes the progression and glycolysis in lung adenocarcinoma via the AMPKmTOR signalling pathway.

This corrects the article DOI 10.3389fcell.2021.771824..

Knockdown of RhoQ, a member of Rho GTPase, accelerates TGF-β-induced EMT in human lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related deaths worldwide, and the most common subtype of lung cancer is adenocarcinoma. RhoQ is a Rho family GTPase with primary sequence and structural similarities to Cdc42 and RhoJ. RhoQ is involved in neurite outgrowth via membrane trafficking and is essential for insulin-stimulated glucose uptake in mature adipocytes. However, the function of RhoQ in lung adenocarcinoma (LUAD) remains unclear. In this study, RhoQ siRNAs were introduced into A549 and PC-9 cells. Expression level of EMT-related genes and invasion ability were investigated using Western blot and transwell assay. To examine the relationship between RhoQ expression and prognosis of LUAD, Kaplan-Meier plotter was used. We discovered that suppressing RhoQ expression promoted TGF-β-mediated EMT and invasion in LUAD cell lines. Furthermore, RhoQ knockdown increased Smad3 phosphorylation and Snail expression, indicating that RhoQ was involved in TGFSmad signaling during the EMT process. Moreover, Kaplan-Meier plotter analysis revealed that low RhoQ levels were associated with poor overall survival in patients with LUAD. In conclusion, these findings shed light on RhoQs role as a negative regulator of TGF-β-mediated EMT in LUAD.

Effect of safranal on the response of cancer cells to topoisomerase I inhibitors Does sequence matter

Lung and colorectal cancers are among the leading causes of death from cancer worldwide. Although topotecan (TPT), a topoisomerase1 inhibitor, is a first- and second-line drug for lung and colon cancers, the development of drug resistance and toxicity still remain as a major obstacle to chemotherapeutic success. Accumulating evidence indicates increased efficacy and reduced toxicity of chemotherapeutic agents upon combining them with natural products. We aimed to investigate the possible interaction of safranal (SAF), a natural compound obtained from

KC-180-2 Exerts Anti-SCLC Effects via Dual Inhibition of Tubulin Polymerization and Src Signaling.

In this study, a series of

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin (

A Clinical Study on the Use of Yiqi Yangxue Decoction Combined with Chemotherapy to Promote Rapid Postoperative Recovery in Patients with Non-Small Cell Lung Cancer.

To observe the promotion effect of Yiqi Yangxue decoction combined with chemotherapy on the rapid recovery of non-small cell lung cancer (NSCLC) patients after surgery. Eighty postoperative NSCLC patients admitted to our hospital from April 2019 to September 2021 were divided into a chemotherapy group ( After treatment, the levels of CEA, CYFRA21-1, and CA-125 were lower than those before treatment in both groups, and they were lower in the TCM group than in the chemotherapy group ( The combination of Yiqi Yangxue decoction combined with chemotherapy for postoperative NSCLC patients can effectively reduce serum tumour marker levels, enhance the bodys immune function and sleep quality, and the patients efficacy and toxicity reduction are obvious, which is conducive to the rapid recovery of many indicators after surgery.

Two non-small cell lung cancer (NSCLC) patients with brain metastasis harboring epidermal growth factor receptor (EGFR) G719X and L861Q mutations benefited from aumolertinib two cases report and review of the literature.

The third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) established a new standard for EGFR mutation positive non-small cell lung cancer (NSCLC) treatment. Brain metastases (BMS) are common in NSCLCs with poor prognosis, and patients with BMS who carry uncommon mutations is lack of treatment options. Aumolertinib is the first third-generation EGFR TKI in China and the second in the global context. There are few reports of the efficacy of aumolertinib in treating NSCLC patients with BMS who harboring uncommon EGFR mutations, which is needs to be investigated. Here we reported two cases of aumolertinib in treating NSCLC patients with BMS harboring EGFR G719XL861Q mutations. The first one was diagnosed with poorly differentiated stage IVB adenocarcinoma with brain metastases. Genetic tests showed mutations in exons of EGFR 18 (G719D) and 21 (L861Q) initially. The patient was administered with pemetrexed 0.8 g and lobaplatin 30 mg, and aumolertinib (110 mg QD) combined with one-month of WBRT(Whole Brain Radiation Therapy) (42 Gy in 7 fractions). In order to avoid the side effects of radiotherapy on brain, radiotherapy was discontinued on February 5, 2020. The regime was continued with pemetrexed 0.75 g, lobaplatin 30 mg, bevacizumab 400 mg, and aumolertinib 110 mg QD. The four-drug combination regimen lasted for 6 months until serum tumor markers were elevated slightly. Then lobaplatin was replaced with nedaplatin, and the new four-drug combination regimen (pemetrexed 0.75 g, nedaplatin 90mg, bevacizumab 400 mg, and aumolertinib 110mg QD) was used with a one-month cycle for 3 cycles. Aumolertinib was administered daily throughout the four-drug combination, with the rest administered on day 1 of this treatment cycle. Chest CT scan were performed each month, which showed no progressed of lung disease. The patient had a progression-free survival of 13 months and is still being treated with aumolertinib. The second patient was diagnosed as right lung adenocarcinoma (T3N2M1) IVB secondary bone and brain malignancy carrying EGFR 18 (G719A) and 21 (L861Q) exon mutation. Aumolertinib combined with local radiotherapy was used after failure of afatinib combined with radiotherapy. Follow-up chest CT and brain MRI revealed that the lung lesions were partially relieved. Furthermore, the multiple nodules in the brain were relieved and cerebral edema was reduced. The aumolertinib monotherapy was continued, and follow-up imaging showed no disease progression. PFS was 13 months during the treatment with aumolertinib. The two cases showed good efficacy of aumolertinib in treating patients with brain metastases (BMS) that harbored EGFR 18 (G719X) and 21 (L861Q) mutations.

ZNF516 suppresses stem cell-like characteristics by regulating the transcription of Sox2 in colorectal cancer.

This study aimed to explore the biological function and the molecular mechanism of the action of zinc-finger protein 516 (ZNF516) in suppressing stem cell-like characteristics and tumor progression in colorectal cancer (CRC). The expression profiles of ZNF516 in clinical samples and from The Cancer Genome Atlas (TCGA) CRC database were analyzed. Cell transfection was used to overexpress and knockdown ZNF516 in CRC cells. Cell counting kit-8 (CCK8) assays, transwell assays and flow cytometry were used to study cell proliferation, invasion and stem cell-like characteristics, respectively. Cycloheximide (CHX) was used to examine the effect of ZNF516 expression on Sox2 degradation. Finally, the effects of ZNF516 on tumor growth and metastasis were tested on xenograft tumor models and lung metastasis models in immunocompromised mice. We found that the expression level of ZNF516 was lower in TCGA CRC tissue and clinical CRC samples compared with that in normal colorectal mucosal cells. Overexpression of ZNF516 in CRC cells inhibited cell proliferation, colony formation, migration and invasion, whereas ZNF516 knockdown showed the opposite effects. In addition, ZNF516 overexpression inhibited the sphere-forming ability of CRC cells and suppressed the expression of CD133, CD44 and Oct4 in CRC cells. ZNF516 decreased the stability of Sox2 through a mechanism mediated by EGFR. By

Fear of cancer recurrence is related to the efficacy of immunotherapy and quality of life in patients with NSCLC during the COVID-19 pandemic in China.

The outbreak of the COVID-19 pandemic has greatly impacted patients with non-small cell lung cancer (NSCLC), making the fear of cancer recurrence (FCR) more pronounced. We explored the effects of FCR on immunotherapy efficacy and quality of life during the COVID-19 pandemic in China among the 124 NSCLC patients enrolled in this study. Quality of life and immunotherapy efficacy were compared between high- and low-FCR groups after completing 4-6 courses of treatment or cancer progression. Worse immunotherapy efficacy and quality of life were reported for the high-FCR group than for the low-FCR group. These findings emphasize the need to pay close attention to the level of FCR in NSCLC patients. Efforts should be taken to alleviate FCR levels among NSCLC patients. Moreover, research is needed to investigate the possible link between immunotherapy efficacy and FCR.

COA3 overexpression promotes non-small cell lung cancer metastasis by reprogramming glucose metabolism.

Recent advances in cancer research have revealed a close relationship between mitochondrial dysfunction and cancer development. Human COX assembly factor 3 (COA3), also known as CCDC56, is a mitochondrial transmembrane protein responsible for cytochrome c oxidase (COX) protein complex assembly. However, the clinical implication and biological functions of COA3 remain unexplored in human cancers, including non-small cell lung cancer (NSCLC). Here, we found that COA3 is overexpressed at both mRNA and protein levels in human NSCLC cells, mainly as a result of decreased miR-338-3p level. The protein expression level of COA3 is positively associated with lymph node metastasis and predicts poor survival in patients with NSCLC. Silencing of COA3 significantly attenuated, while forced COA3 expression enhanced the migration and invasiveness of NSCLC cells. Mechanistically, we found that aerobic glycolysis, induced at least in part by dynamic-related protein 1 (DRP1) phosphorylation-mediated mitochondrial fragmentation, contributed to COA3-promoted NSCLC metastasis. Together, our study illustrates that COA3 plays a crucial role in NSCLC carcinogenesis, implying COA3 as a prognostic marker and treatment target in NSCLC.

Development and validation of a combined ferroptosis- and pyroptosis-related gene signatures for the prediction of clinical outcomes in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a very heterogeneous cancer with a bad prognosis. Pyroptosis and ferroptosis are two newly discovered forms of regulated cell death, which can trigger inflammation-related immunosuppression in tumor microenvironments, thereby promoting tumor growth. So far, there has been no thorough systematic investigation of the predictive values of ferroptosis and pyroptosis-related genes in LUAD. Therefore, in this study, we conducted a combined analyses in the gene expression of ferroptosis and pyroptosis and identified four distinct subgroups immobility, ferroptosis, pyroptosis, and mixed. The gene sets most closely associated to both ferroptosis and pyroptosis were utilized to build a risk prediction model based on their variations in survival and biological activities. More importantly, our conclusions from bioinformatics analyses were validated by external experiments in patients with LUAD. In conclusion, the establishment of LUAD subgroups based on the ferroptosis- and pyroptosis-related gene expression profile provided new insights into understanding the roles of programmed cell death in oncogenesis and might contribute to the development of individualized therapy.

Autophagy in pulmonary fibrosis friend or foe

Autophagy is an evolutionarily conserved process where long-lived and damaged or-ganelles are degraded. Autophagy has been widely associated with several ageing-process as well in diseases such as neurodegeneration, cancer and fibrosis, and is now being utilised as a target in these diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive, interstitial lung disease with limited treatment options available. It is characterised by abnormal extracellular matrix (ECM) deposition by activated myofibroblasts. It is understood that repetitive micro-injuries to aged-alveolar epithelium combined with genetic factors drive the disease. Several groups have demonstrated that autophagy is altered in IPF although whether autophagy has a protective effect or not is yet to be determined. Autophagy has also been shown to influence many other processes including epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT) which are known to be key in the pathogenesis of IPF. In this review, we summarise the findings of evidence of altered autophagy in IPF lungs, as well as examine its roles within lung fibrosis. Given these findings, together with the growing use of autophagy manipulation in a clinical setting, this is an exciting area for further research in the study of lung fibrosis.

Corrigendum to Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50%.

This corrects the article DOI 10.117717588359221105024..

Real-world global data on targeting epidermal growth factor receptor mutations in stage III non-small-cell lung cancer the results of the KINDLE study.

Tyrosine kinase inhibitors (TKIs) are the standard of care for resectable and metastatic non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (EGFRm). We describe the real-world practice of EGFRm testing, prevalence, treatment and outcomes in EGFRm stage III NSCLC from a multi-country, observational study. The KINDLE study retrospectively captured diagnostic information, treatments and survival outcomes in patients with stage III NSCLC from January 2013 to December 2017. Baseline characteristics and treatments were described and real-world outcomes from initial therapy were analysed using Kaplan-Meier methods. A total of 3151 patients were enrolled across three regions Asia ( The KINDLE study showed that a minority of stage III NSCLC patients were tested for EGFRm. Patients with EGFRm with unresectable NSCLC had similar outcomes from cCRT as initial therapy compared with EGFR wild type with a trend in OS favouring the EGFRm group. Outcomes with EGFR-TKI monotherapy as initial therapy, without any irradiation, were worse. The ongoing LAURA study (NCT03521154) will help define the role of EGFR-TKIs in EGFRm stage III NSCLC treated with cCRT. NCT03725475.

Incidence of venous thromboembolism after surgery for adenocarcinoma

Recently, the new World Health Organization (WHO) tumor classification removed adenocarcinoma A retrospective study was performed on AIS and IA adenocarcinoma in our hospital from January 2018 to December 2021, and divided into AIS group and AD group. Propensity score matching (PSM) was used to compare the incidence of VTE and coagulation function, and to analyze whether the RAM is more effective when the malignancy item is not evaluated in AIS. 491 patients were included after screening, including 104 patients in the AIS group and 387 patients in the AD group. After PSM, 83 patients were matched. The incidence of VTE and D-dimer in the AIS group was significantly lower than that in the AD group (P<0.05).When using the RAM to score AIS, compared with retaining the malignancy item, the incidence of VTE in the intermediate-high-risk group was significantly higher after removing the item (7.9% vs. 36.4%, P0.018), which significantly improved the stratification effect of the model. The incidence of postoperative VTE in AIS was significantly lower than that in stage IA adenocarcinoma. The stratification effect was more favorable when the malignancy item was not evaluated in AIS using the RAM.

Survival and clinicopathological significance of PYCR1 expression in cancer A meta-analysis.

Proline metabolism is closely related to the occurrence and development of cancer. Δ1-Pyrroline-5-carboxylate reductase (PYCR) is the last enzyme in proline biosynthesis. As one of the enzyme types, PYCR1 takes part in the whole process of the growth, invasion, and drug resistance of cancer cells. This study investigated PYCR1 expressions in cancers together with their relationship to clinical prognosis. A thorough database search was performed in PubMed, EMBASE, and Cochrane Library. RevMan5.3 software was used for the statistical analysis. Eight articles were selected, and 728 cancer patients were enrolled. The cancer types include lung, stomach, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. The meta-analysis results showed that the expression of PYCR1 was higher in the clinical stage III-IV group than that in the clinical stage I-II group (OR 1.67, 95%CI 1.03-2.71), higher in the lymph node metastasis group than in the non-lymph node metastasis group (OR 1.57, 95%CI 1.06-2.33), and higher in the distant metastasis group than in the non-distant metastasis group (OR 3.46, 95%CI 1.64-7.29). However, there was no statistical difference in PYCR1 expression between different tumor sizes (OR 1.50, 95%CI 0.89-2.53) and degrees of differentiation (OR 0.82, 95%CI 0.54-1.24). PYCR1 had a high expression in various cancers and was associated with cancer volume and metastasis. The higher the PYCR1 expression was, the poorer the cancer prognosis was. The molecular events and biological processes mediated by PYCR1 might be the underlying mechanisms of metastasis.

Adjuvant chemotherapy may improve long-term outcomes in stage IB non-small cell lung cancer patients with previous malignancies A propensity score-matched analysis.

Routine administration of adjuvant chemotherapy for stage IB non-small cell lung cancer (NSCLC) remains controversial. To our knowledge, no available studies have assessed the outcomes of chemotherapy in patients with stage IB NSCLC who had prior malignancies. Patients with pathological stage IB NSCLC with previous malignancies who underwent surgery between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized into chemotherapy and observation group based on whether they received adjuvant chemotherapy. Propensity score matching was performed to reduce confounding bias, and Kaplan-Meier curves and log-rank tests were used to compare overall survival (OS) and cancer-specific survival (CSS) between the two groups. Subgroup analyses of the matched cohorts were then conducted to evaluate the relationship between clinical features and chemotherapy. A total of 894 eligible patients were identified 90 (10.1%) patients received postoperative chemotherapy. Patients who received adjuvant chemotherapy obtained obvious OS benefits compared with those who received observation alone (HR 0.68, 95% CI 0.48-0.97, These findings indicate that adjuvant chemotherapy may improve long-term outcomes for stage IB NSCLC patients with previous malignancies. It is recommended that physicians consider the clinical features of previous cancers when making adjuvant chemotherapy decisions for these patients.

Real-world clinical treatment outcomes in Chinese non-small cell lung cancer with

In our study, we retrospectively collected next-generation sequencing (NGS) data from 7,831 Chinese NSCLC patients and analyzed the relationship between Our data showed that Overall survival was significantly longer in

3D-printed bolus ensures the precise postmastectomy chest wall radiation therapy for breast cancer.

To investigate the values of a 3D-printed bolus ensuring the precise postmastectomy chest wall radiation therapy for breast cancer. In the preclinical study on the anthropomorphic phantom, the 3D-printed bolus was used for dosimetry and fitness evaluation. The dosimetric parameters of planning target volume (PTV) were assessed, including D In preclinical studies, a 3D-printed bolus can better ensure the radiation coverage of PTV (HI 0.05, CI 99.91%), the dose accuracy (%diff 0.99%), and skin fitness (mean air gap 1.01 mm). Of the 27 eligible patients, we evaluated the radiation dose parameter (median(min-max) D A 3D-printed bolus can guarantee the precise radiation dose on skin surface, good fitness to skin, and controllable acute skin toxicity, which possesses a great clinical application value in postmastectomy chest call radiation therapy for breast cancer.

The expression and biological effect of NR2F6 in non-small cell lung cancer.

This study aimed to explore the expression and effect of the nuclear receptor subfamily 2 group F member 6 (NR2F6) gene in non-small cell lung cancer (NSCLC) and provide an experimental basis for the targeted therapy of NSCLC. First, the expression of NR2F6 in lung cancer tissues was analyzed using the Gene Expression Omnibus and the Cancer Genome Atlas (TCGA) databases, and the expression of NR2F6 in lung cancer tissues and cells was verified by Western blotting and quantitative polymerase chain reaction. Next, the relationship between NR2F6 expression and the clinicopathological features of lung cancer was analyzed NR2F6 was highly expressed in lung cancer tissues and cells, and its expression was positively correlated with the depth of invasion, lymphatic metastasis, and clinical stage of lung cancer. High expression of NR2F6 in lung cancer was also significantly associated with poor prognosis. At cell level, NR2F6 knockdown was found to inhibit the proliferation of H460 and H358 in lung cancer cells. Furthermore, the TCGA database and immunohistochemical results showed that HNRNPD was highly expressed in lung cancer tissues and was highly consistent with NR2F6 expression in these tissues. Knockdown of HNRNPD also inhibited the proliferation of lung cancer cells. The co-immunoprecipitation experiment verified that NR2F6 interacted with HNRNPD. NR2F6 may interact with HNRNPD to jointly regulate the progression of lung cancer, and this conclusion provides a new experimental basis for the study of the molecular targeted therapy of NSCLC.

Pulmonary mucoepidermoid carcinoma in the Chinese population A clinical characteristic and prognostic analysis.

Mucoepidermoid carcinoma is dominant in salivary glands and rarely occurs in the lung. Primary pulmonary mucoepidermoid carcinoma is a type of non-small-cell lung cancer, but the prognostic factors in Chinese patients remain controversial. This investigation aimed to review cases of pulmonary mucoepidermoid carcinoma, analyse the prognosis of this disease. Patients with pathologically proven pulmonary mucoepidermoid carcinoma were screened at the Department of Respiratory and Critical Care Medicine at the Peking University Third Hospital, Beijing Friendship Hospital Affiliated to Capital Medical University, and Peking University Cancer Hospital for inclusion in this retrospective study. Demographic data, including age, sex, clinical symptoms, smoking, alcohol consumption, allergies, family history, imaging findings, fibrobronchoscopy findings, surgical procedures, tumour location and pathologic stage, were collected. Telephone follow-up was conducted for all patients not lost to follow-up. The associations of sex, age, smoking, tumour differentiation, tumour size, lymph node metastasis, pathologic stage, and patient survival were retrospectively analysed. Kaplan-Meier, univariate and multivariate analysis curves were used to analyse patient prognosis and prognostic factors. Thirty-one patients, comprising 23 males and 8 females, were enrolled in the analysis. The mean age was 60.77 ± 11.44 years. The first symptom was nonspecific, with cough being the most common (2131, 67.77%) smokers accounted for 16 of the 31 patients, and ten patients had a history of alcohol consumption. Overall, the tumours could occur in either lobe of the lungs tumours occurred in the right lung in 1931 patients, and tumours occurred in the left lung in 1231 patients. Regarding TNM stage, 10 patients had stage I (5 with stage 1a, 5 with stage 1b), 5 had stage II (1 with stage 2a, 4 with stage 2b), 3 had stage III (1 with stage 3a, 2 with stage 3b), and 13 had stage IV (10 with stage 4a, 3 with stage 4b). In our Cox univariate survival analysis of patients with pulmonary mucoepidermoid carcinoma, we found that TNM stage IV, degree of differentiation and lymph node metastasis were risk factors for pulmonary mucoepidermoid carcinoma and that degree of differentiation was an independent risk factor. The clinical, radiographical and pathological features of pulmonary mucoepidermoid carcinoma were systemically analysed and summarized, and the degree of differentiation and lymph node metastasis, as well as prognostic factors in addition to clinical stage, were confirmed.

Acupuncture for adult lung cancer of patient-reported outcomes A systematic review and meta-analysis.

This systematic review and meta-analysis aims to assess the effects of acupuncture on patient-reported outcomes (PROs) in adults with lung cancer. Electronic databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang Data, SinoMed, and gray literatures were retrieved from inception to 1 July 2022 for randomized controlled trials (RCTs). Acupuncture was defined as an experimental intervention, and the patients of the control groups included either treatment including conventional therapy (usual care, shamplacebo acupuncture, pharmacotherapy including Western medicine and Chinese traditional medicine). PROs for this study were measured by seven scales of primary outcomes including the Karnofsky Performance Status (KPS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Functional Assessment of Cancer Therapy-Lung, Functional Assessment of Cancer Therapy Lung Cancer Subscale, Leicester Cough Questionnaire (LCQ score), the Medical Outcomes Study (MOS) item short form health survey (SF-36), and the St Georges Respiratory Questionnaire, and 12 scales of secondary outcomes. Cochrane Collaborations tool was used to assess the risks of bias. Data were combined and analyzed with RevMan 5.4 and StataSE 16.0. We retrieved 3,002 lung cancer patients from 33 trials. KPS included with 1,000 patients showed that acupuncture could significantly improve the quality of life (QOL) compared with the control group regardless of different tumor-node-metastasis stages or the different stages of disease. The study showed that acupuncture significantly improved lung cancer-related symptoms in the QOL, pain, nausea and vomiting, insomnia, anxiety and depression, fatigue, and constipation compared with the control group. Eight RCTs reported the occurrence of adverse events, whereas four reported none and four RCTs reported that the events in the observation group were significantly less than those in the control group. Acupuncture proved to be a promising intervention, both postoperatively and after chemotherapy, and should be recommended as a beneficial alternative strategy to promote PROs in lung cancer patients at all stages of application. Considering the low quality, we suggest more rigorous clinical trials of acupuncture for lung cancer in the future and more emphasis on the effect of acupuncture in patients with lung cancer on their PROs, mainly in the aspect of the QOL. httpswww.crd.york.ac.ukprosperodisplayrecord.php, identifier CRD42021274122.

PD-1 inhibitor therapy causes multisystem immune adverse reactions a case report and literature review.

Immune checkpoint inhibitors(ICIs), including cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), programmed cell death protein 1 and its ligand (PD-1PD-L1) inhibitors, have been shown to have antitumor activity in various solid tumors. Their mechanism of action is to selectively restore and normalize the bodys immune reponses by disrupting the immunosuppressive signals mediated by PD-1, PD-L1 and CTLA-4 in the tumor microenvironment. With the increase in clinical applications of ICIs, reports of immune-related adverse events (irAEs) have also increased. This article reports a case of a lung cancer patient who developed multisystemic adverse effects after PD-1 inhibitor application myocarditis, myositis and thrombocytopenia, and analyzes the role of Interleukin 6(IL-6)in the management of irAEs. Despite the patients eventual discontinuation of antitumor therapy due to severe irAEs, a significant and durable therapeutic response was observed.

Common mechanism of

Same treatment for different diseases is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build ingredient-target-signal pathway network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules. Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer. Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the Same treatment for different diseases strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases.

A robust CD8

Patients with stage III lung adenocarcinoma (LUAD) have significant survival heterogeneity, meanwhile, CD8

Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab Integrated analysis of four multicenter clinical trials.

Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment. This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients. This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct Overall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points. The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLRT3 5, PLRT3 180, and NMRT2 6 were identified as strong predictive biomarkers for atezolizumab (Ate)-treated NSCLC patients in comparison with docetaxel (Dtx)-treated patients regarding OS (BCTscore low risk HR The BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients.

Clinical predictive value of naïve and memory T cells in advanced NSCLC.

Currently, there is no sensitive prognostic biomarker to screen out benefit patients from the non-benefit population in advanced non-small cell lung cancer patients (aNSCLCs). The 435 aNSCLCs and 278 normal controls (NCs) were recruited. The percentages and absolute counts (AC) of circulating naïve and memory T lymphocytes of CD4

Risk Factors for Pulmonary Metastasis in Differentiated Thyroid Carcinoma Patients and the Significance of Changes in Matrix Metalloproteinase 13 and microRNA-142 Levels.

This work aims to explore the risk factors of lung metastasis (LM) in differentiated thyroid cancer (DTC) (LM-DTC) and the effect of treatment and to detect the relationship between LM-DTC and the levels of matrix metalloproteinase-13 (MMP-13) and micro ribonucleic acid (RNA)-142 (miR-142) in peripheral blood. The data of 420 patients with DTC who are admitted from March 2020 to December 2021 are collected and divided into a non-metastasis group (non-LM group) of 400 cases and metastasis group (LM group) of 20 cases according whether the mung metastasis is found. In addition, risk factors of LM-DTC are analysed and compared. The results of multivariate logistic analysis show that age, disease course, and imaging timing are independent influencing factors of the radionuclide treatment effect. Follicular carcinoma, abnormal expressions of MMP-13, and miR-142 can increase the risk of LM-DTC. MMP-13 and miR-142 can be undertaken as auxiliary diagnostic biological indicators.

Pan-cancer analysis of forkhead box Q1 as a potential prognostic and immunological biomarker.

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family involved in the occurrence and development of different tumors. However, the specific expression patterns and functions of FOXQ1 in pan-cancer remain unclear. Therefore, we collected the expression, mutation, and clinical information data of 33 tumors from The Cancer Genome Atlas database. Via public pan-cancer transcriptome data analysis, we found that FOXQ1 is differentially expressed in various tumors at tissue and cell levels, such as liver hepatocellular carcinoma, colon adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, thyroid carcinoma, and kidney renal clear cell carcinoma. Kaplan-Meier and Cox analyses suggested that FOXQ1 expression was associated with poor overall survival of cutaneous melanoma and thymoma. Its expression was also associated with good disease-specific survival (DSS) in prostate adenocarcinoma but poor DSS in liver hepatocellular carcinoma. In addition, FOXQ1 expression was associated with poor disease-free survival of pancreatic adenocarcinoma. Moreover, FOXQ1 expression was closely related to the tumor mutational burden in 14 tumor types and microsatellite instability (MSI) in 8 tumor types. With an increase in stromal and immune cells, FOXQ1 expression was increased in breast invasive carcinoma, pancreatic adenocarcinoma, thyroid carcinoma, lung adenocarcinoma, and ovarian serous cystadenocarcinoma, while its expression was decreased in pancreatic adenocarcinoma, bladder urothelial carcinoma, and stomach adenocarcinoma. We also found that FOXQ1 expression was related to the infiltration of 22 immune cell types in different tumors (

Signature based on RNA-binding protein-related genes for predicting prognosis and guiding therapy in non-small cell lung cancer.

An autophagy-associated lncRNAs model for predicting the survival in non-small cell lung cancer patients.

Long non-coding RNAs (lncRNAs) can influence the proliferation, autophagy, and apoptosis of non-small cell lung cancer (NSCLC). LncRNAs also emerge as valuable prognostic factors for NSCLC patients. Consequently, we set out to discover more autophagy-associated lncRNAs. We acquired autophagy-associated genes and information on lncRNAs from The Cancer Genome Atlas database (TCGA), and the Human Autophagy Database (HADb). Then, the prognostic prediction signature was constructed through using co-expression and Cox regression analysis. The signature was constructed including 7 autophagy-associated lncRNAs (ABALON, NKILA, LINC00941, AL161431.1, AL691432.2, AC020765.2, MMP2-AS1). After that, we used univariate and multivariate Cox regression analysis to calculate the risk score. The survival analysis and ROC curve analysis confirmed good performances of the signature. GSEA indicated that the high-risk group was principally enriched in the adherens junction pathway. In addition, biological experiments showed that ABALON promoted the proliferation, metastasis and autophagy levels of NSCLC cells. These findings demonstrate that the risk signature consisting of 7 autophagy-associated lncRNAs accurately predicts the prognosis of NSCLC patients and should be investigated for potential therapeutic targets in clinic.

Linc00996 is a favorable prognostic factor in LUAD Results from bioinformatics analysis and experimental validation.

Effect of Endurance Training in COPD Patients Undergoing Pulmonary Rehabilitation A Meta-Analysis.

The efficacy of endurance training (ET) on patients with chronic obstructive pulmonary disease (COPD) has been controversial. This study was aimed at meta-analyzing the effect of ET in COPD patients undergoing pulmonary rehabilitation. The literature retrieval was performed in databases to screen relevant literature. Inclusion criteria were as follows (1) subjects-COPD patients (2) inclusion of interventional and control groups (3) intervention measures-the interventional group received whole-body ET and other lung rehabilitation training, while the control group did not receive intervention or other lung rehabilitation training (4) outcome indicators which included at least one of the following-6MWD, modified Medical Research Council questionnaire (mMRC), and COPD Assessment Test (CAT) and (5) study type-randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the risk of bias. The chi-square test was used to evaluate the magnitude of heterogeneity. Subgroup analysis was used to explore the source of heterogeneity. A funnel plot and Eggers test were used to evaluate publication bias. The 6MWD in the ET group was significantly higher than that in the control group (MD 47.20, 95% CI 28.60, 65.79, ET can improve patients motor function and reduce dyspnea. ET might be incorporated as an important part of lung rehabilitation training.

The Effect of PD-1 Inhibitor Combined with Chemotherapy on the Level of Peripheral Blood T Lymphocytes among Patients with Non-Small-Cell Lung Cancer and Its Relationship with Prognosis.

To explore the effect of combined treatment of PD-1 inhibitor and chemotherapy on the level of peripheral blood T lymphocytes in non-small-cell lung cancer (NSCLC) patients and its relationship with prognosis. Retrospective analysis was conducted on 150 NSCLC patients treated in Guangxi Medical University Affiliated Tumor Hospital from June 2018 to September 2020, including 77 patients treated with PD-1 inhibitor combined with chemotherapy as the observation group (OG) and 73 patients with chemotherapy alone as the control group (CG). Therapeutic efficacy, immune function indexes, serum tumor markers, incidence of adverse reactions during hospitalization, 1-year survival rate, and life quality after 6 months of treatment were observed and compared between two groups. Compared to the CG, the therapeutic effect of OG was evidently better. Six months after treatment, levels of CD4 For NSCLC patients, the PD-1 inhibitor given on the basis of chemotherapy can further improve the clinical efficacy and improve immune function and long-term survival rate of patients on the premise of ensuring the safety of treatment, which is worth promoting in clinical practice.

Causal associations between dietary antioxidant vitamin intake and lung cancer A Mendelian randomization study.

Oxidative stress is currently considered to be closely related to the occurrence of respiratory tumors, especially lung cancer. Many observational studies have shown that increased antioxidant intake can reduce the risk of lung cancer, but the results are still controversial. Therefore, we performed a two-sample Mendelian randomized (MR) analysis to clarify the causal relationship between antioxidant vitamins and lung cancer. To assess the causal effect of dietary antioxidant vitamin intake on lung cancer, we conducted a two-sample MR analysis and we extracted single-nucleotide polymorphisms (SNPs) that are associated with antioxidants from genome-wide association studies (GWASs) of the UK biobank. We gathered summary data for lung cancer from the International Lung Cancer Consortium (ILCCO), including 11,348 cases and 15,861 controls, and applied the inverse-variance weighted (IVW) method as the primary MR analysis, and performed a sensitivity analysis to verify the results. The results showed that higher dietary retinol intake was causally associated with lung cancer overall odds ratio ( Our research showed that dietary retinol intake has an adverse impact on lung cancer, and carotene might increase the risk of adenocarcinoma. This highlights the importance of revealing the underlying mechanisms of dietary antioxidant vitamins in lung cancer and delivers an important health message that dietary antioxidant vitamin intake may not be necessary for the prevention of lung cancer. It also provides a basis for future research.

Experience of patients with lung cancer and with targeted therapy-related skin adverse drug reactions A qualitative study.

To explore the experience of non-small-cell lung cancer patients with targeted therapy-related skin adverse drug reactions. This is a descriptive quantitative study conducted in a comprehensive hospital in Henan, China. Purposive sampling was used to recruit patients with non-small-cell lung cancer and with targeted therapy-related skin adverse drug reactions. In total, 23 patients were approached when the data were saturated. Face-to-face interviews were conducted by an independent researcher using a semi-structured interview guide. Interview data were transcribed and analyzed by qualitative inductive content analysis. Based on the analysis, four main categories were identified according to patients descriptions of their experience a lack of self-management ability, psychological and emotional problems, a barrier to social participation, and a need for social support. Suffering from persistent symptoms, insufficient knowledge, skills and strategies for skin adverse drug reaction management, psychological problems, social avoidancewithdrawal, and reduced willingness to work were core experiences that would affect patients compliance with treatment, prognosis, and the overall quality of life. This study revealed the real experience of patients with non-small-cell lung cancer and with targeted therapy-related skin adverse drug reactions which contributed to the development of targeted interventions to manage skin adverse reactions.

Attributable fraction of tobacco smoking on selected cancer deaths in the past decade using mortality case-control study in Tianjin, China.

This study aims to estimate the impact of smoking-attributable mortality of selected cancers, in the period 2010-2019 in Tianjin, China. A case-control study was conducted to assess the smoking-attributed major causes of cancer deaths. Unmatched multiple logistic regression was used to calculate mortality risk ratios. Smoking-attributable cancer deaths were 23709 (28.87%) among adult males and 8648 (13.37%) among adult females in the period 2010-2019 in Tianjin, China. Lung cancer remains the largest cause of smoking-attributable deaths among men, the death rates were 49.06% of lung cancers, 27.55% of mouth, pharynx, larynx, or esophagus cancers, 13.56% of kidney and other urinary cancers, and 10.11% of liver cancers among women the corresponding death rates were 31.56% of lung cancers and 10.59% of the mouth, pharynx, larynx, or esophagus cancer, 10.56% of bladder cancers. Smoking-attributed cancer deaths in men increased from 1817 in 2010 to 2695 in 2019 for women, the number remained stable at just over 800 per year during the past decade. At least one in three cancer deaths in men and one in six in women would be potentially preventable through appropriate control of tobacco smoking in Tianjin, China. Effective control programs against tobacco smoking should be further implemented.

Smoking trajectory and cancer risk A population-based cohort study.

Smoking behavior can change with time and lead to different health outcomes. This study explored the trajectory of smoking and its relationship with cancer incidence and mortality among Korean male adults. We used 2002-2018 data from the National Health Insurance Service (NHIS). Smoking status was repeatedly measured in four waves of general health examinations provided by the NHIS between 2002 and 2009. Cancer incidence and mortality were tracked from 2010 to 2018. Trajectory analysis was used to identify the patterns of smoking. The hazard ratio was calculated using Cox proportional regression models. For the 2448548 men (≥20 years), 137788 cases of cancers and 41146 cancer deaths were found. We identified six trajectory groups never smokers, former smokers, new current smokers, decreasing light smokers, steady moderate smokers, and steady heavy smokers. All smoking groups had an increased risk of cancer. The steady heavy smokers showed higher cancer incidence and mortality rate than the steady non-smokers (hazard ratio, HR1.53 95% CI 1.49-1.58 and HR2.64 95% CI 2.50-2.79, respectively). The cancer-specific analysis showed that the larynx and lung cancer incidence and mortality rate of the smoking group were higher than in never smokers. Smoking, even at low doses, increases the risk of most cancers in men. Quitting or reducing smoking, especially at a young age, can lower cancer incidence and mortality. This study may provide more objective results on the relationship between smoking and cancer, because smoking behavior was examined at multiple time points.

Evaluation of the necessity of Pulmonary Ligament Lymph Node Dissection for Upper Lobe Stage IB NSCLC A Propensity Score-matched Study.

LINC01094SPI1CCL7 Axis Promotes Macrophage Accumulation in Lung Adenocarcinoma and Tumor Cell Dissemination.

Infiltration of tumor-associated macrophages is closely linked to the malignant development of human cancers. This research studies the function of C-C motif chemokine ligand 7 (CCL7) in the macrophage accumulation in lung adenocarcinoma (LUAD) and the underpinning mechanism. The expression profile of CCL7 in LUAD and its correlations with patients prognosis and macrophage infiltration were predicted via bioinformatics systems. Artificial up- or downregulation of CCL7 was induced in LUAD cells to explore its function in the mobility, EMT of cancer cells, and migration of M2 macrophages. Cancer cells were implanted in NODSCID mice to induce xenograft tumors. The CCL7-related transcription factors or factors were predicted by bioinformatic tools, and the molecular interactions were confirmed by immunoprecipitation or luciferase assays. CCL7 was highly expressed in LUAD and linked to increased TAM infiltration. Knockdown of CCL7 suppressed the chemotaxis and M2 skewing of macrophages, and it blocked the EMT and mobility of LUAD cells. CCL7 downregulation also suppressed macrophage infiltration in xenograft tumors in mice. Spi-1 proto-oncogene (SPI1) was confirmed as an upstream factor activating CCL7 transcription, and LINC01094 was found to bind to SPI1 to promote its nuclear translocation. Upregulation of SPI1 restored the chemotactic migration and M2 polarization of macrophages in LUAD cells. This paper reveals that LINC01094 binds to SPI1 to promote its nuclear translocation, which further activates CCL7 transcription by binding to its promoter, leading to M2 macrophage accumulation and dissemination of tumor cells.

Reevaluation of missed lung cancer with artificial intelligence.

Lung cancer is often missed on chest radiographs, despite chest radiography typically being the first imaging modality in the diagnosis pathway. We present a 46 year-old male with chest pain referred for chest X-ray, and initial interpretation reported no abnormality within the patients lungs. The patient was discharged but returned 4 months later with persistent and worsening symptoms. At this time, chest X-ray was again performed and revealed an enlarging left perihilar mass with post-obstructive atelectasis in the left lower lobe. Follow-up chest computerized tomography scan confirmed lung cancer with post-obstructive atelectasis, and subsequent bronchoscopy-assisted biopsy confirmed squamous cell carcinoma. Retrospective analysis of the initial chest radiograph, which had reported normal findings, was performed with Chest-CAD, a Food and Drug Administration (FDA) cleared computer-assisted detection (CAD) software device that analyzes chest radiograph studies using artificial intelligence. The device highlighted the perihilar region of the left lung as suspicious. Additional information provided by artificial intelligence software holds promise to prevent missed detection of lung cancer on chest radiographs.

Clinicopathologic Characteristics and Outcomes for Patients With

Co-occurring mutations in This was a retrospective single-institution study. Patients with NSCLC and A total of 107 patients with Co-occurring mutations were common in patients with

Association of Pathologic Complete Response and Long-Term Survival Outcomes Among Patients Treated With Neoadjuvant Chemotherapy or Chemoradiotherapy for NSCLC A Meta-Analysis.

Increased efforts to optimize outcomes for early stage NSCLC through the investigation of novel perioperative treatment strategies are ongoing. An emerging question is the role of pathologic response and its association with long-term clinical outcomes after neoadjuvant therapy. To investigate the association of pathologic complete response (pCR) and event-free survival (EFS) and overall survival (OS), we performed a systematic review and meta-analysis identifying studies reporting on the prognostic impact of pCR after neoadjuvant chemotherapy or chemoradiotherapy. To evaluate this prognostic value, an aggregated data (AD) meta-analyses was conducted to estimate the pooled hazard ratios (HRs) of EFS and OS for pCR. Using reconstructed individual patient data (IPD), pooled Kaplan-Meier curves were obtained to estimate this association in a more granular fashion. Subgroup analyses were conducted to further explore the impacts of study-level characteristics. A total of 28 studies comprising 7011 patients were included in the AD meta-analysis, of which, IPD was available for 6274 patients from 24 studies. Results from our AD meta-analysis revealed a pooled pCR rate of 18% (95% confidence interval CI 15%-21%), including significant improvements in OS (HR 0.50, 95% CI 0.45-0.56) and EFS (HR 0.46, 95% CI 0.37-0.57) on the basis of pCR status. Our IPD analysis revealed a 5-year OS rate of 63% (95% CI 59.6-67.4) for patients with a pCR compared with 39% (95% CI 34.5-44.5) for those without a pCR. pCR after neoadjuvant chemotherapy plus or minus radiotherapy is associated with significant improvements in EFS and survival for patients with resectable NSCLC.

LncRNA TP73-AS1 Exacerbates the Non-Small-Cell Lung Cancer (NSCLC) Process via Regulating miR-125a-3p-Mediated ACTN4.

LncRNA TP73-AS1 has been revealed to exert a noteworthy impact on the occurrence and advancement of different cancers. In this study, we explored the function of TP73-AS1 in tumor growth, cell progression as well as the relevant molecular mechanism in non-small-cell lung cancer (NSCLC). QRT-PCR was employed to assess the expression of TP73-AS1, miR-125a-3p, and actinin alpha 4 (ACTN4) in NSCLC cells. The biological effect of TP73-AS1 on NSCLC cells was assessed by cell transfection, CCK8, and transwell experiments. We further predicted the interaction among RNAs (TP73-AS1, miR-125a-3p, and ACTN4) through bioinformatics online tools and verified via luciferase reporter, RNA immunoprecipitation, and qRT-PCR assays. Xenograft models of SPC-A1 cells were conducted to test how TP73-AS1 regulates tumorigenesis. Western blot, as well as the immunohistochemistry (IHC) assays, was utilized to measure the expression levels. Functions of TP73-AS1 in NSCLC progression through the miR-125a-3pACTN4 axis were investigated by rescue experiments. Knockdown of TP73-AS1 suppressed the growth and simultaneously attenuated the migration and invasion ability of NSCLC SPC-A1 and A549 cells. Bioinformatics and molecular mechanism assays demonstrated that TP73-AS1 could bind to miR-125a-3pACTN4 and regulate their expression. Moreover, the rescued-function experiment demonstrated that suppressing miR-125a-3p or elevating ACTN4 turned around the suppression effect of sh-TP73-AS1 on NSCLC progression. TP73-AS1 inhibition could also inhibit the NSCLC tumor growth and correspondingly regulated the expression of miR-125a-3p and ACTN4 in the tumor xenograft model. The present study indicated that TP73-AS1 affects NSCLC progression through a new competitive RNA (ceRNA) regulatory network of miR-125a-3pACTN4, providing an underlying target for NSCLC treatment in the future.

Implications of m6A methylation and microbiota interaction in non-small cell lung cancer From basics to therapeutics.

N6-methyladenine (m6A) is one of the most common RNA epigenetic modifications in all higher eukaryotes. Increasing evidence demonstrated that m6A-related proteins, acted as oncogenes or tumor suppressors, are abnormally expressed in the cell lines and tissues of non-small cell lung cancer (NSCLC). In addition, lung as the special immune organ contacts with the outer environments and thereby inevitably suffers from different types of microbial pathogen attack. Those microbial pathogens affect the development, progression, and clinical outcomes of NSCLC

Timing of Organ Procurement From Brain-Dead Donors Associates With Short- and Long-Term Outcomes After Liver Transplantation.

Brain death-induced cytokine storm is thought to harm transplantable organs. However, longer procurement times have been associated with non-inferior or better outcomes in kidney, heart, and lung transplants, while optimal procurement time for liver allografts is unknown. Our aim was to analyze the association of time interval from brain death to organ procurement with liver allograft outcomes in two nationwide cohorts. The association of procurement interval with graft survival and short-term complications was analysed in multivariable models. Altogether 643 and 58,017 orthotopic liver transplantations from brain-dead donors were included from Finland between June 2004 and December 2017 and the US between January 2008 and August 2018, respectively. Median time from brain death to organ procurement was 10.5 h in Finland and 34.6 h in the US. Longer interval associated with better graft survival (non-linearly,

CircFBXW7 Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer Cells by Regulating miR-492.

CircFBXW7 has been determined to be involved in various cancers however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.

Programmed cell death 1 inhibitor plus chemotherapy vs. chemotherapy in advanced drive-gene-negative non-small-cell lung cancer patients A real-world study.

Programmed cell death 1 (PD-1) inhibitor has been in the market in China for several years, which lacks sufficient domestic evidence regarding its application in lung cancer. Thus, this study intended to assess the treatment outcome and tolerance of PD-1 inhibitor plus chemotherapy in advanced, driver-gene-negative, nonsquamous, non-small-cell lung cancer (NSCLC) patients in a real clinical setting. This retrospective cohort study analyzed 68 advanced driver-gene-negative nonsquamous NSCLC patients, among which 38 cases received PD-1 inhibitor plus chemotherapy and 30 cases adopted chemotherapy alone. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were reviewed. Generally, PD-1 inhibitor plus chemotherapy achieved a more satisfying ORR compared with chemotherapy alone (52.6% vs. 30.0%, PD-1 inhibitor plus chemotherapy exhibits a better efficacy and equal tolerance compared with chemotherapy alone in advanced driver-gene-negative nonsquamous NSCLC patients.

Case report A giant lung leiomyosarcoma From an accurate diagnosis to a successful surgery. A rare case and brief literature review.

Primary pulmonary leiomyosarcomas (PPLs) are incredibly rare tumors, characterized by an often-aggressive clinical behavior. Diagnosis is frequently incidental. Whenever present, symptoms are nonspecific, thus PPLs are usually misdiagnosed as other more common respiratory diseases or lung cancer subtypes. Surgery is the best treatment choice and in the therapeutic strategy, timeliness and radicality are of major importance. We report the case of a huge left PPL, successfully treated with salvage surgery after a careful multidisciplinary preoperative assessment, which permitted a prompt diagnostic path and surgery.

Clinical outcome and risk factors for subcutaneous emphysema in patients with lung cancer after video-assisted thorascopic surgery.

With the clinical application of minimally invasive surgery and concept of enhanced recovery after surgery, the incidence of postoperative complications in lung cancer patients has been significantly reduced. However, postoperative subcutaneous emphysema (SE) becomes the main factor affecting the early discharge of patients. The aim of this study was to analyze the clinical outcome and risk factors for postoperative SE in lung cancer patients. The clinical data of 414 lung cancer patients who were admitted to the Department of Thoracic Surgery, West China Hospital, Sichuan University from September 2021 to December 2021 were prospectively collected. The incidence, severity and treatment of patients who had SE, surgery approach, application of drainage tube and clinical information were analyzed. The incidence rate of postoperative SE in patients with lung cancer was 33.09% (137414) and mild cases accounted for the vast majority (30.19%, 125414). Multivariate analysis indicated that male odds ratio (OR) 2.247, Postoperative SE in patients with minimally invasive lung cancer is mainly mild, and conservative treatment is appropriate for most cases.

Case report 18F-FDG PET confirmed pupil-sparing third nerve palsy heralding aseptic cavernous sinus embolism in patient with chest malignancy.

Classical cavernous sinus embolism is a rare clinical finding, presented most commonly by complaints of headache, diplopia, visual field defects, facial pain, and progressive neurological deficits. Many patients exhibit symptoms of III, IV, and VI nerve palsies. We hereby report a rare case of aseptic cavernous sinus embolism developed in a 75-year-old male with primary lung cancer who presented with binocular diplopia due to unilateral third and sixth cranial nerve palsies with pupil-sparing. The possibility of cavernous sinus cancer embolus should be considered if the routine examination excluded metastases, infiltration, carcinomatous meningitis, or the paraneoplastic process.

Cutaneous Metastasis from Lung Adenocarcinoma.

Cutaneous metastases are rare and often portend the aggressive malignancy and poor prognosis. We report a case of a 62-year-old man with a rapidly growing nodule on the left back for 2 months. The patient was diagnosed with lung adenocarcinoma shortly before the skin lesion presented. Physical examination showed a dome-shaped purplish red nodule, with ulceration and hemorrhagic crust. Excision of the skin lesion was performed, and the histopathology showed tumor cells infiltrate with immunohistochemistry (TTF-1CK7CD20-) favoring primary lung adenocarcinoma.

6,6-Bieckol induces apoptosis and suppresses TGF-β-induced epithelial-mesenchymal transition in non-small lung cancer cells.

In this study, the aim was to investigate the inhibitory effect of 6,6-bieckol on the migration and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells, and explore its potential molecular mechanisms. Cell migration was measured using a CCK8, wound healing, and transwell migration assay. Apoptosis was determined using an Annexin Vpropidium iodide staining. Western blotting and immunofluorescence were used to examine the expression level of apoptosis-related proteins and EMT marker proteins. The results showed that 6,6-bieckol inhibited migration and induced apoptosis of NSCLC cells. Furthermore, 6,6-bieckol had significantly up-regulated the E-cadherin and down-regulated Snail1 and Twist1 transcriptional levels. 6,6-Bieckol might inhibit TGF-β-induced EMT by down-regulating Snail1 and Twist1 and up-regulating E-cadherin in lung cancer cells. It is suggested that 6,6-bieckol has the potential to be developed as a therapeutic candidate for lung cancer.

Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

We previously demonstrated that flurbiprofen increased arterial oxygen partial pressure and reduced intrapulmonary shunts. The present study aims to investigate whether flurbiprofen improves intraoperative regional cerebral oxygen saturation (rScO One hundred and twenty patients undergoing thoracoscopic lobectomy were randomly assigned to the flurbiprofen-treated group ( Compared with the control group, treatment with flurbiprofen significantly improved the mean value of intraoperative rScO Treatment with flurbiprofen may improve rScO httpwww.chictr.orgcn, identifier ChiCTR1800020032.

Progress in research of influenza vaccine and 23 valent pneumococcal polysaccharide vaccine immunization in patients with chronic obstructive pulmonary disease.

A comprehensive review of the research of the effectiveness of influenza vaccine and 23 valent pneumococcal polysaccharide vaccine (PPV23) in patients with chronic obstructive pulmonary disease (COPD) both at home and abroad in recent years showed that influenza vaccine and PPV23 immunization can significantly reduce the risk for influenza and pneumonia in COPD patients, and reduce the acute exacerbation of disease and related hospitalization. In particular, the influenza vaccination can also reduce the risk for ischemic heart disease, acute coronary syndrome, ventricular arrhythmia, lung cancer, dementia and death in the patients, and the immunization of both vaccines has a more significant protective effect. It is recommended by authoritative guidelines both at home and abroad that COPD patients can receive influenza vaccine and PPV23. At present, the coverage of domestic influenza and pneumococcal vaccines are low, and there are less studies in the applications of both vaccines in patients with COPD. Effective measures should be taken to strengthen the health education and increase the vaccination coverage. Additionally, the clinical research of influenza vaccine and PPV23 for COPD patients, especially the analysis on clinical benefit of immunization of both vaccines, should be further strengthened to effectively improve the survival and prognosis of COPD patients. 近年来国内外慢性阻塞性肺疾病（COPD）患者流感疫苗和23价肺炎球菌多糖疫苗（PPV23）接种有效性的相关研究发现，接种流感疫苗和PPV23可显著降低COPD患者的流感和肺炎感染风险，减少疾病的急性加重以及与之相关的住院，尤其是接种流感疫苗还可降低患者诱发缺血性心脏病、急性冠脉综合征、室性心律失常、肺癌、痴呆和死亡的风险，二者联合接种保护作用更加显著。国内外权威指南、共识均建议COPD患者接种流感疫苗和PPV23。目前国内流感疫苗和肺炎球菌疫苗接种率均偏低，且在COPD患者中的应用研究较少。应采取有效措施加强知识普及和指南宣传，提高疫苗接种率。同时还应进一步加强COPD患者接种流感和PPV23的临床研究，尤其是联合接种的临床效益分析，以切实改善COPD患者的生存现状和预后。.

Cardiac metastasis from small cell lung cancer origin A case report and review of the literature.

Cardiac metastasis from small cell lung cancer (SCLC) origin is rare, whereas the incidence is anticipated to increase with the extended survival rates. We here describe a case report of a 48-year-old male patient diagnosis with SCLC in 2020. In June 2021, he resorted to hospital due to shortness of breath, no obvious changes were found in repeated echocardiography, electrocardiogram and chest computer tomography from June 2021 to September 2021. Due to the persistence of the complaints, cardiac magnetic resonance (CMR) imaging was performed in September 30th, 2021, which showed a mass in the right atrioventricular groove. The patient underwent pericardiocentesis and small cell carcinoma cells were found in the pericardial effusion, confirming the diagnosis of cardiac metastasis. Patients with a history of SCLC who develop new cardiac symptoms of unknown etiology should undergo imaging studies such as CMR. The importance of CMR for patients with SCLC is highlighted. The literature regarding metastatic cardiac tumors is reviewed.

Lung cancer in patients with idiopathic pulmonary fibrosis A retrospective multicentre study in Europe.

There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR 1.51, 95% CI 1.22-1.86, p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 Kμl than patients with monocyte count ≥0.95 Kμl (HR <0.60 vs. ≥0.95 Kμl 0.35, 95% CI 0.17-0.72, HR 0.60-<0.95 vs. ≥0.95 Kμl 0.42, 95% CI 0.21-0.82, p 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR 0.61, 95% CI 0.42-0.87, p 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR 0.30 95% CI 0.11-0.86, p 0.02). Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.

Pharmacological targeting of CBPp300 drives a redoxautophagy axis leading to senescence-induced growth arrest in non-small cell lung cancer cells.

p300CBP histone acetyltransferases (HAT) are critical transcription coactivators involved in multiple cellular activities. They act at multiple levels in non-small cell lung carcinoma (NSCLC) and appear, therefore, as promising druggable targets. Herein, we investigated the biological effects of A-485, the first selective (potent) drug-like HAT catalytic inhibitor of p300CBP, in human NSCLC cell lines. A-485 treatment specifically reduced p300CBP-mediated histone acetylation marks and caused growth arrest of lung cancer cells via activation of the autophagic pathway. Indeed, A-485 growth-arrested cells displayed phenotypic markers of cell senescence and failed to form colonies. Notably, disruption of autophagy by genetic and pharmacological approaches triggered apoptotic cell death. Mechanistically, A-485-induced senescence occurred through the accumulation of reactive oxygen species (ROS), which in turn resulted in DNA damage and activation of the autophagic pathway. Interestingly, ROS scavengers were able to revert senescence phenotype and restore cell viability, suggesting that ROS production had a key role in upstream events leading to growth arrest commitment. Altogether, our data provide new insights into the biological effects of the A-485 and uncover the importance of the autophagicapoptotic response to design a new combinatorial anticancer strategy.

ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer.

Most colorectal (CRC) tumors are dependent on EGFRKRASBRAFMAPK signaling activation. ARID1A is an epigenetic regulator mutated in approximately 5% of non-hypermutated CRC tumors. Here we show that anti-EGFR but not anti-VEGF treatment enriches for emerging ARID1A mutations in CRC patients. In addition, we find that patients with ARID1A mutations, at baseline, are associated with worse outcome when treated with cetuximab- but not bevacizumab-containing therapies thus, this suggests that ARID1A mutations may provide both an acquired and intrinsic mechanism of resistance to anti-EGFR therapies. We find that, ARID1A and EGFR-pathway genetic alterations are mutually exclusive across lung and colorectal cancers, further supporting a functional connection between these pathways. Our results not only suggest that ARID1A could be potentially used as a predictive biomarker for cetuximab treatment decisions but also provide a rationale for exploring therapeutic MAPK inhibition in an unexpected but genetically defined segment of CRC patients.

C-reactive protein and cancer risk a pan-cancer study of prospective cohort and Mendelian randomization analysis.

Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. During a median follow-up period of 7.1 years (interquartile range 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) 1.02, 95% CI 1.01, 1.02 per 1mgL increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mgL (false-discovery rate adjust (FDR-adjusted) P Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes. Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations. 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pgmL (p < 0.05) stop-gain mutation was significantly related to a higher prevalence of pneumothorax. Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.

Comprehensive analysis reveals the potential value of inflammatory response genes in the prognosis, immunity, and drug sensitivity of lung adenocarcinoma.

Although the relationship between inflammatory response and tumor has been gradually recognized, the potential implications of of inflammatory response genes in lung adenocarcinoma (LUAD) remains poorly investigated. RNA sequencing and clinical data were obtained from multiple independent datasets (GSE29013, GSE30219, GSE31210, GSE37745, GSE42127, GSE50081, GSE68465, GSE72094, TCGA and GTEx). Unsupervised clustering analysis was used to identify different tumor subtypes, and LASSO and Cox regression analysis were applied to construct a novel scoring tool. We employed multiple algorithms (ssGSEA, CIBERSORT, MCP counter, and ESTIMATE) to better characterize the LUAD tumor microenvironment (TME) and immune landscapes. GSVA and Metascape analysis were performed to investigate the biological processes and pathway activity. Furthermore, pRRophetic R package was used to evaluate the half inhibitory concentration (IC50) of each sample to infer drug sensitivity. We identified three distinct tumor subtypes, which were related to different clinical outcomes, biological pathways, and immune characteristics. A scoring tool called inflammatory response gene score (IRGS) was established and well validated in multiple independent cohorts, which could well divide patients into two subgroups with significantly different prognosis. High IRGS patients, characterized by increased genomic variants and mutation burden, presented a worse prognosis, and might show a more favorable response to immunotherapy and chemotherapy. Additionally, based on the cross-talk between TNM stage, IRGS and patients clinical outcomes, we redefined the LUAD stage, which was called IRGS-Stage. The novel staging system could distinguish patients with different prognosis, with better predictive ability than the conventional TNM staging. Inflammatory response genes present important potential value in the prognosis, immunity and drug sensitivity of LUAD. The proposed IRGS and IRGS-Stage may be promising biomarkers for estimating clinical outcomes in LUAD patients.

Construction of PEI-EGFR-PD-L1-siRNA dual functional nano-vaccine and therapeutic efficacy evaluation for lung cancer.

PD-1PD-L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI-LNP)siRNA complex (EPV-PEI-LNP-SiRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptidePD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer in this study. In this study, PEI lipid nanoparticles (PEI-LNP)siRNA complex (EPV-PEI-LNP-siRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptidePD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer and functional evaluation was conducted. On the basis of the construction of the composite nano-drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV-PEI-LNP were tested in vitro, and the downregulation effect of PD-L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non-small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 T cells. Combination therapy is superior to single target therapy. Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD-L1, realizing the tumor-specific expression of immune-stimulating cytokines, which is a highly efficient and safe targeted therapy nano-vaccine.

The Management of Oligometastases in Non-small Cell Lung Cancer - is Stereotactic Ablative Radiotherapy now Standard of Care

Oligometastatic non-small cell lung cancer encompasses a number of distinct clinical scenarios with a pattern of limited tumour burden on imaging. Delivering local ablative therapy to individual metastatic lesions may assist in disease modification and contribute to improved outcomes. We review the published randomised clinical trials that support the implementation of stereotactic ablative radiotherapy as a standard of care in certain oligometastatic non-small cell lung cancer clinical scenarios, and highlight the current knowledge gaps and areas of ongoing research.

Impact of TP53 Mutations on EGFR-Tyrosine Kinase Inhibitor Efficacy and Potential Treatment Strategy.

We investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies. Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fishers exact test and log-rank test were used to determine the statistical differences in this study. A total of 1134 clinical samples were collected from NSCLC patients, and TP53 Various characteristics of TP53

The Microbiome-Immune Axis Therapeutic Effects in Cancer Treatments.

During the last decades, research and therapeutic methods in cancer treatment have been evolving. As the results, nowadays, cancer patients are receiving several types of treatments, ranging from chemotherapy and radiation therapy to surgery and immunotherapy. In fact, most cancer patients take a combination of current anti-cancer therapies to improve the efficacy of treatment. However, current strategies still cause some side effects to patients, such as pain and depression. Therefore, there is the need to discover better ways to eradicate cancer whilst minimizing side effects. Recently, immunotherapy, particularly immune checkpoint blockade, is rising as an effective anti-cancer treatment. Unlike chemotherapy or radiation therapy, immunotherapy has few side effects and a higher tumor cell removal efficacy depend on cellular immunological mechanisms. Moreover, recent studies suggest that tissue immune responses are regulated by their microbiome composition. Each tissue has their specific microenvironment, which makes their microbiome composition different, particularly in the context of different types of cancer, such as breast, colorectal, kidney, lung, and skin. Herein, we review the current understanding of the relationship of immune responses and tissue microbiome in cancer in both animal and human studies. Moreover, we discuss the cancermicrobiome-immune axis in the context of cancer development and treatment. Finally, we speculate on strategies to control tissue microbiome alterations that may synergistically affect the immune system and impact cancer treatment outcomes.

Musculoskeletal immune-related adverse events in 927 patients treated with immune checkpoint inhibitors for solid cancer.

The prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI). We conducted a retrospective study among patients who received ICI from 07272014 to 05082020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs. Among 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgiasmyalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments. Musculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated.

Anti-metastatic effects of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose in colorectal cancer Regulation of cathepsin B-mediated extracellular matrix dynamics and epithelial-to-mesenchymal transition.

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), metastatic colorectal cancer still poses serious threat to CRC patients. The natural gallotannin 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been shown to possess anti-tumor effects on colon cancer cells, but its anti-metastatic effect is yet to be investigated. In this study, the effects of PGG on cell proliferation, colony formation ability, motility, migration were investigated in colon cancer cells using BrdU, colony formation, scratch, and transwell assays, respectively. Western blot assay was used for assessing protein expression. The orthotopic colon tumor-bearing mouse model and human colon cancer metastatic mouse model were employed to evaluate the anti-metastatic effects of PGG. Results showed that PGG exhibited not only anti-proliferative and colony formation inhibitory effects, but also inhibition on cell adhesion, motility, and migration in both HCT116 and colon 26-M01 cells via modulating protein expression of cathepsin B, FAK, cofilin, and epithelial-to-mesenchymal transition related proteins. In addition, PGG (10 or 15 mgkg, i.p.) could significantly inhibit liver and lung metastasis in colon cancer metastatic mice models. Furthermore, PGG could regulate the populations of T cells, macrophages, and MDSCs, while the levels of IL-2, IL-6, IL-10, IFN-γ, and TNF-α were altered after PGG treatment in metastatic CRC mice. This is the first report of the anti-metastatic effects of PGG by regulating cathepsin B-mediated extracellular matrix dynamics and epithelial-to-mesenchymal transition process in CRC. Our findings suggested that PGG has great potential to be developed as an anti-metastatic agent for metastatic CRC.

The role of NUPR1 in response to stress and cancer development.

Stress contributes to the development of many human diseases, including cancer. Based on the source of stress, it can be divided into external stress, such as environmental carcinogens, chemicals, and radiation, and internal stress, like endoplasmic reticulum (ER) stress, hypoxia, and oxidative stress. Nuclear Protein 1 (NUPR1, p8 or Com-1) is a small, highly basic transcriptional regulator that participates in regulating a variety of cellular processes including DNA repair, ER stress, oxidative stress response, cell cycle, autophagy, apoptosis, ferroptosis and chromatin remodeling. A large number of studies have reported that NUPR1 expression can be stimulated rapidly in response to various stresses. Thus, NUPR1 is also known as a stress-response gene. Since the role of NUPR1 in breast cancer was identified in 1999, an increasing number of studies sought to reveal its function in cancer. High expression of NUPR1 has been identified in oral squamous cell carcinoma, breast cancer, lung cancer, multiple myeloma, liver cancer and renal cancer. In this review, we summarize current studies of NUPR1 in response to multiple external stressors and internal stressors, and its role in mediating stressors to cause different cell signaling responses. In addition, this review discusses the function of NUPR1 in carcinogenesis, tumorigenesis, metastasis, and cancer therapy. Thus, this review gives a comprehensive insight into the role of NUPR1 in mediating signals from stress to different cell responses, and this process plays a role in the development of cancer.

Stereotactic Radiotherapy for Adrenal Metastases A Multi-Institutional Review of Patient Characteristics and Outcomes - Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10-004).

This study aimed to report the outcomes of stereotactic body radiotherapy (SBRT) for adrenal metastasis in a retrospective multi-institutional cohort. The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods. The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median biologically effective dose (BED)10 was 61 Gy. The overall LC rate was 83%, and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival, overall survival (OS), and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and <4-cm lesion and PFS with a fraction dose ≥8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity, and late toxicity was observed in 3 patients, including one grade 5. A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients, and systemic treatment options are needed to be improved.

N-glycosylation of CD82 at Asn157 is required for suppressing migration and invasion by reversing EMT via Wntβ-catenin pathway in colon cancer.

CD82, a tetraspanin superfamily member, has been identified to be glycosylated at three specific residues (Asn129, Asn157, and Asn198). However, CD82 post-translational modification and its effect on colorectal cancer (CRC) metastasis remain unclear. Here, we constructed various deficient mutants of CD82 N-glycosylation in SW620 cells and demonstrated that the Asn157 site is necessary for CD82 glycosylation in CRC cells migration and LN-dependent adhesion in vitro. Furthermore, we found that CD82 N-glycosylation at the Asn157 site leads to lower expression levels of vimentin and claudin-1 but higher expression levels of E-cadherin, which are the EMT markers also, there are lower expression levels of phospho-GSK3β and less β-catenin transportation to the nucleus. These findings suggest that CD82 N-glycosylation at the Asn157 site inhibits EMT by down-regulating the Wntβ-catenin pathway. Moreover, we reported that CD82 with N-glycosylation at a single site of the Asn157 reduces lung metastases in vivo. The results indicate that N-glycosylation of CD82 at the Asn157 site regulates CRC metastasis and adhesion. These observations suggest that the N-glycosylation of CD82 might be a potential therapeutic target for CRC.

Defining optimal parameters to maximize the effect of electrochemotherapy on lung cancer cells whilst preserving the integrity of immune cells.

Electrochemotherapy (ECT) is becoming an established therapy for melanoma and is under investigation for application in additional cancer types. One potential cancer type that may benefit from ECT is lung cancer as lung cancer treatments remain unable to deliver long-lasting treatment responses. Given the importance of the immune system in lung cancer, here we have also examined the impact of ECT on immune populations. The impact of electroporation and ECT on three human lung cancer cell lines (A549, H460, SK-MES 1), one murine cell line (LLC) and murine T cells, dendritic cells and macrophages was examined. The viability, metabolic activity and recovery potential post-treatment of all cell types was determined to evaluate the potential utility of ECT as a lung cancer treatment. Our findings demonstrate that cisplatin at 11 µM would be the suggested drug of choice when using ECT for lung cancer treatment. Our study also shows that T cells are not impacted by any tested condition, whilst dendritic cells and macrophages are significantly negatively impacted by electric field strengths surpassing 800 Vcm in vitro. Therefore, current ECT protocols (using 1000 Vcm in vivo) might need to adapted to improve viability of the immune population, thus improving therapy outcomes.

RNA modification writer expression profiles predict clinical outcomes and guide neoadjuvant immunotherapy in non-small cell lung cancer.

RNA modifications, including adenosine-to-inosine RNA editing, alternative polyadenylation, m Nonnegative matrix factorization clustering was applied to identify RNA modification clusters in lung adenocarcinoma, one of the most prevalent subtypes of non-small cell lung cancer (NSCLC). CIBERSORT and ESTIMATE algorithms were performed to depict TME characteristics. Additionally, a scoring system called Writer-Score was established to quantify RNA modification patterns and subsequently predict clinical outcomes. We subsequently used RNA sequencing, targeted DNA sequencing and multiplex immunofluorescence to further evaluate the efficacy of Writer-Score in NSCLC patients receiving neoadjuvant immunotherapy. We identified three distinct RNA modification clusters and two DEGclusters, which were shown to be strongly associated with a variety of TME features and biological processes. Additionally, the Writer-Score served as an important factor in post-transcriptional events and immunotherapy. The Writer-Score was capable of properly predicting the prognosis of NSCLC patients receiving neoadjuvant PD-1 inhibitor therapy. Our work systematically analyzed four types of RNA modifications and constructed a scoring system to guide neoadjuvant immunotherapy in NSCLC, which highlighted the writers roles in post-transcriptional events, TME and neoadjuvant immunotherapy. A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Multi-scale characterization of tumor-draining lymph nodes in resectable lung cancer treated with neoadjuvant immune checkpoint inhibitors.

Regional lymph node (LN) acts as a pivotal organ for antitumor immunity. Paradoxically, tumor-draining LNs (TDLNs) are usually the first site of tumor metastasis in lung cancer. It is largely unknown about the association between the status of TDLNs and the response of primary tumor beds to immune checkpoint inhibitors (ICIs) in lung cancer patients. Also, studies characterizing the TDLNs in response to ICIs are scarce. We characterized and compared the radiological, metabolic (18F-FDG) and pathologic responses between primary tumor beds and paired TDLNs (invadednon-invaded) from 68 lung cancer patients who underwent neoadjuvant ICIs plus surgery. Additionally, we performed the spatial profiling of immune and non-immune cells within TDLNs using multiplexed immunofluorescence. Therapy responses (e.g., pathologic complete (pCR) or major response (MPR)) of primary lung tumor beds and paired TDLNs were investigated separately. We observed that responses of TDLNs to ICIs markedly differ from their paired primary lung tumors regarding the radiological, metabolic (18F-FDG uptake), and pathologic alterations. Neoadjuvant ICIs therapy specifically decreased 18F-FDG-reflected metabolic activity in the primary tumor beds with pCRMPR but not their TDLNs counterparts. Furthermore, the presence of invaded TDLNs was associated with poor pathologic responses in the matched primary tumor beds and predictive of rapid post-treatment tumor relapse. Spatial profiling demonstrated exclusion of T cell infiltrates within the metastatic lesions of invaded TDLNs, and diminished multiple immune and non-immune compositions in non-involved regions surrounding the metastatic lesions. These results provide the first clinically-relevant evidence demonstrating unique response patterns of TDLNs under ICIs treatment and revealing the underappreciated association of TDLNs status with the response of their paired primary tumors to ICIs in lung cancer. This work was supported by the National Natural Science Foundation of China (82072570 to F. Yao 82002941 to B. Sun), the excellent talent program of Shanghai Chest Hospital (to F.Y), the Basic Foundation Program for Youth of Shanghai Chest Hospital (2021YNJCQ2 to H.Yang), and the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212302 to F. Yao).

Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer A multi-center, prospective study (ACTION-2).

Extensive stage small cell lung cancer (ES-SCLC) is associated with poor prognosis. Recently, anlotinib has demonstrated significant clinical activity as a third-line or further on treatment. This study aimed to evaluate the safety and efficacy of a combination of anlotinib and platinum-etoposide as first-line treatment in patients with ES-SCLC. The present multi-center, single-arm, prospective study (NCT04684017) was conducted at three Chinese sites, and included patients with asymptomatic metastasis in the central nervous system. Patients were treated with up to six cycles of chemotherapy comprising etoposide with either carboplatin or cisplatin on day 1 of each cycle. Anlotinib was administered orally once daily on days 1-14 per cycle. The primary end points of the study were safety and investigator assessed objective response rate (ORR). A total of 101 patients were screened from August 2018 to September 2021, of which 86 who had received at least one dose of the treatment were included in the formal analysis. The median follow-up duration was 27.9 months. Complete response and partial response were observed in 2 and 73 patients, respectively, with an ORR of 87.2 % and a disease control rate of 97.7 %. Progression-free survival (PFS) and overall survival (OS) events occurred in 78 and 47 patients, respectively. The median PFS and OS were 9.0 (95 % confidence interval CI 7.5-10.5) and 19 (95 % CI 16.7-21.3) months, respectively. The incidence of grade 3 or higher adverse events (AEs) was 58.1 % and 24 patients (27.9 %) experienced serious treatment-related AEs. No fatalities consequent to AEs were recorded. Given its promising efficacy, safety profile and durability, anlotinib combined with chemotherapy deserves further investigation as first-line anticancer therapy in ES-SCLC (NCT 04684017).

Early change in the clearance of pembrolizumab reflects the survival and therapeutic response A population pharmacokinetic analysis in real-world non-small cell lung cancer patients.

The dosing pattern of pembrolizumab is based on population pharmacokinetic (Pop-PK) analysis of clinical trials. Data for Japanese patients or patient populations with poor conditions such as cachexia are scarce. In this study, we performed a Pop-PK analysis of Japanese non-small cell lung cancer patients and analyzed the relationship between exposure, treatment effect, and survival. A total of 270 blood samples from 76 patients who received 200 mg pembrolizumab every 3 weeks between March 2017 and December 2018 were included. Blood concentrations of pembrolizumab were measured using mass spectrometry, and Pop-PK analysis was conducted using the Phoenix NLME software with a one-compartment model. The estimated median of clearance (CL) in this analysis population was 0.104 Lday, about half of the historical data for Western data. Overall, pembrolizumab CL decreased over time, with some populations showing increased CL early in the treatment and others showing decreased CL over time. When the time-varying CL was stratified by quartile, the group with decreasing CL showed significantly better treatment response and survival than the group with increasing CL, even though the group included more patients with cachexia. Detailed analysis suggested that the patient population that responded to pembrolizumab treatment had an improved general condition and reduced protein catabolism, further decreasing CL. In populations that benefit from pembrolizumab treatment, CL may be reduced early in their treatment, which may be a predictive and prognostic factor. However, further prospective validation of our findings is needed.

Proposal for multiple new lesions as complement of hyperprogressive disease in NSCLC patients treated with PD-1PD-L1 immunotherapy.

Hyperprogressive disease (HPD) is a progression pattern of rapid increase in tumor burden during immunotherapy. However, current HPD definitions are mainly based on the diameter of target lesions. How to take new lesions into account remains unknown. In this retrospectively analysis, 393 patients received PD-1PD-L1 inhibitors monotherapy. 237 patients were eligible for HPD evaluation based on tumor growth rate (TGR) ratio, ΔTGR or tumor growth kinetic (TGK) ratio. Among them, 214 patients were eligible for evaluation of new lesions. The impact of new lesions on overall survival (OS) was investigated by Kaplan-Meier methods. The optimal threshold for new lesion number was investigated by one-year time-dependent receiver operating characteristic (ROC) curves. Developing more than one new lesions (n ≥ 2) was defined as multiple new lesions (MNL). New HPD was redefined as both developing MNL and meeting the requirement of current HPD definitions (TGR ratio, ΔTGR or TGK ratio). The survival difference between the newly defined HPD and non-HPD patients was investigated. HPD occurred in 5.1-18.1 % patient based on current definitions (TGR ratio, 15.6 % ΔTGR, 5.1 % TGK ratio, 18.1 %). However, there is no significant difference between OS of HPD and non-HPD patient. New lesion was associated with a shorter median OS in PD（with or without HPD) patients (6.1 vs 18.9 months, p 0.001). Time-dependent ROC analysis suggested that the optimal threshold for new lesion number in survival prediction was two. After the redefinition of HPD, New HPD patients had a significantly shorter median OS compared with non-HPD patients (TGR ratio with MNL 5.6 vs 11.8 months, p lt 0.001 ΔTGR with MNL 5.0 vs 11.4 months, p 0.034 TGK ratio with MNL 5.7 vs 12.3 months, p lt 0.001 respectively). Current HPD definitions had a better prognostic value when complemented with MNL. MNL should be integrated into the new definition of HPD.