Datasets:

Gaborandi

/

Lung_Cancer_pubmed_abstracts

like 1

Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients.

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020 fAE dipped significantly from 4.6-4.6 to 4.3-4.2 LVEF dipped to 58.4% versus the expected 60.3% (PDixon 0.021, PGrubbs 0.054) forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon 0.043, PGrubbs 0.181) carbon-monoxide diffusing capacity dipped to 12.6 mLminmmHg vs. 15.2 (PDixon 0.008, PGrubbs 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.

Pre-Existing Interstitial Lung Abnormalities Are Independent Risk Factors for Interstitial Lung Disease during Durvalumab Treatment after Chemoradiotherapy in Patients with Locally Advanced Non-Small-Cell Lung Cancer.

Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70 95% confidence interval, 1.69-7.72 We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs.

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma.

Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAPPOPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC

Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma.

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1miR-335-5pDMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.

The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy A Retrospective Observational Study.

Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020 the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. We identified 478 patients who underwent combined ICI therapy and chemotherapy 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS 6.2 months versus 9.1 months PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.

Multimodal Lung Cancer Subtyping Using Deep Learning Neural Networks on Whole Slide Tissue Images and MALDI MSI.

Artificial intelligence (AI) has shown potential for facilitating the detection and classification of tumors. In patients with non-small cell lung cancer, distinguishing between the most common subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SqCC), is crucial for the development of an effective treatment plan. This task, however, may still present challenges in clinical routine. We propose a two-modality, AI-based classification algorithm to detect and subtype tumor areas, which combines information from matrix-assisted laser desorptionionization (MALDI) mass spectrometry imaging (MSI) data and digital microscopy whole slide images (WSIs) of lung tissue sections. The method consists of first detecting areas with high tumor cell content by performing a segmentation of the hematoxylin and eosin-stained (HE-stained) WSIs, and subsequently classifying the tumor areas based on the corresponding MALDI MSI data. We trained the algorithm on six tissue microarrays (TMAs) with tumor samples from N 232 patients and used 14 additional whole sections for validation and model selection. Classification accuracy was evaluated on a test dataset with another 16 whole sections. The algorithm accurately detected and classified tumor areas, yielding a test accuracy of 94.7% on spectrum level, and correctly classified 15 of 16 test sections. When an additional quality control criterion was introduced, a 100% test accuracy was achieved on sections that passed the quality control (14 of 16). The presented method provides a step further towards the inclusion of AI and MALDI MSI data into clinical routine and has the potential to reduce the pathologists work load. A careful analysis of the results revealed specific challenges to be considered when training neural networks on data from lung cancer tissue.

HER3 Alterations in Cancer and Potential Clinical Implications.

In recent years, the third member of the HER family, kinase impaired HER3, has become a target of interest in cancer as there is accumulating evidence that HER3 plays a role in tumor growth and progression. This review focuses on HER3 activation in bladder, breast, colorectal, and lung cancer disease progression. HER3 mutations occur at a rate up to 10% of tumors dependent on the tumor type. With patient tumors routinely sequenced for gene alterations in recent years, we have focused on HER3 mutations in bladder, breast, colon, and lung cancers particularly in response to targeted therapies and the potential to become a resistance mechanism. There are currently several HER3 targeting drugs in the pipeline, possibly improving outcomes for cancer patients with tumors containing HER3 activation andor alterations.

The Biology and Therapeutic Potential of the Src-YAP Axis in Non-Small Cell Lung Cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is the most common lung cancer type which accounts for the majority (85%) of all lung cancer cases ....

Minimally Invasive Anatomical Segmentectomy versus Lobectomy in Stage IA Non-Small Cell Lung Cancer A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis was performed to assess potential differences in perioperative outcomes and disease-free survival (DFS) and overall survival (OS) of patients with pathological stage IA non-small cell lung cancer (NSCLC) who underwent minimally invasive anatomical segmentectomy or lobectomy. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of EMBASE (through Ovid), MEDLINE (via PubMed), and Cochrane CENTRAL was conducted. Two researchers independently reviewed each eligible study that included patients with stage IA NSCLC who underwent minimally invasive anatomical segmentectomy and lobectomy and compared perioperative andor survival outcomes of patients. A total of 887 publications were identified. Of these, 10 articles met our eligibility criteria. A significantly higher number of lymph nodes were harvested in lobectomies. The two groups did not significantly differ in postoperative complication rates, DFS, and OS. Patients who underwent segmentectomy had shorter postoperative hospital stays. Minimally invasive lobectomy and segmentectomy showed comparable short-term and long-term outcomes in stage IA NSCLC patients. Postoperative complication rates were similar. Minimally invasive lobectomies are associated with a higher number of harvested lymph nodes, although this did not affect the final staging or the survival outcomes.

PDX Models A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer.

The pivotal role of myeloid-derived suppressive cells (MDSCs) in cancer has become increasingly apparent over the past few years. However, to fully understand how MDSCs can promote human tumor progression and to develop strategies to target this cell type, relevant models that closely resemble the clinical complexity of human tumors are needed. Here, we show that mouse MDSCs of both the monocytic (M-MDCS) and the granulocytic (PMN-MDSC) lineages are recruited to human breast cancer patient-derived xenograft (PDX) tumors in mice. Transcriptomic analysis of FACS-sorted MDSC-subpopulations from the PDX tumors demonstrated the expression of several MDSC genes associated with both their mobilization and immunosuppressive function, including

Effectiveness of Nivolumab in Second-Line and Later in Patients with Advanced Non-Small Cell Lung Cancer in Real-Life Practice in France and Germany Analysis of the ESME-AMLC and CRISP Cohorts.

This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB-CIV) receiving nivolumab in 2L were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France 2015-2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany 2016-2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5-3.2) in squamous and 2.5 months (2.3-2.8) in non-squamousothers patients in ESME-AMLC, and 2.3 months (1.4-3.1) and 2.3 months (2.0-2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamousothers patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.

Lung Cancer Immunotherapy Beyond Common Immune Checkpoints Inhibitors.

Immunotherapy is an ever-expanding field in lung cancer treatment research. Over the past two decades, there has been significant progress in identifying immunotherapy targets and creating specific therapeutic agents, leading to a major paradigm shift in lung cancer treatment. However, despite the great success achieved with programmed death protein 1ligand 1 (PD-1PD-L1) monoclonal antibodies and with anti-PD-1PD-L1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), only a minority of lung cancer patients respond to treatment, and of these many subsequently experience disease progression. In addition, immune-related adverse events sometimes can be life-threatening, especially when anti-CTLA-4 and anti-PD-1 are used in combination. All of this prompted researchers to identify novel immune checkpoints targets to overcome these limitations. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin (Ig) and Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM) domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3) are promising molecules now under investigation. This review aims to outline the current role of immunotherapy in lung cancer and to examine efficacy and future applications of the new immune regulating molecules.

A Multicenter Retrospective Cohort Study on Superior Vena Cava Resection in Non-Small-Cell Lung Cancer Surgery.

Surgery for non-small-cell lung cancers (NSCLCs) invading the superior vena cava (SVC) is rarely performed due to surgical complexities and reported poor prognoses. Different methods have been described to reconstruct the SVC, such as direct suture, patch use or prosthesis, according to its circumferential involvement. The aim of our study was to analyze the short- and long-term results of different types of SVC resection and reconstruction for T4 NSCLCs. Between January 2000 and December 2019, 80 patients received an anatomical lung resection with SVC surgery in this multicenter retrospective study. The partial resection and direct suture or patch reconstruction group included 64 patients, while the complete resection and prosthesis reconstruction group included 16 patients. The primary endpoints were as follows long-term survival and disease-free survival. The secondary endpoints were as follows perioperative complications and 30- and 90-day mortality. Unpaired t-tests or Mann-Whitney U tests for non-parametric variables were applied to discrete or continuous data, and the chi-square test was applied to dichotomous or categorical data. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. No differences were found between the two groups in terms of general characteristics and surgical, oncological and survival outcomes. In particular, there were no differences in terms of early (50.0% vs. 68.8%, According to our results, SVC resection has good oncological and survival outcomes, regardless of the proportion of circumferential involvement and the type of reconstruction.

A Novel Therapeutic Target for Small-Cell Lung Cancer Tumor-Associated Repair-like Schwann Cells.

Small-cell lung cancer (SCLC), representing 15-20% of all lung cancers, is an aggressive malignancy with a distinct natural history, poor prognosis, and limited treatment options. We have previously identified Schwann cells (SCs), the main glial cells of the peripheral nervous system, in tumor tissues and demonstrated that they may support tumor spreading and metastasis formation in the in vitro and in vivo models. However, the role of SCs in the progression of SCLC has not been investigated. To clarify this issue, the cell proliferation assay, the annexin V apoptosis assay, and the transwell migration and invasion assay were conducted to elucidate the roles in SCLC of tumor-associated SCs (TA-SCs) in the proliferation, apoptosis, migration, and invasion of SCLC cells in vitro, compared to control group. In addition, the animal models to assess SC actions effects on SCLC in vivo were also developed. The result confirmed that TA-SCs have a well-established and significant role in facilitating SCLC cell cancer migration and invasion of SCLC in vitro, and we also observed that SC promotes tumor growth of SCLC in vivo and that TA-SCs exhibited an advantage and show a repair-like phenotype, which allowed defining them as tumor-associated repair SCs (TAR-SCs). Potential molecular mechanisms of pro-tumorigenic activity of TAR-SCs were investigated by the screening of differentially expressed genes and constructing networks of messenger-, micro-, and long- non-coding RNA (mRNA-miRNA-lncRNA) using DMS114 cells, a human SCLC, stimulated with media from DMS114-activated SCs, non-stimulated SCs, and appropriate controls. This study improves our understanding of how SCs, especially tumor-activated SCs, may promote SCLC progression. Our results highlight a new functional phenotype of SCs in cancer and bring new insights into the characterization of the nervous system-tumor crosstalk.

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration-A Narrative Review.

Non-small cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Savolitinib (Orpathys

Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer A Systematic Review and Meta-Analysis.

In breast, prostate, and other epithelial tumors, circulating tumor cells (CTC) in peripheral blood may predict survival. Our study evaluated the prognostic significance of baseline and postoperative CTC in patients with early non-small cell lung cancer (NSCLC) through a meta-analytic approach. Prospective studies comparing survival outcomes between positive (CTC) and negative CTC (CTC-) patients were systematically searched. Primary outcomes were overall (OS) and disease-free survival (DFS) with hazard ratio (HR) and 95% confidence interval (CI) as the effect measure. Pooled HR determined the prognostic role under a fixed-effect or random-effect model depending on heterogeneity. Eighteen studies with 1321 patients were eligible. CTC patients were associated with an increased risk of death (HR 3.53, 95% CI 2.51-4.95 Our meta-analysis revealed that CTC is a promising predictive biomarker for stratifying survival outcomes in patients with early-stage NSCLC. However, future studies are required to validate these findings and standardize detection methods.

Proteome-Wide Identification of RNA-Dependent Proteins in Lung Cancer Cells.

Following the concept of RNA dependence and exploiting its application in the R-DeeP screening approach, we have identified RNA-dependent proteins in A549 lung adenocarcinoma cells. RNA-dependent proteins are defined as proteins whose interactome depends on RNA and thus entails RNA-binding proteins (RBPs) as well as proteins in ribonucleoprotein complexes (RNPs) without direct RNA interaction. With this proteome-wide technique based on sucrose density gradient ultracentrifugation and fractionation followed by quantitative mass spectrometry and bioinformatic analysis, we have identified 1189 RNA-dependent proteins including 170 proteins which had never been linked to RNA before. R-DeeP provides quantitative information on the fraction of a protein being RNA-dependent as well as it allows the reconstruction of protein complexes based on co-segregation. The RNA dependence of three newly identified RNA-dependent proteins, DOCK5, ELMO2, also known as CED12A, and ABRAXAS1, also known as CCDC98, was validated using western blot analysis, and the direct RNA interaction was verified by iCLIP2 for the migration-related protein DOCK5 and the mitosis-related protein ABRAXAS1. The R-DeeP 2.0 database provides proteome-wide and cell line-specific information from A549 and HeLa S3 cells on proteins and their RNA dependence to contribute to understanding the functional role of RNA and RNA-binding proteins in cancer cells.

Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors.

Epithelial-to-mesenchymal transition (EMT) may drive the escape of ALK-rearranged non-small-cell lung cancer (NSCLC) tumors from ALK-tyrosine kinase inhibitors (TKIs). We investigated whether first-generation ALK-TKI therapy-induced EMT promotes cross-resistance to new-generation ALK-TKIs and whether this could be circumvented by the flavonolignan silibinin, an EMT inhibitor. ALK-rearranged NSCLC cells acquiring a bona fide EMT phenotype upon chronic exposure to the first-generation ALK-TKI crizotinib exhibited increased resistance to second-generation brigatinib and were fully refractory to third-generation lorlatinib. Such cross-resistance to new-generation ALK-TKIs, which was partially recapitulated upon chronic TGFβ stimulation, was less pronounced in ALK-rearranged NSCLC cells solely acquiring a partialhybrid EM transition state. Silibinin overcame EMT-induced resistance to brigatinib and lorlatinib and restored their efficacy involving the transforming growth factor-beta (TGFβ)SMAD signaling pathway. Silibinin deactivated TGFβ-regulated SMAD23 phosphorylation and suppressed the transcriptional activation of genes under the control of SMAD binding elements. Computational modeling studies and kinase binding assays predicted a targeted inhibitory binding of silibinin to the ATP-binding pocket of TGFβ type-1 receptor 1 (TGFBR1) and TGFBR2 but solely at the two-digit micromolar range. A secretome profiling confirmed the ability of silibinin to normalize the augmented release of TGFβ into the extracellular fluid of ALK-TKIs-resistant NSCLC cells and reduce constitutive and inducible SMAD23 phosphorylation occurring in the presence of ALK-TKIs. In summary, the ab initio plasticity along the EMT spectrum may explain the propensity of ALK-rearranged NSCLC cells to acquire resistance to new-generation ALK-TKIs, a phenomenon that could be abrogated by the silibinin-driven attenuation of the TGFβSMAD signaling axis in mesenchymal ALK-rearranged NSCLC cells.

Predictive Value of Baseline FDG-PETCT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors.

We aimed to investigate the predictive value of baseline 2-deoxy-2- For the purpose of this single-center study, the imaging data of the patients with a first diagnosis of NSCLC and an available baseline FDG-PETCT between 2020 and 2021 were retrospectively assessed. The baseline characteristics were collected based on clinical reports and interdisciplinary tumor board documentation. The metabolic (such as standardized uptake value SUV maximum and mean (SUV A total of 125 patients (median age ± standard deviation (SD) 72.0 ± 9.5 years) were enrolled 64 men (51.2%) and 61 women (48.8%). Adenocarcinoma was by far the most common histological subtype of NSCLC (47.2%). At the initial diagnosis, the vast majority of all the included patients showed either locally advanced disease (34.4%) or metastatic disease (36.8%). Fifty patients were treated with ICIs either as a first-line (20%) or second-line (20%) therapy, while 75 patients did not receive ICIs. The median values ± SD of PT SUV

Dual NGS Comparative Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Samples of Non-Small Cell Lung Carcinoma (NSCLC).

Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13% EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time.

Long-Term Projections of Cancer Incidence and Mortality in Japan and Decomposition Analysis of Changes in Cancer Burden, 2020-2054 An Empirical Validation Approach.

The aim of this study was to project new cancer casesdeaths forward to 2054, and decompose changes in cancer casesdeaths to assess the impact of demographic transitions on cancer burden. We collected data on cancer casesdeaths up to 2019, empirically validated the projection performance of multiple statistical models, and selected optimal models by applying time series cross-validation. We showed an increasing number of new cancer cases but decreasing number of cancer deaths in both genders, with a large burden attributed to population aging. We observed the increasing incidence rates in most cancer sites but reducing rates in some infection-associated cancers, including stomach and liver cancers. Colorectal and lung cancers were projected to remain as leading cancer burdens of both incidence and mortality in Japan over 2020-2054, while prostate and female breast cancers would be the leading incidence burdens among men and women, respectively. Findings from decomposition analysis require more supportive interventions for reducing mortality and improving the quality of life of Japanese elders. We emphasize the important role of governments and policymakers in reforming policies for controlling cancer risk factors, including oncogenic infections. The rapid increase and continued presence of those cancer burdens associated with modifiable risk factors warrant greater efforts in cancer control programs, specifically in enhancing cancer screening and controlling cancer risk factors in Japan.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFRALK negative and PD-L1 lt 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56-92) years, MF 165(74.6%)56(25.4%), ECOG performance status (PS) 01 ≥ 2 23(10.9%)94(42.5%)103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3-4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFRALK negative and PD-L1 lt 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (gt70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.

Targeted Imaging of Lung Cancer with Hyperpolarized

Hyperpolarized

Non-Small Cell Lung Cancer (NSCLC) in Young Adults, Age lt 50, Is Associated with Late Stage at Presentation and a Very Poor Prognosis in Patients That Do Not Have a Targeted Therapy Option A Real-World Study.

(1) Background Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods We conducted a retrospective cohort study of young NSCLC patients, age lt 50 years at diagnosis, who were treated between 2011-2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results Of 248 NSCLC patients, median age was 46 years, 50% (

ARDS after Pneumonectomy How to Prevent It Development of a Nomogram to Predict the Risk of ARDS after Pneumonectomy for Lung Cancer.

(1) Background The cause of ARDS after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. (2) Methods We reviewed a large panel of pre-, peri- and postoperative data of 211 patients who underwent pneumonectomy during the period 2014-2021. Univariable and multivariable logistic regression was used to quantify the association between preoperative parameters and the risk of developing ARDS, in addition to odds ratios and their respective 95% confidence intervals. A backward stepwise selection approach was used to limit the number of variables in the final multivariable model to significant independent predictors of ARDS. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing ARDS. Statistical significance was defined by a two-tailed

Circulating Tumor DNA-A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques.

Cancer is the second leading cause of death in the world and seriously affects the quality of life of patients. The diagnostic techniques for tumors mainly include tumor biomarker detection, instrumental examination, and tissue biopsy. In recent years, liquid technology represented by circulating tumor DNA (ctDNA) has gradually replaced traditional technology with its advantages of being non-invasive and accurate, its high specificity, and its high sensitivity. ctDNA may carry throughout the circulatory system through tumor cell necrosis, apoptosis, circulating exosome secretion, etc., carrying the characteristic changes in tumors, such as mutation, methylation, microsatellite instability, gene rearrangement, etc. In this paper, ctDNA mutation and methylation, as the objects to describe the preparation process before ctDNA analysis, and the detection methods of two gene-level changes, including a series of enrichment detection techniques derived from PCR, sequencing-based detection techniques, and comprehensive detection techniques, are combined with new materials. In addition, the role of ctDNA in various stages of cancer development is summarized, such as early screening, diagnosis, molecular typing, prognosis prediction, recurrence monitoring, and drug guidance. In summary, ctDNA is an ideal biomarker involved in the whole process of tumor development.

Dinactin A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer.

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1-1 µM of dinactin suppresses cell growth through induction of the G

Deep-Learning Algorithm and Concomitant Biomarker Identification for NSCLC Prediction Using Multi-Omics Data Integration.

Early diagnosis of lung cancer to increase the survival rate, which is currently at a low range of mid-30%, remains a critical need. Despite this, multi-omics data have rarely been applied to non-small-cell lung cancer (NSCLC) diagnosis. We developed a multi-omics data-affinitive artificial intelligence algorithm based on the graph convolutional network that integrates mRNA expression, DNA methylation, and DNA sequencing data. This NSCLC prediction model achieved a 93.7% macro F1-score, indicating that values for false positives and negatives were substantially low, which is desirable for accurate classification. Gene ontology enrichment and pathway analysis of features revealed that two major subtypes of NSCLC, lung adenocarcinoma and lung squamous cell carcinoma, have both specific and common GO biological processes. Numerous biomarkers (i.e., microRNA, long non-coding RNA, differentially methylated regions) were newly identified, whereas some biomarkers were consistent with previous findings in NSCLC (e.g.,

A Systematic Analysis of the Role of Unc-5 Netrin Receptor A (UNC5A) in Human Cancers.

Unc-5 netrin receptor A (UNC5A), a netrin family receptor, plays a key role in neuronal development and subsequent differentiation. Recently, studies have found that UNC5A plays an important role in multiple cancers, such as bladder cancer, non-small cell lung carcinoma, and colon cancer but its pan-cancer function is largely unknown. Herein, the R software and multiple databases or online websites (The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource (TIMER), The Gene Set Cancer Analysis (GSCA), Gene Expression Profiling Interactive Analysis (GEPIA), and cBioPortal etc.) were utilized to examine the role of UNC5A in pan-cancer. UNC5A was found to be highly expressed across multiple human cancer tissues and cells, was linked to clinical outcomes of patients, and was a potential pan-cancer biomarker. The mutational landscape of UNC5A exhibited that patients with UNC5A mutations had poorer progress free survival (PFS) in head and neck squamous cell carcinoma (HNSC) and prostate adenocarcinoma (PRAD). Furthermore, UNC5A expression was associated with tumor mutation burden (TMB), neoantigen, tumor microenvironment (TME), tumor microsatellite instability (MSI), immunomodulators, immune infiltration, DNA methylation, immune checkpoint (ICP) genes, and drug responses. Our results suggest the potential of UNC5A as a pan-cancer biomarker and an efficient immunotherapy target, which may also guide drug selection for some specific cancer types in clinical practice.

Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer.

Lysophosphatidic acid (LPA), a multifunctional endogenous phospholipid, plays a vital role in cellular homeostasis and the malignant behavior of cancer cells through G-protein-coupled receptors. However, the role of LPA in β-catenin-mediated gastric cancer is unknown. Here, we have noted the high expression of LPAR2 in human gastric cancer tissues, and that LPA treatment significantly increased the proliferation, migration, and invasion of human gastric cancer cells. Results from our biochemical experiments showed that an LPA exposure increased the expression of β-catenin and its nuclear localization, increased the phosphorylation of glycogen synthase kinase 3β (GSK-3β), decreased the expression of Axin2, and increased the expression of the target genes of the β-catenin signaling pathway. The LPA2 receptor (LPAR2) antagonist significantly reduced the LPA-induced nuclear localization of β-catenin, the primary signaling event. The knockdown of LPAR2 in the gastric cancer cell lines robustly reduced the LPA-induced β-catenin activity. An LPA exposure increased the ATP production by both oxidative phosphorylation and glycolysis, and this effect was abrogated with the addition of an LPAR2 antagonist and XAV393, which stabilizes the Axin and inhibits the β-catenin signaling pathway. Based on our findings, the possibility that LPA contributes to gastric cancer initiation and progression through the β-catenin signaling pathway as well as by the dysregulation of the energy metabolism via the LPAR2 receptor and Axin2, respectively, provides a novel insight into the mechanism of and possible therapeutic targets of gastric cancer.

PRR11 in Malignancies Biological Activities and Targeted Therapies.

Proline rich 11 (PRR11), initially renowned for its relevance with cell-cycle progression, is a proline-rich protein coding gene in chromosome 17q22-23. Currently, accumulating studies have demonstrated that PRR11 plays a critical role in cellular proliferation, colony formation, migration, invasion, cell-cycle progression, apoptosis, autophagy and chemotherapy resistance via multiple signaling pathways and biological molecules in several solid tumors. In particular, PRR11 also serves as a promising prognostic indicator in a limited number of human cancers, gradually manifesting its potential application for targeted therapies. In this review, we summarize functional activities, related signaling pathways and biological molecules of PRR11 in various malignancies and generalize potential application of PRR11 for targeted therapies, thereby contributing to further exploration of PRR11 in cancer treatment.

Hub Genes in Non-Small Cell Lung Cancer Regulatory Networks.

There are currently no accurate biomarkers for optimal treatment selection in early-stage non-small cell lung cancer (NSCLC). Novel therapeutic targets are needed to improve NSCLC survival outcomes. This study systematically evaluated the association between genome-scale regulatory network centralities and NSCLC tumorigenesis, proliferation, and survival in early-stage NSCLC patients. Boolean implication networks were used to construct multimodal networks using patient DNA copy number variation, mRNA, and protein expression profiles.

Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute

Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary

Evaluation of AMG510 Therapy on

A 3D tumor spheroid has been increasingly applied in pharmaceutical development for its simulation of the tumor structure and microenvironment. The embedded-culture of a tumor spheroid within a hydrogel microenvironment could help to improve the mimicking of in vivo cell growth and the development of 3D models for tumor invasiveness evaluation, which could enhance its drug efficiency prediction together with cell viability detection. NCI-H23 spheroids and CT-26 spheroids, from a non-small cell lung cancer and colorectal cancer cell line, respectively, together with extracellular matrix were generated for evaluating their sensitivity to AMG510 (a

Controlled Release of Encapsuled Stromal-Derived Factor 1α Improves Bone Marrow Mesenchymal Stromal Cells Migration.

Stem cell treatment is a promising method of therapy for the group of patients whose conventional options for treatment have been limited or rejected. Stem cells have the potential to repair, replace, restore and regenerate cells. Moreover, their proliferation level is high. Owing to these features, they can be used in the treatment of numerous diseases, such as cancer, lung diseases or ischemic heart diseases. In recent years, stem cell therapy has greatly developed, shedding light on stromal-derived factor 1α (SDF-1α). SDF-1α is a mobilizing chemokine for application of endogenous stem cells to injury sites. Unfortunately, SDF-1α presented short-term results in stem cell treatment trials. Considering the tremendous benefits of this therapy, we developed biodegradable polymeric microspheres for the release of SDF-1α in a controlled and long-lasting manner. The microspheres were designed from poly(L-lactideglycolidetrimethylene carbonate) (PLAGATMC). The effect of controlled release of SDF-1α from microspheres was investigated on the migration level of bone marrow Mesenchymal Stromal Cells (bmMSCs) derived from a pig. The study showed that SDF-1α, released from the microspheres, is more efficient at attracting bmMSCs than SDF-1α alone. This may enable the controlled delivery of selected and labeled MSCs to the destination in the future.

Pomegranate Pomace Extract with Antioxidant, Anticancer, Antimicrobial, and Antiviral Activity Enhances the Quality of Strawberry-Yogurt Smoothie.

Valorizing the wastes of the food industry sector as additives in foods and beverages enhances human health and preserves the environment. In this study, pomegranate pomace (PP) was obtained from the company Schweppes and exposed to the production of polyphenols and fiber-enriched fractions, which were subsequently included in a strawberry-yogurt smoothie (SYS). The PP is rich in carbohydrates and fibers and has high water-absorption capacity (WAC) and oil-absorption capacity (OAC) values. The LCMS phenolic profile of the PP extract indicated that punicalagin (199 gL) was the main compound, followed by granatin B (60 gL) and pedunculagin A (52 gL). Because of the high phenolic content of PP extract, it (

Identification of prognostic values of the transcription factor-CpG-gene triplets in lung adenocarcinoma A narrative review.

Abnormal DNA methylation can regulate carcinogenesis in lung adenocarcinoma (LUAD), while transcription factors (TFs) mediate methylation in a site-specific manner to affect downstream transcriptional regulation and tumor progression. Therefore, this study aimed to explore the TF-methylation-gene regulatory relationships that influence LUAD prognosis. Differential analyses of methylation sites and genes were generated by integrating transcriptome and methylome profiles from public databases. Through target gene identification, motif enrichment in the promoter region, and TF prediction, TF-methylation and methylation-gene relation pairs were obtained. Then, the prognostic TF-methylation-gene network was constructed using univariate Cox regression analysis. Prognostic models were constructed based on the key regulatory axes. Finally, Kaplan-Meier curves were created to evaluate the model efficacy and the relationship between candidate genes and prognosis. A total of 1878 differential expressed genes and 1233 differential methylation sites were screened between LUAD and normal samples. Then 10 TFs were predicted to bind 144 enriched motifs. After integrating TF-methylation and methylation-gene relations, a prognostic TF-methylation-gene network containing 4 TFs, 111 methylation sites, and 177 genes was constructed. In this network, ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were selected to construct the prognostic models, which showed robust abilities in predicting 1-, 3-, and 5-year survival probabilities. Finally, ERG and MTURN were downregulated in LUAD samples, whereas FOXM1 and PTPR were upregulated. Their expression levels were related to LUAD prognosis. ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were proposed as potential biomarkers for predicting the prognosis of LUAD.

Efficacy and safety of Kanglaite plus EGFR-TKI in the treatment of advanced non-small cell lung cancer A meta-analysis of 13 RCTs.

Kanglaite (KLT) is a Chinese medicine antitumor drug independently developed in China, which has been widely used in the treatment of advanced non-small cell lung cancer (NSCLC). The purpose of this study was to systematically evaluate the efficacy and safety of KLT plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the treatment of advanced NSCLC. Up to September 1, 2022, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, Chinese Biomedical Literature, China Science and Technology Journal, and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of KLT plus EGFR-TKI in the treatment of advanced NSCLC were included. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Revman5.4 software was used for meta-analysis. A total of 1057 patients were included in 13 RCTs. The results of meta-analysis showed that KLT plus EGFR-TKI could improve the objective response rate (ORR) (risk ratio (RR) confidence interval (CI) RR 1.54, 95% CI 1.27-1.86, P < .00001), the disease control rate (DCR) (RR 1.23, 95% CI 1.14-1.32, P < .00001), and quality of life (QOL) (RR 1.79, 95% CI 1.36-2.36, P < .0001) in patients with advanced NSCLC. The percentages of CD3T cells (standardized mean difference SMD 2.37, 95% CI 0.80-3.93, P .003), CD4T cells (SMD 1.39, 95% CI 0.85-1.93, P < .00001), NK cells (SMD 1.59, 95% CI 0.88-2.30, P < .0001), and CD4CD8ratio (SMD 0.37, 95% CI 0.19-0.55, P < .0001) were also increased. However, the results of subgroup analysis showed that in patients with EGFR mutation NSCLC, compared with EGFR-TKI alone, KLT plus EGFR-TKI did not significantly increase ORR and DCR (RR 1.43, 95% CI 0.88-2.32, P .15 RR 1.07, 95% CI 0.96-1.20, P .21). In terms of adverse events of drugs, the incidence of diarrhea, rash, anorexia, nausea and vomiting, liver and renal function damage of KLT plus EGFR-TKI was similar to that of EGFR-TKI alone (P > .05). KLT plus EGFR-TKI has some clinical benefits and good safety compared with EGFR-TKI alone in the treatment of advanced NSCLC. However, it seems that patients with EGFR mutations do not get significant clinical benefits, and more high-quality RCTs are needed to prove the efficacy of the combined regimen.

Efficacy and safety of PD-1PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma A systematic review and meta-analysis of clinical trials.

Immunotherapy with programmed cell death protein-1 (PD-1)programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval CI, 0.33-0.54), 0.21 (95% CI, 0.13-0.31), 0.72 (95% CI, 0.58-0.89), and 0.42 (95% CI, 0.29-0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (CRD 42022316805). Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1PD-L1 inhibitors in NHL. Our results suggested that PD-1PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.

Coexistence of primary pulmonary meningioma and metastatic papillary renal cell carcinoma of the lung A rare case report with review of the literature.

Primary pulmonary meningioma (PPM) is extremely rare tumor and only a few reports have been reported to date. PPM may be overlooked when it coexists with other types of tumors in the lung. It is essential to have a knowledge of the clinicopathological features of PPM and to recognize this rare coexistence. A 57-year-old male underwent surgery for papillary renal cell carcinoma, when 2 pulmonary nodules were detected using chest computed tomography. The coexistence of benign PPM and metastatic papillary renal cell carcinoma was histologically confirmed. A lobectomy was performed. The patient recovered well after surgery and was discharged on postoperative day 4. Duo to the rarity of PPM, it is easily overlooked, especially when it coexists with other tumors in the lung. The possibility of PPM needs to be taken into account when diagnosing pulmonary nodules in clinical practice.

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations A real-life data of Turkish Oncology Group.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n 33) and 46.8% (n 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval CI 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI 6.7-21.7) for patients with MET mutation (P .217). Median PFS was significantly longer in patients who have never smoked (P .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI 15.9-35.3) compared to the patients with MET amplification (11.0 months 95% CI 5.2-16.8) (P .049). In never-smokers, median OS was longer than smoker patients (25.6 months 95% CI 11.8-39.3 vs 16.5 months 95% CI 9.3-23.6 P .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.

A comprehensive bioinformatics analysis of FOXP3 in nonsmall cell lung cancer.

Fork head box p3 (FOXP3), the specific transcription factors of Tregs, not only in Tregs, but also expressed in cancer cells of certain malignant tumors. The histological positioning of FOXP3 in nonsmall cell lung cancer (NSCLC) and its biological significance are still unclear. This study aims to clarify the biological function of FOXP3 in NSCLC through bioinformatics analysis. Tumor immune estimation resource database was used to analyze the mRNA expression of FOXP3 in pan cancer, and to analyze the correlation between FOXP3 expression and tumor microenvironment cell infiltration. Overall survival and disease-free survival analyses were performed using a Kaplan-Meier plotter. Immunohistochemistry staining of FOXP3 was performed using human protein atalas (HPA) database, and immunofluorescence (IF) staining was used to verify gene expression and identify cell types. Protein-protein interaction (PPI) networks were drawn using STRING and visualized by Cytoscape. The functional and pathway enrichment analysis of FOXP3 used the DAVID database. In NSCLC, whether it is lung squamous cell carcinoma (P < .001) or lung adenocarcinoma (P < .001), FOXP3 is highly expressed in cancer tissue compared with normal tissue. Immunohistochemistry results showed that FOXP3 was mainly expressed in Tregs, but not in lung cancer tissues. IF staining showed that FOXP3 and CD3 (a marker of T cells) were co-expressed in immune cells. Moreover, survival analysis showed that high FOXP3 expression could be used as a predictor of poor overall survival (HR 1.25, P .00065) and disease-free survival (HR 1.88, P 1.1E-10) in patients with NSCLC. Next, we identified an important module containing 11 genes in the PPI network, including JUN, NFATC, STAT3, IRF4, IL2, IFGN, CTLA4, TNFRSF18, IL2A, KAT5, and FOXP3. KEGG signaling pathway was enriched in T cell receptor signaling pathway, Jak-STAT signaling pathway, cytokine-cytokine receptor interaction. Finally, we observed that FOXP3 expression correlated with infiltration of CD8 T cells (R 0.276, P 5.90E-10), CD4 T cells (R 0.643, P 6.81E-58), neutrophils (R 0.525, P 1.57E-35), and dendritic cells (R 0.608, P 1.35E-50) in lung adenocarcinoma, the same results were observed in lung squamous cell carcinoma. The infiltration of FOXP3-positive Tregs might promote the malignant progression of NSCLC, and targeted intervention of Tregs may be a potential treatment option for patients with NSCLC.

Dual-energy computed tomography iodine uptake in differential diagnosis of inflammatory and malignant pulmonary nodules.

PURPOSE The aim of this study was to evaluate the diagnostic performance of iodine uptake parameters using dual-energy computed tomography (DECT) in discriminating inflammatory nodules from malignant tumors. METHODS This retrospective study included 116 solid pulmonary nodules from 112 patients who were admitted to our hospital between January and September 2018. All nodules were confirmed by surgery or puncture. The degree of enhancement of a single-section region of interest was evalu ated. After total tumor volume-of-interest segmentation, the mean iodine density of the whole tumor was measured. Meanwhile, iodine uptake parameters, including total iodine uptake vol ume, total iodine concentration, vital iodine uptake volume, and vital iodine concentration, were calculated, and a predictive model was established. The overall ability to discriminate between inflammatory and malignant nodules was analyzed using an independent samples t-test for normally distributed variables. The diagnostic accuracy and prognostic performance of DECT parameters were evaluated and compared using receiver operating characteristic curve analysis and logistic regression analysis. A multivariate logistic regression analysis was used to determine the prognostic factors and goodness-of-fit of the whole tumor mean iodine and iodine uptake parameters for discriminating malignant nodules. RESULTS There were 116 non-calcified nodules, including 64 inflammatory nodules and 52 malignant nodules. The degree of enhancement in malignant nodules was significantly lower than that in inflammatory nodules (P.043). All iodine uptake parameters in malignant nodules were signifi cantly higher than those in inflammatory nodules (P < .001). The area under the receiver operat ing curve value, accuracy, sensitivity, and specificity of the established model based on iodine uptake parameters were 0.803, 76.72%, 82.69%, and 84.37%, respectively, which exhibited bet ter diagnostic performance than the degree of enhancement on weighted average images with respective values of 0.609, 59.48%, 61.54%, and 59.38%. CONCLUSION The iodine uptake parameters of DECT exhibited better diagnostic accuracy in discriminating inflammatory nodules from malignant nodules than the degree of enhancement on weighted average images.

Current concepts in evaluation and management of preoperative anaemia in patients undergoing thoracic surgery.

The purpose of this review is to evaluate the current recommendations for management of perioperative anaemia in patients undergoing thoracic surgery, present the impact of anaemia on outcomes in this patient population and suggest an algorithm for evaluating and treating anaemia preoperatively. Anaemia is a common medical issue noted preoperatively in patients presenting for thoracic surgery and carries significant morbidity. Preoperative anaemia increases the likelihood of receiving a perioperative transfusion, which represents a significant risk factor for morbidity and reduced disease-free survival in lung cancer patients presenting for thoracic surgery. It is also associated with longer hospital lengths of stay and increased risk for reoperation following lung transplantation. An algorithm-based approach to management of anaemia is beneficial and treatment with iron has been shown to reduce transfusions. Patients undergoing thoracic surgery have a high incidence of preoperative anaemia that increases the risk of transfusion and postoperative morbidity. Preoperative evaluation and tailored treatment based on the underlying cause of anaemia reduces the incidence of anaemia prior to surgery and decreases transfusion rates.

Presurgical radiation and chemotherapy in preparation for thoracic tumor resection.

This article aims at describing the role of neoadjuvant chemotherapy, radiation therapy as well the novel immunotherapy and targeted therapy in thoracic oncology with focus on anesthetic considerations of such treatments for the surgical patient. In recent years, immune check point inhibitors have changed the landscape of thoracic oncology treatment. In this review, we summarize the key studies that have been fundamental in this change. Rather than a comprehensive review, the purpose of this work is to provide the reader with an overview of the most common neoadjuvant regimens used in current practice, with the corresponding most prevalent adverse effects as it pertains for patients with esophageal and lung cancer, malignant pleural mesothelioma and mediastinal tumors. Considerations relevant to the anesthesiologist, including specific toxicities related to each treatment type, and the impact of each treatment type on perioperative outcomes and complications will be discussed.

The efficacy and safety of thermal ablation for patients with lung malignancy a meta-analysis of 12 studies in China.

Thermal ablation has been increasingly used in the treatment of lung cancer in recent years. This meta-analysis aims to investigate the therapeutic effect and safety of thermal ablation plus chemotherapy as compared with chemotherapy alone in treating patients with lung malignancy in China based on current evidence. Databases including PubMed, Web of Science, Embase and the Cochrane Library were searched for clinical reports. Additional literature search was also performed by searching the reference list of included studies and latest reviews. Raw data including objective response rate, disease control rate, progression-free survival, overall survival and the incidence of major complication were extracted and pooled. A total of 12 studies in China including 1282 patients with lung malignancy were included in this meta-analysis. The number of studies that reported data of objective response rate, disease control rate, progression-free survival, overall survival and major complication was 8, 7, 7, 6 and 7, respectively. The combination therapy of thermal ablation plus chemotherapy showed a significantly better efficacy in improving objective response rate (odds ratio 2.73 P < 0.001) and disease control rate (odds ratio 2.43 P < 0.001) as compared with chemotherapy alone. Thermal ablation was also a significant protective factor for progression-free survival (hazard ratio 0.43 P < 0.001) and overall survival (hazard ratio 0.49 P < 0.001). Besides, thermal ablation did not increase the risk of major complication (odds ratio 0.75 P 0.252). The present meta-analysis based on these studies in China suggested that thermal ablation is a promising technique to provide better disease response and survival outcomes for patients with lung malignancy. Thermal ablation is worth further promotion in treating lung malignancy and application in clinical practice.

Ground-glass opacity in a patient with right aortic arch and no left pulmonary artery.

Here we report a case of patients with mixed ground glass opacity in the left lung combined with congenital right aortic arch, which is only present in 0.01-0.1% of adults. A 60-year-old woman was referred to our department with a mixed ground-glass opacity (GGO) in the upper lobe of her left lung. She had congenital right aortic arch, and the left pulmonary artery was absent. Enhanced chest computed tomography, pulmonary perfusion imaging, and three-dimensional reconstruction were performed to confirm the blood supply in the left lung and the exact location of the GGO. Because of the unusual left pulmonary vascular structure, wedge resection was performed to prevent massive hemorrhage. The final pathological examination revealed that the mixed GGO was a well-differentiated pulmonary adenocarcinoma. The surgical options should be evaluated carefully in view of the complications and the prognosis of the patient, when ground glass opacity is combined with congenital cardiovascular anomalies.

Model selection for survival individualized treatment rules using the jackknife estimator.

Precision medicine is an emerging field that involves the selection of treatments based on patients individual prognostic data. It is formalized through the identification of individualized treatment rules (ITRs) that maximize a clinical outcome. When the type of outcome is time-to-event, the correct handling of censoring is crucial for estimating reliable optimal ITRs. We propose a jackknife estimator of the value function to allow for right-censored data for a binary treatment. The jackknife estimator or leave-one-out-cross-validation approach can be used to estimate the value function and select optimal ITRs using existing machine learning methods. We address the issue of censoring in survival data by introducing an inverse probability of censoring weighted (IPCW) adjustment in the expression of the jackknife estimator of the value function. In this paper, we estimate the optimal ITR by using random survival forest (RSF) and Cox proportional hazards model (COX). We use a Z-test to compare the optimal ITRs learned by RSF and COX with the zero-order model (or one-size-fits-all). Through simulation studies, we investigate the asymptotic properties and the performance of our proposed estimator under different censoring rates. We illustrate our proposed method on a phase III clinical trial of non-small cell lung cancer data. Our simulations show that COX outperforms RSF for small sample sizes. As sample sizes increase, the performance of RSF improves, in particular when the expected log failure time is not linear in the covariates. The estimator is fairly normally distributed across different combinations of simulation scenarios and censoring rates. When applied to a non-small-cell lung cancer data set, our method determines the zero-order model (ZOM) as the best performing model. This finding highlights the possibility that tailoring may not be needed for this cancer data set. The jackknife approach for estimating the value function in the presence of right-censored data shows satisfactory performance when there is small to moderate censoring. Winsorizing the upper and lower percentiles of the estimated survival weights for computing the IPCWs stabilizes the estimator.

Design of a self-driven probiotic-CRISPRCas9 nanosystem for sono-immunometabolic cancer therapy.

Reprogramming the tumor immunosuppressive microenvironment is a promising strategy for improving tumor immunotherapy efficacy. The clustered regularly interspaced short palindromic repeat (CRISPR)CRISPR-associated protein 9 system can be used to knockdown tumor immunosuppression-related genes. Therefore, here, a self-driven multifunctional delivery vector is constructed to efficiently deliver the CRISPR-Cas9 nanosystem for indoleamine 2,3-dioxygenase-1 (IDO1) knockdown in order to amplify immunogenic cell death (ICD) and then reverse tumor immunosuppression. Lactobacillus rhamnosus GG (LGG) is a self-driven safety probiotic that can penetrate the hypoxia tumor center, allowing efficient delivery of the CRISPRCas9 system to the tumor region. While LGG efficiently colonizes the tumor area, it also stimulates the organism to activate the immune system. The CRISPRCas9 nanosystem can generate abundant reactive oxygen species (ROS) under the ultrasound irradiation, resulting in ICD, while the produced ROS can induce endosomallysosomal rupture and then releasing Cas9sgRNA to knock down the IDO1 gene to lift immunosuppression. The system generates immune responses that effectively attack tumor cells in mice, contributing to the inhibition of tumor re-challenge in vivo. In addition, this strategy provides an immunological memory effect which offers protection against lung metastasis.

Actin-microtubule cytoskeletal interplay mediated by MRTF-ASRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.

Mutations in the lamin AC gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK12 in the heart. We recently showed that ERK12 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus. Inhibiting the MRTF-ASRF axis leads to decreased α-tubulin acetylation by reducing the expression of ATAT1 gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients with LMNA mutations and in heart and isolated cardiomyocytes from Lmna

Hsacirc0092887 targeting miR-490-5pUBE2T promotes paclitaxel resistance in non-small cell lung cancer.

Chemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsacirc0092887 in paclitaxel (PTX) resistance in non-small cell lung cancer (NSCLC). RT-qPCR as well as western blotting were used for the analysis of hsacirc0092887, miR-490-5p and UBE2T expression in PTX-resistant NSCLC tumor tissues and cells. CCK-8 assay was done to determine the IC50 value of PTX. CCK-8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl-2), and xenograft mouse models were utilized to investigate the role of hsacirc0092887 in PTX-resistance in NSCLC. The binding sites of miR-490-5p to hsacirc0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual-luciferase assays. Expression of hsaCirc0092887 was upregulated in NSCLC tumor samplescell lines, and its expression was also higher in PTX-resistant tumor samplescell lines when compared with their respective controls. Silencing of hsacirc0092887 in PTX-treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR-490-5p was a direct target of hsacirc0092887, and UBE2T was a functional downstream target of hsacirc0092887miR-490-5p axis. Hsacirc0092887 depletion-induced anti-cancer effects in PTX-treated NSCLC cells were reversed by miR-490-5p inhibitor. Furthermore, inhibition of miR-490-5p strengthened UBE2T expression, thereby attenuating the anti-cancer effects caused by UBE2T knockdown. Hsacirc0092887 depletion alleviated PTX-resistance in NSCLC cells via modulating the miR-490-5pUBE2T axis, and the targeted management of hsacirc0092887-mediated signaling axis might contribute to PTX-resistance intervention in NSCLC.

Effect of chemotherapy, immunotherapy, and targeted therapies on removal of indwelling pleural catheters in non-small cell lung cancer patients with malignant pleural effusions.

Indwelling pleural catheters (IPCs) are a mainstay therapy for malignant pleural effusions (MPEs). Many patients treated with IPCs achieve pleurodesis. We aimed to identify the effect of systemic therapies for non-small cell lung cancer (NSCLC) on IPC removal in patients with associated MPEs. We completed a retrospective cohort study of adult IPC recipients with metastatic NSCLC at the pleural effusion clinic at the Royal Alexandra Hospital from 2009 to 2020. We used logistic regression to assess the rates of IPC removal and Cox regression to assess the time to IPC removal. 232 patients met inclusion criteria with 248 IPCs reviewed. The overall pleurodesis rate was 42.7% with a median time to pleurodesis of 68 (IQR 38-140) days. In univariate analysis, chemotherapy (OR 1.86, CI 0.99-3.49) and epidermal growth factor receptor (EGFR) targeted therapy (OR 3.81, CI 1.86-7.79) were associated with higher rates of pleurodesis. In multivariate analysis, increased rates of pleurodesis were associated with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (OR 4.82, CI 2.24-10.37) and EGFR targeted therapy (OR 3.87, CI 1.80-8.32). Earlier IPC removal was associated with EGFR targeted therapy in both univariate (HR 1.84, CI 1.20-2.83) and multivariate analysis (HR 1.86, CI 1.19-2.92). Treatment with EGFR targeted therapy is associated with increased rates and earlier removal of IPC in patients with NSCLC in our cohort. Further large cohort studies are required to determine if this relationship persists.

Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development.

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development.

Design, synthesis, and biological evaluation of novel protopanoxadiol derivatives based PROTACs technology for the treatment of lung cancer.

Protopanoxadiol is a key active ingredient derived from Panax ginseng that is well-known to exhibit anti-tumor activity. Previous research focused on the natural protopanaxadiol derivative AD-1 has demonstrated that it possesses broad spectrum anti-tumor activities in vitro and in vivo. However, its limited activity, selectivity, and cell permeability have impeded its therapeutic application. Herein, a series of novel AD-1 derivatives were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technology by linking AD-1 at the C-3 and C-12 positions with pomalidomide through linkers of alkyl chain of differing lengths to achieve the goal of improving the efficacy of the parent compound. Among these synthesized PROTACs, the representative compound A05 exhibited the most potent anti-proliferative activity against A549 cells. Furthermore, mechanistic studies revealed that compound A05 was able to suppress MDM2 expression, disrupt interactions between p53 and MDM2 and readily induce apoptotic death via the mitochondrial apoptosis pathway. Moreover, the in vivo assays revealed that compound A05 exhibited both anti-proliferative and anti-metastatic activities in the zebrafish tumor xenograft model with A549 cells. Together, our findings suggest that AD-1 based PROTACs associated with the degradation of MDM2 may have promising effects for the treatment of lung cancer and this work provide a foundation for future efforts to develop novel anti-tumor agents from natural products.

A Clinical Prediction Model for Postoperative Pneumonia After Lung Cancer Surgery.

Postoperative pneumonia (POP) is a common complication following lung cancer surgery and is associated with increased hospitalization costs and mortalities. We aimed to identify risk factors associated with POP and to develop a reliable predictive model. Patients who underwent lung cancer surgery between January 2015 and December 2021 in our hospital were enrolled. Least absolute shrinkage and selection operator regression analysis was used to select predictors of POP. Multivariable logistic regression was performed to construct the nomogram. Bootstrap resampling was conducted for internal validation. The performance of the model was evaluated by discrimination and calibration. A total of 5269 consecutive patients were enrolled. POP occurred in 1.7% of patients (925269). Five independent predictors were identified age, predicted forced expiratory volume in 1 s, predicted diffusing capacity of the lungs for carbon monoxide, tuberculosis history, and surgery duration. The multivariable regression model showed good discrimination (C-index 0.821, 95% confidence interval, 0.783-0.859), which was well validated by internal validation. The calibration curve illustrated good agreement between the predicted probability and observed probability of POP. Based on the easily available risk factors, our nomogram could predict the risk of POP with good discrimination and calibration. The model has good clinical practicability, enabling precise and targeted interventions to reduce the incidence of POP in high-risk patients.

Entanglements and imagined futures The subject(s) of precision in oncology.

Precision oncology holds an increasingly powerful social function. In the era of precision, how people encounter, live with, and experience cancer, how they imagine their lives, how they navigate treatment regimens, and experience side effects, have been radically transformed. Innovations in oncology - in this case precision-related - are always more-than-clinical their circulation exceeds the laboratory and the hospital, but what this circulation of innovation produces has been thus far opaque. To begin to comprehend what is emergent at the cancer-precision nexus in peoples everyday lives, we draw on qualitative interviews with twenty people diagnosed with metastatic non-small cell lung cancer undergoing immunotherapy andor targeted therapy and we discuss how precision inflects survivorship, entangles subjects in chronic living, and induces novel temporalities. Through such inflections of survivorship, precision innovation re-shapes expectations and possibilities, and sometimes enacts new, unexpected (or, for some, unwanted) futures. Such illness and survivorship narratives indicate the importance of orientating the social science scholarship toward considerations of temporality and entanglements for comprehending precision innovation in oncology. And in doing so, provide a nuanced account of how innovations unsettle and recast, rather than unravel, the normative scene of cancer.

Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells.

Loss of heterozygosity and promoter hypermethylation of APC is frequently observed in human endometrial cancer, which is the most common gynecological cancer in the US, but its carcinogenic driver status in the endometrial epithelium has not been confirmed. We have identified a novel population of progenitor endometrial epithelial cells (EECs) in mice that express LysM and give rise to approximately 15% of all EECs in adult mice. Lysozyme M (LysM) is a glycoside hydrolase that is encoded by Lyz2 and functions to protect cells from bacteria as part of the innate immune system. Its expression has been shown in a subset of hematopoietic stem cells and in specialized lung and small intestinal epithelial cells. Conditional deletion of Apc in LysM EECs results in significantly more epithelial cells compared to wild type mice. At five months of age, the Apc cKO mice have enlarged uterine horns with pathology that is consistent with endometrial hyperplasia with cystic endometrial glands, non-villous luminal papillae, and nuclear atypia. Nuclear accumulation of β-catenin and ERα, both of which are known to induce endometrial hyperplasia, was observed in the EECs of the Apc cKO mice. These results confirm that loss of APC in EECs can result in a phenotype similar to endometrial hyperplasia.

Towards Whole Health Toxicology In-Silico Prediction of Diseases Sensitive to Multi-Chemical Exposures.

Chemical exposures from diverse sources merge on a limited number of molecular pathways described as toxicity pathways. Changes in the same set of molecular pathways in different cell and tissue types may generate seemingly unrelated health conditions. Today, no approaches are available to predict in an unbiased way sensitivities of different disease states and their combinations to multi-chemical exposures across the exposome. We propose an inductive in-silico workflow where sensitivities of genes to chemical exposures are identified based on the overlap of existing genomic datasets, and data on sensitivities of individual genes is further used to sequentially derive predictions on sensitivities of molecular pathways, disease states, and groups of disease states (syndromes). Our analysis predicts that conditions representing the most significant public health problems are among the most sensitive to cumulative chemical exposures. These conditions include six leading types of cancer in the world (prostatic, breast, stomach, lung, colorectal neoplasms, and hepatocellular carcinoma), obesity, type 2 diabetes, non-alcoholic fatty liver disease, autistic disorder, Alzheimers disease, hypertension, heart failure, brain and myocardial ischemia, and myocardial infarction. Overall, our predictions suggest that environmental risk factors may be underestimated for the most significant public health problems.

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention.

Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.

Accuracy of CT-Guided Core-Needle Biopsy in Diagnosis of Thoracic Lesions Suspicious for Primitive Malignancy of the Lung A Five-Year Retrospective Analysis.

Lung cancer represents a heterogeneous group of neoplasms, with the highest frequency and mortality in both sexes combined. In a clinical scenario characterized by the widespread of multidetector-row spiral CT, core-needle biopsy under tomographic guidance is one of the main and safest methods to obtain tissue specimens, even though there are relatively high rates of pneumothorax (0-60% incidence) and pulmonary hemorrhage (4-27% occurrence rates). The aim of this retrospective study is to assess the diagnostic accuracy of CT-guided core-needle biopsy in the diagnosis of primary lung malignancies and to compare our results with evidence from the literature. Our analysis included 350 thoracic biopsies, performed from 2017 to 2022 with a 64-row CT guidance and 1618 G needles mounted on a biopsy gun. We included in the final cohort all samples with evidence of primary lung malignancies, precursor lesions, and atypia, as well as inconclusive and negative diagnoses. There was sensitivity of 90.07% (95% CI 86.05-93.25%), accuracy of 98.87% (95% CI 98.12-99.69%), positive predictive value of 100%, and negative value of 98.74% (95% CI 98.23-99.10%). Specificity settled at 100% (93.84-100%). The AUC was 0.952 (95% CI 0.924-0.972). Only three patients experienced major complications after the procedure. Among minor complications, longer distances from the pleura, the presence of emphysema, and the lower dimensions of the lesions were correlated with the development of pneumothorax after the procedure, while longer distances from the pleura and the lower dimensions of the lesions were correlated with intra-alveolar hemorrhage. Immunohistochemistry analysis was performed in 51% of true positive cases, showing TTF-1, CK7, and p40 expression, respectively, in 26%, 24%, and 10% of analyzed samples. The CT-guided thoracic core-needle biopsy is an extremely accurate and safe diagnostic procedure for the histological diagnosis of lung cancer, a first-level interventional radiology exam for peripheral and subpleural lesions of the lung, which is also able to provide adequate samples for advanced pathologic assays (e.g., FISH, PCR) to assess molecular activity and genetic sequencing.

Current treatment approaches for brain metastases in

Oncogene-addicted non-small cell lung cancer (NSCLC) patients present a high incidence of CNS metastases either at diagnosis or during the course of the disease. In this case, patients present with worse prognosis and are often excluded from clinical trials unless brain metastases are pre-treated or clinically stable. As a result of the discovery of several oncogenic drivers in Last-generation ALK inhibitors have shown slightly superior intracranial activity but pivotal trials do not consider the same endpoints for intracranial efficacy, therefore data are not comparable. Local treatments for BM including surgical resection, stereotactic radiosurgery (SRS) and WBRT, should be integrated with systemic therapies basing on specific criteria like presence of oligoprogression or symptomatic progression.

The UBE2CCDH1DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells.

Ubiquitin-conjugating enzyme E2C (UBE2C) mediates ubiquitylation chain formation via the K11 linkage. While previous in vitro studies showed that UBE2C plays a growth-promoting role in cancer cell lines, the underlying mechanism remains elusive. Still unknown is whether and how UBE2C plays a promoting role in vivo. Here we report that UBE2C was indeed essential for growth and survival of lung cancer cells harboring Kras mutations, and UBE2C was required for KrasG12D-induced lung tumorigenesis, since Ube2c deletion significantly inhibited tumor formation and extended the lifespan of mice. Mechanistically, KrasG12D induced expression of UBE2C, which coupled with APCCCDH1 E3 ligase to promote ubiquitylation and degradation of DEPTOR, leading to activation of mTORC signaling. Importantly, DEPTOR levels fluctuated during cell cycle progression in a manner dependent on UBE2C and CDH1, indicating their physiological connection. Finally, Deptor deletion fully rescued the tumor inhibitory effect of Ube2c deletion in the KrasG12D lung tumor model, indicating a causal role of Deptor. Taken together, our study shows that the UBE2CCDH1DEPTOR axis forms an oncogene and tumor suppressor cascade that regulates cell cycle progression and autophagy and validates UBE2C an attractive target for lung cancer associated with Kras mutations.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer A National COVID Cancer Cross-sectional Evaluation.

Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UKs third-dose vaccination booster program. Anti-SARS-CoV-2 COV-S antibody test (Elecsys Roche). Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results 4.68% vs 376 of 294 230 0.13% P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio OR, 3.05 95% CI, 1.96-4.72 P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48 95% CI, 3.31-12.67 P < .001) than individuals who had a positive antibody response. The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

Anticancer Activity of Mannose-Specific Lectin, BPL2, from Marine Green Alga

Lectin is a carbohydrate-binding protein that recognizes specific cells by binding to cell-surface polysaccharides. Tumor cells generally show various glycosylation patterns, making them distinguishable from non-cancerous cells. Consequently, lectin has been suggested as a good anticancer agent. Herein, the anticancer activity of

Design and Synthesis of Novel Phenylahistin Derivatives Based on Co-Crystal Structures as Potent Microtubule Inhibitors for Anti-Cancer Therapy.

Phenylahistin is a naturally occurring marine product with a diketopiperazine structure that can bind to the colchicine site of microtubulin as a possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on the co-crystal complexes of phenylahistin derivatives and microtubulin. We established a focused library of imidazole-type molecules for the introduction of different groups to the C-ring and A-ring of phenylahistin. Structure-activity relationship studies indicated that appropriate hydrocarbon substituents and unsaturated alkenyl substituents at the 1-position of the imidazole group are important for improving the activity of such compounds. In addition, this study found that propylamine groups could maintain the activity of these compounds, as exemplified by compound

Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model.

Selenium (Se) and fish oil (FO) exert anti-epidermal growth factor receptor (EGFR) action on tumors. This study aimed to compare the anti-cancer efficacy of EGFR inhibitors (gefitinib and erlotinib) alone and in combination with nutritional supplements of SeFO in treating lung cancer. Lewis LLC1 tumor-bearing mice were treated with a vehicle or SeFO, gefitinib or gefitinib plus SeFO, and erlotinib or erlotinib plus SeFO. The tumors were assessed for mRNA and protein expressions of relevant signaling molecules. Untreated tumor-bearing mice had the lowest body weight and highest tumor weight and volume of all the mice. Mice receiving the combination treatment with SeFO and gefitinib or erlotinib had a lower tumor volume and weight and fewer metastases than did those treated with gefitinib or erlotinib alone. The combination treatment exhibited greater alterations in receptor signaling molecules (lower EGFRTGF-βTβRAXLWnt3aWnt5aFZD7β-catenin higher GSK-3β) and immune checkpoint molecules (lower PD-1PD-L1CD80CTLA-4IL-6 higher NKp46CD16CD28IL-2). These mouse tumors also had lower angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastases, and proliferation of Ki-67, as well as higher cell cycle arrest and apoptosis. These preliminary results showed the SeFO treatment enhanced the therapeutic efficacies of gefitinib and erlotinib via modulating multiple signaling pathways in an LLC1-bearing mouse model.

Developing Artificial Intelligence Models for Extracting Oncologic Outcomes from Japanese Electronic Health Records.

A framework that extracts oncological outcomes from large-scale databases using artificial intelligence (AI) is not well established. Thus, we aimed to develop AI models to extract outcomes in patients with lung cancer using unstructured text data from electronic health records of multiple hospitals. We constructed AI models (Bidirectional Encoder Representations from Transformers BERT, Naïve Bayes, and Longformer) for tumor evaluation using the University of Miyazaki Hospital (UMH) database. This data included both structured and unstructured data from progress notes, radiology reports, and discharge summaries. The BERT model was applied to the Life Data Initiative (LDI) data set of six hospitals. Study outcomes included the performance of AI models and time to progression of disease (TTP) for each line of treatment based on the treatment response extracted by AI models. For the UMH data set, the BERT model exhibited higher precision accuracy compared to the Naïve Bayes or the Longformer models, respectively (precision 0.42 vs. 0.47 or 0.22, recall 0.63 vs. 0.46 or 0.33 and F1 scores 0.50 vs. 0.46 or 0.27). When this BERT model was applied to LDI data, prediction accuracy remained quite similar. The Kaplan-Meier plots of TTP (months) showed similar trends for the first (median 14.9 95% confidence interval 11.5, 21.1 and 16.8 12.6, 21.8), the second (7.8 6.7, 10.7 and 7.8 6.7, 10.7), and the later lines of treatment for the predicted data by the BERT model and the manually curated data. We developed AI models to extract treatment responses in patients with lung cancer using a large EHR database however, the model requires further improvement. The use of artificial intelligence (AI) to derive health outcomes from large electronic health records is not well established. Thus, we built three different AI models Bidirectional Encoder Representations from Transformers (BERT), Naïve Bayes, and Longformer to serve this purpose. Initially, we developed these models based on data from the University of Miyazaki Hospital (UMH) and later improved them using the Life Data Initiative (LDI) data set of six hospitals. The performance of the BERT model was better than the other two, and it showed similar results when it was applied to the LDI data set. The Kaplan–Meier plots of time to progression of disease for the predicted data by the BERT model showed similar trends to those for the manually curated data. In summary, we developed an AI model to extract health outcomes using a large electronic health database in this study however, the performance of the AI model could be improved using more training data.

Communication with patients with limited prognosis-an integrative mixed-methods evaluation study.

Oncological societies advocate the continuity of care, specialized communication, and early integration of palliative care. To comply with these recommendations, an interprofessional, longitudinally-structured communication concept, the Milestone Communication Approach (MCA), was previously developed, implemented, and evaluated. Our research question is what are possible explanations from the patient perspective for prognosis and advance care planning being rarely a topic and for finding no differences between MCA and control groups concerning distress, quality of life, and mood A pragmatic epistemological stance guided the study. A mixed-methods design was chosen including a pragmatic randomized trial (n 171), qualitative interviews with patients (n 13) and caregivers (n 12), and a content analysis (133 milestone conversations, 54 follow-up calls). Data analysis involved the pillar integration process. Two pillar themes emerged 1 approaching prognosis and advance care planning 2 living with a life-threatening illness. Information on prognosis seemed to be offered, but patients reactions were diverse. Some patients have to deal with having advanced lung cancer while nonetheless feeling healthy and seem not to be ready for prognostic information. All patients seemed to struggle to preserve their quality of life and keep distress under control. Attending to patients questions, worries and needs early in a disease trajectory seems key to helping patients adjust to living with lung cancer. If necessary clinicians should name their predicament having to inform about prognosis versus respecting the patients wish to avoid it. Research should support better understanding of patients not wishing for prognostic information to successfully improve communication strategies. Registration German Clinical Trial Register No. DRKS00013649, registration date 12222017, ( httpswww.drks.dedrkswebnavigate.donavigationIdtrial.HTMLTRIALIDDRKS00013649 ) and No. DRKS00013469, registration date 12222017, ( httpswww.drks.dedrkswebnavigate.donavigationIdtrial.HTMLTRIALIDDRKS00013469 ).

Coupled folding-upon-binding of human tumor suppressor MIG6 to lung cancer EGFR kinase domain and molecular trimmingstapling of MIG6-derived β-hairpins to target the coupling event.

Human epidermal growth factor receptor (EGFR) is involved in strong association with malignant proliferation, which has been shown to play a central role in the development and progression of non-small cell lung cancer and other solid tumors. The tumor-suppressor protein MIG6 is a negative regulator of EGFR kinase activity by binding at the activation interface of asymmetric dimer of EGFR kinase domain to disrupt EGFR dimerization and then inactivate the kinase. The protein adopts two discrete fragments 1 and 2 to directly interact with EGFR. It is revealed that the MIG6 fragment 2 is intrinsically disordered in free unbound state, but would fold into a well-structured β-hairpin when binding to EGFR, thus characterized by a so-called coupled folding-upon-binding process, which can be regarded as a compromise between favorable direct readout and unfavorable indirect readout. Here, a 23-mer F2P peptide was derived from MIG6 fragment 2, trimmed into a 17-mer tF2P peptide that contains the binding hotspot region of the fragment 2, and then constrained with an ordered hairpin conformation in free unbound state by disulfide stapling, finally resulting in a rationally stapledtrimmed stF2P peptide that largely minimizes the unfavorable indirect readout effect upon its binding to EGFR kinase domain, with affinity improved considerably upon the trimming and staplingtrimming. These rationally designed β-hairpin peptides may be further exploited as potent anti-lung cancer agents to target the activation event of EGFR dimerization.

Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.

To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort. A total of 25 subjects were involved in this study including COPD (n 8), MCTE (n 3), and healthy (n 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins. The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p 0.02) and (ii) dependent on the age of the subjects in the healthy group (p 0.0008) while their CVs (p 0.13) were not. The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group. • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort.

Virtual clinical trials A tool for predicting patients who may benefit from treatment beyond progression with pembrolizumab in non-small cell lung cancer.

Enrolling patients in immunotherapy clinical trials is becoming increasingly competitive. Virtual clinical trials can help investigators answer key questions despite this. For example, pembrolizumab is the recommended first-line treatment for non-small cell lung cancer (NSCLC) with no driver alterations and a programmed death ligand 1 (PD-L1) Tumor Proportion Score ≥50%. Salvage therapies for relapsedrefractory patients are limited. Retrospective studies suggest that a subset of patients may benefit from pembrolizumab beyond progression these results have not been validated in a prospective study. We constructed digital twins of patients and simulated clinical trials to predict the best salvage therapy after progressive disease (PD) on pembrolizumab. Response dynamics were evaluated at the lesion level to represent patients who experience systemic PD while individual lesions continue shrinking. With >25,000 radiographic lesion measurements from >500 patients, we simulated responses to pembrolizumab, chemotherapy, and PD on pembrolizumab followed by either pembrolizumab beyond progression or salvage chemotherapy. Switching all progressors to salvage chemotherapy was suboptimal. Virtual trials predicted progression-free survival (PFS) from pembrolizumab beyond progression to be comparable with salvage chemotherapy in patients whose PD was due to nontarget progression. A PFS-optimized regimen may improve disease control rates ≥15%. Pembrolizumab beyond progression may benefit a subset of patients with PD-L1-high, driver alteration-free NSCLC, but prospective studies are warranted.

Novel

Ataxia-telangiectasia is an autosomal recessive disorder that usually manifests in childhood due to mutations in the Ataxia-Telangiectasia Mutated (

Real World Patient Eligibility for Second Line Lurbinectedin Based Treatment in Small Cell Lung Cancer Understanding Epidemiology and Estimating Health Care Utilization.

In the ATLANTIS study, second-line lurbinectedindoxorubicin did not improve overall survival (OS), however patients with a chemotherapy-free interval (CTFI) of ≥180 days had an improved progression free survival (PFS). The objective of this retrospective study was to identify the proportion of real-world small cell lung cancer (SCLC) patients who are suitable for lurbinectedin-based therapy based on these criteria. A retrospective study of all SCLC referred to BC Cancer between 2012 and 2017 was conducted. Patient demographics, staging, treatment, and survival data were collected retrospectively. Baseline characteristics were compared using descriptive statistics. OS was calculated using Kaplan-Meier curves. Statistically significant A total of 1048 patients were identified. Baseline characteristics median age 68 years, 47% male, 61% current smoking status, 68% extensive disease. Best supportive care was received by 22%. First-line systemic therapy was platinum doublet for 71% of the population. Second-line systemic therapy was delivered to 22%. Of the 219 patients who received second-line systemic therapy after platinum doublet, 183 patients had a CTFI of ≥90 days and 107 patients had a CTFI of ≥180 days. Patients originally treated as limited stage disease, received platinum doublet as second line, received thoracic radiation (RT) or prophylactic cranial irradiation (PCI) were more likely to have a CTFI of ≥90 and ≥180 days. In our real-world SCLC population, only 21% of the SCLC population received second-line therapy after platinum doublet with 17% achieving CTFI of ≥90 days and 10% CTFI of ≥180 days. Based on this retrospective review, only a small fraction of platinum-treated patients would be preferentially offered lurbinectedin in the second-line setting.

Characterizing Regional Variability in Lung Cancer Outcomes across Ontario-A Population-Based Analysis.

A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors.

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on standard of care chemotherapy were enrolled in a 3 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mgm

Medical Assistance in Dying in Oncology Patients A Canadian Academic Hospitals Experience.

Medical assistance in dying (MAID) was legislatively enacted in Canada in June 2016. Most studies of patients who received MAID grouped patients with cancer and non-cancer diagnoses. Our goal was to analyze the characteristics of oncology patients who received MAID in a Canadian tertiary care hospital. We conducted a retrospective review of all patients with cancer who received MAID between June 2016 and July 2020 at London Health Sciences Centre (LHSC). We describe patients demographics, oncologic characteristics, symptoms, treatments, and palliative care involvement. Ninety-two oncology patients received MAID. The median age was 72. The leading cancer diagnoses among these patients were lung, colorectal, and pancreatic. At the time of MAID request, 68% of patients had metastatic disease. Most patients (90%) had ECOG performance status of 3 or 4 before receiving MAID. Ninety-nine percent of patients had distressing symptoms at time of MAID request, most commonly pain. One-third of patients with metastatic or recurrent cancer received early palliative care. The median time interval between the first MAID assessment and receipt of MAID was 7 days. Most oncology patients who received MAID at LHSC had poor performance status and almost all had distressing symptoms. The median time interval between first MAID assessment and receipt of MAID was shorter than expected. Only one-third of patients with metastatic or recurrent cancer received early palliative care. Improving access to early palliative care is a priority in patients with advanced cancer. We received research approval from Western Universitys Research Ethics Board (REB) with project ID number 115367, and from Lawsons Research Database Application (ReDA) with study ID number 9579.

Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC) A Systematic Review and Meta-Analysis.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. The standard-of-care treatment has not changed in years. Recent studies report improved progression-free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We conducted a systematic review and meta-analysis to assess the magnitude of survival benefits. We searched MEDLINE, EMBASE, and Cochrane between 1 January 2010 and 15 July 2022 and conference proceedings from 2018 to 2022, for randomised controlled trials, evaluating chemo-ICI compared with platinum-doublet chemotherapy in untreated ES-SCLC. Outcomes assessed were PFS, OS, objective response rate (ORR), duration of response (DoR), toxicity, and health-related quality of life (HRQoL). The search identified 8061 studies, with 8 (56 publications) included in the final analysis. PFS and OS were significantly improved for patients randomised to chemo-ICI (PFS hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.70-0.80) and (OS HR 0.79, 95% CI 0.73-0.85). Subgroup analysis demonstrated a differential effect between PD-1PD-L1 and CTLA-4 inhibitors. There was no difference in ORR and DoR. All-grade adverse events (RR 1.06, 95% CI 1.00-1.12) were similar. The addition of ICI to chemotherapy in untreated ES-SCLC results in a 22% risk reduction in death, and a 25% risk reduction in disease progression with a minimal increase in toxicity. These improvements are modest but represent progress beyond the standard of care.

The Role of MRE11 in the IL-6STAT3 Pathway of Lung Cancer Cells.

MRE11 is a pivotal protein for ATM activation during double-strand DNA break. ATM kinase activations may act as lung cancer biomarkers. The IL-6STAT3 pathway plays an important role in tumor metastasis, including lung cancer. However, the mechanism between MRE11 and the IL-6STAT3 pathway is still unclear. In this study, we discovered that MRE11 can interact with STAT3 under IL-6 treatment and regulate STAT3 Tyr705 phosphorylation. After the knockdown of MRE11 in lung cancer cells, we discovered that IL-6 or the conditional medium of THP-1 cells can induce the mRNA expression of STAT3 downstream genes, including

Facile Fabrication of Methyl Gallate Encapsulated Folate ZIF-L Nanoframeworks as a pH Responsive Drug Delivery System for Anti-Biofilm and Anticancer Therapy.

Zeolitic imidazole frameworks are emerging materials and have been considered an efficient platform for biomedical applications. The present study highlights the simple fabrication of methyl gallate encapsulated folate-ZIF-L nanoframeworks (MGFolate ZIF-L) by a simple synthesis. The nanoframeworks were characterized by different sophisticated instruments. In addition, the drug-releasing mechanism was evidenced by in vitro releasing kinetics at various pH conditions. The anti-biofilm potential confirmed by the biofilm architectural deformations against human infectious pathogens MRSA and N7 clinical strains. Furthermore, anticancer efficacy assessed against A549 lung cancer cells. The result reveals that the MGFolate ZIF-L exposed a superior cytotoxic effect due to the pH-responsive and receptor-based drug-releasing mechanism. Based on the unique physicochemical and biological characteristics of nanoframeworks, it has overcome the problems of undesired side effects and uncontrolled drug release of existing drug delivery systems. Finally, the in vitro toxicity effect of MGFolate ZIF-L was tested against the

Antigen-Loaded Extracellular Vesicles Induce Responsiveness to Anti-PD-1 and Anti-PD-L1 Treatment in a Checkpoint Refractory Melanoma Model.

Extracellular vesicles (EV) are important mediators of intercellular communication and are potential candidates for cancer immunotherapy. Immune checkpoint blockade, specifically targeting the programmed cell death protein 1 (PD-1)programmed death-ligand 1 (PD-L1) axis, mitigates T-cell exhaustion, but is only effective in a subset of patients with cancer. Reasons for therapy resistance include low primary T-cell activation to cancer antigens, poor antigen presentation, and reduced T-cell infiltration into the tumor. Therefore, combination strategies have been extensively explored. Here, we investigated whether EV therapy could induce susceptibility to anti-PD-1 or anti-PD-L1 therapy in a checkpoint-refractory B16 melanoma model. Injection of dendritic cell-derived EVs, but not checkpoint blockade, induced a potent antigen-specific T-cell response and reduced tumor growth in tumor-bearing mice. Combination therapy of EVs and anti-PD-1 or anti-PD-L1 potentiated immune responses to ovalbumin- and α-galactosylceramide-loaded EVs in the therapeutic model. Moreover, combination therapy resulted in increased survival in a prophylactic tumor model. This demonstrates that EVs can induce potent antitumor immune responses in checkpoint refractory cancer and induce anti-PD-1 or anti-PD-L1 responses in a previously nonresponsive tumor model.

Initial Elevated Myocardial Enzymes were Neglected in Lung Adenocarcinoma ICIS Associated Myocarditis a Case Report.

In recent years, immunotherapy has gradually become the first or second-line drug for non-small cell lung cancer. However, the side effects associated with immunotherapy should not be underestimated. Toxic reactions are commonly seen in the skin, endocrine, and liver, and rarely in the heart and nerves. These effects are often life-threatening when they occur. In this paper, we present a case of ICIs-associated myocarditis in advanced lung adenocarcinoma with unappreciated initial cardiac enzyme elevation in a driver gene negative. After electronic bronchoscopy and pathological examination, the patient was diagnosed with driver gene-negative advanced lung adenocarcinoma and treated with ICIs. Driver gene-negative advanced lung adenocarcinoma, effectively treated with ICIs, initially had elevated cardiac enzymes and unilateral ptosis, but was not taken seriously and the patient eventually died after discharge from the hospital. For patients with driver gene-negative advanced lung adenocarcinoma treated with ICIs, regular and periodic monitoring of myocardial damage markers is a top priority, followed by timely initiation of hormonal therapy as a means to improve prognosis.

Risk factors for long-term decline in post-operative pulmonary function after lung resection.

The study aimed to examine the risk factors for long-term decline in pulmonary function after anatomical resection for lung cancer and the effects of the decrease on survival. We retrospectively examined 489 patients who underwent anatomical resection for lung cancer between 2010 and 2020. Pulmonary function tests were performed preoperatively and at 1, 3, 6 and 12 months after surgery. The lower interquartile medians of the reduction rates of forced expiratory volume in 1 s and vital capacity at 12 months after surgery were taken as the cut-off values of risk factors for the decrease in post-operative pulmonary function. Forced expiratory volume in 1 s and vital capacity decreased the most in the first month after surgery and then gradually recovered. Vital capacity continued to increase even after 6 months post-surgery, whereas forced expiratory volume in 1 s stabilized. Multivariable logistic analysis showed that the number of resected segments (odds ratio, 2.09 95% confidence interval, 1.12-3.89 P 0.019) was a risk factor for the decrease in forced expiratory volume in 1 s at 12 months, and the numbers of resected segments (odds ratio, 1.36 95% confidence interval, 1.13-1.63 P < 0.001) and post-operative complications (odds ratio, 2.32 95% confidence interval, 1.01-5.35 P 0.047) were independent risk factors for decrease in vital capacity. Multivariate cox regression analysis showed that the decrease in vital capacity at 12 months was significantly associated with overall survival (hazard ratio, 2.02 95% confidence interval, 1.24-3.67 P 0.004). Long-term decrease in vital capacity, which was influenced by the number of resected segments and post-operative complications, adversely affected survival.

Sotorasib in

We conducted a single-group, phase 1-2 trial to assess the safety and efficacy of sotorasib treatment in patients with The pooled population from phases 1 and 2 consisted of 38 patients, all of whom had metastatic disease at enrollment and had previously received chemotherapy. At baseline, patients had received a median of 2 lines (range, 1 to 8) of therapy previously. All 38 patients received sotorasib in the trial. A total of 8 patients had a centrally confirmed objective response (21% 95% confidence interval CI, 10 to 37). The median progression-free survival was 4.0 months (95% CI, 2.8 to 5.6), and the median overall survival was 6.9 months (95% CI, 5.0 to 9.1). Treatment-related adverse events of any grade were reported in 16 patients (42%) 6 patients (16%) had grade 3 adverse events. No treatment-related adverse events were fatal or led to treatment discontinuation. Sotorasib showed anticancer activity and had an acceptable safety profile in patients with

Lung cancer awareness training experiences of community health workers in KwaZulu-Natal, South Africa.

Lung cancer is the leading cause of cancer mortality worldwide. Awareness interventions in the developing world remain scarce. Community health workers (CHWs) are a critical component towards ensuring efficient delivery of healthcare services in low- and middle-income countries. This study explored the experiences of CHWs of their training as lung cancer awareness intervention implementers. The study was conducted in a resource-poor setting, with CHWs from previously disadvantaged communities. On the last day of training, 10 CHWs were requested to voluntarily participate in a focus group discussion regarding their experiences of the training, utilising a discussion guide. The participants expressed positive experiences with the training. They cited the amenable and conducive learning environment established by the facilitator. The participants felt empowered through the newly acquired knowledge and wanted to help their communities. However, some participants expressed a desire to have other forms of learning incorporated in future training. The participants were also cognisant of existing gaps in their own knowledge that could be elaborated upon in preparation for potential questions by the community. Some participants confirmed their role as agents of change. The authors propose large-scale intervention studies of lung cancer awareness utilising the CHW programme to gather conclusive evidence regarding their effectiveness at a community level.Contribution This article provides insight into the training of community health workers on lung cancer awareness and future research on the integration of the intervention into already existing programmes.

spaCI deciphering spatial cellular communications through adaptive graph model.

Cell-cell communications are vital for biological signalling and play important roles in complex diseases. Recent advances in single-cell spatial transcriptomics (SCST) technologies allow examining the spatial cell communication landscapes and hold the promise for disentangling the complex ligand-receptor (L-R) interactions across cells. However, due to frequent dropout events and noisy signals in SCST data, it is challenging and lack of effective and tailored methods to accurately infer cellular communications. Herein, to decipher the cell-to-cell communications from SCST profiles, we propose a novel adaptive graph model with attention mechanisms named spaCI. spaCI incorporates both spatial locations and gene expression profiles of cells to identify the active L-R signalling axis across neighbouring cells. Through benchmarking with currently available methods, spaCI shows superior performance on both simulation data and real SCST datasets. Furthermore, spaCI is able to identify the upstream transcriptional factors mediating the active L-R interactions. For biological insights, we have applied spaCI to the seqFISH data of mouse cortex and the NanoString CosMx Spatial Molecular Imager (SMI) data of non-small cell lung cancer samples. spaCI reveals the hidden L-R interactions from the sparse seqFISH data, meanwhile identifies the inconspicuous L-R interactions including THBS1-ITGB1 between fibroblast and tumours in NanoString CosMx SMI data. spaCI further reveals that SMAD3 plays an important role in regulating the crosstalk between fibroblasts and tumours, which contributes to the prognosis of lung cancer patients. Collectively, spaCI addresses the challenges in interrogating SCST data for gaining insights into the underlying cellular communications, thus facilitates the discoveries of disease mechanisms, effective biomarkers and therapeutic targets.

A review on the role of miR-671 in human disorders.

miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinsons disease, rheumatoid arthritis, acute myocardial infarction and Crohns disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies.

Anticarcinogenic potentials of tea catechins.

Catechins are a cluster of polyphenolic bioactive components in green tea. Anticarcinogenic effects of tea catechins have been reported since the 1980s, but it has been controversial. The present paper reviews the advances in studies on the anticarcinogenic activities of tea and catechins, including epidemiological evidence and anticarcinogenic mechanism. Tea catechins showed antagonistic effects on many cancers, such as gynecological cancers, digestive tract cancers, incident glioma, liver and gallbladder cancers, lung cancer, etc. The mechanism underlying the anticarcinogenic effects of catechins involves in inhibiting the proliferation and growth of cancer cells, scavenging free radicals, suppressing metastasis of cancer cells, improving immunity, interacting with other anticancer drugs, and regulating signaling pathways. The inconsistent results and their causes are also discussed in this paper.

Association Between Serum Midkine Level and Gastric Precancerous Lesion in Patients with Gastritis.

Gastric cancer is the fifth most common malignancy and the third highest cancer-related mortality worldwide after lung and colorectal cancers. The gastric carcinogenesis is started with precancerous lesion. Prompt diagnosis and management of gastric precancerous lesion may prevent disease progression. Midkine is a growth factor associated with various cancers and proposed as a marker for detecting gastric precancerous lesion. The aim of the study is to determine the association between serum midkine level and gastric precancerous lesion in patients with gastritis. A cross sectional study was conducted at Haji Adam Malik general hospital. Subjects were obtained by consecutive sampling. Inclusion criteria were patients aged 18 years or older, diagnosed with gastritis from gastroscopy and histopathology results, and willing to cooperate in the study. Each subjects underwent interview and endoscopic examination. Serum midkine level was determined using enzyme-linked immunosorbent assay (ELISA) method. Chi square, receiver operating characteristic (ROC) curve, and logistic regression tests were applied. A total of 160 subjects were enrolled with 29.4% had gastric precancerous lesion. Serum midkine level was associated with gastric premalignant lesion. Cut off point for serum midkine level was 252 pgmL with area under the curve of 0.816 (p<0.001). Its sensitivity, specificity, and accuracy in diagnosing gastric precancerous lesion were 74.5%, 71.7%, and 72.5%, respectively. Helicobacter pylori infection, high serum midkine level, heavy alcohol drinker, and family history of gastric cancer were risk factors for gastric precancerous lesion. Serum midkine level is associated with gastric premalignant lesion in patients with gastritis and has good diagnostic values.

Phase 1 Study of Ceritinib Combined With Trametinib in Patients With Advanced ALK- or ROS1-Positive NSCLC.

In patients with NSCLC harboring oncogenic ALK or ROS1 rearrangements, tyrosine kinase inhibitors have yielded high response rates and improvements in progression-free survival compared with cytotoxic chemotherapy however, acquired resistance eventually develops. In preclinical models, ALK and MEK coinhibition was able to overcome ALK inhibitor resistance. A phase 1 study of the ALKROS1 inhibitor ceritinib and the MEK inhibitor trametinib in patients with refractory NSCLC harboring ALK or ROS1 fusions was initiated. A three plus three dose-escalation scheme was used. Two dose levels were investigated. The primary end point was to determine the safety and tolerability of the combination. Nine patients (n 8 ALK, n 1 ROS1) were enrolled in the study and completed at least one cycle of therapy. The most common adverse events (all grades) were diarrhea (n 9 100%), rash (n 8 89%), abdominal pain (n 5 56%), and elevated aspartate transaminasealanine transaminase level (n 4 44%). The overall response rate was 22%, whereas disease control rate was 56%. Median duration of response was 7.85 months. The median progression-free survival was 3.0 months (95% confidence interval 1.5-7.0 mo). The median overall survival was 8.9 months (95% confidence interval 2.0-not reached). Data from this trial indicate that the combination of ceritinib and trametinib had no unexpected toxicities and that a tolerable dose could be identified. A subset of patients seemed to obtain clinical benefit from this treatment after progression on prior ALKROS1 inhibitor treatment.ClinicalTrials.gov Identifier NCT03087448.

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs Perspectives in pharmacogenomics.

Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

Matrine Regulates Proliferation, Apoptosis, Cell Cycle, Migration, and Invasion of Non-Small Cell Lung Cancer Cells Through the circFUT8miR-944YES1 Axis Retraction.

This retracts the article DOI 10.2147CMAR.S290966..

ZIF-90 nanoparticles modified with a homing peptide for targeted delivery of cisplatin.

To improve the selective delivery of cisplatin (Cis) to cancer cells, we report and establish the significance of active, targeting drug delivery nanosystems for efficient treatment of lung cancer. Specifically, pH-responsive nano-sized zeolitic imidazolate framework (nZIF-90) was synthesized, post-synthetically modified with an Arg-Gly-Asp peptide motif (RGDnZIF-90), a known cancer cell homing peptide, and loaded with a large amount of Cis (RGDCis⊂nZIF-90). RGDCis⊂nZIF-90 was shown to be highly stable under physiological conditions (pH 7.4) with framework dissociation occurring under slightly acidic conditions (pH 5.0)-conditions relevant to tumor cells-from which 90% of the encapsulated Cis was released in a sustained manner.

YH29407 with anti-PD-1 ameliorates anti-tumor effects

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8

Dual Roles of Lactate in EGFR-TKI-Resistant Lung Cancer by Targeting GPR81 and MCT1.

Lactate is critical in modeling tumor microenvironment causing chemotherapy resistance however, the role of lactate in tyrosine kinase inhibitor (TKI) resistance has not been fully known. The aim of this study was to evaluate whether lactate could mediate TKI resistance through GPR81 and MCT1 in non-small-cell lung cancer (NSCLC). Here, we showed that lactate enhanced the cell viability and restrained erlotinib-induced apoptosis in PC9 and HCC827 cells. GPR81 and AKT expression were significantly increased with the addition of lactate, and siGPR81 reduced AKT expression resulting in a raised apoptosis rate with erlotinib treatment. Furthermore, we found that lactate also promoted MCT1 exposure, and inhibiting MCT1 with AZD3965 markedly impaired the glycolytic capacity. A significant increase of GPR81 and MCT1 expression was observed in insensitive tissues compared with sensitive ones by immunostaining in NSCLC patients. Our results indicate that lactate adopts dual strategies to promote TKI resistance in NSCLC, not only activating AKT signaling by GPR81, but also giving energy supply through MCT1-mediated input. Targeting GPR81 and MCT1 may provide new therapeutic modalities for TKI resistance in NSCLC.

Metastatic patterns and prognosis of patients with primary malignant cardiac tumor.

Distant metastases are independent negative prognostic factors for patients with primary malignant cardiac tumors (PMCT). This study aims to further investigate metastatic patterns and their prognostic effects in patients with PMCT. This multicenter retrospective study included 218 patients with PMCT diagnosed between 2010 and 2017 from Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was utilized to identify metastatic risk factors. A Chi-square test was performed to assess the metastatic rate. Kaplan-Meier methods and Cox regression analysis were used to analyze the prognostic effects of metastatic patterns. Sarcoma ( Patients with PMCT who had sarcoma or a tumor larger than 4 cm had a higher risk of distant metastases. Lung was the most common metastatic site, and brain metastases had worst survival among others, such as lung, bone, liver, and brain. The results of this study provide insight for early detection, diagnosis, and treatment of distant metastases associated with PMCT.

The Prevalence and 5-Year Incidence Rate of Cigarette Smoking and Water-Pipe Tobacco Smoking and Their Associated Factors among 15 to 80 Years Old Urban Population in Southeast Iran Results from KERCADR Study.

Cigarette and tobacco smoking are closely associated with chronic cardiovascular disease and lung cancer. We aimed to assess the prevalence and 5-year incidence rate (IR) of these two risk factors for cardiovascular diseases in Kerman, southeastern of Iran. 10015 individuals aged 15-80 were recruited to the study between 2014 and 2018 (Kerman coronary artery disease (CAD) risk factors study, KERCADRS) of which 2820 had also participated in the first phase (5 years earlier). We took fasting blood samples and collected demographic information and data on cigarette and water-pipe tobacco smoking (WPTS) through interviews. The overall prevalence of cigarette smoking increased from 8.1% in phase1 to 8.8% in phase 2. During the same period, the prevalence of WPTS increased from 10% to 14%, especially in the age groups of 15-45 years. The prevalence of opium dependance was higher among cigarette smokers compared to WPT users. The overall 5-year IR of cigarette and WPTS was 3.6 and 4.65 per 1000 person-years respectively. The highest IRs of cigarette smoking and WPTS were reported in the age group of 15-39 years, and IR of WPTS was higher among women. Obesity, diabetes, and hypertension associated with a reduced IRs of cigarette and WPTS. Over the past five years, the prevalence of cigarette smoking has increased slightly, but WPTS has increased more rapidly, especially among women. The highest prevalence of cigarette and WPT smoking was in the age groups of 15-39 years. Smoking is shifting from cigarette smoking to WPTS. Age- and gender-oriented interventions would help correct the unhealthy life style in the community and prevent further smoking-related morbidities and mortalities.

Anti-cancer effects of ginsenoside CK on acute myeloid leukemia in vitro and in vivo.

Acute myeloid leukemia (AML) is a malignant disease characterized by clonal proliferation of myeloid cells, and its treatment continues to be a challenge due to high morbidity and mortality. Ginsenoside compound K, a major active metabolite of the protopanaxadiol-type ginsenosides, exhibits biological activities in various cancer cells and animal models. Here, we investigated the role of CK in anticancer potential in AML both in vitro and in vivo. To investigate the inhibitory effects of CK in AML cells, in vitro experiments, including cell viability assays, colony forming assays, and cell cycle and apoptosis assays were performed. AML animal experiment was established and quantitative analysis of lung tumor growth nodules and spleen weight and HE staining were carried out to further determine the effects of CK on AML. In addition, the potential key genes induced and influenced by CK during treatment was identification by RNA-seq and qRT-PCR. CK suppressed AML cell activity and induced apoptosis and G1 cell cycle arrest based on the experiment results. Moreover, significantly down-regulated expression genes of BCL2, KIT, DNMT3A, MYC and CSF-1 and up-regulated expression gene of TET2 in CK treatment AML cells were discovered. Our results demonstrated that CK could be used as an anti-AML drug with significant therapeutic efficacy and good biosafety.

Pan-cancer analysis of LINC02535 as a potential biomarker and its oncogenic role in lung adenocarcinoma.

LINC02535 has gained much attention for its oncogenicity across several cancers, but the systematic pan-cancer analysis of LINC02535 has not been carried out before. Herein, we explored the expression level, prognostic value, and hallmark pathways of LINC02535 across multiple cancers using the Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases. Moreover, the expression and biological features of LINC02535 in lung adenocarcinoma (LUAD) were confirmed by qRT-PCR, LINC02535 is differentially expressed in 10 of 17 human cancers and serves as a favorable or unfavorable biomarker in distinct cancer types. Gene set enrichment analysis (GSEA) indicated that key oncogenic pathwaysphenotypes were remarkably activated in most cancers with intratumoral increased LINC02535, whereas these pathwaysphenotypes were suppressed in other cancer types (colon adenocarcinoma, kidney renal clear cell carcinoma, rectal adenocarcinoma) with intratumoral decreased LINC02535. Of note, the epithelial-mesenchymal transition (EMT) phenotype was greatly enriched in LUAD patients with elevated LINC02535. Based on the TCGA and CCLE datasets, LINC02535 was positively correlated with the EMT-related gene CD73 (also named as NT5E, an immunosuppressive gene) in almost all cancer types (Spearman The findings from our pan-cancer analysis provide a relatively comprehensive understanding of the potential value of LINC02535 across multiple cancers, and the oncogenic role of LINC02535 in LUAD has been confirmed.

Accurate classification of lung nodules on CT images using the TransUnet.

Computed tomography (CT) is an effective way to scan for lung cancer. The classification of lung nodules in CT screening is completely doctor dependent, which has drawbacks, including difficulty classifying tiny nodules, subjectivity, and high false-positive rates. In recent years, deep convolutional neural networks, a deep learning technology, have been shown to be effective in medical imaging diagnosis. Herein, we propose a deep convolutional neural network technique (TransUnet) to automatically classify lung nodules accurately. TransUnet consists of three parts the transformer, the Unet, and global average pooling (GAP). The transformer encodes discriminative features via global self-attention modeling on CT image patches. The Unet, which collects context by constricting route, enables exact lunge nodule localization. The GAP categorizes CT images, assigning each sample a score. Python was employed to pre-process all CT images in the LIDI-IDRI, and the obtained 8,474 images (3,259 benign and 5,215 lung nodules) were used to evaluate the methods performance. The accuracies of TransUnet in the training and testing sets were 87.90 and 84.62%. The sensitivity, specificity, and AUC of the proposed TransUnet on the testing dataset were 70.92, 93.17, and 0.862%, respectively (0.844-0.879). We also compared TransUnet to three well-known methods, which outperformed these methods. The experimental results on LIDI-IDRI demonstrated that the proposed TransUnet has a great performance in classifying lung nodules and has a great potential application in diagnosing lung cancer.