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Antisynthetase syndrome-related interstitial lung disease (ASyS-ILD) longitudinal imaging findings.

Interstitial lung disease (ILD) impacts mortality in antisynthetase syndrome (ASyS). Computed tomographic (CT) patterns and evolution in ASyS ILD are not well described. We report longitudinal CT patterns in ASyS-ILD and their impact on survival. This is a monocentric retrospective study of 47 patients with ASyS-ILD. Longitudinal CT patterns and fibrosis severity (severity of radiographic features indicating fibrosis) were analyzed by two radiologists in consensus. The association between imaging features and survival was examined using univariate Cox regression analysis. In total, 211 CT scans were analyzed with an average of 4 ± 2 CT scanspatient with a median follow-up of 79 months in 47 patients. Non-fibrotic patterns were present initially in 63.8% (n 30) of patients, while fibrotic patterns occurred in 36.2% (n 17). The initial non-fibrotic patternsabnormalities resolved in 23.3% (n 7), evolved in 6.7% (n 2), persisted in 13.3% (n 4), and progressed in 56.7% (n 17), while initial fibrotic patterns persisted in 82.4% (n 14) and progressed in 17.6% (n 3). Radiographic progression of ILD (progression in CT pattern or increased fibrosis severity) occurred in 53.2% (n 25) of patients. Advanced age and radiographic progression were associated with decreased survival (all p < 0.05). The presence of ground-glass opacities (GGO) and predominant lower lung distribution of abnormalities on initial CTs were associated with increased survival (all p < 0.05). Progression occurred in 56.7% of ASyS-ILD patients presenting with non-fibrotic patterns. Fibrotic patterns tended to persist. Age and radiographic progression were associated with reduced survival while the initial presence of GGO and predominant lower lobe distribution were associated with increased survival. • In ASyS-ILD, initial non-fibrotic patterns such as OP, cNSIP, or OP-cNSIP tended to progress to fNSIP. • Fibrotic patterns such as fNSIP or UIP in ASyS-ILD tended to persist without pattern changes. • GGO and lower lung predominance on initial CT were associated with better survival while advanced baseline age and radiographic ILD progression during follow-up were associated with decreased survival.

Effect of isolated grandivittin from Ferulago trifida Boiss. (Apiaceae) on the proliferation and apoptosis of human lung cancer A549 cells.

Lung cancer is one of the deadliest cancers in the world. Introducing new promising agents can help the chemotherapeutic management of cancer. In the knowledge of oncology, plants are of special interest as a rich source of new antineoplastic and chemotherapeutic agents. Grandivittin (GRA) is one of the main constituents of Ferulago trifida Boiss. with established medicinal, phytochemical, and pharmacological properties. This study aimed to isolate and evaluate the antineoplastic potential of grandivittin and its underlying mechanisms in human lung cancer A549 cells. The viability of the A549 cells after being treated with 0.1, 0.4, 0.7, 1, and 1.3 mM of GRA for three following days was measured using the MTT method. The early apoptosis and late apoptosis were assessed by fluorescence-activated cell sorter analysis through annexin VPI staining. The expression of apoptotic agents genes (caspase 3, caspase 9, Bcl2, Bax, and P53) was evaluated by the RT-PCR method. GRA increased apoptotic cells and decreased cell viability in a dose- and time-dependent manner, in which only 50% of cells survived at a dose of 0.7 mM. The expression of Bax, P53, caspase 3, and caspase 9 genes in the A549 cells was significantly upregulated after GRA treatment compared to control cells (P < 0.05). On the other hand, Bcl2 was significantly downregulated after GRA treatment (P < 0.05). The results indicated that GRA can activate cell death in A549 lung carcinoma cells by inducing both DNA toxicity p53 and cascade-dependent pathways. Therefore, GRA may be a potential new therapeutic agent for the treatment of lung cancer.

Dosimetric evaluation of the benefit of deep inspiration breath hold (DIBH) for locoregional irradiation of right breast cancer with volumetric modulated arctherapy (VMAT).

Right-lateralized cardiac substructures can be substantially exposed during right breast cancer (R-BC) radiotherapy. The cardiac benefit of deep inspiration breath hold (DIBH) is established in combination with volumetric modulated arctherapy (VMAT) for left breast cancer with regional node irradiation but is unknown for R-BC. This study evaluated the dosimetric benefit of DIBH for locoregional irradiation of R-BC with VMAT. All patients treated for R-BC with adjuvant locoregional DIBH-VMAT in the Department of Radiation Oncology of the Institut Curie (Paris, France) until December 2022 were included, corresponding to 15 patients. FB- and DIBH-VMAT plans were compared both for a normofractionated regimen (50 Gy25fx) used for treatment and a replanned hypofractionated regimen (40 Gy15fx). Dose to the heart, cardiac substructures (sinoatrial node (SAN), atrio-ventricular node (AVN), right coronary artery, left anterior descending coronary artery, left ventricle), ipsilateral lung and liver were retrieved and compared. Mean heart dose (MHD) was 3.33 Gy with FB vs. 3.10 Gy with DIBH on normofractionated plans ( Adding DIBH to efficient cardiac-sparing radiotherapy techniques, such as VMAT, is not justified in the general case for locoregional R-BC irradiation. Specific R-BC patient subpopulations who could benefit from additional DIBH combination with locoregional VMAT are yet to be identified.

Inula viscosa (L.) Aiton Ethanolic Extract Inhibits the Growth of Human AGS and A549 Cancer Cell Lines.

The present study shows the chemical profile and cytotoxic properties of the ethanolic extracts of Inula viscosa from Northeast Algeria. The extract was obtained by maceration using ethanol. Its phenolic profile was determined using ultra-high-performance liquid chromatography coupled with a diode array detector and an electrospray mass spectrometer (UHPLC-DAD-ESIMS), which allowed the identification and quantification of 17 compounds, 1,5-O-caffeoylquinic acid being the most abundant. The cytotoxic activity was assessed against human gastric cancer (AGS) and human non-small-cell lung cancer (A549) cell lines, whereas ethanolic extract elicited nearly 60 % and 40 % viability loss toward AGS and A549 cancer cells, respectively. Results also showed that cell death is caspase-independent and confirmed the involvement of RIPK1 and the necroptosis pathway in the toxicity induced by the I. viscosa extract. In addition, the ethanolic extract would not provoke morphological traits in the cancer cells. These findings suggest that I. viscosa can be a source of new antiproliferative drugs or used in preparation plant-derived pharmaceuticals.

The importance microRNAs as a biomarker in lung cancer.

Lung cancer (LC) is the most common cancer in the world.Well known causes are long term smoking, environmental influences and genetic variations. LC is divided into two main types based on their histological phenotypes small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). The high specificity of these new screening methods, which are non-invasive, safe, inexpensive and simple to perform, is important in the early diagnosis and prognosis of cancer. MicroRNAs are significant biomarkers on the diagnosis metastasis and targeted therapies of NSCLC. In our study, we aimed to investigate the potential of using microRNAs as a biomarker in the early diagnosis of lung cancer. Twenty patients diagnosed with lung cancer and twenty healthy individuals of the same age and gender were selected as the control group. Sixteen microRNAs were studied from blood samples. Sixteen miRNAs (Let -7c, Let-7g, miR-1, miR-21, miR-29a, miR-31, miR-34a, miR 103a, miR-141, miR-155, miR-193b, miR-200b, miR-205, miR-340, miR-486, miR-708) were selected for tests and MiR 181 and miR 192 were used as the endogenous control group in line with their binding potentials and gene expression levels. The most specific and sensitive miRNAs were mirR-29a, miR-103a, and miR486 according to endogen controls in patients and healthy subjects. A meta-analysis study showed that circulating miRNAs could be promising biomarkers for early diagnosis of lung cancer. Overall, 17 studies were included evaluating 35 miRNA markers and 19 miRNA panels in serum or plasma. The potential role of circulating miRNAs for non-invasive lung screening has been highlighted. In conclusion, there is a need for further validation studies for the use of three miRNAs as a biomarker in the early diagnosis and prognosis of lung cancer.

Light Pareto robust optimization for IMRT treatment planning.

Robust optimization (RO) has been proposed to mitigate breathing motion uncertainty during treatment in intensity-modulated radiation therapy (IMRT) planning for breast or lung cancer. RO is a pessimistic approach that implicitly trades off average-case for worst-case treatment plan quality. Pareto robust optimization (PRO) provides amechanism for improving non-worst-case plan outcomes, but often remains overly-conservative in the average case. The goal of this study is to characterize the trade-off between the optimality of robust IMRT plans in the worst case and the treatment quality in non-worst-case realizations of breathing motion. We provide a light Pareto robust optimization (LPRO) method for IMRT and test its clinical viability for improving the average-case plan quality while preserving robustness, in comparison to RO and PRO plans. Five clinical left-sided breast cancer patients were included in the study, each with an associated 4D-CT dataset approximating their breathing cycle. Using simulation, 50 different breathing patterns were generated for each patient. A first-stage optimization was solved with the objective of cardiac sparing while ensuring robustness on the target dose under breathing uncertainty. Next, a second-stage objective of overdose minimization was considered to improve plan quality in a controlled LPRO framework. For the simulated breathing scenarios, the trade-off between loss of average cardiac sparing at worst-case and the overdose to the breast was quantified by calculating theaccumulated dose for each plan in each breathing scenario. Finally, the RO, PRO and LPRO plans were each evaluated using eight clinical dose-volume criteria on the target and organs at risk. The LPRO models allowed for significantly sharper dose falloffs in the expected dose instances, relative to both RO and PRO models. Plans began looking valid for delivery with average allowances of as little as 0.1 Gy additional dose to the heart, and most patients experienced diminishing returns beyond 0.2 Gy. Without sacrificing robustness, the LPRO approach produces viable plans with true total-target irradiation. Furthermore, the plans produced were able to reduce the non-worst-case downside typical of RO, without the characteristic overdosing or average-case pessimism seen in prior models. This article is protected by copyright. All rights reserved.

Spontaneous large volume hemothorax managed with a small-bore chest tube.

A 67-year-old male with metastatic lung cancer presented with acute shortness of breath and increasing oxygen requirements. He had a decreasing hemoglobin for which he required red blood cell transfusions. His chest x-ray showed near complete white-out of the left lung. Bedside ultrasound (Handheld Sonostar C4PL) showed a large pleural effusion with swirling echogenic material suggestive of plankton sign. The pleural effusion was aspirated and showed frank blood, after which a small-bore chest tube (SBCT) was inserted. A total of 3200ml of blood was drained with the SBCT. There was complete clearance of the pleural space, and no further blood product transfusions were needed. This case highlights that conservative management can be considered in patients with spontaneous hemothorax due to metastatic disease.

Widespread vitiligo and poliosis following ipilimumab-nivolumab combination therapy.

Combined immune checkpoint inhibitor therapy has been successfully used in the treatment of several malignancies. Adverse effects with the combination therapy may be more severe than the ones seen with single immune checkpoint inhibitors. We report a unique case of a 59-year-old man of dark skin complexion who underwent treatment with intravenous ipilimumab-nivolumab every 3 weeks for metastatic malignant melanoma. After three cycles of this therapy, he developed extensive skin depigmentation that within 6 weeks, affected nearly the entire skin surface, along with progressive poliosis. Ipilimumab-nivolumab therapy was subsequently discontinued due to grade 3 enterocolitis requiring high-dose steroids and intravenous infliximab. About six months later, imaging studies showed a relapse of malignant melanoma. At that juncture, vitiligo affected the total body surface area, resembling albinism, along with near-total poliosis and significant photosensitivity. Pembrolizumab was tried but had to be stopped after three cycles due to the reoccurrence of grade 3 enterocolitis. Progression of malignant melanoma with new brain, lung, liver, subcutaneous, and colonic metastases led to the patients demise. We report a unique case of severe vitiligo and poliosis that involved total body surface area in a Caucasian man with dark complexion, resembling albinism. Further studies are warranted to evaluate the severity of dermatologic side effects with combination immune checkpoint inhibitor therapy.

Alcohol use, suicidality and virologic non-suppression among young adults with perinatally acquired HIV in Thailand a cross-sectional study.

Young adults with perinatally acquired HIV (YA-PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA-PHIV. A cross-sectional study was conducted in Thai YA-PHIV aged 18-25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face-to-face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drugsubstance use (Drug Abuse Screening Test DAST-10), depression (Patient Health Questionnaire for Adolescents PHQ-A), anxiety (Generalized Anxiety Disorder GAD-7) and QOL (World Health Organization QOL Brief-Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Of 355 YA-PHIV, 163 (46%) were males their median age was 21.7 (interquartile range, IQR 20.2-23.5) years. There were 203 YA-PHIV (58%) who reported ever having sex 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugssubstances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA-PHIV (14%) with CD4 <200 cellsmm Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA-PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life.

Multiple Impacts of Urban Built and Natural Environment on Lung Cancer Incidence A Case Study in Bengbu.

Tumours are the main disease affecting the health of the Chinese population, and lung cancer is the malignancy with the highest incidence. Hence, the need to study and analyse the population of lung cancer incidence in order to effectively control and prevent it. In this research, we discuss the demographic characteristics of lung cancer incidence population of 2014 to 2020 from the perspective of multiple urban environmental factors, taking Bengbu city in the Huaihe River Basin of China as the research area, analyse the correlation between environmental indicators and lung cancer incidence population through the Spearmans rank correlation assessment model, and analyse the interaction between the influence factors of a geographic detector to analyse the influence of urban environmental factors. The results showed the followings (1) The distribution characteristics of lung cancer incidence population were mainly geriatric population and spatially mainly fell in the old urban area of the study area, and the population distribution had clustered characteristics. (2) Through Spearmans rank correlation analysis, the land use, road traffic, spatial form, service facilities, and the open space of green space of the urban-built environment as well as the natural environment are all correlated with the incidence of lung cancer. (3) Factor detection and interaction analysis revealed a greater effect of spring and winter on lung cancer prevalence. In addition, the road intersection density and the distance to industrial are the most important potential influencing factors, and the interaction of any two factors will increase the risk of lung cancer.

An Efficient Model for Lungs Nodule Classification Using Supervised Learning Technique.

Lung cancer has the highest death rate of any other cancer in the world. Detecting lung cancer early can increase a patients survival rate. The corresponding work presents the method for improving the computer-aided detection (CAD) of nodules present in the lung area in computed tomography (CT) images. The main aim was to get an overview of the latest tools and technologies used acquisition, storage, segmentation, classification, processing, and analysis of biomedical data. After the analysis, a model is proposed consisting of three main steps. In the first step, threshold values and component labeling of 3D components were used to segment the lung volume. In the second step, candidate nodules are identified and segmented with an optimal threshold value and rule-based trimming. It also selects 2D and 3D features from the candidate segmented node. In the final step, the selected features are used to train the SVM and classify the nodes and classify the non-nodes. To assess the performance of the proposed framework, experiments were performed on the LIDC data set. As a result, it was observed that the number of false positives in the nodule candidate was reduced to 4 FP per scan with a sensitivity of 95%.

Applications of Neural Network-Based Plan-Cancer Method for Primary Diagnosis of Mesothelioma Cancer.

Malignant mesothelioma (MM) is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is malignant mesothelioma. Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination epithelialmesenchymal appearance of MM, however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful Malignant Mesothelioma illness identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support Vector Machine, Neural Network, and Decision Tree are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.

A prognostic baseline blood biomarker and tumor growth kinetics integrated model in paclitaxelplatinum treated advanced non-small cell lung cancer patients.

Paclitaxelplatinum chemotherapy, the backbone of standard first-line treatment of advanced non-small cell lung cancer (NSCLC), exhibits high interpatient variability in treatment response and high toxicity burden. Baseline blood biomarker concentrations and tumor size (sum of diameters) at week 8 relative to baseline (RS8) are widely investigated prognostic factors. However, joint analysis of data on demographicclinical characteristics, blood biomarker levels, and chemotherapy exposure-driven early tumor response for improved prediction of overall survival (OS) is clinically not established. We developed a Weibull time-to-event model to predict OS, leveraging data from 365 patients receiving 3-weekly paclitaxelplatinum combination chemotherapy for ≤6 cycles. A developed tumor growth inhibition model, combining linear tumor growth and first-order paclitaxel area under the concentration-time curve-induced tumor decay, was used to derive individual RS8. The median model-derived RS8 in all patients was a 20.0% tumor size reduction (range -78%, 15%). While baseline carcinoembryonic antigen, cytokeratin fragments and thyroid stimulating hormone levels were not significantly associated with OS in a subset of 221 patients, and lactate dehydrogenase, interleukin-6 and neutrophil-to-lymphocyte ratio levels were significant only in univariate analyses (p-value<0.05), C-reactive protein in combination with RS8 most significantly affected OS (p-value<0.01). Compared to the median population OS of 11.3 months, OS was 128% longer at the 5

Interstitial lung abnormalities in a large clinical lung cancer screening cohort association with mortality and ILD diagnosis.

Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis. This was a retrospective study of individuals enrolled in a CT lung cancer screening program from 2012 to 2014. Baseline and longitudinal CT scans were scored for ILA per Fleischner Society guidelines. The primary analyses examined the association between baseline ILA and mortality, all-cause hospitalization, and incidence of lung cancer. Kaplan-Meier plots were generated to visualize the associations between ILA and lung cancer and all-cause mortality. Cox regression proportional hazards models were used to test for this association in both univariate and multivariable models. 1699 subjects met inclusion criteria. 41 (2.4%) had ILA and 101 (5.9%) had indeterminate ILA on baseline CTs. ILD was diagnosed in 10 (24.4%) of 41 with ILA on baseline CT with a mean time from baseline CT to diagnosis of 4.47 ± 2.72 years. On multivariable modeling, the presence of ILA remained a significant predictor of death, HR 3.87 (2.07, 7.21 p < 0.001) when adjusted for age, sex, BMI, pack years and active smoking, but not of lung cancer and all-cause hospital admission. Approximately 50% with baseline ILA had progression on the longitudinal scan. ILA identified on baseline lung cancer screening exams are associated with all-cause mortality. In addition, a significant proportion of patients with ILA are subsequently diagnosed with ILD and have CT progression on longitudinal scans. ClinicalTrials.gov No. NCT04503044.

Epidermal growth factor receptor inhibitors as adjuvant treatment for patients with resected non-small cell lung cancer harboring EGFR mutation a meta-analysis of randomized controlled clinical trials.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation. Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS. After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval CI 0.30-0.74 P 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84 P 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85 P 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74 P 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14 P 0.20). EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed.

Diffuse pulmonary meningotheliomatosis with pan-TRK expression by immunohistochemistry a novel finding and potential pitfall.

Pulmonary meningothelial-like nodules (PMNs) are benign proliferations of unclear clinical significance. They are mainly asymptomatic lesions that are usually discovered during the pathologic evaluation of resected pulmonary specimens or following post-mortem examination. Diffuse pulmonary meningotheliomatosis (DPM), which presents as bilateral multiple PMNs throughout the lungs, has been described less frequently. DPMs are benign lesions associated with both neoplastic and non-neoplastic pulmonary conditions. We report the case of a 59-year-old female patient who presented with a history of cough. Computerized tomography (CT) imaging revealed multiple subcentimeter bilateral pulmonary nodules. transbronchial biopsies were obtained which revealed foci of nodular interstitial proliferations composed of epithelioid to spindled cells in a vague whorled pattern. Immunohistochemical stains were diffusely positive for EMA and progesterone receptor. Furthermore, pan-TRK exhibited strong and diffuse membranous expression in the lesional cells. INSM1 was negative for expression. RNA-based next-generation sequencing for the detection of NTRK fusions was performed and was negative for gene rearrangements involving NTRK1, NTRK2, and NTRK3. Here, we report a rare case of DPM and report pan-TRK expression in PMNs which has not been described. We provide a brief review of the literature and provide insight into the potential physiologic nature of PMNs. Lastly, we emphasize the recognition of pan-TRK immunoexpression in PMNs to avoid potential diagnostic errors.

Clinical impact of tetracyclines andor proton pump inhibitors on the efficacy of epidermal growth factor receptor inhibitors in non-small cell lung cancer a retrospective cohort study.

This retrospective cohort study examined the impact of tetracyclines (TCs) and proton pump inhibitors (PPIs) alone or in combination on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC treated with gefitinib or erlotinib for at least 1 week between January 2009 and October 2021 were enrolled and divided into four groups based on the presenceabsence of TC andor PPI in the therapeutic regimen TC-PPI-, TC PPI-, TC-PPI , TC PPI . Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. The estimated median PFS and OS of 347 included patients with NSCLC were 8.57 (95% confidence interval CI 7.66-9.48) months and 13.10 (95% CI 11.03-15.17) months, respectively. Co-administration of EGFR-TKIs with PPIs decreased the PFS and OS, while that with TCs improved the PFS and OS. However, the concomitant use of EGFR-TKIs, TCs, and PPIs yielded survival rates similar to that of EGFR-TKI therapy alone. The administration of EGFR-TKIs with other drugs poses a challenge in managing patients with NSCLC. Therefore, reassessing the indications and necessity of TC or PPI therapy is essential for patients receiving erlotinib or gefitinib. The benefits and risks of possible discontinuation due to the clinical relevance of this interaction should be considered.

Identification of four metabolic subtypes and key prognostic markers in lung adenocarcinoma based on glycolytic and glutaminolytic pathways.

Glucose and glutamine are the main energy sources for tumor cells. Whether glycolysis and glutaminolysis play a critical role in driving the molecular subtypes of lung adenocarcinoma (LUAD) is unknown. This study attempts to identify LUAD metabolic subtypes with different characteristics and key genes based on gene transcription profiling data related to glycolysis and glutaminolysis, and to construct prognostic models to facilitate patient outcome prediction. LUAD related data were obtained from the Cancer Genome Atlas and Gene Expression Omnibus, including TCGA-LUAD, GSE42127, GSE68465, GSE72094, GSE29013, GSE31210, GSE30219, GSE37745, GSE50081. Unsupervised consensus clustering was used for the identification of LUAD subtypes. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and CytoNCA App in Cytoscape 3.9.0 were used for the screening of key genes. The Cox proportional hazards model was used for the construction of the prognostic risk model. Finally, qPCR analysis, immunohistochemistry and immunofluorescence colocalization were used to validate the core genes of the model. This study identified four distinct characterized LUAD metabolic subtypes, glycolytic, glutaminolytic, mixed and quiescent types. The glycolytic type had a worse prognosis than the glutaminolytic type. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) were identified as hub genes driving the glycolyticglutaminolytic LUAD. In addition, the risk assessment model constructed based on three genes (SPP1, SLC2A1 and AGER) had good predictive performance and could be validated in multiple independent external LUAD cohorts. These three genes were differentially expressed in LUAD and lung normal tissues, and might be potential prognostic markers for LUAD. LUAD can be classified into four different characteristic metabolic subtypes based on the glycolysis- and glutaminolysis-related genes. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) may play an important role in the subtype-intrinsic drive. This metabolic subtype classification, provides new biological insights into the previously established LUAD subtypes.

Cross-protective antibodies against common endemic respiratory viruses.

Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.

Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation.

Epithelial tissues provide front-line barriers shielding the organism from invading pathogens and harmful substances. In the airway epithelium, the combined action of multiciliated and secretory cells sustains the mucociliary escalator required for clearance of microbes and particles from the airways. Defects in components of mucociliary clearance or barrier integrity are associated with recurring infections and chronic inflammation. The timely and balanced differentiation of basal cells into mature epithelial cell subsets is therefore tightly controlled. While different growth factors regulating progenitor cell proliferation have been described, little is known about the role of metabolism in these regenerative processes. Here we show that basal cell differentiation correlates with a shift in cellular metabolism from glycolysis to fatty acid oxidation (FAO). We demonstrate both in vitro and in vivo that pharmacological and genetic impairment of FAO blocks the development of fully differentiated airway epithelial cells, compromising the repair of airway epithelia. Mechanistically, FAO links to the hexosamine biosynthesis pathway to support protein glycosylation in airway epithelial cells. Our findings unveil the metabolic network underpinning the differentiation of airway epithelia and identify novel targets for intervention to promote lung repair.

Long-Read Whole-Genome Sequencing Using a Nanopore Sequencer and Detection of Structural Variants in Cancer Genomes.

Long-read sequencing technologies enable us to precisely identify structural variants (SVs), which would be occasionally associated with various types of diseases, including cancers. In this section, we introduce experimental and computational procedures for conducting long-read whole-genome sequencing (WGS) of cancer genomes from fresh frozen tissuescells. We also demonstrate the analysis of SVs in cancer genomes using long-read WGS data from lung cancer cell lines by several representative computational tools, such as cuteSV and Sniffles2, as examples.

Prognostic Prediction of Cancer Based on Radiomics Features of Diagnostic Imaging The Performance of Machine Learning Strategies.

Tumor phenotypes can be characterized by radiomics features extracted from images. However, the prediction accuracy is challenged by difficulties such as small sample size and data imbalance. The purpose of the study was to evaluate the performance of machine learning strategies for the prediction of cancer prognosis. A total of 422 patients diagnosed with non-small cell lung carcinoma (NSCLC) were selected from The Cancer Imaging Archive (TCIA). The gross tumor volume (GTV) of each case was delineated from the respective CT images for radiomic features extraction. The samples were divided into 4 groups with survival endpoints of 1 year, 3 years, 5 years, and 7 years. The radiomic image features were analyzed with 6 different machine learning methods decision tree (DT), boosted tree (BT), random forests (RF), support vector machine (SVM), generalized linear model (GLM), and deep learning artificial neural networks (DL-ANNs) with 7030 cross-validation. The overall average prediction performance of the BT, RF, DT, SVM, GLM and DL-ANNs was AUC with 0.912, 0.938, 0.793, 0.746, 0.789 and 0.705 respectively. The RF and BT gave the best and second performance in the prediction. The DL-ANN did not show obvious advantage in predicting prognostic outcomes. Deep learning artificial neural networks did not show a significant improvement than traditional machine learning methods such as random forest and boosted trees. On the whole, the accurate outcome prediction using radiomics serves as a supportive reference for formulating treatment strategy for cancer patients.

Is physical activity effective against cancer-related fatigue in lung cancer patients An umbrella review of systematic reviews and meta-analyses.

To discuss the effects of physical activity on cancer-related fatigue (CRF) in lung cancer patients, summarize the types of physical activity in the published reviews, assess the quality of the evidence, and provide suggestions for the clinical selection of exercise intervention. PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews were searched through 8 November 2021 to identify relevant systematic reviews and meta-analyses. We also performed a manual search of the reference lists of included articles as supplements. Two researchers independently performed literature screening, data extraction, and quality assessment. The umbrella review has been registered in the International Prospective Register of Systematic Review (PROSPERO) registry (CRD42021292548). From the 13 systematic reviews or meta-analyses identified, 10 physical activity interventions were included. The most mentioned intervention was aerobic combined with resistance exercise however, no reduction of the symptoms of CRF was observed in lung cancer patients by this exercise intervention. Most of the patients who performed aerobic exercises alone showed improvement in CRF after the intervention. In addition, Tai Chi and breathing exercises have been shown to improve fatigue, but more high-quality research is still needed to support its effectiveness. Aerobic exercise, respiratory muscle training, aerobic combined with balance training, and other exercise interventions have been shown to improve CRF in lung cancer patients. But it should be noted that according to the different treatment methods and disease stages of patients, individualized rehabilitation programs should be developed for patients. Due to the low methodological quality and evidence quality of some systematic reviews and meta-analyses included in this study, more high-quality clinical studies and systematic reviews are still needed for validation in the future. This umbrella review helps to identify effective ways of exercise to improve fatigue in lung cancer patients before dedicated evidence-based medical guidelines are established.

Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family.

Lung cancer is the most common form of cancer and the leading cause of cancer death. For familial lung cancer, identification of causing genetic factors is essential for prevention and control of non-lung cancer in carriers. We studied two generations of a family with suspected inherited lung cancer susceptibility. Four individuals in this family had lung adenocarcinoma. To identify the gene(s) that cause the lung cancer in this pedigree, we extracted DNA from the peripheral blood of four cancer individuals and blood from three cancer-free family members as the control and performed whole-genome sequencing. Our filtering strategy includes, assessment of allele frequency, functional affection on amino acids, mutation accumulation, phased blocks and evolution analysis towards the alterations. We identified two possible mutations, including PLEKHM2 (D134N) and MCC (R448Q) in all affected family members but did not found in the control group. Then, we performed a genetic susceptibility screening for 10 non-lung cancer relatives and found two individuals with PLEKHM2 (D134N) mutation, two with MCC (R448Q) mutation and one carrying both mutations. 3 carriers performed LDCT scan and 2 of them carried MCC (R448Q) also had ground-glass opacity (GGO) lesion in their lung. Our data suggested that WGS together with our filtering strategy was successful in identifying PLEKHM2 (D134N) and MCC (R448Q) as the possible driver mutations in this family. Genetic susceptibility screening of non-lung cancer carriers will be a useful approach to prevent and control lung cancer in families with high-risk for the disease.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.

Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P 0.6915). Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

Oncological surgery follow-up and quality of life meta-analysis.

Previous trials found that more intensive postoperative surveillance schedules did not improve survival. Oncological follow-up also provides an opportunity to address psychological issues (for example anxiety, depression, and fear of recurrence). This systematic review assessed the impact of a less intensive surveillance strategy on health-related quality of life (HRQoL), emotional well-being, and patient satisfaction. A systematic search was conducted in PubMedMEDLINE, Embase, Web of Science, Cochrane database, PsycINFO, and Google Scholar to identify studies comparing different follow-up strategies after oncological surgery and their effect on HRQoL and patient satisfaction, published before 4 May 2022. A meta-analysis was conducted on the most relevant European Organisation for Research and Treatment of Cancer QLQ-C30 and Hospital Anxiety and Depression Scale subscales. Thirty-five studies were identified, focusing on melanoma (4), colorectal (10), breast (7), prostate (4), upper gastrointestinal (4), gynaecological (3), lung (2), and head and neck (1) cancers. Twenty-two studies were considered to have a low risk of bias, of which 14 showed no significant difference in HRQoL between follow-up approaches. Five studies with a low risk of bias showed improved HRQoL or emotional well-being with a less intensive follow-up approach and three with an intensive approach. Meta-analysis of HRQoL outcomes revealed no negative effects for patients receiving less intensive follow-up. Low-intensity follow-up does not diminish HRQoL, emotional well-being, or patient satisfaction.

Association of Reported Candidate Monogenic Genes With Lung Cancer Risk.

Published studies on association of germline monogenic genes and lung cancer risk were inconsistent. Our objective is to assess the validity of reported candidate monogenic genes for their association with lung cancer. A systematic review of published papers prior to August 2022 was performed first to identify all genes where germline mutations were associated with lung cancer risk. We then performed a confirmation study in 2,050 lung cancer cases and 198,553 controls in the UK Biobank (UKB). Germline mutations of these genes were identified from sequencing data and annotated using The American College of Medical Genetics criteria. The robust SKAT-O, a gene-based analysis that properly controls for false positives due to unbalanced case-control ratio, was used for association tests adjusting for age at recruitment, gender, and genetic background. The systematic review identified 12 genes that were statistically significantly associated with lung cancer risk in at least one study (P < .05), including ATM, BLM, BRCA2, BRIP1, CHEK2, FANCA, FANCD2, MSH6, PMS1, RAD51C, RAD51D, and TP53. When pathogeniclikely pathogenic mutations were aggregated within each gene, the association was confirmed for ATM (P 4.47E-4) at the study-wise significance level (P < .0042, Bonferroni correction for 12 tests). Suggestive evidence of association was found for 2 other genes, BRCA2 (P .007) and TP53 (P .03). Among these 3 genes, the lung cancer risks range from 1.95 (BRCA2) to 5.28 (TP53). This study provides statistical evidence for association of previously reported genes and lung cancer risk and has clinical utility for risk assessment and genetic counseling.

PDQ Cancer Information Summaries

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of non-small cell lung cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

PDQ Cancer Information Summaries

This PDQ cancer information summary has current information about the treatment of non-small cell lung cancer. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (Date Last Modified) is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.

PDQ Cancer Information Summaries

This PDQ cancer information summary has current information about the treatment of rare cancers of childhood. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary (Date Last Modified) is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis.

Current status and outlook of medical treatment for

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as 近年来，靶向药物治疗和免疫检查点抑制剂的临床应用极大地改变了晚期非小细胞肺癌(NSCLC)的治疗格局。表皮生长因子受体和间变性淋巴瘤受体酪氨酸激酶等驱动基因改变NSCLC的TKI靶向治疗均已取得了良好临床疗效，而Kirsten大鼠肉瘤病毒基因同源物(KRAS)作为较早发现和突变频率较高的癌基因之一，其靶向药物治疗研究进展缓慢，法尼基转移酶抑制剂、KRAS信号通路下游蛋白抑制剂等靶向治疗研究均未取得预期结果，使得KRAS长期以来被定义为不可成药的靶点。KRAS蛋白作为分子开关，通过与三磷酸鸟苷结合而被激活，引发系列级联反应，在细胞增殖和有丝分裂中发挥作用。KRAS突变的NSCLC患者对内科系统性治疗反应性差，预后不佳。随着对KRAS晶体结构认识的不断深入，研究者发现了KRAS潜在的治疗位点，进而开发出了多个直接针对KRAS的靶向药物，尤其是KRAS G12C抑制剂，如AMG510(sotorasib)和MRTX849(adagrasib)，其临床试验获得了令人鼓舞的结果。文章在系统介绍KRAS突变NSCLC患者临床特征及内科治疗方法的基础上，重点就KRAS靶向治疗的研究进展进行了总结和展望。.

Critical review on emerging health effects associated with the indoor air quality and its sustainable management.

Indoor air quality (IAQ) is one of the fundamental elements affecting peoples health and well-being. Currently, there is a lack of awareness among people about the quantification, identification, and possible health effects of IAQ. Airborne pollutants such as volatile organic compounds (VOCs), particulate matter (PM), sulfur dioxide (SO2), carbon monoxide (CO), nitrous oxide (NO), polycyclic aromatic hydrocarbons (PAHs) microbial spores, pollen, allergens, etc. primarily contribute to IAQ deterioration. This review discusses the sources of major indoor air pollutants, molecular toxicity mechanisms, and their effects on cardiovascular, ocular, neurological, women, and foetal health. Additionally, contemporary strategies and sustainable methods for regulating and reducing pollutant concentrations are emphasized, and current initiatives to address and enhance IAQ are explored, along with their unique advantages and potentials. Due to their longer exposure times and particular physical characteristics, women and children are more at risk for poor indoor air quality. By triggering many toxicity mechanisms, including oxidative stress, DNA methylation, epigenetic modifications, and gene activation, indoor air pollution can cause a range of health issues. Low birth weight, acute lower respiratory tract infections, Sick building syndromes (SBS), and early death are more prevalent in exposed residents. On the other hand, the main causes of incapacity and early mortality are lung cancer, chronic obstructive pulmonary disease, and cardiovascular disorders. Its crucial to acknowledge anticipated research needs and implemented efficient interventions and policies to lower health hazards.

Invasive Procedures Associated with Lung Cancer Screening in Clinical Practice.

The harm associated with imaging abnormalities related to lung cancer screening (LCS) is not well-documented, especially outside the clinical trial and academic setting. What is the frequency of invasive procedures and complications associated with a community-based LCS program, including procedures for false-positive and benign but clinically important incidental findings We performed a single center, retrospective study of a LCS program at a non-university teaching hospital from 2016 to 2019 to identify invasive procedures prompted by LCS, including their indication and complications. Among 2003 LCS participants, 58 (2.9%) were diagnosed with lung cancer and 71 (3.5%) with any malignancy. Invasive procedures were performed 160 times in 103 (5.1%) participants, including 1.7% of those without malignancy. Eight invasive procedures (0.4% of participants), including four surgeries (12% of diagnostic lung resections), were performed for false-positive lung nodules. Only 1% of Lung Imaging Reporting and Data System category 4A nodules that proved benign underwent an invasive procedure. Among those without malignancy, an invasive procedure was performed in eight participants for extrapulmonary false-positive findings (0.4%) and in 19 (0.9%) to evaluate incidental findings considered benign but clinically important. Procedures for the latter indication resulted in treatment, change in management, or diagnosis in 79% of individuals. Invasive procedures in those without malignancy resulted in three complications (0.15%). Seventy non-surgical procedures (6% complication rate) and 48 thoracic surgeries (4% major complication rate) were performed in those with malignancy. The use of invasive procedures to resolve false-positive findings was uncommon in the clinical practice of a non-university LCS program that adhered to a nodule management algorithm and employed a multidisciplinary approach. Incidental findings considered benign but clinically important resulted in invasive procedure rates that were similar to those for false-positive findings and frequently had clinical value.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Metastatic Ovarian High-Grade Serous Carcinoma A Case Report and Literature Review.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity with poor prognosis, and often diagnosed postmortem. PTTM is resulting from tumor emboli induced activation of coagulation cascade, fibrin clot formation and fibrocellular intimal proliferation in pulmonary microvasculature. The patient was a 65-year-old female, with past medical history of ovarian high-grade serous carcinoma, presented with chest pain and shortness of breath. The chest computed tomography (CT) revealed innumerable new lung nodules as well as small hazy and patchy opacities compared to the chest CT two months before current presentation. She developed progressive respiratory failure and expired. A lung-restricted autopsy showed diffuse subcentimetric nodules in bilateral lungs grossly. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor emboli consisting of pleomorphic tumor cells with varying degrees of fibrin deposition and fibrocellular intimal proliferation in the pulmonary arterioles, small arteries, and capillaries in the alveolar septa. Immunohistochemistry confirmed the ovarian origin of the tumor cells. The findings were consistent with PTTM secondary to metastasis of ovarian high-grade serous carcinoma. Literature review of PTTM caused by ovarian cancer was conducted. PTTM is a fatal entity with rare association with primary ovarian malignancy. This case study demonstrates the clinicopathological features of PTTM associated with high-grade serous carcinoma, and it will be the second case of PTTM with this association in the literature. Preliminary findings have been reported in abstract form 1.

A systematic review on botany, ethnopharmacology, quality control, phytochemistry, pharmacology and toxicity of Arctium lappa L. fruit.

Arctium lappa L., is a biennial plant that grows around the Eurasia. Many parts of Arctium lappa L. (roots, leaves and fruits, etc.) are medically used in different countries. Arctium lappa L. fruit, also called Arctii Fructus, is traditionally applied to dispel wind-heat, ventilate lung to promote eruption, remove toxicity substance and relieve sore throat. The review aims to integrate the botany, ethnopharmacology, quality control, phytochemistry, pharmacology, derivatives and toxicity information of Arctii Fructus, so as to facilitate future research and explore the potential of Arctii Fructus as an agent for treating diseases. Related knowledge about Arctii Fructus were acquired from Science Direct, GeenMedical, PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Pharmacopoeia of the Peoples Republic of China, Doctoral and Masters thesis, ancient books, etc. RESULTS Arctii Fructus as an herb used for medicine and food was pervasively distributed and applicated around the world. It was traditionally used to treat anemopyretic cold, dyspnea and cough, sore throat, etc. To date, more than 200 compounds have been isolated and identified from Arctii Fructus. It contained lignans, phenolic acids and fatty acids, terpenoids, volatile oils and others. Lignans, especially arctigenin and arctiin, had the extensive pharmacological effects such as anti-cancer, antiviral, anti-inflammatory activities. The ester derivatives of arctigenin had the anti-cancer, anti-Alzheimers disease and immunity enhancing effects. Although Arctii Fructus extract had no toxicity, arctigenin was toxic at a certain dose. The alleviating effects of Arctii Fructus on chronic inflammation and ageing have been demonstrated by clinical studies. Arctii Fructus is regarded as a worthy herb with many chemical components and various pharmacological effects. Several traditional applications have been supported by modern pharmacological research. However, their action mechanisms need to be further studied. Although many chemical components were isolated from Arctii Fructus, the current research mainly focused on lignans, especially arctiin and arctigenin. Therefore, it is very important to deeply clarify the pharmacological activities and action mechanism of the compounds and make full medicinal use of the resources of Arctii Fructus.

Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists in inflammatory diseases and cancers.

C-X-C motif chemokine receptor 2 (CXCR2) is G protein-coupled receptor (GPCR) and plays important roles in various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), atherosclerosis, asthma, and pancreatic cancer. Upregulation of CXCR2 is closely associated with the migration of neutrophils and monocytes. To date, many small-molecule CXCR2 antagonists have entered clinical trials, showing favorable safety and therapeutic effects. Hence, we provide an overview containing the discovery history, protein structure, signaling pathways, biological functions, structure-activity relationships and clinical significance of CXCR2 antagonists in inflammatory diseases and cancers. According to the latest development and recent clinical progress of CXCR2 small molecule antagonists, we speculated that CXCR2 can be used as a biomarker and a new target for diabetes and that CXCR2 antagonists may also attenuate lung injury in coronavirus disease 2019 (COVID-19).

Virtual screening, molecular simulations and bioassays Discovering novel microsomal prostaglandin E Synthase-1 (mPGES-1) inhibitors.

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible prostaglandin E synthase expressed following exposure to pro-inflammatory stimuli. The mPGES-1 enzyme represents a new target for the therapeutic treatment of acute and chronic inflammatory disorders and cancer. In the present study, compounds from the ZINC15 database with an indole scaffold were docked at the mPGES-1 binding site using Glide (high-throughput virtual screening HTVS, standard precision SP and extra precision XP), and the stabilities of the complexes were determined by molecular simulation studies. Following HTVS, the top 10% compounds were retained and further screened by SP. Again, the top 10% of these compounds were retained. Finally, the Glide XP scores of the compounds were determined, 20% were analyzed, and the Prime MM-GBSA total free binding energies of the compounds were calculated. The molecular simulations (100 ns) of the reference ligand, LVJ, and the two best-scoring compounds were performed with the Desmond program to analyze the dynamics of the target protein-ligand complexes. In human lung cells treated with the hit compounds, cell viability by colorimetric method and PGE

Characterization of Central Nervous System Clinico-Genomic Outcomes in ALK-Positive Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Alectinib.

Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT. We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 12012 and 52021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay. A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51-2.89 p 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77-46.6 p 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74-44.2 p 0.009). Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.

Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening.

Thioredoxin reductase 1 (TrxR1) is considered as an important anti-cancer drug target, inhibition of which can induce reactive oxygen species (ROS)-mediated apoptosis of human cancer cells. Here, we developed and optimized a high-throughput screening (HTS) assay based on enzyme kinetics for the discovery of TrxR1 inhibitors. By utilizing this assay, we performed a HTS for 2500 compounds from an in-house library against TrxR1. We found that a vaccine preservative, thimerosal, strongly inhibited TrxR1 in a competitive and reversible manner with an IC

Nuclear protein in testis carcinoma of the lung.

Nuclear protein in testis (NUT) carcinoma is a kind of highly aggressive and fatal solid tumor characterized by a rearrangement of the NUT carcinoma family member 1 (NUTM1) gene located on chromosome 15 q l4, where the most common form of fusion is BRD4-NUT. NUT carcinoma occurred in different organs and was most commonly found in the midline organs and the lungs. NUT carcinoma can occur in patients of almost all ages, having a roughly consistent incidence in both sexes. Most of the patients were diagnosed in advanced stages with an extremely poor prognosis due to the lack of effective treatment. After years of research, the mechanism of NUT carcinoma is still not fully clear, and its therapeutic approaches need to be further studied and explored. In order to gain a more comprehensive understanding of NUT carcinoma and explore the effective treatments, this review aimed to summarize the clinical features, pathological characteristics, differential diagnosis, and treatment strategies for this disease.

G-CSF filgrastim biosimilar-Sandoz reduces the incidence of febrile neutropenia in patients receiving chemotherapy regimens with rest periods not exceeding 14 days A French, multicenter, prospective, non-interventional study.

The objective of this study was to describe filgrastim biosimilar-Sandoz modalities of use in patients receiving cytotoxic chemotherapy regimens with a rest period of ≤14 days and to investigate the incidence of febrile neutropenia (FN) in routine clinical practice. This was a French, multicenter, prospective and descriptive, non-interventional study including patients with breast, lung, gastrointestinal cancer or a lymphoma initiating filgrastim biosimilar-Sandoz treatment and in the context of cytotoxic chemotherapy with a rest period not exceeding 14 days. Data were collected during two routine clinical visits on the modalities of use of filgrastim biosimilar-Sandoz, on the incidence of neutropenia events and on adverse events. Between November 2015 and June 2018, 1080 patients were enrolled in the study in 129 centers. Overall, 941 patients were evaluable for efficacy and 937 for safety. Of the 941 patients, 84.8% had a solid tumor and 15.2% had a lymphoid hemopathy. Filgrastim biosimilar-Sandoz was prescribed as primary prophylaxis in 74.0% of the patients and as secondary prophylaxis in 22.4% of the patients. FN was reported in 1.5% of patients with a solid tumor and 12.6% of patients with a lymphoma. A chemotherapy relative dose intensity of over 85% with regard to the reference dose was achieved by more than 80% of the patients in all tumor localizations. The study showed that filgrastim biosimilar-Sandoz is safe to use and effective in preventing FN and in allowing to maintain the dose intensity of chemotherapy.

Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer.

The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01 90% confidence interval CI, 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

An HLA-GSPAG9STAT3 axis promotes brain metastases.

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade-the premetastatic or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-GSPAG9STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive andor more efficacious BM therapies.

Muscular tissue desaturation and pneumonia in patients receiving lung cancer surgery a cohort study.

Post-operative pneumonia (POP) is a common complication of lung cancer surgery, and muscular tissue oxygenation is a root cause of post-operative complications. However, the association between muscular tissue desaturation and POP in patients receiving lung cancer surgery has not been specifically studied. This study aimed to investigate the potential use of intra-operative muscular tissue desaturation as a predictor of POP in patients undergoing lung cancer surgery. This cohort study enrolled patients (≥55 years) who had undergone lobectomy with one-lung ventilation. Muscular tissue oxygen saturation (SmtO2) was monitored in the forearm (over the brachioradialis muscle) and upper thigh (over the quadriceps) using a tissue oximeter. The minimum SmtO2 was the lowest intra-operative measurement at any time point. Muscular tissue desaturation was defined as a minimum baseline SmtO2 of <80% for >15 s. The area under or above the threshold was the product of the magnitude and time of desaturation. The primary outcome was the association between intra-operative muscular tissue desaturation and POP within seven post-operative days using multivariable logistic regression.The secondary outcome was the correlation between SmtO2 in the forearm and that in the thigh. We enrolled 174 patients. The overall incidence of muscular desaturation (defined as SmtO2 < 80% in the forearm at baseline) was approximately 47.1% (82174). The patients with muscular desaturation had a higher incidence of pneumonia than those without desaturation (28.0% 2382 vs. 12.0% 1192 P 0.008). The multivariable analysis revealed that muscular desaturation was associated with an increased risk of pneumonia (odds ratio 2.995, 95% confidence interval 1.080-8.310, P 0.035) after adjusting for age, American Society of Anesthesiologists status, Assess Respiratory Risk in Surgical Patients in Catalonia score, smoking, use of peripheral nerve block, propofol, and study center. Muscular tissue desaturation, defined as a baseline SmtO2 < 80% in the forearm, may be associated with an increased risk of POP. No. ChiCTR-ROC-17012627.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6% Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

Five years after PACIFIC Update on multimodal treatment efficacy based on real-world reports.

The growing body of real-life data on maintenance treatment with durvalumab suggests that immunological markers of the cancer-host interplay may have significant effects on the efficacy of multimodal therapy in patients with unresectable stage III NSCLC. We summarize real-world clinical data regarding this new tri-modal approach and report on potential biomarker landscape. The obvious question posed in this context of a very heterogeneous inoperable stage III NSCLC disease is How can we augment an ability to predict checkpoint inhibition success or failure Which tools and biomarkers, which clinical metadata and genetic background are relevant and feasible No single biomarker will ever fully dominate the unresectable stage III NSCLC space, so we advocate multilevel and multivariate analysis of biomarkers. In this particular opinion piece, we explore the impact of PD-L1 expression on tumor cells, neutrophil-to-lymphocyte ratio, EGFR and STK11 mutational status, interferon-gamma signature, and tumor-infiltrating lymphocytes among others.

Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

Open-source, fully-automated hybrid cardiac substructure segmentation development and optimisation.

Radiotherapy for thoracic and breast tumours is associated with a range of cardiotoxicities. Emerging evidence suggests cardiac substructure doses may be more predictive of specific outcomes, however, quantitative data necessary to develop clinical planning constraints is lacking. Retrospective analysis of patient data is required, which relies on accurate segmentation of cardiac substructures. In this study, a novel model was designed to deliver reliable, accurate, and anatomically consistent segmentation of 18 cardiac substructures on computed tomography (CT) scans. Thirty manually contoured CT scans were included. The proposed multi-stage method leverages deep learning (DL), multi-atlas mapping, and geometric modelling to automatically segment the whole heart, cardiac chambers, great vessels, heart valves, coronary arteries, and conduction nodes. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD), and volume ratio. Performance was reliable, with no errors observed and acceptable variation in accuracy between cases, including in challenging cases with imaging artefacts and atypical patient anatomy. The median DSC range was 0.81-0.93 for whole heart and cardiac chambers, 0.43-0.76 for great vessels and conduction nodes, and 0.22-0.53 for heart valves. For all structures the median MDA was below 6 mm, median HD ranged 7.7-19.7 mm, and median volume ratio was close to one (0.95-1.49) for all structures except the left main coronary artery (2.07). The fully automatic algorithm takes between 9 and 23 min per case. The proposed fully-automatic method accurately delineates cardiac substructures on radiotherapy planning CT scans. Robust and anatomically consistent segmentations, particularly for smaller structures, represents a major advantage of the proposed segmentation approach. The open-source software will facilitate more precise evaluation of cardiac doses and risks from available clinical datasets.

Current Status and Challenges of Vaccination Therapy for Glioblastoma.

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and deadly type of central nervous system malignancy in adults. Despite significant breakthroughs in current GBM treatments such as surgery, radiotherapy, and chemotherapy, the prognosis for late-stage glioblastoma remains bleak due to tumor recurrence following surgical resection. The poor prognosis of GBM patients highlights the evident and pressing need for more efficient and targeted treatment. Vaccination has shown some success in treating patients with advanced colorectal and lung cancer. Therefore, the potential value of using tumor vaccines in treating glioblastoma is increasingly discussed as a monotherapy or in combination with other cellular immunotherapies. Cancer vaccination includes both passive administration of monoclonal antibodies and active vaccination procedures to activate, boost, or bias antitumor immunity against cancer cells. This article focuses on active immunotherapy with peptide, genetic (DNA, mRNA), and cell-based vaccines in treating GBM and reviews the various treatment approaches currently being tested. Although the ease of synthesis, relative safety, and ability to elicit tumor-specific immune responses have made these vaccines an invaluable tool for cancer treatment, more extensive cohort studies and better guidelines are needed to improve the efficacy of these vaccines in anti-GBM therapy.

A systematic review and multilevel regression analysis reveals the comorbidity prevalence in cancer.

Comorbidities can have major implications for cancer care, as they might impact the timing of cancer diagnosis, compromise optimal care, affect treatment outcomes, and increase healthcare costs. Thus, it is important to comprehensively evaluate cancer comorbidities and examine trends over time. Here, we performed a systematic literature review on the prevalence and types of comorbidities for the five most common forms of cancer. Observational studies from Organisation for Economic Co-operation and Development (OECD) countries published between 1990 and 2020 in English or Dutch that used routinely collected data from a representative population were included. The search yielded 3,070 articles of which 161 were eligible for data analyses. Multilevel analyses were performed to evaluate determinants of variation in comorbidity prevalence and trends over time. The weighted average comorbidity prevalence was 33.4%, and comorbidities were the most common in lung cancer (46.7%) and colorectal cancer (40.0%), followed by prostate (28.5%), melanoma (28.3%), and breast (22.4%). The most common types of comorbidities were hypertension (29.7%), pulmonary diseases (15.9%), and diabetes (13.5%). After adjusting for gender, type of comorbidity index, age, data source (patient records versus claims), and country, a significant increase in comorbidities of 0.54% per year was observed. Overall, a large and increasing proportion of the oncological population is dealing with comorbidities, which could be used to inform and adapt treatment options to improve health outcomes and reduce healthcare costs.

Predicting pulmonary ventilation damage after radiation therapy for Non-Small cell lung cancer using a ResNet generative adversarial network.

Functional lung avoidance radiation therapy (RT) is a technique being investigated to preferentially avoid specific regions of the lung that are predicted to be more susceptible to radiation-induced damage. Reducing the dose delivered to high functioning regions may reduce the occurrence radiation-induced lung injuries and toxicities. However, in order to develop effective lung function-sparing plans, accurate predictions of post-RT ventilation change are needed to determine which regions of the lung should be spared. To predict pulmonary ventilation change following radiation therapy (RT) for non-small cell lung cancer using machine learning. A conditional generative adversarial network (cGAN) was developed with data from 82 human subjects enrolled in a randomized clinical trial approved by the institutions IRB to predict post-RT pulmonary ventilation change. The inputs to the network were the pre-RT pulmonary ventilation map and radiation dose distribution. The loss function was a combination of the binary cross-entropy loss and an asymmetrical structural similarity index measure (aSSIM) function designed to increase penalization of under-prediction of ventilation damage. Network performance was evaluated against a previously developed polynomial regression model using a paired sample t-test for comparison. Evaluation was performed using 8-fold cross-validation. From the 8-fold cross-validation we found that relative to the polynomial model, the cGAN model significantly improved predicting regions of ventilation damage following radiotherapy based on true positive rate (TPR), 0.14±0.15 to 0.72±0.21, and Dice similarity coefficient (DSC), 0.19±0.16 to 0.46±0.14, but significantly declined in true negative rate, 0.97±0.05 to 0.62±0.21, and accuracy, 0.79±0.08 to 0.65±0.14. Additionally, the average true positive volume increased from 104±119 cc in the POLY model to 565±332 cc in the cGAN model, and the average false negative volume decreased from 654±361 cc in the POLY model to 193±163 cc in the cGAN model. The proposed cGAN model demonstrated significant improvement in TPR and DSC. The higher sensitivity of the cGAN model can improve the clinical utility of functional lung avoidance RT by identifying larger volumes of functional lung that can be spared and thus decrease the probability of the patient developing radiation-induced lung injuries. This article is protected by copyright. All rights reserved.

Systemic juvenile xanthogranuloma A systematic review.

To perform a systematic review to investigate the available literature regarding systemic juvenile xanthogranuloma (SJXG) and report the population characteristics, clinical manifestation, therapy, and outcome. A search of PubMed, Embase, and Cochrane Library for all articles published between 1981 and 2022 was performed with variations and combinations of the following search terms extracutaneous, visceral, systemic, and juvenile xanthogranuloma (JXG). Data extracted included demographics, organ involvement, treatment, outcome, and permanent sequelae. A total of 103 articles encompassing 159 patients met the inclusion criteria. The median onset age was 9 months, with a male predominance (61%). The distribution of major involved organs varied by age, and younger onset age was associated with more organ involvement. The most commonly involved site was the central nervous system (CNS) (40.9%), followed by the liver (31.4%), the lung (18.9%), and the eye (18.2%). At the termination of follow-up, 93 patients (58.5%) were alive with no disease, 56 (35.2%) were alive with disease, and 10 (6.3%) were dead of disease. There was a significant difference in outcome between patients with and without spleen involvement (p .0003), and patients with spleen involvement suffered a higher risk of death. Permanent sequelae mainly comprised CNS symptoms and ocular manifestations. SJXG can involve varying numbers and combinations of extracutaneous sites. There is no standard therapy for SJXG and clinicians should choose individualized therapy modalities.

Efficacy and safety of immune checkpoint inhibitors combined with recombinant human endostatin and chemotherapy as the first-line treatment of advanced non-small-cell lung cancer.

This study retrospectively analyzed the effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. Among them, 58 patients received a PD-1 inhibitor combined with Rh-endostatin and chemotherapy (treatment group), and 42 patients received Rh-endostatin combined with chemotherapy (control group). Patients in the treatment group had a significantly improved objective response rate (67.2 vs 42.9% p 0.015) and prolonged survival without their disease getting worse (10.2 vs 6.5 months p < 0.001). No significant differences were found in the adverse events between the two groups.

Atezolizumab-Induced Lambert-Eaton Myasthenic Syndrome in a Patient With Small-Cell Lung Cancer.

The case of a 70-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) while receiving

A Case of Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer Multi-Line Treatment and Resistance Mechanisms.

In the non-small-cell lung cancer (NSCLC) subtype, adenocarcinoma is the most common histology. The choice of first-line treatment depends on the mutational status. We present a case of a 54-year-old non-smoker woman with lung adenocarcinoma and extensive metastatic disease at diagnosis. The genetic analysis demonstrated a sensitizing epidermal growth factor receptor (EGFR) exon 19 mutation and she began treatment with a first-generation EGFR tyrosine kinase inhibitor (TKI), erlotinib. Due to successively acquired resistances and disease progression, six treatment lines were pursued, including third-generation EGFR TKI and chemotherapy. The patient accomplished an overall survival of 47 months. This case emphasized the importance of monitoring tumor mutational alterations, allowing us to implement a multi-line treatment. Targeted therapy in advanced NSCLC largely improved the overall survival of these patients.

Trends in Survival and Surgical Methods in Patients Surgically Treated for Metastatic Spinal Tumors 25-Year Experience in a Single Institution.

This study aimed to examine trends in postoperative survival and surgical methods over a 25-year period in patients surgically treated for metastatic spinal tumors. We performed a retrospective study of patients who underwent surgical treatment for metastatic spinal tumors between 1996 and 2020. For trend analysis, the study cohort was divided into three groups according to the year of surgery 1996-2004, 2005-2012, and 2013-2020. A Kaplan-Meier survival analysis was performed to examine survival, and the log-rank test was used to compare the survival of the top six common cancers among the periods. The surgical methods were grouped and examined as follows fixation only, palliative decompression and fixation, gross total removal and fixation, and total This study included a total of 608 patients. There were 78 patients in 1996-2004, 236 in 2005-2012, and 294 in 2013-2020. Regarding the overall survival trend, the group 2013-2020 had a significantly improved survival as compared to the other two groups ( During the past 25 years, significant survival improvement was observed in patients with lung, kidney, and breast cancers. There was no improvement in survival in patients with liver, colorectal, and prostate cancers. In terms of surgical techniques, palliative decompression and fixation only procedures increased, while gross total tumor removal declined.

Applying PET-CT for predicting the efficacy of SBRT to inoperable early-stage lung adenocarcinoma A Brazilian case-series.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage inoperable primary lung cancer. Here we report a thorough description of the prognostic value of pre-SBRT SUVmax for predicting the efficacy of SBRT in early-stage lung adenocarcinoma. This is a retrospective study of consecutive cases of early-stage inoperable lung adenocarcinoma, staged with PET-CT, treated with SBRT between 2007 and 17. Kaplan-Meier (KM) curves were used to assess overall survival and compare time to event between those with PET-CT SUVmax values ≤ 5.0 and those > 5. Fishers Exact tests and the Mann-Whitney U were used to compare the patient and clinical data of those with SUVmax≤5.0 and >5.0, and those with and without any failure. Amongst 50 lung carcinoma lesions, from 47 patients (34 (68%)-T1a or <T1b), estimated median overall survival from the KM was 44.9 months (95% confidence interval 35.5-54.3). Five experienced a local failure, which was inadequate for detecting differences between those with PET-CT SUVmax ≤5.0 and those >5 ( Patients with early-stage inoperable lung adenocarcinoma present good clinical outcomes when treated with SBRT. We raised the hypothesis that the value of PET-CT SUVmax before SBRT may be an important predictive factor in disease control. None.

Case report Highly differentiated endometrial adenocarcinoma that collided with uterine cervical carcinosarcoma.

Uterine collision tumor is a rare pathological type composed of two or more malignant tumors. The components of these malignant tumors do not have histological mixing and are separated by the normal mesenchyme. Collision cancer is very rare, with uterine collision tumors being even rarer. Only a few cases have been reported in relation to uterine collision tumors. At present, there is no standard treatment guideline for uterine collision tumors, and a comprehensive treatment composed of surgery, radiotherapy, and chemotherapy is suggested. In this study, we report a 54-year-old female patient diagnosed with highly differentiated endometrial adenocarcinoma with cervical carcinosarcoma. The endometrial adenocarcinoma component invaded the deep myometrium (> 12 layer), involving the cervical glands and interstitium. The regional lymph node metastasis from endometrial adenocarcinoma was also detected. The patient underwent transabdominal tumor cytoreduction (total hysterectomy right adnexal resection greater omentectomy pelvic lymph node dissection para-aortic lymph node dissection) pelvic adhesion release. In addition, she has completed adjuvant radiotherapy and chemotherapy. After reviewing previous reports of collision tumors in different positions of the uterus, we found that collision tumors between the cervix and uterine body are very uncommon. In addition, we have not found any reports on the metastasis of sarcoid components, no matter what the composition is.

Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities.

Long noncoding RNAs (lncRNAs) are widely dysregulated in cancer, yet their functional roles in cancer hallmarks remain unclear. We employ pooled CRISPR deletion to perturb 831 lncRNAs detected in KRAS-mutant non-small cell lung cancer (NSCLC) and measure their contribution to proliferation, chemoresistance, and migration across two cell backgrounds. Integrative analysis of these data outperforms conventional dropout screens in identifying cancer genes while prioritizing disease-relevant lncRNAs with pleiotropic and background-independent roles. Altogether, 80 high-confidence oncogenic lncRNAs are active in NSCLC, which tend to be amplified and overexpressed in tumors. A follow-up antisense oligonucleotide (ASO) screen shortlisted two candidates,

The Cancer Testes Antigen, HORMAD1, is a Tumor-Specific Replication Fork Protection Factor.

Tumors frequently activate the expression of genes that are only otherwise required for meiosis. HORMAD1, which is essential for meiotic recombination in multiple species, is expressed in over 50% of human lung adenocarcinoma cells (LUAD). We previously found that HORMAD1 promotes DNA double strand break (DSB) repair in LUAD. Here, we report that HORMAD1 takes on an additional role in protecting genomic integrity. Specifically, we find HORMAD1 is critical for protecting stalled DNA replication forks in LUAD. Loss of HORMAD1 leads to nascent DNA degradation, an event which is mediated by the MRE11-DNA2-BLM pathway. Moreover, following exogenous induction of DNA replication stress, HORMAD1 deleted cells accumulate single stranded DNA (ssDNA). We find that these phenotypes are the result of a lack of RAD51 and BRCA2 loading onto stalled replication forks. Ultimately, loss of HORMAD1 leads to increased DSBs and chromosomal aberrations in response to replication stress. Collectively, our data support a model where HORMAD1 expression is selected to mitigate DNA replication stress, which would otherwise induce deleterious genomic instability.

Glucose deprivation promotes pseudo-hypoxia and de-differentiation in lung adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) induces cancer cell de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. We further show that this de-differentiated phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1α (HIF1α), triggering epithelial to mesenchymal transition. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to therapies targeting glucose metabolism.

Fully accessible fitness landscape of oncogene-negative lung adenocarcinoma.

Cancer genomes are almost invariably complex with genomic alterations cooperating during each step of carcinogenesis. In cancers that lack a single dominant oncogene mutation, cooperation between the inactivation of multiple tumor suppressor genes can drive tumor initiation and growth. Here, we shed light on how the sequential acquisition of genomic alterations generates oncogene-negative lung tumors. We couple tumor barcoding with combinatorial and multiplexed somatic genome editing to characterize the fitness landscapes of three tumor suppressor genes NF1, RASA1, and PTEN, the inactivation of which jointly drives oncogene-negative lung adenocarcinoma initiation and growth. The fitness landscape was surprisingly accessible, with each additional mutation leading to growth advantage. Furthermore, the fitness landscapes remained fully accessible across backgrounds with additional tumor suppressor mutations. These results suggest that while predicting cancer evolution will be challenging, acquiring the multiple alterations required for the growth of oncogene-negative tumors can be facilitated by the lack of constraints on mutational order.

Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation.

Xanthine dehydrogenase (XDH) is the rate-limiting enzyme in purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. The altered expression and activity of XDH are associated with the development and prognosis of multiple types of cancer, while its role in lung adenocarcinoma (LUAD) remains unknown. Herein, we demonstrated that XDH was highly expressed in LUAD and was significantly correlated with poor prognosis. Though inhibition of XDH displayed moderate effect on the viability of LUAD cells cultured in the complete medium, it significantly attenuated the survival of starved cells. Similar results were obtained in XDH-knockout cells. Nucleosides supplementation rescued the survival of starved LUAD cells upon XDH inhibition, while inhibition of purine nucleoside phosphorylase abrogated the process, indicating that nucleoside degradation is required for the XDH-mediated survival of LUAD cells. Accordingly, metabolic flux revealed that ribose derived from nucleoside fueled key carbon metabolic pathways to sustain the survival of starved LUAD cells. Mechanistically, down-regulation of XDH suppressed unfolded protein response (UPR) and autophagic flux in starved LUAD cells. Inhibition of XDH decreased the level of amino acids produced by autophagic degradation, which was accompanied with down-regulation of mTORC1 signaling. Supplementation of amino acids including glutamine or glutamate rescued the survival of starved LUAD cells upon knockout or inhibition of XDH. Finally, XDH inhibitors potentiated the anti-cancer activity of 2-deoxy-D-glucose that induced UPR andor autophagy in vitro and in vivo. In summary, XDH plays a crucial role in the survival of starved LUAD cells and targeting XDH may improve the efficacy of drugs that induce UPR and autophagy in the therapy of LUAD.

Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity.

Although current cancer immunotherapies that target PD-1PD-L1 immune checkpoint to reinvigorate exhausted T cells have achieved impressive clinical outcomes, only a small proportion of patients respond. New therapeutic targets are therefore needed to be identified to further unleash the anti-tumor potential of T cells and benefit more patients. Galectin-9 (Gal-9), initially identified as a ligand for TIM-3 to induce T cell death, acts as an immunosuppressive regulator in the tumor microenvironment (TME) but its potential as a therapeutic target remains largely elusive. Here we show that antibody neutralization of Gal-9, in combination with inhibition of Ataxia telangiectasia mutated (ATM), a kinase essential for DNA damage response (DDR), is a promising modality for cancer immunotherapy. Genetic depletion of ATM in tumors markedly potentiated anti-Gal-9 therapy in a syngeneic mouse model. Mechanistically, ATM inhibition greatly upregulated Gal-9 expression and secretion in a variety of human and murine tumor cells via the cGAS-STING-interferon β (IFNβ) innate immune pathway. Combination of Gal-9 inhibition with AZD1390, a selective ATM inhibitor currently evaluated in clinical trials, significantly suppressed tumor growth and prolonged survival in multiple syngeneic mouse models, including the poorly-immunogenic LLC lung tumors that do not respond to PD-1PD-L1 blockade, concomitant with increased T cell infiltration. These results reveal Gal-9 induction via STINGIFNβ signaling as an important mechanism mediating tumor immune escape that could be targeted for cancer immunotherapies, and unveil a novel anti-Gal-9-based combination strategy for cancer immunotherapies in a wide variety of malignancies, including those resistant to PD-1PD-L1 blockade.

Acquired resistance to EGFR-TKIs in NSCLC mediates epigenetic downregulation of MUC17 by facilitating NF-κB activity via UHRF1DNMT1 complex.

Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has brought significant benefits to non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, most patients eventually develop acquired resistance after treatment. This study investigated the epigenetic effects of mucin 17 (MUC17) in acquired drug-resistant cells of EGFR-TKIs. We found that GROR (gefitinibosimertinib-resistance) cells enhance genome-wide DNA hypermethylation, mainly in 5-UTR associated with multiple oncogenic pathways, in which GROR cells exerted a pro-oncogenic effect by downregulating mucin 17 (MUC17) expression in a dose- and time-dependent manner. Gefitinibosimertinib acquired resistance mediated down-regulation of MUC17 by promoting DNMT1UHRF1 complex-dependent promoter methylation, thereby activating NF-κB activity. MUC17 increased the generation of IκB-α and inhibit NF-κB activity by promoting the expression of MZF1.

Cytotoxic and pro-apoptotic effects of botanical drugs derived from the indigenous cultivated medicinal plant

Emerging role of non-coding RNAs in resistance to platinum-based anti-cancer agents in lung cancer.

Platinum-based drugs are the first line of therapeutics against many cancers, including lung cancer. Lung cancer is one of the leading causes of cancer-related death worldwide. Platinum-based agents target DNA and prevent replication, and transcription, leading to the inhibition of cell proliferation followed by cellular apoptosis. About twenty-three platinum-based drugs are under different stages of clinical trials, among cisplatin, carboplatin, and oxaliplatin are widely used for the treatment of various cancers. Among them, cisplatin is the most commonly used drug for cancer therapy, which binds with RNA, and hinders the cellular RNA process. However, long-term use of platinum-based drugs can cause different side effects and has been shown to develop chemoresistance, leading to poor clinical outcomes. Chemoresistance became an important challenge for cancer treatment. Platinum-based chemoresistance occurs due to the influence of intrinsic factors such as overexpression of multidrug resistance proteins, advancement of DNA repair mechanism, degradation, and deactivation of intracellular thiols. Recently, epigenetic modifications, especially non-coding RNAs (ncRNAs) mediated gene regulation, grasp the attention for reversing the sensitivity of platinum-based drugs due to their reversible nature without altering genome sequence. ncRNAs can also modulate the intrinsic and non-intrinsic mechanisms of resistance in lung cancer cells. Therefore, targeting ncRNAs could be an effective approach for developing novel therapeutics to overcome lung cancer chemoresistance. The current review article has discussed the role of ncRNA in chemoresistance and its underlying molecular mechanisms in human lung cancer.

Paraneoplastic stiff-person syndrome with lung cancer a case report and literature review.

Stiff person syndrome is a rare autoimmune disease of the central nervous system that manifests as stiffness and painful spasms of the trunk axis and lower limb muscles. Benzodiazepines are the first choice for the clinical treatment of the disease. We reported a case of SPS. The patient presented with stiffness and convulsions of lower limbs, weakness after convulsions, falling off easily, abdominal muscle stiffness, and painful spasms lasting for several minutes and alleviating spontaneously. This was caused or aggravated by fatigue or mental stimulation. Left stiffness and weakness of the muscle after relief was present. A chest-enhanced computed tomography scan (CT) suggested two large ground glass nodules in the upper lobe of the left lung. Biopsy pathology indicated the nodules as adenocarcinoma in situ. The patients symptoms were significantly relieved after treatment with clonazepam and diazepam combined with pregabalin. The clinical manifestations of SPS vary among patients. The symptoms of the disease are mild or severe. Early identification and treatment can improve the prognoses of these patients.

Application effect of low-dose spiral CT on pulmonary nodules and its diagnostic value for benign and malignant nodules.

This study was designed to determine the application effect of low-dose computed tomography (LDCT) on detecting pulmonary nodules (PNs) and its diagnostic value for benign and malignant pulmonary nodules. Data of 432 patients with PNs admitted to Julu County Hospital between March 2018 and June 2021 in were collected and analysed retrospectively. All patients underwent LDCT and conventional-dose spiral computed tomography (CT). The detection rate and image characteristics of the two methods were compared, and the image quality and radiation dose of the two diagnostic methods were also compared. No significant difference was found between LDCT and conventional-dose spiral CT in the detection rate of lung cancer (P>0.05). The area under the curve of conventional-dose CT was 0.932, with a specificity and sensitivity of 93.87% and 92.45%, and the area under the curve of LDCT was 0.902, with a specificity and sensitivity of 90.80% and 89.62%. The radiation dose consumed during LDCT was greatly less than that consumed by conventional-dose CT (P<0.05). Additionally, the two methods were not different in CT image quality and superior vena cava artifact (P>0.05). No notable difference was found between LDCT and conventional-dose CT in terms of the diagnosis rate of PNs in vascular aggregation sign, pleural indentation sign, lobulation sign and spiculation sign. LDCT can clearly show the typical images of early lung cancer, with less effective radiation dose, and can thus contribute to a high detection rate, so it is worth popularizing.

CASZ1 promotes migration, invasion, and metastasis of lung cancer cells by controlling expression of ITGAV.

CASZ1, a zinc finger transcription factor with two isoforms, is known to play important roles in cardiac and neural development. The abnormal expression of CASZ1 is also frequently found in a variety of tumors but has different effects on different tumors for example, it acts as a tumor suppressor in neuroblastoma but promotes cancer metastasis in ovarian cancer. However, the effect of CASZ1 in lung cancer, the most lethal cancer, remains unclear. Here, we found that the expression of CASZ1 in lung cancer is positively associated with cancer metastasis and poor prognosis. The overexpression of CASZ1b promotes lung cancer cell migration, invasion, and epithelial-mesenchymal transition and is associated with poor prognosis in lung cancer patients. The knockdown of CASZ1 resulted in the suppression of epithelial-mesenchymal transition, migration, and invasion of lung cancer cells and reduced metastasis in vivo. The results of an RNA-sequencing analysis of CASZ1-silenced cells showed that CASZ1 considerably affected the integrin-mediated pathways. CASZ1 bound to the

Synergistic activity of ABT-263 and ONC201TIC10 against solid tumor cell lines is associated with suppression of anti-apoptotic Mcl-1, BAG3, pAkt, and upregulation of pro-apoptotic Noxa and Bax cleavage during apoptosis.

A major underlying cause of the resistance of solid tumor cells to cancer therapy is the evasion of cell death following anti-cancer drug treatment. We explored the combination of TRAIL-inducing compound ONC201TIC10 and Bcl-xLBcl-2 inhibitor ABT-263 to target the extrinsic and intrinsic apoptotic pathways, respectively, in solid tumor cell lines (N 13) derived from different tissues (colon, prostate, lung, breast, ovary, bladder). We found an IC50 range of 0.83-20.10 μM for ONC201 and 0.06-14.75 μM for ABT-263 among the 13 cancer cell lines. We show that combination of ONC201 and ABT-263 produces a strong synergistic effect leading to tumor cell death, and that the combination is not toxic to human fibroblast cells. In OVCAR-3 ovarian cancer cells, 2.5 μM ONC201 and 1.25 μM ABT-263 yielded 37% and 27% inhibition of viability, respectively, while the combination of the two agents yielded 92% inhibition of viability, resulting in a high synergy score of 52 conversely, the same combination in the HFF-1 human fibroblast cells yielded 2.45% inhibition of viability and a synergy score of 6.92 (synergy scores were calculated using SynergyFinder scores greater than 10 are considered synergistic). We also found that the combination of these two agents resulted in synergistic caspase activation and PARP cleavage consistent with induction of apoptosis. Combination therapy-induced cell death correlated with decreased levels of Mcl-1, BAG3, pAkt, and upregulation of Noxa along with Bax cleavage during apoptosis at 48 hours, and ATF4, TRAIL, and DR5 induction at 24 hours. There was some heterogeneity in the cell lines with regard to these responses. Our data provide evidence for synergy from the combination of ONC201 and ABT-263 against human solid tumor cell lines associated with alterations in cell death and pro-survival mediators. The combination of ONC201 and ABT-263 merits further exploration

Establishing a Pulmonary Nodule Clinic Service for Early Diagnosis of Lung Cancer - Review of International Options and Considerations for Greece.

Early diagnosis of lung cancer in pulmonary nodules identified by computed tomography (CT) may be critical in reducing the epidemiological burden of the disease, particularly in countries where such a burden is considerably high and risk factors for lung cancer very prevalent. The establishment and operation of pulmonary nodule clinics (PNCs), ie, multidisciplinary services that watch and evaluate nodules found through deliberate screening efforts or as incidental findings, is increasingly becoming a key tool to implement such early-intervention, cancer-risk management policies elsewhere in the world. This review aims to research and present in a structured manner findings from published sources on options and considerations for setting up a PNC in a country such as Greece. These refer to the type of services a PNC would provide to optimize diagnosis of suspect pulmonary nodules, its structure and organization, including processes, human resources and technology infrastructure, its target audience, ie, who would be eligible to use its services, and the expected outcomes of its operation, in terms of a set of key performance indicators. Our review also revealed critical key success factors that should be considered when designing the introduction of a PNC in a health care setting, including optimal referral pathways, aligned clinical decision making and patient preferences and participationempowerment. Our findings may inform health care systems with a high lung cancer burden and no available PNC service on options and considerations before introducing such a service in their respective settings.

Cost-effectiveness of stereotactic body radiotherapy versus conventional radiotherapy for the treatment of surgically ineligible stage I non-small cell lung cancer in the Brazilian public health system.

The Brazilian public health system does not pay for the use of Stereotactic body radiotherapy (SBRT) due to its costs and the absence of cost-effectiveness analysis showing its benefit. The present study aims to evaluate whether the SBRT is a more cost-effective strategy than the conventional fractionated radiotherapy (CFRT) for surgically ineligible stage I non-small cell lung cancer (NSCLC) in the Brazilian public health system. Adopting the perspective of the Brazilian Unified Healthcare System (SUS) as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 75-years-old men with medically inoperable NSCLC after treatment with SBRT or CFRT. Transition probabilities and health states utilities were adapted from the literature. Costs were based on the public health system reimbursement values and simulated in the private sector. The SBRT strategy results in more quality-adjusted life-year (QALYs) and costs with an incremental cost-effectiveness ratio (ICER) of R$ 164.86 (U$ 65.16) per QALY and R$ 105 (U$ 41.50) per life-year gained (LYG). This strategy was cost-effective, considering a willingness-to-pay of R$ 25,000 (U$ 9,881.42) per QALY. The net monetary benefit (NMB) was approximately twice higher. The outcomes were confirmed with 92% of accuracy in the probabilistic sensitivity analysis. Using a threshold of R$25,000 per QALY, SBRT was more cost-effective than CFRT for NSCLC in a public health system of an upper-middle-income country. SBRT generates higher NMB than CFRT, which could open the opportunity to incorporate new technologies. Varian Medical Systems.

Investigating nanoplastics toxicity using advanced stem cell-based intestinal and lung

Plastic particles in the nanometer range-called nanoplastics-are environmental contaminants with growing public health concern. As plastic particles are present in water, soil, air and food, human exposure

Effects of dyadic-based physical activity intervention on cancer-related fatigue among cancer survivors A scoping review.

Cancer-related fatigue is one of the most common adverse reactions to cancer survivors, which has a significant impact on the daily life. As a traumatic event, cancer not only brings great physical and mental harm to patients, but also poses a threat to the physical and psychological health of caregivers. Current studies have shown that physical activity improves cancer-related fatigue in cancer survivors. And studies have suggested that dyadic interventions are more effective in improving patient outcomes and may also provide some benefits to caregivers. But the literature on the effects of dyadic-based physical activity on improving cancer-related fatigue has not been synthesized. This scoping review described the scope and impact of studies on cancer-related fatigue with dyadic-based physical activity interventions. Six databases which is PubMed, Cochrane Library, Web of Science, Embase, CINAHL and Medline were searched for all studies of dyadic-based physical activity interventions with outcome measures including cancer-related fatigue published since the inception of the databases through May 2022. The search strategy was developed based on PICO principles. This article includes 6 pre and post-test designs and 2 randomized controlled trial design. The majority of participants were survivors with breast and lung cancer. The overall results showed that the effectiveness of dyadic-based physical activity interventions in improving cancer-related fatigue was unsatisfactory. This scoping review suggests that current dyadic-based physical activity interventions are not well-researched among cancer survivors. In the future, more high-quality studies with more sophisticated and rigorous interventions are needed.

A case of disseminated intravascular coagulation following tumour lysis syndrome due to small cell carcinoma of the lung.

A 64-year-old man was diagnosed with small cell lung cancer (SCLC) with multiple bone and liver metastases and bone marrow metastases. Spontaneous tumour lysis syndrome (TLS) was observed before starting chemotherapy with carboplatin, etoposide, and atezolizumab. The tumour further collapsed, and the patient developed disseminated intravascular coagulation (DIC) on day 4 of chemotherapy. The patient was successfully treated with intravenous hydration and rasburicase for TLS and subcutaneous unfractionated heparin for DIC. A large amount of tissue factor may be released in TLS, which could induce DIC. However, to the best of our knowledge, this is the first report of DIC following TLS in a case of SCLC. DIC following TLS in SCLC is a rare but life-threatening oncologic complication. Therefore, clinicians should be aware of this possibility when treating patients with advanced SCLC.

Lung Diseases Detection Using Various Deep Learning Algorithms.

The primary objective of this proposed framework work is to detect and classify various lung diseases such as pneumonia, tuberculosis, and lung cancer from standard X-ray images and Computerized Tomography (CT) scan images with the help of volume datasets. We implemented three deep learning models namely Sequential, Functional Transfer models and trained them on open-source training datasets. To augment the patients treatment, deep learning techniques are promising and successful domains that extend the machine learning domain where CNNs are trained to extract features and offers great potential from datasets of images in biomedical application. Our primary aim is to validate our models as a new direction to address the problem on the datasets and then to compare their performance with other existing models. Our models were able to reach higher levels of accuracy for possible solutions and provide effectiveness to humankind for faster detection of diseases and serve as best performing models. The conventional networks have poor performance for tilted, rotated, and other abnormal orientation and have poor learning framework. The results demonstrated that the proposed framework with a sequential model outperforms other existing methods in terms of an F1 score of 98.55%, accuracy of 98.43%, recall of 96.33% for pneumonia and for tuberculosis F1 score of 97.99%, accuracy of 99.4%, and recall of 98.88%. In addition, the functional model for cancer outperformed with an accuracy of 99.9% and specificity of 99.89% and paves way to less number of trained parameters, leading to less computational overhead and less expensive than existing pretrained models. In our work, we implemented a state-of-the art CNN with various models to classify lung diseases accurately.

PSMA1, a Poor Prognostic Factor, Promotes Tumor Growth in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) has a poor clinical prognosis and lacks effective targeted therapy. This study is aimed at investigating the role of PSMA1 (proteasome subunit alpha type-1) in LUSC. The differential expression genes (DEGs) in LUSC were retrieved from The Cancer Genome Atlas (TCGA) by edgR algorithm and by limma R package. Then, the relationship between genes and overall survival (OS) was explored by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox (multi-Cox) regression. Next, the PSMA1 expression in tissues of LUSC was detected by IHC, qRT-PCR, and western blot (WB). Moreover, the effects of PSMA1 on the proliferation and viability of LUSC cell were explored by cell counting kit 8 (CCK-8) assays, colony formation assays, and flow cytometry (FCM) analysis. All 4421 DEGs were screened by TCGA database, and 26 genes associated with OS were selected by multi-Cox. Based on TCGA database, PSMA1 was highly expressed in tissues of LUSC patients, and OS and FP of patients with PSMA1 overexpression were significantly lower than those of patients with low PSMA1 expression. Furthermore, PSMA1 knockdown significantly decreased the proliferation of LUSC cells and promoted the apoptosis of LUSC cells, and these effects were reversed by PSMA1 overexpression. The results of this project supported that PSMA1 might be a critical gene regulating the development of LUSC and has the potential to be explored as a prognostic biomarker of LUSC.

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer.

Immune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy. The present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLRNLRPLR and increased MLRNLRPLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed. A total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P0.007) and multivariate (P0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P0.001) and prolonged PFS in univariate analysis (P0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions. Decreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

Resistance to immune checkpoint inhibitors in advanced lung cancer Clinical characteristics, potential prognostic factors and next strategy.

Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical benefit in cancer immunotherapy and are rapidly transforming the practice of advanced lung cancer. However, resistance routinely develops in patients treated with ICIs. We conducted this retrospective study to provide an overview on clinical characteristics of ICI resistance, optimal treatment beyond disease progression after prior exposure to immunotherapy, as well as potential prognostic factors of such resistance. 190 patients diagnosed with unresectable lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)anti-programmed cell death-ligand 1(PD-L1) at any treatment line at Zhongshan Hospital Fudan University between Sep 2017 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed. Levels of plasma cytokines were evaluated for the prognostic value of ICI resistance. We found that EGFRALKROS1 mutation and receiving ICI treatment as second-line therapy were risk factors associated with ICI resistance. Patients with bone metastasis at baseline had a significantly shorter PFS1 time when receiving initial ICI treatment. Whether or not patients with oligo-progression received local treatment seemed to have no significant effect on PFS2 time. Systemic therapies including chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. TNF, IL-6 and IL-8 were significantly elevated when ICI resistance. Lower plasma TNF level and higher plasma IL-8 level seemed to be significantly associated with ICI resistance. A nomogram was established to prognosis the clinical outcome of patients treated with ICIs. Patients with EGFRALKROS1 mutation, or those receiving ICI treatment as second-line therapy had higher risk of ICI resistance. Patients with bone metastasis had poor prognosis during immunotherapy. For those patients with oligo-progression after ICI resistance, combination with local treatment did not lead to a significantly longer PFS2 time. Chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. Levels of plasma cytokines including TNF, IL-6 and IL-8 were associated with ICI resistance.

Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients A meta-analysis.

Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiotas diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis. In this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis. Forty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR1.37 95%CI, 1.23-1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR1.28 95%CI, 1.15-1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for patients treated with anti PD-1 (OS) and anti PD-L1 (OS and PFS) immunotherapies when administered in non-first line and when PPI was received as baseline treatment or in 60 days before ICI initiation. PPI and ICI use also showed the worst OS and PFS for patients from Europe and Asia. This meta-analysis suggests that PPI treatment leads to significantly worse outcomes in advanced cancer patients treated by ICIs in terms of PFS and OS.

By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs. The most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells. A total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate. The eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD.

Immunotherapy with immune checkpoint inhibitors and predictive biomarkers in malignant mesothelioma Work still in progress.

Malignant mesothelioma (MM) is a rare and aggressive neoplasm, usually associated with a poor prognosis (5 years survival rate <10%). For unresectable disease, platinum and pemetrexed chemotherapy has been the only standard of care in first line for more than two decades, while no standard treatments have been approved in subsequent lines. Recently, immunotherapy has revolutionized the therapeutic landscape of MM. In fact, the combination of ipilimumab plus nivolumab has been approved in first line setting. Moreover, immune checkpoint inhibitors (ICIs) showed promising results also in second-third line setting after platinum-based chemotherapy. Unfortunately, approximately 20% of patients are primary refractory to ICIs and there is an urgent need for reliable biomarkers to improve patients selection. Several biological and molecular features have been studied for this goal. In particular, histological subtype (recognized as prognostic factor for MM and predictive factor for chemotherapy response), programmed death ligand 1 (PD-L1) expression, and tumor mutational burden (widely hypothesized as predictive biomarkers for ICIs in several solid tumors) have been evaluated, but with unconclusive results. On the other hand, the deep analysis of tumor infiltrating microenvironment and the improvement in genomic profiling techniques has led to a better knowledge of several mechanisms underlying the MM biology and a greater or poorer immune activation. Consequentially, several potential biomarkers predictive of response to immunotherapy in patients with MM have been identified, also if all these elements need to be further investigated and prospectively validated. In this paper, the main evidences about clinical efficacy of ICIs in MM and the literature data about the most promising predictive biomarkers to immunotherapy are reviewed.

T lymphocyte cell A pivotal player in lung cancer.

Lung cancer is responsible for the leading cause of cancer-related death worldwide, which lacks effective therapies. In recent years, accumulating evidence on the understanding of the antitumor activity of the immune system has demonstrated that immunotherapy is one of the powerful alternatives in lung cancer therapy. T cells are the core of cellular immunotherapy, which are critical for tumorigenesis and the treatment of lung cancer. Based on the different expressions of surface molecules and functional points, T cells can be subdivided into regulatory T cells, T helper cells, cytotoxic T lymphocytes, and other unconventional T cells, including γδ T cells, nature killer T cells and mucosal-associated invariant T cells. Advances in our understanding of T cells functional mechanism will lead to a number of clinical trials on the discovery and development of new treatment strategies. Thus, we summarize the biological functions and regulations of T cells on tumorigenesis, progression, metastasis, and prognosis in lung cancer. Furthermore, we discuss the current advancements of technologies and potentials of T-cell-oriented therapeutic targets for lung cancer.

Transport-based morphometry of nuclear structures of digital pathology images in cancers.

Alterations in nuclear morphology are useful adjuncts and even diagnostic tools used by pathologists in the diagnosis and grading of many tumors, particularly malignant tumors. Large datasets such as TCGA and the Human Protein Atlas, in combination with emerging machine learning and statistical modeling methods, such as feature extraction and deep learning techniques, can be used to extract meaningful knowledge from images of nuclei, particularly from cancerous tumors. Here we describe a new technique based on the mathematics of optimal transport for modeling the information content related to nuclear chromatin structure directly from imaging data. In contrast to other techniques, our method represents the entire information content of each nucleus relative to a template nucleus using a transport-based morphometry (TBM) framework. We demonstrate the model is robust to different staining patterns and imaging protocols, and can be used to discover meaningful and interpretable information within and across datasets and cancer types. In particular, we demonstrate morphological differences capable of distinguishing nuclear features along the spectrum from benign to malignant categories of tumors across different cancer tissue types, including tumors derived from liver parenchyma, thyroid gland, lung mesothelium, and skin epithelium. We believe these proof of concept calculations demonstrate that the TBM framework can provide the quantitative measurements necessary for performing meaningful comparisons across a wide range of datasets and cancer types that can potentially enable numerous cancer studies, technologies, and clinical applications and help elevate the role of nuclear morphometry into a more quantitative science. The source codes implementing our method is available at httpsgithub.comrohdelabnuclearmorphometry.

A Heuristic Machine Learning-Based Optimization Technique to Predict Lung Cancer Patient Survival.

Cancer has been a significant threat to human health and well-being, posing the biggest obstacle in the history of human sickness. The high death rate in cancer patients is primarily due to the complexity of the disease and the wide range of clinical outcomes. Increasing the accuracy of the prediction is equally crucial as predicting the survival rate of cancer patients, which has become a key issue of cancer research. Many models have been suggested at the moment. However, most of them simply use single genetic data or clinical data to construct prediction models for cancer survival. There is a lot of emphasis in present survival studies on determining whether or not a patient will survive five years. The personal issue of how long a lung cancer patient will survive remains unanswered. The proposed technique Naive Bayes and SSA is estimating the overall survival time with lung cancer. Two machine learning challenges are derived from a single customized query. To begin with, determining whether a patient will survive for more than five years is a simple binary question. The second step is to develop a five-year survival model using regression analysis. When asked to forecast how long a lung cancer patient would survive within five years, the mean absolute error (MAE) of this techniques predictions is accurate within a month. Several biomarker genes have been associated with lung cancers. The accuracy, recall, and precision achieved from this algorithm are 98.78%, 98.4%, and 98.6%, respectively.

Novel nutritional indicator as predictors among subtypes of lung cancer in diagnosis.

Lung cancer is a serious global health concern, and its subtypes are closely linked to lifestyle and dietary habits. Recent research has suggested that malnutrition, over-nutrition, electrolytes, and granulocytes have an effect on the development of cancer. This study investigated the impact of combining patient nutritional indicators, electrolytes, and granulocytes as comprehensive predictors for lung cancer treatment outcomes, and applied a machine learning algorithm to predict lung cancer. 6,336 blood samples were collected from lung cancer patients classified as lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and small cell lung cancer (SCLC). 2,191 healthy individuals were used as controls to compare the differences in nutritional indicators, electrolytes and granulocytes among different subtypes of lung cancer, respectively. Our results demonstrated significant differences between men and women in healthy people and NSCLC, but no significant difference between men and women in SCLC patients. The relationship between indicators is basically that the range of indicators for cancer patients is wider, including healthy population indicators. In the process of predicting lung cancer through nutritional indicators by machine learning, the AUC of the random forest model was as high as 93.5%, with a sensitivity of 75.9% and specificity of 96.5%. This study supports the feasibility and accuracy of nutritional indicators in predicting lung cancer through the random forest model. The successful implementation of this novel prediction method could guide clinicians in providing both effective diagnostics and treatment of lung cancers.

Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients.

The third-generation epidermal growth factor receptor ( A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues andor blood samples. The results showed that the sensitivity and the specificity of Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of

Tumor regression rate, PD-L1 expression, pembrolizumabnab-paclitaxel-based regimens, squamous cell carcinoma, and comorbidities were independently associated with efficacy of neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

Neoadjuvant chemoimmunotherapy (NCIO) is more effective than neoadjuvant immunotherapy alone for pathological response in non-small cell lung cancer (NSCLC) patients, but the processes for determining patient suitability for its implementation are not clear. We aimed to identify the most relevant factors and build a convenient model to select NSCLC patients who would benefit most from NCIO. A total of 101 eligible stage IIB-IIIC NSCLC patients were included. After NCIO, all patients successfully underwent surgical resection. A total of 46.53% (47101) of patients achieved pathological complete response (pCR), and 70.30% (71101) achieved major pathologic response (MPR). Tumor regression rate (adjusted odds ratio OR 12.33), PD-L1 expression (adjusted odds ratio (OR) 9.66), pembrolizumabnab-paclitaxel-based regimens (adjusted OR 4.92), and comorbidities (adjusted OR 0.16) were independently associated with pCR rate (all The tumor regression rate, PD-L1 expression, pembrolizumabnab-paclitaxel-based regimens, presence of squamous cell carcinoma, and comorbidities were the main influential factors for incidence of pCRMPR in patients with stage IIB-IIIC NSCLC in the present study. Through predictive models, we can predict who will benefit most from NCIO prior to the emergence of clinical outcomes in locally advanced NSCLC.

What is the appropriate first lymph node in the era of segmentectomy for non-small cell lung cancer

The place of segmentectomy in the management of lung cancer is shifting following the inspiring results of the Japanese JCOG0802 trial. I n this study, authors suggested that performing segmentectomy would require in an optimal way an intraoperative confirmation of pN0 tumor with a frozen section. Our objective was to determine whether the proposed technique, i.e. adjacent lymph node analysis, is consistent with the results of our study on sentinel lymph node (SLN) detection using fluorescence. This is a retrospective, observational, single center study. Eighty-one patients with suspected localized stage NSCLC (IA to IIA) were included between December 2020 and March 2022. All patients received an intra-operative injection of indocyanine green (ICG) directly in the peritumoral area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed by using an infrared fluorescence camera. In our cohort, SLN was identified in 6081 patients (74.1%). In 1560 patients with identified SLN (25%), NIR-guided SLN was concordant with the suggestions of JCOG0802 study. A retrospective SLN pathological analysis was performed in 43 patients60 cases with identified SLN (71.2%), including 37 cases of malignant disease. Occult micro-metastases were found in 4 patients out of 37 SLN analyzed, leading to a 10.8% upstaging with NIR-guided SLN analysis. At the time of segmentectomies, ICG technique allowed the identification of the SLN in a high percent of cases and in some areas usually out of the recommended stations for lymph node dissection.

Screening versus multidimensional assessment of symptoms and psychosocial distress in cancer patients from the time of incurability.

Previous symptom prevalence studies show a diverse spectrum of symptoms and a large diversity in symptom intensities in patients being just diagnosed as having incurable cancer. It is unclear, how physical symptoms and psychosocial burden should be recorded in order to determine the variable need for palliative care and further support. Therefore, we compared two different strategies for detecting physical symptoms and psychosocial burden of patients with newly diagnosed incurable cancer and their effects on the further course of the disease. SCREBEL is a controlled, randomized, non-blinded, longitudinal study of the research network of the Palliative Medicine Working Group (APM) of the German Cancer Society (DKG). We compared a less complex repeated brief 504 patients were included in the study. 262 patients were lost to follow-up, including 155 fatalities. There were no significant differences between the low-threshold A comprehensive, multidimensional

A population-based study of synchronous distant metastases and prognosis in patients with PDAC at initial diagnosis.

Cancer of the pancreas is a life-threatening condition and has a high distant metastasis (DM) rate of over 50% at diagnosis. Therefore, this study aimed to determine whether patterns of distant metastases correlated with prognosis in pancreatic ductal adenocarcinoma (PDAC) with metastatic spread, and build a novel nomogram capable of predicting the 6, 12, 18-month survival rate with high accuracy. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for cases of PDAC with DM. Kaplan-Meier analysis, log-rank tests and Cox-regression proportional hazards model were used to assess the impact of site and number of DM on the cancer-specific survival (CSS) and over survival (OS). A total of 2709 patients with DM were randomly assigned to the training group and validation group in a 73 ratio. A nomogram was constructed by the dependent risk factors which were determined by multivariate Cox-regression analysis. An assessment of the discrimination and ability of the prediction model was made by measuring AUC, C-index, calibration curve and decision curve analysis (DCA). In addition, we collected 98 patients with distant metastases at the time of initial diagnosis from Ningbo University Affiliated LiHuili Hospital to verify the efficacy of the prediction model. There was a highest incidence of liver metastases from pancreatic cancer (2387,74.36%), followed by lung (625,19.47%), bone (190,5.92%), and brain (8,0.25%). The prognosis of liver metastases differed from that of lung metastases, and the presence of multiple organ metastases was associated with poorer prognosis. According to univariate and multivariate Cox-regression analyses, seven factors (i.e., diagnosis age, tumor location, grade of tumor differentiation, T-stage, receipt of surgery, receipt of chemotherapy status, presence of multiple organ metastases) were included in our nomogram model. In internal and external validation, the ROC curves, C-index, calibration curves and DCA were calculated, which confirmed that this nomogram can precisely predict prognosis of PDAC with DM. Metastatic PDAC patients with liver metastases tended to have a worse prognosis than those with lung metastases. The number of DM had significant effect on the overall survival rate of metastatic PDAC. This study had a high prediction accuracy, which was helpful clinicians to analyze the prognosis of PDAC with DM and implement individualized diagnosis and treatment.

Adjuvant immunotherapy in early-stage resectable non-small cell lung cancer A new milestone.

Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4-5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.

Adaptive hypofractionted and stereotactic body radiotherapy for lung tumors with real-time MRI guidance.

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gatingtracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively.

Identification of thioredoxin-1 as a biomarker of lung cancer and evaluation of its prognostic value based on bioinformatics analysis.

Thioredoxin-1 (TXN), a redox balance factor, plays an essential role in oxidative stress and has been shown to act as a potential contributor to various cancers. This study evaluated the role of TXN in lung cancer by bioinformatics analyses. Genes differentially expressed in lung cancer and oxidative stress related genes were obtained from The Cancer Genome Atlas, Gene Expression Omnibus and GeneCards databases. Following identification of TXN as an optimal differentially expressed gene by bioinformatics, the prognostic value of TXN in lung cancer was evaluated by univariatemultivariate Cox regression and Kaplan-Meier survival analyses, with validation by receiver operation characteristic curve analysis. The association between TXN expression and lung cancer was verified by immunohistochemical analysis of the Human Protein Atlas database, as well as by western blotting and qPCR. Cell proliferation was determined by cell counting kit-8 after changing TXN expression using lentiviral transfection. Twenty differentially expressed oxidative stress genes were identified. Differential expression analysis identified five genes ( High expression of TXN plays an important role in lung cancer development and prognosis. Because it is a prospective prognostic factor, targeting TXN may have clinical benefits in the treatment of lung cancer.

KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma.

The incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC. The mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1. KNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes. KNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC.

The efficacy of neoadjuvant

Epidermal growth factor receptor tyrosine kinase inhibitors ( Between 2013 and 2020, A total of 43 patients were divided into T-S-Arm (n 21) and T-Arm (n 22). Patients were well-balanced between the two arms. The majority of patients were female (n 25, 58.1%), non-smokers (n 35, 81.4%), first-generation of For stage IIIB

STK11 loss and SMARCB1 deficiency mutation in a dedifferentiated lung cancer patient present response to neo-adjuvant treatment with pembrolizumab and platinum doublet A case report.

Cancers harboring serine threonine kinase (STK11) alteration or SWISNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily B, member 1 (SMARCB1) mutation are conventionally considered as treatment-refractory to immune checkpoint inhibitors or chemotherapy, respectively. However in the present report, we demonstrated a case of dedifferentiated non-small cell lung cancer, characterized by STK11 loss (due to promoter loss) mutation co-mutated with SMARCB1 deficiency mutation, has achieved significantly partial response to neo-adjuvant treatment with pembrolizumab and platinum doublet regimen. Our case highlighted that either STK11 loss, or SMARCB1 deficiency mutation, might not be used to select patients for PD-(L)1 blockade therapy or chemotherapy, respectively. SKT11 loss accompanied with SMARCB1 deficiency mutation may benefit from immunotherapy combined with chemotherapy.