Datasets:

Gaborandi

/

Lung_Cancer_pubmed_abstracts

like 1

Bevacizumab biosimilar candidate TAB008 compared to Avastin

Bevacizumab (Avastin In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (11) into TAB008 or Avastin A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin TAB008 is similar to Avastin ClinicalTrials.gov number NCT05427305.

Effect of antimicrobial therapy on progression-free survival of immunotherapy and chemo-immunotherapy in patients with non-small cell lung cancer.

The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There are some data that the effect of CPI therapy is impaired by antimicrobial therapy (AMT). Little is known about the influence of AMT on CIT. We retrospectively analysed 114 patients (age 68 ± 8.5 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (CarboplatinPemetrexedPembrolizumab, CarboplatinPaclitaxelPembrolizumab). We registered patients characteristics including presence and timing of AMT. Group 1 consisted of 42 patients with AMT in the month before CPI or CIT, group 2 were 49 patients with AMT during CPI or CIT, and group 3 were 64 patients without AMT and CPI or CIT. Group 1-3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.02 vs. 4 ± 1.02 months, p 0.002, 95% CI 1.88-9). In patients, who were treated with CIT, there was no difference in PFS in those with or without AMT in the month before therapy (10 ± 2.5 vs. 6 ± 1.2 months, p 0.7). Interestingly, AMT during CIT or CPI therapy showed no effect on PFS. In a real-life setting, we found that AMT reduces PFS when given in the month before CIT therapy. AMT before or during CIT does not seem to influence PFS. As a consequence, AMT before start of therapy might be a factor that could lead to a preference of CIT instead of CPI in NSCLC stage IV patients.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyrimidinone Derivatives as Potential Anticancer Agents and Tubulin Polymerization Inhibitors.

The severity and prevalence of cancer in modern time are a huge global health burden. Continuous efforts are being made toward the development of newer therapeutic candidates to treat and manage this ailment. The dihydropyrimidinone scaffold is one of the key nuclei that have been highly explored and investigated against cancer. It has the potential to combat the consequences of cancer by interacting with several biological targets. Tubulin polymerization inhibition is one such strategy to prevent the progression of cancer. In the presented work, we have synthesized a series of sixteen dihydropyrimidinone derivatives by following a rational drug design. The synthesized compounds have been characterized by

Advances in Understanding the Roles of Mesenchymal Stem Cells in Lung Cancer.

Lung cancer is the most common and deadliest type of cancer worldwide. Research concerning lung cancer has made considerable progress in recent decades, but lung cancer remains the leading cause of malignancy-related mortality rate. Mesenchymal stem cells (MSCs) mainly exist in fat, umbilical cord blood, bone marrow, bone, and muscle. MSCs are a primary component of the tumor microenvironment (TME). Recent studies have shown that MSCs have roles in lung cancer-related proliferation, invasion, migration, and angiogenesis, but the underlying mechanisms are poorly understood. Because MSCs can migrate to the TME, there is increasing attention toward the use of MSCs in drugs or gene vectors for cancer treatment. This review summarizes the roles and effects of MSCs in lung cancer, while addressing clinical applications of MSCs in lung cancer treatment.

Switching of the Polarity-Sensitive Aggregation Pattern of a Thiosemicarbazone-Based Anticancer Luminophore and Its Involvement in Cellular Apoptosis of the Human Lung Cancer Cell Line.

Elucidation of the photophysical and biochemical properties of small molecules can facilitate their applications as prospective therapeutic imaging (theragnostic) agents. Herein, we demonstrate the luminescence behavior of a strategically designed potential therapeutic thiosemicarbazone derivative, (

Analysis of influencing factors of postoperative myasthenic crisis in 564 patients with myasthenia gravis in a single center.

To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period. A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymomathymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded. Osserman-stages IIB III IV (odds ratio OR 16.091, 95% confidence interval CI 5.170-50.076, p value < 0.001), the dosage of pyridostigmine bromide more than 240 mg (OR 6.462, 95% CI 3.110-13.427, p value < 0.001), ASA score 2 and 3 (OR 3.203, 95% CI 1.461-7.020, p value 0.004), low diffusion lung capacity for carbon monoxide (DLCO%) (OR 0.981, 95% CI 0.963-1.000 p value 0.049), and blood loss greater than 1000 ml (OR 16.590, 95% CI 1.911-144.011, p value 0.011) were independent risk factors for myasthenic crisis. Patients with poor Osserman stages, higher preoperative dosage of pyridostigmine bromide, higher ASA score, poor pulmonary function (low DLCO%), and more intraoperative bleeding should be highly vigilant for the occurrence of postoperative myasthenic crisis.

Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling.

Understanding the regulatory mechanisms of PD-L1 expression in tumors provides key clues for improving immune checkpoint blockade efficacy or developing novel oncoimmunotherapy. Here, we showed that the FDA-approved sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin dramatically suppressed PD-L1 expression and enhanced T cell-mediated cytotoxicity. Mechanistic study revealed that SGLT2 colocalized with PD-L1 at the plasma membrane and recycling endosomes and thereby prevented PD-L1 from proteasome-mediated degradation. Canagliflozin disturbed the physical interaction between SGLT2 and PD-L1 and subsequently allowed the recognition of PD-L1 by Cullin3SPOP E3 ligase, which triggered the ubiquitination and proteasome-mediated degradation of PD-L1. In mouse models and humanized immune-transformation models, either canagliflozin treatment or SGLT2 silencing significantly reduced PD-L1 expression and limited tumor progression - to a level equal to the PD-1 mAb - which was correlated with an increase in the activity of antitumor cytotoxic T cells. Notably, prolonged progression-free survival and overall survival curves were observed in the group of PD-1 mAb-treated patients with non-small cell lung cancer with high expression of SGLT2. Therefore, our study identifies a regulator of cell surface PD-L1, provides a ready-to-use small-molecule drug for PD-L1 degradation, and highlights a potential therapeutic target to overcome immune evasion by tumor cells.

Update on Adjuvant Treatment in Resectable Non-Small Cell Lung Cancer and Potential Biomarkers Predicting Postoperative Relapse.

A significant proportion of patients with non-small cell lung cancer (NSCLC) is diagnosed in the early and resectable stage. Despite the use of platinum-based adjuvant chemotherapy, there was only a marginal increase in overall survival and a 15% decrease in relapse. With the advents of immunotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), the landscape of adjuvant treatment in completely resectable NSCLC is changing. Postoperative radiotherapy can be beneficial to patients who underwent surgical resection in certain clinical settings. In addition, new biomarkers that predict efficacy of EGFR TKI and immunotherapy as adjuvant treatment are also necessary. In this review, recent updates in adjuvant treatment in resectable NSCLC were briefly explained.

Clinical characteristics of immune checkpoint inhibitor-related type 1 diabetes mellitus.

The clinical data of ten patients with immune checkpoint inhibitor-related type 1 diabetes mellitus were enrolled in the Second Xiangya Hospital of Central South University from January 2020 to October 2022 including 9 males and 1 female, with an average age of (57±8) years. There were 7 cases of fulminant type 1 diabetes and 3 cases of acute type 1 diabetes. Among the 10 patients, there were 5 cases of lung cancer, 2 cases of esophageal cancer, 1 case of gastric carcinom, 1 case of renal cell carcinoma, and 1 case of nasopharyngeal cancer. The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. Among them, 8 patients had diabetic ketoacidosis (DKA), 1 patient had ketosis, and 1 case had no ketosis at onset 9 patients were negative for diabetes-related antibodies, and 1 patient was positive. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy. 收集2020年1月至2022年10月于中南大学湘雅二医院就诊的10例免疫检查点抑制剂相关1型糖尿病患者的临床资料，男9例，女1例，年龄（57±8）岁，其中暴发性1型糖尿病7例，急性1型糖尿病3例。10例中肺癌5例，食管癌2例，胃癌、肾细胞癌、鼻咽癌各1例。10例患者所使用的药物均为程序性细胞死亡受体1抑制剂，其中派姆单抗5例，信迪利单抗3例，替雷珠单抗1例，特瑞普利单抗1例。其中8例以糖尿病酮症酸中毒起病，1例以糖尿病酮症起病，1例起病时无酮症；9例胰岛相关抗体阴性，另1例阳性。10例均获得成功救治，且依赖胰岛素治疗。免疫检查点抑制剂可导致1型糖尿病，包括暴发性1型糖尿病，多以糖尿病酮症酸中毒起病，需要早期识别，积极胰岛素治疗。.

Challenges of the eighth edition of the American Joint Committee on Cancer staging system for pathologists focusing on early stage lung adenocarcinoma.

The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The latter is based on the size of stromal invasion. It is quite challenging for lung pathologists. All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed. In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow-up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p < 0.0001). In addition, 95.2%, 100%, and 77.5% of pTis, pT1a(mi), and pT1a tumors, respectively, had tumor sizes ≤1.0 cm by gross examination. All pTis, pT1a(mi), and pT1a tumors exhibited only lepidic, acinar, or papillary patterns histologically. This study demonstrated excellent survival for lung ADC patients with pTis, pT1a(mi), and pT1a tumors when completely excised. To reduce the inconsistencies between pathologists, staging lung ADC with tumors of ≤1 cm in size grossly as pTis, pT1a(mi), or pT1a may not be necessary when the tumors exhibit only lepidic, acinar, or papillary histological patterns. A larger cohort study with sufficient follow-up data is necessary to support this proposal.

Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer A systematic review and network meta-analysis.

The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR-TKIs) and chemotherapy with EGFR-TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). This network meta-analysis was performed to evaluate the differences between them. We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta-analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR-TKIs and chemotherapy plus EGFR-TKIs. Pooled data of included studies were demonstrated that chemotherapy plus EGFR-TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR-TKIs in patients with EGFR mutated NSCLC (RR 1.1, 95% CI 1.0-1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS HR 1.0, 95% CI 0.74-1.6 OS HR 0.78, 95% CI 0.45-1.5 DCR RR 1.0, 95% CI 0.94-1.1). The common treatment-related AEs in the two groups were relatively manageable. Based on the efficacy and safety, the combination of chemotherapy with EGFR-TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation.

The development of a tumor-associated autoantibodies panel to predict clinical outcomes for immune checkpoint inhibitor-based treatment in patients with advanced non-small-cell lung cancer.

Immune checkpoint inhibitors (ICIs) have become one important therapeutic strategy for advanced non-small-cell lung cancer (NSCLC). It remains imperative to identify reliable and convenient biomarkers to predict both the efficacy and toxicity of immunotherapy, and tumor-associated autoantibodies (TAAbs) are recognized as one of the promising candidates for this. This study enrolled 97 advanced NSCLC patients with ICI-based immunotherapy treatment, who were divided into a training cohort (n 48) and a validation cohort (n 49), and measured for the serum level of 35 TAAbs. According to the statistical association between the serum positivity and clinical outcome of each TAAb in the training cohort, a TAAb panel was developed to predict the progression-free survival (PFS), and further examined in the validation cohort and in different subgroups. Similarly, another TAAb panel was derived to predict the occurrence of immune-related adverse events (irAEs). In the training cohort, a 7-TAAb panel composed of p53, CAGE, MAGEA4, GAGE7, UTP14A, IMP2, and PSMC1 TAAbs was derived to predict PFS (median PFS mPFS 9.9 vs. 4.3 months, p 0.043). The statistical association between the panel positivity and longer PFS was confirmed in the validation cohort (mPFS 11.1 vs. 4.8 months, p 0.015) and in different subgroups of patients. Moreover, another 4-TAAb panel of BRCA2, MAGEA4, ZNF768, and PARP TAAbs was developed to predict the occurrence of irAEs, showing higher risk in panel-positive patients (71.43% vs. 28.91%, p 0.0046). Collectively, our study developed and validated two TAAb panels as valuable prognostic biomarkers for immunotherapy.

A stapled chromogranin A-derived peptide homes in on tumors that express αvβ6 or αvβ8 integrins.

Histopathological, ultrastructural, and biochemical traits of apoptosis induced by peroxisomicine A1 (toxin T-514) from

Peroxisomicine A1 (PA1) is a toxin isolated from the

Hsacirc0000520 Promotes Non-Small Cell Lung Cancer Progression through the miR-1258AKT3 Axis.

There are several previous studies suggesting that circular RNAs (circRNAs) are involved in tumorigenesis of non-small cell lung cancer (NSCLC). Nevertheless, the role of circRNA0000520 (circ0000520) in this disease has not yet been studied. circ0000520, microRNA (miR)-1258, and AKT serinethreonine kinase 3 (AKT3) mRNA expression levels were detected by qPCR. CCK-8, EdU, and Transwell assays were utilized to detect NSCLC cells malignant biological behaviors. The targeted relationship between miR-1258 and AKT3 3-UTR or circ0000520 was verified through the dual-luciferase reporter gene assay. Western blotting was utilized to measure the AKT3 expression after circ0000520 and miR-1258 were selectively regulated. circ0000520 was upregulated in NSCLC. Highly expressed circ0000520 is linked to the NSCLC patients advanced TNM stage and lymph node metastasis. circ0000520 overexpression facilitated NSCLC cell growth, migration, and invasion. miR-1258 was identified as the downstream target of circ0000520. miR-1258 overexpression weakened the effect of circ0000520 overexpression on NSCLC cells. miR-1258 targeted and inhibited AKT3. circ0000520 positively regulated the AKT3 expression in NSCLC cells by sponging miR-1258. circ0000520 upregulates AKT3 by competitively binding with miR-1258 to facilitate NSCLC progression.

Ginsenoside Rg3 alleviates the migration, invasion, and angiogenesis of lung cancer cells by inhibiting the expressions of cyclooxygenase-2 and vascular endothelial growth factor.

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 μgml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.

Myasthenia gravis, myositis and myocarditis a fatal triad of immune-related adverse effect of immune checkpoint inhibitor treatment.

Pembrolizumab, a humanised monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks programmed death receptor 1 and its ligands, is an effective immunotherapy for malignancies such as melanoma, lung, head and neck, cancers, and Hodgkins lymphoma. It has an overall response rate between 73% and 83%, with complete response rate of 27%-30%. It is well tolerated with minor side effects in 70% of cases characterised by fatigue, rash, pruritus and diarrhoea. In rare cases, more serious and life-threatening complications can occur at a rate of 0.3%-1.3%. We report a case of a woman in her 70s with non-small-cell lung cancer treated with ICI. She presented to the emergency department with left-sided ptosis and muscle weakness 3 weeks of her first dose of pembrolizumab infusion as a treatment plan of her cancer. She was diagnosed with myasthenia gravis, myocarditis and myositis as ICI-induced immune-related adverse effects resistant to medical intervention. We wish to raise awareness of the triad of life-threatening complication of ICI therapy that accounts for 30%-50% of fatal complications.

Individual patient data to allow a more elaborated comparison of trial results with real-world outcomes from first-line immunotherapy in NSCLC.

Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD. This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n 141) with IPD from participants in the Checkmate-057 clinical trial (n 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial. Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively). This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.

Evaluation of TET Family Gene Expression and 5-Hydroxymethylcytosine as Potential Epigenetic Markers in Non-small Cell Lung Cancer.

DNA methylation is the most studied epigenetic modification in cancer. Ten-eleven translocation enzymes (TET) catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA. In the current research, we aimed to evaluate the role of 5-hmC and TET enzymes in non-small cell lung cancer (NSCLC) patients and their possible association with outcomes. ELISA was used to measure the 5-hmC levels in genomic DNA and qRT-PCR was used to evaluate TET1, TET2, and TET3 mRNAs expression levels in NSCLC tissues and their paired normal controls. The levels of 5-hmC were significantly lower in NSCLC tissues than in normal tissues, with a mean ±SD of 0.28±0.37 vs. 1.84±0.58, respectively (t22.77, p<0.0001), and this reduction was correlated with adverse clinical features. In addition, all TET genes were significantly down-regulated in NSCLC tissues in comparison to their matched normal tissues. The mean±SD level of TET1-mRNA was 38.48±16.38 in NSCLC vs. 80.65±11.25 in normal tissues (t21.33, p<0.0001), TET2-mRNA level in NSCLC was 5.25±2.78 vs. 9.52±1.01 in normal tissues (t14.48, p<0.0001), and TET3-mRNA level in NSCLC was 5.21±2.8 vs. 9.51±0.86 in normal tissues (t14.75, p<0.0001). Downregulation of TET genes was correlated with poor clinical features. 5-HmC levels as well as TET1, TET2, and TET3 mRNA levels were reduced in NSCLC tissues. The reduced levels of 5-hmC and TET mRNAs were associated with adverse clinical features, suggesting that the level of 5-hmC may serve as a valuable prognostic biomarker for NSCLC.

Association of Volatile

A recent preclinical study reported that renal cell carcinoma was more susceptible to sevoflurane-mediated metastatic potentiation, compared to non-small cell lung cancer, suggesting that the effect of anesthetic agents on the metastatic potential varies according to cancer type. Based on this report, we conducted a retrospective cohort study to compare recurrence-free survival after nephrectomy, between renal cell carcinoma patients receiving volatile anesthesia and those receiving intravenous anesthesia. We reviewed the electronic medical records of patients who underwent partial or radical nephrectomy for renal cell carcinoma at the Seoul National University Hospital. Patients were divided into two groups according to whether volatile or intravenous anesthesia was used for nephrectomy. A total of 651 patients (582 in the volatile and 69 in the intravenous group) were enrolled in the study. Recurrence-free survival after nephrectomy was compared using Cox proportional hazards regression analysis with inverse probability of treatment weighting. Cox regression analysis with inverse probability of treatment weighting revealed that volatile anesthesia had no impact on recurrence-free survival hazard ratio (HR)0.45 95% confidence interval (CI)0.07-2.85 p0.398 or overall survival (HR1.41 95% CI0.31-6.44 p0.661). We found no significant association between volatile anesthesia and poor outcomes after nephrectomy for renal cell carcinoma. Volatile anesthetic-promoted metastatic potentiation of renal cell carcinoma, shown in a preclinical study, does not seem to be translated in the clinical setting.

Expression of Three Clones of PD-L1 in Lung Cancer A Single-center Experience.

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein involved in immune evasion of malignant tumors. Confirmation of PD-L1 expression in non-small cell lung cancer (NSCLC) is necessary for the determination of immunotherapy using immune checkpoint inhibitors (ICIs). PDL-1 expression is currently analyzed by immunohistochemistry and is the only available biomarker that can guide the treatment of NSCLC using ICIs. The present study was conducted to compare the expression of three different commercial clones of PD-L1 in order for immunohistochemistry (IHC) for these clones to become more reliable for surgical pathologists. This study examined the expression of PD-L1 in 76 cases of resected lung cancer using IHC. Three clones were examined SP263, SP142, and 22C3PharmDx, which are commercially approved for quantifying PD-L1 expression in lung cancer. Of the 76 patients whose samples were evaluated for PD-L1 using the IHC 22C3pharmDx assay, 19 (25.0%) had a tumor proportion score (TPS) of ≥50% and 41 (53.9%) had a PD-L1 TPS of ≥1%. Furthermore, using the SP263, 48.7% had a TPS of ≥1% and 18.4% of >50%. The SP142 assay was used to evaluate tumor cells (TCs) and immune cells (ICs). Twenty (26.3%) cases were positive for TCs and 25 (32.9%) were reactive for ICs. These three commercial PD-L1 clones are comparable for detecting primary targets for anti-tumor immunotherapies. Careful evaluation by a pathologist is necessary to minimize misinterpretation errors.

A novel combination for the treatment of small cell lung cancer Active targeted irinotecan and stattic co-loaded PLGA nanoparticles.

Polymeric nanoparticles are widely used drug delivery systems for cancer treatment due to their properties such as ease of passing through biological membranes, opportunity to modify drug release, specifically targeting drugs to diseased areas, and potential of reducing side effects. Here, we formulated irinotecan and Stattic co-loaded PLGA nanoparticles targeted to small cell lung cancer. Nanoparticles were successfully conjugated with CD56 antibody with a conjugation efficiency of 84.39 ± 1.01%, and characterization of formulated nanoparticles was conducted with in-vitro and in-vivo studies. Formulated particles had sizes in the range of 130-180 nm with PDI values smaller than 0.3. Encapsulation and active targeting of irinotecan and Stattic resulted in increased cytotoxicity and anti-cancer efficiency in-vitro. Furthermore, it was shown with ex-vivo biodistribution studies that conjugated nanoparticles were successfully targeted to CD56-expressing SCLC cells and distributed mainly to tumor tissue and lungs. Compliant with our hypothesis and literature, the STAT3 pathway was successfully inhibited with Stattic solution and Stattic loaded nanoparticles. Additionally, intravenous injection of conjugated co-loaded nanoparticles resulted in decreased side effects and better anti-tumor activity than individual solutions of drugs in SCLC tumor-bearing mice. These results may indicate a new treatment option for clinically aggressive small cell lung cancer.

Attribution of value for combination immune checkpoint inhibitors in non-small cell lung cancer.

Immunotherapy represents a significant breakthrough in the treatment of cancer, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) are used in combination with other treatments to provide clinically meaningful outcomes for NSCLC patients. However, there are distinct mechanisms of action that an ICI may provide such clinically meaningful benefits. We focused on the valuation of ICIs when used in combination with existing treatments for NSCLC, by addressing the following questions (1) do combination ICIs improve clinical outcomes due to independent, rather than synergistic or additive drug action and (2) how should we attribute value to the constituent parts of combination ICIs To address these questions, we reviewed the United States Food and Drug Administration (FDA) drug database and Clinicaltrials.gov from January 1, 2012, until June 1, 2022, to identify approved indications of combination ICIs in NSCLC. For valuation methods, a separate search was conducted in PubMed, health technology assessment databases, and grey literature to identify published value assessment or attribution methods, specifically in the context of combination (cancer) treatments. As of June 1, 2022, the FDA approved eight combination ICI indications for NSCLC. The underlying mechanisms for the improved clinical benefits of these ICI therapies are not well studied. The superiority of combination ICI therapies compared to monotherapy in multiple indications does not indicate whether synergy or additivity is involved, or necessary. Policy statement We encourage further research on the development of value attribution framework methods for combination therapies to quantify their added health benefits and economic value in the future. Given the valuation challenges of combination ICIs, their mechanism of action poses significant uncertainty and requires further clinical investigation to address whether synergy or additivity is existent.

Heterodimers with a cucurbitane-type triterpenoid skeleton from the branches of Elaeocarpus dubius.

Four undescribed and two known cucurbitane-type triterpenoids, including two heterodimers, elaeocarpudubins A and B, were isolated from the branches of Elaeocarpus dubius (Elaeocarpaceae). The chemical structures of these undescribed isolates were determined by analyses of 1D and 2D NMR and MS data, electronic circular dichroism (ECD) calculations, and chemical transformation. Biogenetically, elaeocarpudubins A and B might be derived from cucurbitacin F through Michael addition with vitamin C and (-)-catechin, respectively. These six isolates were evaluated for their cytotoxic activities against human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, human colon cancer SW480, and paclitaxel-resistant A549 (A549Taxol) cell lines, for their antioxidant properties using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and for their differentiation effects on nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells. Cucurbitacins F (IC

IL-13 and the hydroperoxy fatty acid 13(S)HpODE play crucial role in inducing an apoptotic pathway in cancer cells involving MAO-AROSp53p21 signaling axis.

This study depicted the effect of IL-13 and 13(S)HpODE (the endogenous product during IL-13 activation) in the process of cancer cell apoptosis. We examined the role of both IL-13 and 13(S)HpODE in mediating apoptotic pathway in three different in vitro cellular models namely A549 lung cancer, HCT116 colorectal cancer and CCF52 GBM cells. Our data showed that IL-13 promotes apoptosis of A549 lung carcinoma cells through the involvement of 15-LO, PPARγ and MAO-A. Our observations demonstrated that IL-1313(S)HpODE stimulate MAO-A-mediated intracellular ROS production and p53 as well as p21 induction which play a crucial role in IL-13-stimulated A549 cell apoptosis. We further showed that 13(S)HpODE promotes apoptosis of HCT116 and CCF52 cells through the up-regulation of p53 and p21 expression. Our data delineated that IL-13 stimulates p53 and p21 induction which is mediated through 15-LO and MAO-A in A549 cells. In addition, we observed that PPARγ plays a vital role in apoptosis as well as in p53 and p21 expression in A549 cells in the presence of IL-13. We validated our observations in case of an in vivo colon cancer tumorigenic study using syngeneic mice model and demonstrated that 13(S)HpODE significantly reduces solid tumor growth through the activation of apoptosis. These data thus confirmed that IL-13 > 15-LO>13(S)HpODE > PPARγ>MAO-A > ROS > p53>p21 axis has a major contribution in regulating cancer cell apoptosis and further identified 13(S)HpODE as a potential chemo-preventive agent which can improve the efficacy of cancer treatment as a combination compound.

Epigenetic regulator KDM4A activates Notch1-NICD-dependent signaling to drive tumorigenesis and metastasis in breast cancer.

Altered epigenetic reprogramming and events contribute to breast cancer (Bca) progression and metastasis. How the epigenetic histone demethylases modulate breast cancer progression remains poorly defined. We aimed to elucidate the biological roles of KDM4A in driving Notch1 activation and Bca progression. The KDM4A expression in Bca specimens was analyzed using quantitative PCR and immunohistochemical assays. The biological roles of KDM4A were evaluated using wound-healing assays and an in vivo metastasis model. The Chromatin Immunoprecipitation (ChIP)-qPCR assay was used to determine the role of KDM4A in Notch1 regulation. Here, we screened that targeting KDM4A could induce notable cell growth suppression. KDM4A is required for the growth and progression of Bca cells. High KDM4A enhances tumor migration abilities and in vivo lung metastasis. Bioinformatic analysis suggested that KDM4A was highly expressed in tumors and high KDM4A correlates with poor survival outcomes. KDM4A activates Notch1 expressions via directly binding to the promoters and demethylating H3K9me3 modifications. KDM4A inhibition reduces expressions of a list of Notch1 downstream targets, and ectopic expressions of ICN1 could restore the corresponding levels. KDM4A relies on Notch1 signaling to maintain cell growth, migration and self-renewal capacities. Lastly, we divided a panel of cell lines into KDM4A Taken together, KDM4A could drive Bca progression via triggering the activation of Notch1 pathway by decreasing H3K9me3 levels, highlighting a promising therapeutic target for Bca.

Economic impact of using risk models for eligibility selection to the International lung screening Trial.

Using risk models as eligibility criteria for lung screening can reduce race and sex-based disparities. We used data from the International Lung Screening Trial(ILST NCT02871856) to compare the economic impact of using the PLCOm2012 risk model or the US Preventative Services categorical age-smoking history-based criteria (USPSTF-2013). The cost-effectiveness of using PLCOm2012 versus USPSTF-2013 was evaluated with a decision analytic model based on the ILST and other screening trials. The primary outcomes were costs in 2020 International Dollars ($), quality-adjusted life-years (QALY) and incremental net benefit (INB, in $ per QALY). Secondary outcomes were selection characteristics and cancer detection rates (CDR). Compared with the USPSTF-2013 criteria, the PLCOm2012 risk model resulted in $355 of cost savings per 0.2 QALYs gained (INB$4294 at a willingness-to-pay threshold of $20 000QALY (95 %CI $4205-$4383). Using the risk model was more cost-effective in females at both a 1.5 % and 1.7 % 6-year risk threshold (INB$6616 and $6112, respectively), compared with males ($5221 and $695). The PLCOm2012 model selected more females, more individuals with fewer years of formal education, and more people with other respiratory illnesses in the ILST. The CDR with the risk model was higher in females compared with the USPSTF-2013 criteria (Risk Ratio 7.67, 95 % CI 1.87-31.38). The PLCOm2012 model saved costs, increased QALYs and mitigated socioeconomic and sex-based disparities in access to screening.

The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer.

Carboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. This was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kgm Overweight patients (n174) had a significantly better OS (aHR0.72, 95%-CI0.59-0.89) and PFS (aHR0.74, 95%-CI0.61-0.90) compared to normal weight patients (n268). OS nor PFS were different in obese (n51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR3.47, 95%-CI1.75-6.90). This study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kgm

Effects of lymphopenia on survival in proton therapy with chemotherapy for non-small cell lung cancer.

Lymphocytes play an important role in the cancer immune system. In the present study, we aimed to evaluate the associations of lymphopenia during proton beam therapy (PBT) and concurrent chemotherapy with clinical outcomes and to determine whether lung or bone is more influential on lymphopenia during PBT. Data from 41 patients with stage III non-small cell lung cancer (NSCLC) who received PBT of 74 GyE with concurrent chemotherapy between 2007 and 2017 were reviewed retrospectively. The correlation between dosimetry parameters obtained from dose-volume histograms of the bone and lung and lymphopenia during PBT were analyzed. Minimum absolute lymphocyte count (ALCmin) and maximum neutrophillymphocyte ratio (NLRmax) were used as indicators of lymphopenia. Bone V5-20 and lung V5-50 were significantly correlated with the ALCmin and NLRmax during PBT. Multivariable analysis showed that the NLRmax, but not the ALCmin, was associated with overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). The 3-year rates of OS, PFS and DMFS of patients with a low (≤ 6.3) versus high (> 6.3) NLRmax were 73.9% vs 44.4% (P 0.042), 26.1% vs 5.6% (P 0.022) and 39.1% vs 5.6% (P < 0.001), respectively. Lung V20 was significantly associated with DMFS on multivariable analyses (hazard ratio 1.094, P 0.008), whereas bone V5 had no impact on survival outcomes. We concluded that the NLRmax was a better prognostic indicator than the ALCmin, and the lung dose had more influence than the bone dose on the main survival outcomes in stage III NSCLC patients treated with PBT combined with concurrent chemotherapy.

Inhibitory effect of aspirin on inflammation-induced lung metastasis of cancer cells associated with neutrophil infiltration.

Systematic inflammation has been reported to contribute to cancer progression through various mechanisms however, the exact mechanism is still the subject of research. In this study, we evaluated the influence of systematic inflammation on lung metastasis, using a murine abdominal sepsis model, and assessed its relationship with pneumonia after curative esophagectomy in patients with esophageal cancer. We used a murine abdominal sepsis model given highly metastatic osteosarcoma, to reveal the mechanism of systematic inflammation and its potential for lung metastasis. The therapeutic effect of aspirin (ASA) in preventing distant metastasis was also investigated. Subsequently, we analyzed, retrospectively, the relationship between pneumonia and lung metastasis after esophagectomy in patients who underwent esophagectomy at Keio University between January, 2007 and October, 2020. Abdominal sepsis provoked lung injury in the acute phase. ASA inhibited the recruitment of neutrophils triggered by the lung injury, and it also suppressed lung metastasis. Our retrospective study revealed that lung metastasis was more frequent in patients with postoperative pneumonia. Postoperative acute lung injury is associated with a higher risk of lung metastasis. ASA may be a potential preoperative treatment for inhibiting lung metastasis by preventing the recruitment of neutrophils.

Bronchial carcinoma metastatic pathways with involvement of hilar and mediastinal lymph nodes.

Lung cancer has enormous socioeconomical impact on our society due to its high prevalence and mortality. About 59,700 new cases of lung cancer were forecasted for 2022. Correct staging is the basis for therapy planning, prognosis estimation, and future analyses. Staging is performed using the TNM scheme from the Union for International Cancer Control (UICC). Involvement of lymph nodes is used to differentiate between stage IIB and IIIC. Knowledge of the intrathoracic lymph node levels is crucial for the exact classification and its involvement has direct implications on therapy. The International Association for the Study of Lung Cancer (IASLC) proposed a unified lymph node map with exact anatomic definitions, which is recommended by the German national lung cancer guideline. The extent of lymph node involvement is stratified into N0-N3. Different metastatic paths are known depending on the location of the primary tumor, but the burden of disease has a greater influence on survival, than the location of metastases. Computed tomography can assess operability of the primary tumor safely in most cases. Invasive procedures to confirm the diagnosis by sampling tissue should be performed after noninvasive diagnostics. Systematic lymph node dissection for all patients with non-small cell lung cancer intended for curative resection is recommended in the current German national guideline for lung cancer. BEDEUTUNG DES LUNGENKARZINOMS Das Lungenkarzinom hat aufgrund seiner hohen Prävalenz und Mortalität enorme sozioökonomische Auswirkungen auf unsere Gesellschaft. Für das Jahr 2022 wurden ca. 59.700 Neuerkrankungen an Lungenkrebs prognostiziert. Die korrekte Ausbreitungsdiagnostik ist für die Therapieplanung, Prognoseabschätzung und zukünftige Analysen von grundlegender Bedeutung. Die Stadieneinteilung des Lungenkarzinoms erfolgt nach dem TNM-Schema der Union for International Cancer Control (UICC). Für die Stadien IIB–IIIC wird der Lymphknotenbefall zur Differenzierung herangezogen. Die Kenntnis der intrathorakalen Lymphknotenstationen ist für die genaue Klassifikation von entscheidender Bedeutung, und deren Befall hat unmittelbare Auswirkungen auf die Therapie. Die International Association for the Study of Lung Cancer (IASLC) hat eine vereinheitlichte Lymphknotenkarte vorgeschlagen, die sich durch ihre exakten anatomischen Definitionen auszeichnet und in der aktuellen S3-Leitlinie für das Lungenkarzinom berücksichtigt wird. Der Lymphknotenbefall wird abhängig vom Ausmaß in N0–N3 stratifiziert. Je nach Lokalisation des Primärtumors lassen sich bevorzugte Metastasierungspfade nachweisen. Die Krankheitslast hat einen größeren Einfluss auf das Überleben als die Lokalisation der Metastasen. Mit der Computertomographie (CT) kann die Operabilität des Primärtumors meistens sicher beurteilt werden. Invasive Verfahren zur Diagnosesicherung durch Probengewinnung sollten erst im Anschluss an nichtinvasive Diagnostik eingesetzt werden. EMPFEHLUNG FüR DIE PRAXIS In der aktuellen Leitlinie des Lungenkarzinoms wird bei allen Patienten mit nichtkleinzelligem Lungenkarzinom, die einer kurativen Resektion zugeführt werden, eine systematische Lymphknotenresektion empfohlen.

Characteristics of anti-transcriptional intermediary factor 1 gamma autoantibody-positive dermatomyositis patients in Singapore.

This study aimed to determine the clinical profile and outcome of anti-transcriptional intermediary factor 1 gamma autoantibody (anti-TIF1-γ Ab)-positive dermatomyositis patients and propose cancer screening programmes based on regional cancer trends. Data on history, physical findings and investigations were collected using chart review on dermatomyositis patients seen at a tertiary hospital in Singapore from 1 January 2015 to 30 June 2021. Comparisons were made between anti-TIF1-γ Ab-positive and anti-TIF1-γ Ab-negative dermatomyositis. Ninety-six dermatomyositis patients were analysed and 36 patients were positive for anti-TIF1-γ Ab. Anti-TIF1-γ Ab-positive patients had more frequent heliotrope rashes, shawl sign, periungual erythema, holster sign, Gottrons papules, dysphagia and truncal weakness ( These observational data support periodic screening of NPC and other malignancies in patients with anti-TIF1-γ Ab-positive dermatomyositis in Singapore.

Establishing 3-Dimensional Spheroids from Patient-Derived Tumor Samples and Evaluating their Sensitivity to Drugs.

Despite remarkable advances in understanding tumor biology, the vast majority of oncology drug candidates entering clinical trials fail, often due to a lack of clinical efficacy. This high failure rate illuminates the inability of the current preclinical models to predict clinical efficacy, mainly due to their inadequacy in reflecting tumor heterogeneity and the tumor microenvironment. These limitations can be addressed with 3-dimensional (3D) culture models (spheroids) established from human tumor samples derived from individual patients. These 3D cultures represent real-world biology better than established cell lines that do not reflect tumor heterogeneity. Furthermore, 3D cultures are better than 2-dimensional (2D) culture models (monolayer structures) since they replicate elements of the tumor environment, such as hypoxia, necrosis, and cell adhesion, and preserve the natural cell shape and growth. In the present study, a method was developed for preparing primary cultures of cancer cells from individual patients that are 3D and grow in multicellular spheroids. The cells can be derived directly from patient tumors or patient-derived xenografts. The method is widely applicable to solid tumors (e.g., colon, breast, and lung) and is also cost-effective, as it can be performed in its entirety in a typical cancer researchcell biology lab without relying on specialized equipment. Herein, a protocol is presented for generating 3D tumor culture models (multicellular spheroids) from primary cancer cells and evaluating their sensitivity to drugs using two complementary approaches a cell-viability assay (MTT) and microscopic examinations. These multicellular spheroids can be used to assess potential drug candidates, identify potential biomarkers or therapeutic targets, and investigate the mechanisms of response and resistance.

Co-Fermentation of Marsdenia tenacissima with Ganoderma lucidum and Anti-Lung Cancer Effect of the Fermentation Products.

Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), as a traditional Chinese and Dai herbal medicine, has anti-inflammatory, antibacterial, and antitumor properties. However, most of its main active substances are aglycones, such as tenacigenin A and tenacigenin B. As the bioavailability of MT is low and its medicinal active components are challenging to synthesize, it is primarily studied by biotransformation. This study aims to produce biotransformation products rich in pungent saponins by using MT as a fermentation medium for Ganoderma lucidum (G. lucidum). Through the preliminary screening of three medicinal fungi, it was found that G. lucidum and Ophiocordyceps sinensis (O. sinensis) can generally grow in the medium for MT hence, the efficacy of the fermentation of the two types of fungi was screened using a mouse model of lung cancer. Finally, the co-fermentation of G. lucidum and MT was selected for further investigation. Non-target metabolomics analysis was performed on the products of MT with G. lucidum co-fermentation. We identified 12 specific saponins of MT from the fermentation products, and obtained a monomeric compound, tenacigenin A, from fermentation products. Most of the tenacigenin showed a significant upward trend, through tenacigenin A and tenacigenin B levels. The results showed that the efficacy of MT improved after fermentation by G. lucidum. Furthermore, the biotransformation of C21 steroidal glycosides in MT was the central reaction in this fermentation process. In summary, this study established a systematic and comprehensive co-fermentation system and pharmacodynamic evaluation method for MT, which not only enhanced the full utilization of effective active substances in MT but also provided a methodological reference for the development of other ethnic drugs.

PDGF-β and IL-18 Expressions on Carcinoma Cervical by

ltbgtBackground and Objectiveltbgt Cervical cancer, along with lung and breast cancer, is one of Indonesias most aggressive gynaecological diseases. ltigtRhodomyrtus tomentosaltigt has antioxidant and antiproliferative properties that could be developed into herbal medicines for molecular therapy. The IL-18 and PDGF-β are tumour-promoting agent proteins that may be therapeutic targets for a variety of cancers that were investigated in this study. ltbgtMaterials and Methodsltbgt Rats were classified into five groups Group C- is the control group, Group C is the cancer model group and Group RHO200 is the ltigtRhodomyrtus tomentosaltigt 100 mgltsupgt1ltsupgt b.wt., rat group, Group RHO400 is the ltigtRhodomyrtus tomentosaltigt 200 mgltsupgt1ltsupgt b.wt., rat group and Group RHO400 is the ltigtRhodomyrtus tomentosaltigt 400 mgltsupgt1ltsupgt b.wt., rat group. The rats were dissected 30 days after receiving ltigtRhodomyrtus tomentosaltigt. Immunohistochemistry is used to stain cervical tissues. ltbgtResultsltbgt The expression of IL-18 and PDGF-β was significantly different (p<0.01). The IL-18 and PDGF-β were most abundant at the lowest ltigtRhodomyrtus tomentosaltigt doses (100-200 mg kgltsupgt1ltsupgt b.wt.), while they were least abundant at the 400 mg kgltsupgt1ltsupgt b.wt., doses. Histological analysis revealed that the highest dose of IL-18 and PDGF-β expression reduced abnormal tissue and the space between tumours, followed by several carcinoma cells that stopped growing. ltbgtConclusionltbgt ltigtRhodomyrtus tomentosaltigt can be used as a herbal therapy to reduce the expression of PDGF-β and IL-18 (two cancer marker agents).

High-Performance Delivery of a CRISPR Interference System via Lipid-Polymer Hybrid Nanoparticles Combined with Ultrasound-Mediated Microbubble Destruction for Tumor-Specific Gene Repression.

The dCas9-based CRISPR interference (CRISPRi) system efficiently silences genes without causing detectable off-target activity, thus showing great potential for the treatment of cancer at the transcriptional level. However, due to the large size of the commonly used CRISPRi system, effective delivery of the system has been a challenge that hinders its application in the clinic. Herein, a combination of pH-responsive lipid-polymer hybrid nanoparticles (PLPNs) and ultrasound-mediated microbubble destruction (UMMD) is used for the delivery of the CRISPRi system. The core-shell structure of PLPNs can effectively be loaded with the CRISPRi plasmid, and increases the time spent in the circulating in vivo, and actively target cancer cells. Moreover, the combination of PLPNs with UMMD achieves a higher cellular uptake of the CRISPRi plasmid in vitro and retention in vivo. Furthermore, when PLPNs loaded with a CRISPRi plasmid that targets microRNA-10b (miR-10b) are used in combination with UMMD, it results in the effective repression of miR-10b in breast cancer, simultaneous disturbance of multiple cell migration and invasion-related signaling pathways, and a significant inhibition of lung metastasis. Thus, the established system presents a versatile, highly efficient, and safe strategy for delivery of the CRISPRi system both in vitro and in vivo.

Analysis of clinical features, treatment, and prognosis of primary Xlymphoepithelioma-like carcinoma of the lung.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare lung malignancy occurring most frequently in young non-smokers from Southeast Asia. Given its low incidence, PPLELC clinical features, treatment methods, and the factors affecting its prognosis remain elusive. To date, PPLELC data are mainly derived from clinical case reports, and no cohort studies are available. Therefore, we retrospectively analyzed a group of PPLELC cases and summarized the clinical features of patients, treatment responses, and the factors affecting patient prognosis. A total of 91 patients having primary pulmonary lymphoepithelioma-like carcinoma were recruited in this study. These included sex, age, place of birth, smoking history, pre-treatment symptoms, tumor location, tumor markers, maximum tumor diameter, treatment regimen, lymph node presence metastasis after an operation, pathological picture, immunohistochemistry, genetic findings, and tumor stage grading. We determined the overall survival (OS), progression-free survival (PFS), basic clinical characteristics, treatment option, treatment response, and recurrence pattern among the patients. In addition, we understood the influence of sex, age, tumor, nodes, and metastases (TNM) stage, tumor size, and surgery over patient prognosis. Primary pulmonary lymphoepithelioma-like carcinoma is more common among young non-smokers, with a slightly higher incidence in women than in men. The expression of Epstein-Barr virus-encoded small RNA (EBER), pancytokeratin (PCK), Cytokeratin 56 (CK56), and tumor protein 63 (P63) was positive in immunohistochemistry. Serum cytokeratin 19 fragment antigen (CYFRA21-1) and Epstein-Barr DNA (EB-DNA) could be used as markers to diagnose primary pulmonary lymphoepithelioma-like carcinoma. TNM stage and surgery were independent prognostic factors. Primary pulmonary lymphoepithelioma-like carcinoma is rare, showing a good prognosis.

Multiple targets of Nrf 2 inhibitor trigonelline in combating urethane-induced lung cancer by caspase-executioner apoptosis, cGMP and limitation of cyclin D1 and Bcl2.

OBJECTIVE Among other types of cancerous lesions, lung cancer is one of the prevalent causes of death. Trigonelline is a plant alkaloid, a significant constituent in coffee, and has shown health benefits in several disorders. The present study aims to investigate the potential therapeutic role of trigonelline in lung cancer. MATERIALS AND METHODS Seventy-five BALBC mice were assigned to five groups and treated for 150 days as follows (1) normal control group (2) trigonelline only (50 mgkg P.O) daily for the last thirty days (3) urethane (1.5 gkg B.wi.p) at day one and sixty (4) urethane and carboplatin (15 mgkg i.p) for the last thirty days and (5) urethane and trigonelline for the last thirty days. Tumor size was measured while blood and lung were collected for biochemical, western blotting analysis, and histological examinations. RESULTS Urethane demonstrated significant changes in all biochemical and molecular parameters and histological examinations. In animals pretreated with urethane, trigonelline significantly reduced tumor size and restored Nrf2, NF-кB p65, Bcl-2, Cyclin D1, ICAM-1, and MMP-2, along with improving cGMP and active caspase three and refining histological architectures. CONCLUSIONS Nrf2 signaling may be a promising therapeutic target for adenocarcinoma protection or management. Due to its multiple therapeutic effects on Nrf2, cyclin D1, NF-кB pathways, and the BAXBcl2 axis, trigonelline significantly induced cell cycle arrest and apoptosis. httpswww.europeanreview.orgwpwp-contentuploadsGraphicalAbstract-1.jpg.

Clinical characteristics and prognostic value of EGFR mutation in stage I lung adenocarcinoma with spread through air spaces after surgical resection.

The clinical data of stage I invasive lung adenocarcinoma patients with spread through air spaces (STAS) who underwent lobectomy from January 1, 2013 to January 1, 2016 at the Department of Thoracic Surgery of Hebei Medical University were analyzed retrospectively, and statistical analysis was carried out to explore their clinical features and prognostic value of EGFR mutation. A total of 280 patients were included in the study cohort, and EGFR mutations were detected in 154 patients. EGFR mutations were more common in non-smokers (p0.045), females (p<0.001), without vascular tumor thrombus (p0.037), and histological subtype LPAAPAPPA (p0.001). Multivariate analysis of the Cox risk regression model showed that EGFR gene mutation (p0.807) was not an independent influencing factor of recurrence-free survival (RFS), but EGFR mutation was an independent influencing factor of overall survival (OS) (p0.012), and OS of patients with EGFR mutation was better. The EGFR mutation also significantly increased the progression-free survival (PFS) of relapsed patients (p<0.001), but the PFS of relapsed EGFR mutation patients who received adjuvant chemotherapy after the operation was worse than that of patients who did not receive adjuvant chemotherapy (p0.029). EGFR gene mutation is not a risk factor for postoperative recurrence in patients with stage I lung adenocarcinoma with STAS but the 5-year survival rate of patients with EGFR gene mutation is better than that of wild-type. Postoperative adjuvant chemotherapy for patients with EGFR mutation should be carefully considered.

Circ0030411 aggravates cisplatin-resistance in non-small cell lung cancer by serving as a miR-495-3p sponge to enhance CCND1 expression.

Circular RNAsplay important modulators in cisplatin (DDP) resistant non-small cell lung cancer (NSCLC). Herein, the role and mechanism of circ0030411 in DDP-resistant NSCLC was explored. Circ0030411, miR-495-3p, CCND1, PCNA, Bax, E-cadherin, and ki-67 expression were examined byqRT-PCR, western blot and IHC. DDP resistance, cell proliferation, apoptosis, and motility were assessed usingCCK, EdU flow cytometry, and transwell. Xenograft tumour model was established to explore the role of circ0030411 in DDP-resistant NSCLC. Interaction between miR-495-3p and circ0030411 or CCND1 wasverified

Primary pulmonary hyalinising clear cell carcinoma Two cases and literature review.

Hyalinising clear cell carcinoma (HCCC) of the lung is an extremely rare tumour that is just recently recognised as one of the salivary gland-type tumours (SGTT) in the latest WHO classification of thoracic tumours. Eleven cases have been reported in English literature since Joaquín et al. reported the first case. Given the very limited number of cases, the clinical and histological features of pulmonary HCCC are equivocal. Herein, we present two cases of pulmonary HCCC. The patients were a 66-year-old man and a 48-year-old woman. The mass was located on the right main bronchus and right middle lobar bronchus separately. One was 2 cm and the other was 3.3 cm in the greatest dimension. The tumours were comprised of small monomorphic cells with clear or eosinophilic cytoplasm and infiltrated in a hyalinising stroma arranged in nests, cords, sheets and trabeculae. Their morphology resembled their head and neck counterparts. Immunohistochemically, the tumour cells were positive for AE1AE3, P63, while negative for TTF1, Calponin, S-100, HMB45 and PAX8. Ki-67 labeling ranges from 3% to 10%. Fluorescence in situ hybridisation (FISH) demonstrated EWSR1 rearrangement and Next-generation sequencing (NGS) demonstrated EWSR1- ATF1 (exon 11 exon 3) fusion in case one and EWSR1- ATF1 (exon 2 exon 12) fusion in case two. This is the first time to report the EWSR1-ATF1fusion point other than exon 11 exon 3 in pulmonary HCCC. Case one recurred two years after local resection but didnt metastasise during follow-up 36 months. Case two is alive without disease after lobectomy during follow-up 14 months.

Evaluation of breast cancer metastasis and mortality rates based on molecular subtype A description study.

Breast cancer in Indonesia has continued to increase. One diagnostic modality is immunohistochemical examination to determine breast cancer subtypes. To determine breast cancer metastasis and mortality rates based on molecular subtypes. A descriptive study was conducted based on retrospective data from hospital medical records from January 2016 to December 2019. The data comprised age, clinical stage, histopathological grade, molecular subtype, location, metastasis, and breast cancer mortality. The data were processed and analyzed. This study involved 172 patients. The most prevalent breast cancer subtypes were luminal A (60, 34.8%), followed by HER2 (47, 27.4%), triple-negative (38, 22.4%), and luminal B (27, 15.4%). The metastasis rate was 37.21% (64172), with bone the tissue most affected (32 cases, 50%), followed by lung (24 cases, 37.5%) and liver (8 cases, 12.5%). The highest rates of bone, lung, and liver metastases were subtypes luminal A (31%), HER2 (29%), and triple-negative (38%), respectively. The mortality rate was 21% (36172), with most in the triple-negative group (28.9%), followed by luminal B (25.9%), HER2 (21.2%), and luminal A (13.3%). Determination of breast cancer molecular subtypes through immunohistochemistry can determine the level of metastasis and mortality in breast cancer.

Prognostic score and sex-specific nomograms to predict survival in resectable lung cancer A French nationwide study from the Epithor cohort database.

Prognostic assessment in patients undergoing cancer treatments is of paramount importance to plan subsequent management. In resectable lung cancer availability of an easy-to use nomogram to predict long-term outcome would be extremely useful to identify high-risk patients in the era of perioperative targeted and immune therapies. We retrieved clinical, surgical and pathological data of all consecutive patients included in Epithor, the database of French Society of Thoracic and Cardiovascular Surgery, and operated on between 2003 and 2020 for non-small cell lung cancer in a curative intent. The primary endpoint was overall survival up to 5 years. We assessed prognostic significance of available variables using Cox modelling, in the whole dataset, and in men and in women separately, and performed temporal validation. Finally, we constructed two sex-specific nomograms. Survivals by fifths of score were assessed in the development and temporal validation sets. The study included 62,633 patients (43,551 men and 19,082 women). Median survival time was 9.2 years. Nine factors had strong prognostic impact and were used to construct nomograms. The optimism-corrected c statistic for the prognostic score was 0.689 in the development sample, and 0.726 (95% CI 0.718-0.735) in the temporal validation sample. All differences between adjacent fifths of score were significant (P < 0.0001). Figures of 3-year OS by fifths of score were 92.2%, 83.0%, 74.3%, 64.0%, and 43.4%, respectively, in the development set and 93.3%, 88.4%, 81.0%, 73.7%, 55.7% in the temporal validation set. Performance of score was maintained when stratifying by stage of diseases. In the present work, we report evidence that long-term overall survival after resection of NSCLC can be predicted by an easy to construct and use composite score taking into account both host and tumour related factors. Epithor is funded by FSTCVS.

Modulators of radiation-induced cardiopulmonary toxicities for non-small cell lung cancer Integrated cytokines, single nucleotide variants, and HBP systems imaging.

Radiation therapy (RT)-induced cardiopulmonary toxicities remain dose-limiting toxicities for patients receiving radiation dosages to the thorax, especially for lung cancer. Means of monitoring and predicting for those receiving RT or concurrent chemoradiation therapy before treatment begins in individual patients could benefit early intervention to prevent or minimize RT-induced side effects. Another aspect of an individuals susceptibility to the adverse effects of thoracic irradiation is the immune system as reflected by phenotypic factors (patterns of cytokine expressions), genotypic factors (single nucleotide variants SNVs formerly single nucleotide polymorphisms SNPs), and aspects of quantitative cellular imaging. Levels of transcription, production, and functional activity of cytokines are often influenced by SNVs that affect coding regions in the promoter or regulatory regions of cytokine genes. SNVs can also lead to changes in the expression of the inflammatory cytokines, interferons, interleukins (IL-6, IL-17) and tumor necrosis factors (TNF-α) at the protein level. RT-induced cardiopulmonary toxicities could be quantified by the uptake of

Whole exome sequencing in Chinese mucinous pulmonary adenocarcinoma uncovers specific genetic variations different from lung adenocarcinoma.

As a rare subtype of primary lung adenocarcinoma (LUAD), mucinous pulmonary adenocarcinoma (MPA) was considered a distinctive entity with unfavorable outcomes. Therefore, there is a great need for a better understanding of the genomic and immunological landscape of this rare tumor type, which would inform improved therapeutic strategies. A total of 96 patients histologically confirmed with MPA were recruited from Shandong Cancer Hospital and Institute (SCH). Single nucleotide variation (SNV), copy number variation (CNV), genomic instability, and immunological landscape insights into 96 MPA patients were identified using WES. We demonstrated that MPAs had marked different genomic alterations and were more complex in genomic profiles than LUADs. Mutations in Tumor Protein 53 ( We not only depicted the genetic and immunologic landscape of Chinese MPA but also reveal its distinction from LUAD in genomic and immune context. Our findings may provide opportunities for therapeutic susceptibility among Chinese MPA patients.

Case report Liquid biopsy, the sooner the better

The detection of circulating tumor DNA (ctDNA) by liquid biopsy is taking an increasing role in thoracic oncology management due to its predictive and prognostic value. For non-small cell lung cancer, it allows the detection of molecular mutations that can be targeted with tyrosine kinase inhibitors (TKIs). We report the case of a patient with life-threatening hepatocellular failure and thrombotic microangiopathy at the diagnosis. A salvage chemotherapy was attempted, resulting in a major worsening of her general condition and the decision to stop all anti-cancer treatment. The liquid biopsy performed at the time of immunohistochemical non-small cell lung cancer diagnosis revealed within 7 days the presence of an epidermal growth factor receptor (

The role of IL-6JAK2STAT3 signaling pathway in cancers.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation. It can activate janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. As one of the important signal transduction pathways in cells, JAK2STAT3 signaling pathway plays a critical role in cell proliferation and differentiation by affecting the activation state of downstream effector molecules. The activation of JAK2STAT3 signaling pathway is involved in tumorigenesis and development. It contributes to the formation of tumor inflammatory microenvironment and is closely related to the occurrence and development of many human tumors. This article focuses on the relationship between IL-6JAK2STAT3 signaling pathway and liver cancer, breast cancer, colorectal cancer, gastric cancer, lung cancer, pancreatic cancer and ovarian cancer, hoping to provide references for the research of cancer treatment targeting key molecules in IL-6JAK2STAT3 signaling pathway.

Case Report Bronchial artery embolization and chemoradiotherapy for central squamous cell lung carcinoma with rapid regression.

Interventional embolization is a common treatment for hemoptysis, one of the complications of lung cancer. However, there are no official guidelines for the use of this method in antitumor therapy. Herein, we describe a case of a patient who was pathologically diagnosed as central squamous cell lung cancer. The patient received chemotherapy, interventional embolization and radiotherapy successively. The tumor regressed rapidly within 48 hours of receipt of interventional embolization. Furthermore, the tumor decreased by more than 50% in size within 7 days during radiotherapy. Unfortunately, the patient has since developed lymph node metastases and remains under treatment. Thus, finding the suitable blood vessel embolized may be a suitable option to reduce the local tumor load and can be considered as antitumor therapy in combination with other treatments. The patients theoretical hypoxia state after interventional therapy still produced a good tumor regression after radiotherapy. However, so far, no related studies have reported the changes of tumor immune microenvironment in human body after intervention and radiotherapy.

Current status and challenges of immunotherapy in ALK rearranged NSCLC.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene account for 5-6% in non-small cell lung cancer (NSCLC). ALK rearranged NSCLC is sensitive to ALK tyrosine kinase inhibitors (TKIs) but prone to drug resistance. Meanwhile, ALK rearranged NSCLC has poor response to single immunotherapy. Here we mainly describe the immune escape mechanisms of ALK mutated NSCLC and the role of related biomarkers. Additionally, we collate and evaluate preclinical and clinical studies of novel immune combination regimens, and describe the prospects and perspectives for the

Investigation of M2 macrophage-related gene affecting patients prognosis and drug sensitivity in non-small cell lung cancer Evidence from bioinformatic and experiments.

The progression process of lung cancer can be accelerated by M2 macrophages. However, genes that affect M2 macrophage polarization remain unidentified. The Cancer Genome Atlas, Gene Expression Omnibus, and Arrayexpress databases were used to obtain open-access data. The analysis of public data was mostly performed with R studio. The RNA levels of specific genes were detected using quantitative real-time PCR. The proliferation ability of the cells was assessed by CCK8, colony formation, and EdU assays. Based on the multiple datasets, we noticed a poor prognosis in patients with high M2 macrophage infiltration. There were 114 genes differentially expressed between high and low M2 macrophages infiltrated samples, regarded as M2 macrophage-related genes. Subsequently, a prognosis prediction signature consisting of ABHD5, HS3ST2, TM6SF1, CAPZA2, LEPROT, HNMT, and MRO was identified and presented a satisfactory performance. The pathway enrichment results revealed a positive correlation between riskscore and enrichment scores for most immunotherapy-related positive terms. Also, there might be an increase in genomic instability among patients at high risk. Interestingly, low risk patients are most likely to benefit from PD-1 therapy, while high risk patients may benefit from CTLA-4 therapy. Meanwhile, the estimated IC50 of seven drugs differs significantly between two risk groups, including Cisplatin, Docetaxel, Doxorubicin, Gefitinib, Paclitaxel, Sunitinib and Vinorelbine. Moreover, further experiments indicated that HNMT was overexpressed and can enhance the proliferation ability in lung cancer cells. In summary, our study identified the molecules significantly affecting M2 macrophage infiltration and identified a prognosis signature that robustly indicated patients prognosis. Moreover, we validated the cancer-promoting effect of HNMT using

Next-generation sequencing of homologous recombination genes could predict efficacy of platinum-based chemotherapy in non-small cell lung cancer.

With the widespread use of next-generation sequencing (NGS) in clinical practice, an increasing number of biomarkers that predict a response to anti-tumor therapy in non-small cell lung cancer (NSCLC) has been identified. However, validated biomarkers that can be used to detect a response to platinum-based chemotherapy remain unavailable. Several studies have suggested that homologous recombination deficiency (HRD) may occur in response to platinum-based chemotherapy in ovarian cancer and breast cancer. However, currently there is a lack of proven and reliable HRD markers that can be used to screen for patients who may benefit from platinum-based chemotherapy, especially in NSCLC. NGS was used to screen for gene mutations, including homologous recombination (HR) genes and common driver gene mutations in NSCLC. Cox regression analysis was performed to identify potential clinicopathological or gene mutation factors associated with survival in patients receiving platinum-based chemotherapy, while Kaplan-Meier analysis with the log-rank test was performed to assess the effect of HR gene mutations on progression-free survival (PFS). In a retrospective cohort of 129 patients with advanced NSCLC, 54 who received platinum-based chemotherapy with or without anti-angiogenic therapy were included in the analysis. Univariate and multivariate Cox proportional hazard regression analyses showed that HR gene mutations were associated with platinum-based chemotherapy sensitivity. Efficacy results indicated that the objective response rates (ORR) for patients with HR gene mutations show potential as promising biomarkers that may predict sensitivity to platinum-based chemotherapy in advanced and metastatic NSCLC.

Iodine-125 brachytherapy treatment for newly diagnosed brain metastasis in non-small cell lung cancer A biocentric analysis.

The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC). The study included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy ( The 6-month PFS rate was significantly higher in the Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.

Added survival benefit of whole brain radiotherapy in brain metastatic non-small cell lung cancer Development and external validation of an individual prediction model.

The heterogeneous survival benefit of whole brain radiotherapy (WBRT) in brain metastatic non-small cell lung cancer (NSCLC) was prospectively evidenced in the Quality of Life after Treatment for Brain Metastases (QUARTZ) trial, resulting in inconsistent guideline recommendations and diverse clinical practices for giving WBRT. The objective of this study was to develop and externally validate an individual prediction model to demonstrate the added survival benefit of WBRT to assist decision making when giving WBRT is undetermined. For model development, we collected 479 brain metastatic NSCLC patients unfit for surgery or stereotactic radiotherapy techniques at Siriraj Hospital. Potential predictors were age, sex, performance status, histology, genetic mutation, neurological symptoms, extracranial disease, previous systemic treatment, measurable lesions, further systemic treatment, and WBRT. Cox proportional hazard regression was used for survival analysis. We used multiple imputations to handle missing data and a backward selection method for predictor selection. Bootstrapping was used for internal validation, while model performance was assessed with discrimination (c-index) and calibration prediction accuracy. The final model was transformed into a nomogram and a web-based calculator. An independent cohort from Sawanpracharak Hospital was used for external validation. In total, 452 patients in the development cohort died. The median survival time was 4.4 (95% CI, 3.8-4.9) months, with 5.1 months for patients who received WBRT and 2.3 months for those treated with optimal supportive care (OSC). The final model contained favorable predictors female sex, KPS > 70, receiving additional systemic treatment, and WBRT. Having active extracranial disease, experiencing neurological symptoms, and receiving previous systemic treatment were adverse predictors. After optimism correction, the apparent c-index dropped from 0.71 (95% CI, 0.69-0.74) to 0.70 (95% CI, 0.69-0.73). The predicted and observed values agreed well in all risk groups. Our model performed well in the external validation cohort, with a c-index of 0.66 (95% CI, 0.59-0.73) and an acceptable calibration. This model (httpssiriraj-brainmetscore.netlify.app) predicted the added survival benefit of WBRT for individual brain metastatic NSCLC patients, with satisfactory performance in the development and validation cohorts. The results certify its value in aiding treatment decision-making when the administration of WBRT is unclear.

m

Recent research has confirmed the critical role that epigenetic factors play in regulating the immune response. Nonetheless, what role m Herein, the gene expression, copy number variations (CNVs), and somatic mutations of 31 m Consensus clustering classified all NSCLC samples into two m In conclusion, methylation modification patterns mediated by the m

Study protocol of an open-label

The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis. The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simons two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis. This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients. Chinese Clinical Trial Registry. Trial registration number ChiCTR2100053021. There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes. httpswww.chictr.org.cn, identifier ChiCTR2100053021.

Gou Qi Zi inhibits proliferation and induces apoptosis through the PI3KAKT1 signaling pathway in non-small cell lung cancer.

Gou Qi Zi ( The TCMSP, TCMID, SwissTargetPrediction, DrugBank, DisGeNET, GeneCards, OMIM and TTD databases were searched for the active components of Gou Qi Zi and their potential therapeutic targets in NSCLC. Protein-protein interaction networks were identified and the interactions of target proteins were analyzed. Involved pathways were determined by GO enrichment and KEGG pathway analyses using the Metascape database, and molecular docking technology was used to study the interactions between active compounds and potential targets. These results were verified by cell counting kit-8 assays, BrdU labeling, flow cytometry, immunohistochemistry, western blotting, and qRT-PCR. Database searches identified 33 active components in Gou Qi Zi, 199 predicted biological targets and 113 NSCLC-related targets. A network of targets of traditional Chinese medicine compounds and potential targets of Gou Qi Zi in NSCLC was constructed. GO enrichment analysis showed that Gou Qi Zi targeting of NSCLC was mainly due to the effect of its associated lipopolysaccharide. KEGG pathway analysis showed that Gou Qi Zi acted mainly through the PI3KAKT1 signaling pathway in the treatment of NSCLC. Molecular docking experiments showed that the bioactive compounds of Gou Qi Zi could bind to AKT1, C-MYC and TP53. These results were verified by experimental assays. Gou Qi Zi induces apoptosis and inhibits proliferation of NSCLC

Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer Where do we go from here

In the US, there are 250,000 new lung cancer diagnoses and 130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with potentially curable locoregional disease, instead of distant disease. Exciting developments in molecular targeted therapy and immunotherapy have resulted in dramatic improvement in patients survival, in combination with new surgical, pathological, radiographical, and radiation techniques. Concurrent platinum-based doublet chemoradiation therapy followed by immunotherapy has set the benchmark for survival in these patients. However, despite these advances, 50% of patients diagnosed with locally advanced NSCLC (LA-NSCLC) survive long-term. In patients with local andor locoregional disease, chemoradiation is a critical component of curative therapy. However, there remains a significant clinical gap in improving the efficacy of this combined therapy, and the development of non-overlapping treatment approaches to improve treatment outcomes is needed. One potential promising avenue of research is targeting cancer metabolism. In this review, we will initially provide a brief general overview of tumor metabolism as it relates to therapeutic targeting. We will then focus on the intersection of metabolism on both oxidative stress and anti-tumor immunity. This will be followed by discussion of both tumor- and patient-specific opportunities for metabolic targeting in NSCLC. We will then conclude with a discussion of additional agents currently in development that may be advantageous to combine with chemo-immuno-radiation in NSCLC.

Corrigendum Immune cell-lipoprotein imbalance as a marker for early diagnosis of non-small cell lung cancer metastasis.

This corrects the article DOI 10.3389fonc.2022.942964..

Low-dose computed tomography for lung cancer screening in Anhui, China A randomized controlled trial.

Lung cancer is the leading cause of cancer-related death worldwide, with risk factors such as age and smoking. Low-dose computed tomography screening can reduce lung cancer mortality. However, its effectiveness in Asian populations remains unclear. Most Asian women with lung cancer are non-smokers who have not been screened. We conducted a randomized controlled trial to evaluate the performance of low-dose computed tomography screening in a Chinese population, including high-risk smokers and non-smokers exposed to passive smoking. The baseline data are reported in this study. Between May and December 2019, eligible participants were randomized in a ratio of 111 to a screening (two arms) or control cohort. Non-calcified nodulesmasses with a diameter >4 mm on low-dose computed tomography were considered positive findings. In total, 600 patients (mean age, 59.1 ± 6.9 years) underwent low-dose computed tomography. Women accounted for 31.5% (189600) of patients 89.9% (170189) were non-smokerspassive smokers. At baseline, the incidence of lung cancer was 1.8% (11600). The incidence of lung cancer was significantly lower in smokers than in female non-smokerspassive smokers (1.0% 4415 We demonstrate the importance of including active smokers and female non-smokerspassive smokers in lung cancer screening programs. Further studies are needed to explore the risk factors, and long-term cost-benefit of screening Asian non-smoking women. httpchictr.org.cnshowproj.aspxproj39003, identifier ChiCTR1900023197.

A bibliometric analysis of autophagy in lung diseases from 2012 to 2021.

Autophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis. Publications were retrieved from the 2012-2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease. A total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that autophagy and apoptosis were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases. The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19-related lung diseases.

Characteristics of the immunogenicity and tumor immune microenvironment in

Besides breast and gastric cancer, We integrated public databases (discovery set) and internal data (validated set) of 288 patients representing three distinct Compared with Patients with

A Versatile Pd-Catalyzed Alkyne Annulation Process for Benzo

A Pd-catalyzed, simple, and divergent approach for the direct synthesis of benzo

Atezolizumab-Conjugated Poly(lactic acid)Poly(vinyl alcohol) Nanoparticles as Pharmaceutical Part Candidates for Radiopharmaceuticals.

The necessity of new drugs for lung cancer therapy and imaging is increasing each day. The development of new drugs that are capable of reaching the tumor with specificity and selectivity is required. In this direction, the design of nanoparticles for tumor therapy represents an important alternative. The aim of this study was to develop, characterize, and evaluate target-specific atezolizumab-conjugated poly(lactic acid)poly(vinyl alcohol) (PLAPVA) nanoparticles as pharmaceutical fragment candidates for new radiopharmaceuticals. For this purpose, PLAPVA nanoparticle formulations were prepared by the double emulsificationsolvent evaporation method with a high-speed homogenizer. A special focus was oriented to the selection of a suitable method for modification of the nanoparticle surface with a monoclonal antibody. For this purpose, atezolizumab was bound to the nanoparticles during the preparation by solvent evaporation or either by adsorption or covalent binding. PLAPVAatezolizumab nanoparticles are characterized by dynamic light scattering, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy. An

Double awareness-adolescents and young adults coping with an uncertain or poor cancer prognosis A qualitative study.

Adolescents and young adults with an uncertain or poor cancer prognosis (UPCP) are confronted with ongoing and unique age-specific challenges, which forms an enormous burden. To date, little is known about the way AYAs living with a UPCP cope with their situation. Therefore, this study explores how AYAs with a UPCP cope with the daily challenges of their disease. We conducted semi-structured in-depth interviews among AYAs with a UPCP. Patients of the three AYA subgroups were interviewed (traditional survivors, new survivors, low-grade glioma survivors), since we expected different coping strategies among these subgroups. Interviews were analyzed using elements of the Grounded Theory by Corbin and Strauss. AYA patients were actively involved as research partners. In total 46 AYAs with UPCP participated, they were on average 33.4 years old (age range 23-44) and most of them were woman (63%). Most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6) and lung cancers (6). We identified seven coping strategies in order to reduce the suffering from the experienced challenges (1) minimizing impact of cancer, (2) taking and seeking control, (3) coming to terms, (4) being positive, (5) seeking and receiving support, (6) carpe diem and (7) being consciously alive. This study found seven coping strategies around the concept of double awareness and showcases that AYAs are able to actively cope with their disease but prefer to actively choose life over illness. The findings call for CALM therapy and informal AYA support meetings to support this group to cope well with their disease.

Pulmonary Nodule Detection Based on Multiscale Feature Fusion.

As cancer with the highest morbidity and mortality in the world, lung cancer is characterized by pulmonary nodules in the early stage. The detection of pulmonary nodules is an important method for the early detection of lung cancer, which can greatly improve the survival rate of lung cancer patients. However, the accuracy of conventional detection methods for lung nodules is low. With the development of medical imaging technology, deep learning plays an increasingly important role in medical image detection, and pulmonary nodules can be accurately detected by CT images. Based on the above, a pulmonary nodule detection method based on deep learning is proposed. In the candidate nodule detection stage, the multiscale features and Faster R-CNN, a general-purpose detection framework based on deep learning, were combined together to improve the detection of small-sized lung nodules. In the false-positive nodule filtration stage, a 3D convolutional neural network based on multiscale fusion is designed to reduce false-positive nodules. The experiment results show that the candidate nodule detection model based on Faster R-CNN integrating multiscale features has achieved a sensitivity of 98.6%, 10% higher than that of the other single-scale model, the proposed method achieved a sensitivity of 90.5% at the level of 4 false-positive nodules per scan, and the CPM score reached 0.829. The results are higher than methods in other works of literature. It can be seen that the detection method of pulmonary nodules based on multiscale fusion has a higher detection rate for small nodules and improves the classification performance of true and false-positive pulmonary nodules. This will help doctors when making a lung cancer diagnosis.

Prognostic Value of Lymphocyte-to-Monocyte Ratio (LMR) in Cancer Patients Undergoing Immune Checkpoint Inhibitors.

There is accumulating evidence that the lymphocyte-to-monocyte ratio (LMR) is related to the outcomes of cancer patients treated with immune checkpoint inhibitors (ICIs). However, the results remain controversial. Electronic databases were searched to retrieve the studies that explore the relationship between LMR and the efficacy of ICIs. The primary endpoints were overall survival (OS) and progression-free survival (PFS), evaluated by the hazard ratios (HRs) with 95% confidence intervals (CI), and the secondary endpoints included disease control rate (DCR) and immune-related adverse events (irAEs), assessed by the odd ratios (ORs) with 95% CI. A total of 27 studies involving 4,322 patients were eligible for analysis. The results indicated that increased LMR at baseline was associated with a superior OS (HR 0.46, 95% CI 0.39-0.56, Higher LMR at baseline was positively correlated with a superior OS, PFS, and DCR for ICIs, but not with irAEs.

Activation of the TGF-

Platinum-based chemotherapy is the first choice of treatment for patients diagnosed with small lung cell cancer (SCLC). However, many patients exhibit resistance to it. Therefore, it is imperative to further investigate a prognostic biomarker indicating sensitivity to this therapy. We collected and performed RNA sequencing on 45 SCLC samples from the Zhujiang Hospital (Local-SCLC). In addition, we used a public cohort from George et al. as a validation cohort (George-SCLC). The transforming growth factor A high activation status of the TGFB pathway was associated with improved prognosis in SCLC patients receiving platinum-based chemotherapy (Local-SCLC HR 0.0238, (95% CI, 0.13-0.84), SCLC patients exhibiting a high activation status of the TGFB pathway demonstrate an improved prognosis with platinum-based chemotherapy. The potential underlying mechanism may be related to antitumor immune enhancement and DNA damage repair inhibition.

Intraoperative challenges after induction therapy for non-small cell lung cancer Effect of nodal disease on technical complexity.

Neoadjuvant therapy has been theorized to increase complexity of non-small cell lung cancer resections however, specific factors that contribute to intraoperative challenges after induction therapy have not been well described. We aimed to characterize the effect of nodal involvement and nodal treatment response on surgical complexity after neoadjuvant therapy. We identified patients treated with neoadjuvant therapy followed by anatomic lung resection for cN non-small cell lung cancer between 2010 and 2020. Patients were categorized according to clinical N1 versus N2 disease. To evaluate the effect of nodal response to therapy, thoracic radiologists measured clinically suspected and pathologically involved lymph nodes before and after induction therapy. Operative reports were reviewed to identify technical challenges specifically related to nodal disease. Categorical outcomes were compared using Fisher exact test. One hundred twenty-four patients met inclusion criteria, among whom 107 (86.3%) were treated with neoadjuvant chemotherapy, whereas chemoradiation (n 8) and targeted therapy (n 9) were less common. In cases with N1 disease, 838 (21.0%) required proximal pulmonary arterial control, whereas this was necessary in only 288 (2.3%) of N2 cases ( After induction therapy, N1 disease was associated with greater need for complex surgical maneuvers than N2 disease. Likewise, substantial treatment response was associated with increased intraoperative technical challenges. Recognizing such factors enables surgical teams to engage in appropriate operative planning to ensure patient safety.

Trends of utilization and perioperative outcomes of robotic and video-assisted thoracoscopic surgery in patients with lung cancer undergoing minimally invasive resection in the United States.

The objective of this study was to evaluate utilization and perioperative outcomes of video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery (RATS) for lung cancer in the United States using a nationally representative database. Hospital admissions for lobectomy or sublobar resection (segmentectomy or wedge resection) using VATS or RATS in patients with nonmetastatic lung cancer from October 2015 through December 2018 in the National Inpatient Sample were studied. Patient and hospital characteristics, perioperative complications and mortality, length of stay (LOS), and total hospital cost were compared. Logistic regression was used to assess whether the surgical approach was independently associated with adverse outcomes. There were 83,105 patients who had VATS (n 65,375) or RATS (n 17,710) for lobectomy (72.7% VATS) or sublobar resection (84.2% VATS). Utilization of RATS for lobectomy and sublobar resection increased from 19.2% to 34% and 7.3% to 22%, respectively. Mortality, LOS, and conversion rates were comparable. The cost was higher for RATS ( The utilization of robotic-assisted lung resection for cancer has increased in the United States between 2015 and 2018 for sublobar resection and lobectomy. In adjusted regression analysis, compared with VATS, patients who underwent RATS had similar complication rates and LOS. The robotic approach was associated with increased total hospital cost. LOS and thoracic complication rates trended down after RATS lobectomy.

Germline mutations in high penetrance genes are associated with worse clinical outcomes in patients with non-small cell lung cancer.

To determine the frequency of pathogenic mutations in high-penetrance genes (HPGs) in patients with non-small cell lung cancer (NSCLC) and identify whether such mutations are associated with clinicopathologic outcomes. Patients with NSCLC who had consented to participate in a linked clinical database and biorepository underwent germline DNA sequencing using a next-generation sequencing panel that included cancer-associated HPGs and cancer risk-associated single nucleotide polymorphisms (SNPs). These data were linked to the clinical database to assess for associations between germline variants and clinical phenotype using Fishers exact test and multivariable logistic and Cox regression. We analyzed 151 patients, among whom 33% carried any pathogenic HPG mutation and 23% had a genetic risk score (GRS) >1.5. Among the patients without any pathogenic mutation, 31% were at cancer stage II or higher, compared with 55% of those with 2 types of HPG mutations ( The presence of mutations in HPGs is associated with higher cancer stage, increased risk of recurrence, and worse cancer-specific and overall survival in patients with NSCLC. Further large studies are needed to better delineate the role of HPGs in cancer recurrence and the potential benefit of adjuvant treatment in patients harboring such mutations.

Visualization of patterns of lymph node metastases in non-small cell lung cancer using network analysis.

We aimed to visualize complicated patterns of lymph node metastases in surgically resected non-small cell lung cancer by applying a data mining technique. In this retrospective study, 783 patients underwent lobectomy or pneumonectomy with systematic mediastinal lymph node dissection for non-small cell lung cancer between January 2010 and December 2018. Surgically resected lymph nodes were classified according to the International Association for the Study of Lung Cancer lymph node map. Network analysis generated patterns of lymph node metastases from stations 1 to 14, and the degree of connection between 2 lymph node stations was assessed. The median number of lymph nodes examined per patient was 20, and the pathological N category was pN0 in 428 cases, pN1 in 132, pN2 in 221, and pN3 in 2. N1 lymph node stations had strong associations with superior mediastinal lymph node stations for patients with primary tumors in the upper lobes and with station 7 for the lower lobes. There was also a connection from the N1 lymph node stations to superior mediastinal lymph node stations in the lower lobes. In the right middle lobe, an even distribution from station 12m toward stations 2R, 4R, and 7 was noted. We released an interactive web application to visualize these data httpwww.canexapp.com. Lymph node metastasis patterns differed according to the lobe bearing the tumor. Our results support the need for clinical trials to further investigate selective mediastinal lymph node dissection.

Long-term survival of a patient with lung cancer treated with pembrolizumab after recurrent cardiac tamponade.

A 69-year-old man with non-small cell lung cancer presenting with pericardial effusion and rapid progression of dyspnea achieved long-term disease stabilization after radiation therapy and immunotherapy. This case shows that pembrolizumab may improve prognosis in advanced lung cancer, even when complicated by cardiac tamponade.

Serum protein profiling of lung, pancreatic, and colorectal cancers reveals alcohol consumption-mediated disruptions in early-stage cancer detection.

While the link between serum proteins and cancer has been studied in an effort to enable early-stage cancer detection, factors that might perturb this link has been poorly understood. To ask this question, we performed serum protein profiling on a prospective cohort of 601 individuals with or without lung, pancreatic, or colorectal cancers and identified ten distinct serum protein signatures with distinct link to the patient metadata. Importantly, we discovered that a positive history of alcohol consumption is a major factor that diminishes the sensitivity of serum protein-mediated liquid biopsy in early-stage malignancies, resulting in a 44% decline in the sensitivity of detecting American Joint Committee on Cancer (AJCC) stage I malignancies. Our data provide evidence that patient lifestyle can affect the sensitivity of liquid biopsy and suggest the potential need for abstinence from alcohol before measurement during serum protein-based cancer screening.

Green synthesis of AgFe

Herein, a bio-inspired synthetic method for Ag NP adorned biofunctionalized magnetic nanocomposite has been demonstrated. In the procedure,

Studies on biotransformation mechanism of

Paridis Rhizoma is a natural medicine with strong anti-tumor and anti-inflammatory activities. Our previous research have found that

PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer.

About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for CC, 44.7% for CG and 41.1% for GG. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of CC genotype was 44.6% ± 0.170, which was higher than that of genotype CG and GG (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F 3.169

circPOLR1C Promotes the Development of Esophageal Cancer by Adsorbing miR-361-3p and Regulating Cancer Cell Apoptosis and Metastasis.

The effect of circular RNA-RNA polymerase I and III subunit C (circPOLR1C) on esophageal cancer (EC) has not been reported. Herein, this study is designed to unveil the effect and the regulatory mechanism of circPOLR1C on EC. The expression of circPOLR1C in EC tissues and cells was detected by qRT-PCR. Circular structure, stability, and cell localization of circPOLR1C were confirmed by qRT-PCR, RNase R, actinomycin D, and fluorescence Highly expressed circPOLR1C in EC was related to tumor differentiation and invasion. circPOLR1C, which mainly exists in the cytoplasm, is a stable circular RNA. circPOLR1C silencing inhibited circPOLR1C expression and EC cell malignant function, while circPOLR1C overexpression promoted the growth of transplanted tumors and lung metastasis. The enrichment of miR-361-3p was higher than that of other targeted miRNAs. circPOLR1C adsorbed miR-361-3p to regulate apoptosis- and EMT-related genes and partially reversed the tumor suppressive effect of miR-361-3p, which was lowly expressed in EC tissues. Silencing the target genes of miR-361-3p also inhibited the malignant development of EC cells. circPOLR1C adsorbs miR-361-3p and regulates apoptosis- and EMT-related gene expressions to promote the development of EC.

Bee Venom Triggers Autophagy-Induced Apoptosis in Human Lung Cancer Cells via the mTOR Signaling Pathway.

In oriental medicine, bee venom has long been used as a therapeutic agent against inflammatory diseases. Several studies have reported that isolated and purified bee venom components are effective in treating dementia, arthritis, inflammation, bacterial infections, and cancer. In previous studies, we reported that bee venom inhibits cell growth and induces apoptotic cell death in lung cancer cells. In the present study, we assessed whether bee venom affects autophagy and thereby induces apoptosis. Bee venom treatment increased the levels of autophagy-related proteins (Atg5, Beclin-1, and LC3-II) and the accumulation of LC3 puncta. We found that bee venom could induce autophagy by inhibiting the mTOR signaling pathway. In addition, we found that hydroxychloroquine (HCQ)- or si-ATG5-induced autophagy inhibition further demoted bee venom-induced apoptosis. Bee venom-induced autophagy promotes apoptosis in lung cancer cells and may become a new approach to cancer treatment.

Current investigative modalities for detecting and staging lung cancers a comprehensive summary.

This narrative review compares the advantages and drawbacks of imaging and other investigation modalities which currently assist with lung cancer diagnosis and staging, as well as those which are not routinely indicated for this. We examine plain film radiography, computed tomography (CT) (alone, as well as in conjunction with positron emission tomography (PET)), magnetic resonance imaging (MRI), ultrasound, and newer techniques such as image-guided bronchoscopy (IGB) and robotic bronchoscopy (RB). While a chest X-ray is the first-line imaging investigation in patients presenting with symptoms suggestive of lung cancer, it has a high positive predictive value (PPV) even after negative X-ray findings, which calls into question its value as part of a potential national screening programme. CT lowers the mortality for high-risk patients when compared to X-ray and certain scoring systems, such as the Brock model can guide the need for further imaging, like PET-CT, which has high sensitivity and specificity for diagnosing solitary pulmonary nodules as malignant, as well as for assessing small cell lung cancer spread. In practice, PET-CT is offered to everyone whose lung cancer is to be treated with a curative intent. In contrast, MRI is only recommended for isolated distant metastases. Similarly, ultrasound imaging is not used for diagnosis of lung cancer but can be useful when there is suspicion of intrathoracic lymph node involvement. Ultrasound imaging in the form of endobronchial ultrasonography (EBUS) is often used to aid tissue sampling, yet the diagnostic value of this technique varies widely between studies. RB is another novel technique that offers an alternative way to biopsy lesions, but further research on it is necessary. Lastly, thoracic surgical biopsies, particularly minimally invasive video-assisted techniques, have been used increasingly to aid in diagnosis and staging.

Synergy of arsenic with smoking in causing cardiovascular disease mortality A cohort study with 27 follow-up years in China.

To explore the patterns of the exposure-response relationship between arsenic exposure and cardiovascular disease (CVD) mortality and investigate the effect of cigarette smoking on the association. Seven thousand seven hundred thirty-five tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. Each individuals air arsenic exposure at workplace was calculated by time weighted average arsenic concentration × exposure months. Detailed information on smoking was collected at baseline, and information on smoking status was collected for five consecutive years from 1992 to 1996. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of CVD were estimated using Cox proportional hazards models. A total of 1,046 CVD deaths occurred in this cohort over 142,287.7 person-years of follow up. We firstly reported that for equal cumulative exposure, participants exposed to higher concentrations over shorter duration had a higher risk of CVD mortality than those exposed to lower concentration over longer duration. The HR and 95% CI were 1.38 (95%CI 1.03-1.85) in participants exposed to arsenic concentration (45.5-99.5 mgm Exposure to air arsenic at workplace is adversely associated with mortality from CVD, especially among smokers younger than 18 years and smokers.

Detection of

XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma.

Dysregulation of eukaryotic translation initiation factor 1A, X-linked (

Fumarate hydratase inhibits non-small cell lung cancer metastasis via inactivation of AMPK and upregulation of DAB2.

Lung cancer is one of the leading causes of cancer mortality worldwide. As it is often first diagnosed only when cancer metastasis has already occurred, the development of effective biomarkers for the risk prediction of cancer metastasis, followed by stringent monitoring and the early treatment of high-risk patients, is essential for improving patient survival. Cancer cells exhibit alterations in metabolic pathways that enable them to maintain rapid growth and proliferation, which are quite different from the metabolic pathways of normal cells. Fumarate hydratase (FH, fumarase) is a well-known tricarboxylic acid cycle enzyme that catalyzes the reversible hydrationdehydration of fumarate to malate. The current study sought to investigate the relationship between FH expression levels and the outcome of patients with lung cancer. FH was knocked down in lung cancer cells using shRNA or overexpressed using a vector, and the effect on migration ability was assessed. Furthermore, the role of AMP-activated protein kinase (AMPK) phosphorylation and disabled homolog 2 in the underlying mechanism was investigated using an AMPK inhibitor approach. The results showed that in lung cancer tissues, low FH expression was associated with lymph node metastasis, tumor histology and recurrence. In addition, patients with low FH expression exhibited a poor overall survival in comparison with patients having high FH expression. When FH was overexpressed in lung cancer cells, cell migration was reduced with no effect on cell proliferation. Furthermore, the level of phosphorylated (p-)AMPK, an energy sensor molecule, was upregulated when FH was knocked down in lung cancer cells, and the inhibition of p-AMPK led to an increase in the expression of disabled homolog 2, a tumor suppressor protein. These findings suggest that FH may serve as an effective biomarker for predicting the prognosis of lung cancer and as a therapeutic mediator.

Hesperidin inhibits tobacco smoke-induced pulmonary cell proliferation and EMT in mouse lung tissues via the p38 signaling pathway.

Tobacco smoke (TS) is the major cause of lung cancer. The abnormal proliferation and epithelial-mesenchymal transition (EMT) of lung cells promote occurrence and development of lung cancer. The p38 pathway intervenes in this cancer development. Hesperidin also serves a role in human health and disease prevention. The roles of p38 in TS-mediated abnormal cell proliferation and EMT, and the hesperidin intervention thereof are not yet understood. In the present study, it was demonstrated that TS upregulated proliferating cell nuclear antigen, vimentin and N-cadherin expression, whereas it downregulated E-cadherin expression, as assessed using western blotting and reverse transcription-quantitative PCR. Furthermore, it was observed that inhibition of the p38 pathway inhibit TS-induced proliferation and EMT. Hesperidin treatment prevented the TS-induced activation of the p38 pathway, EMT and cell proliferation in mouse lungs. The findings of the present study may provide insights into the pathogenesis of TS-related lung cancer.

Primary vaginal sarcoma in a single center.

To investigate the clinical characteristics and prognosis of primary vaginal sarcoma. A retrospective analysis of patients with primary vaginal sarcoma treated at our center from 2000 to 2020 was conducted. Fifteen patients were identified, among which 9 (60.0 %) patients had leiomyosarcoma, 2 (13.3 %) patients had Ewings sarcoma, 2 (13.3 %) patients had rhabdomyosarcoma, 1 (6.7 %) patient had undifferentiated sarcoma, and 1 (6.7 %) patient had malignant peripheral schwannoma. Nine patients presented with vaginal mass that was the most common primary symptoms. Eleven patients received their primary surgery, and 7 of them received postoperative adjuvant chemotherapy or radiation therapy. The remaining 4 patients received initial chemotherapy andor radiotherapy because of advanced stage. The distribution by stage was as follows stage I in 10 patients, stage II in 1 patient, stage III in 2 patients and stage IV in 2 patients. The median follow-up was 43.7 months (10.1-137.5 months). Thirteen patients (86.7 %) had disease extent during follow-up, and among them, 11 patients (1113, 84.6 %) developed local relapse or adjacent organ metastases, 1 patient (113, 7.7 %) developed liver metastases, and the remaining 1 patient (113, 7.7 %) developed lung metastases and local relapse during follow-up. Ten (1013, 76.9 %) patients relapsed within 2 years after diagnosis. Eight patients (811, 72.7 %) with local recurrence or adjacent organ metastases received a secondary surgery treatment, and only 2 of them relapsed again. Two-year overall survival (OS) and 5-year OS were 80.0 % and 66.7 %, respectively. Patients with leiomyosarcoma had a tendency toward a better 5-year OS than those with other sarcomas (74.1 % vs 66.7 %, Primary vaginal sarcomas are aggressive neoplasms with different presenting characteristics. Surgery is the main treatment for primary vaginal sarcoma and for local relapse vaginal sarcoma.

Male breast An unusual case of metastasis of squamous cell carcinoma of the skin.

Breast metastasis from extra-mammary neoplasm is a rare condition, accounting for approximately 1.2%-2% of all breast malignancies. Melanoma, lung cancer, gynecological, and hematological cancers can metastasis to the breast. Male breast metastasis is extremely rare and, no evidence of metastasis from cutaneous squamous cell carcinoma in a male breast have been reported to our knowledge. We describe a case of an 81-year-old man who came to our attention for a palpable solid mass in the upper-outer aspect of the left breast with the final histological diagnosis of breast metastasis from non-keratoblastic cutaneous squamous cell carcinoma.

Effective treatment with mitotane for a canine case of presumed ectopic Cushings syndrome-related pheochromocytoma.

In humans, ectopic Cushings syndrome (ECS) is characterized by hypercortisolemia, which is caused by small lung carcinoma, bronchial carcinoids, and pheochromocytoma. In dogs, only a few cases of ECS associated with pheochromocytoma have been reported to date. Herein, we describe a canine case of malignant pheochromocytoma that is presumed to be the cause of ECS. An 11-year-old, castrated, male Toy Poodle with hypercortisolemia was diagnosed with an adrenal tumor (AT) and treated with mitotane. Although repeated adrenocorticotropic hormone stimulation tests revealed improvement in the dogs condition by mitotane treatment, its condition started declining 197 days post-diagnosis, and he died on day 280. The necropsy revealed the AT was a pheochromocytoma, not an adrenocortical tumor. However, because of no pathological change in the pituitary gland and the other adrenal gland, pheochromocytoma was presumed to be the cause of ECS. This is the first report that describes the effectiveness of mitotane against presumed ECS-related pheochromocytoma.

Targeting GSTP1-dependent ferroptosis in lung cancer radiotherapy Existing evidence and future directions.

Radiotherapy is applied in about 70% patients with tumors, yet radioresistance of tumor cells remains a challenge that limits the efficacy of radiotherapy. Ferroptosis, an iron-dependent lipid peroxidation regulated cell death, is involved in the development of a variety of tumors. Interestingly, there is evidence that ferroptosis inducers in tumor treatment can significantly improve radiotherapy sensitivity. In addition, related studies show that Glutathione S-transferase P1 (GSTP1) is closely related to the development of ferroptosis. The potential mechanism of targeting GSTP1 to inhibit tumor cells from evading ferroptosis leading to radioresistance has been proposed in this review, which implies that GSTP1 may play a key role in radiosensitization of lung cancer

Association between increased peripheral blood CD86-positive plasmacytoid dendritic cells and immune-related adverse events in patients with non-small cell lung cancer.

The occurrence of immune-related adverse events (irAEs) after immune checkpoint inhibitors (ICIs) is unpredictable. Profiles of peripheral blood mononuclear cells (PBMCs) represent the host immune system and have the potential to predict irAEs. We analyzed PBMC subsets using multicolor flow cytometry before and at weeks 2 and 8 after the start of ICIs in patients with non-small cell lung cancer. Sixteen eligible patients were evaluated. The irAEs occurred in 6 patients (37.5%) diarrhea in 2, diarrhea and a rash in 1, pituitary dysfunction in 1, cholangitis in 1, and pneumonitis in 1. Patients experiencing irAEs had higher levels of CD86

Anaplastic Transformation of Follicular Thyroid Carcinoma in Pulmonary Metastasis With Gradually Progressive Intra-tumoral Cavitation A Case Report.

Anaplastic transformation of differentiated thyroid cancer is rare but clinically important because of the dismal prognosis after anaplastic transformation. Therefore, cases and findings of anaplastic transformation must be accumulated, which could ultimately lead to an earlier diagnosis and an improved prognosis. Here, we present a case of anaplastic transformation of follicular thyroid carcinoma (FTC) in a pulmonary metastatic lesion associated with gradually progressive tumor cavitation. The patient with FTC was diagnosed with multiple lung metastases three years after surgery for the primary tumor and metastatic neck lymph nodes. Annual treatment with radioactive iodine resulted in disease stability for 10 years. However, one lung metastasis in the left lower lobe gradually enlarged and was associated with intra-tumoral cavitation. The growing lung nodule was resected and pathologically diagnosed as an anaplastic transformation of FTC. Fourteen months after diagnosis, the patient died of pneumothorax caused by pleural dissemination despite multiple treatment interventions. This case highlights pulmonary metastasis with progressive cavitary lesions as a potential early sign of the anaplastic transformation of differentiated thyroid cancer.

Utility of serum homocysteine in oral squamous cell carcinoma patients as a potential biomarker.

In India, Oral cancer is one of the most common cancers. Despite advances in treatments, prognosis for oral cancer has remained poor with a five-year survival rate of 40-50%. Therefore, it is necessary to develop effective diagnostic methods for early diagnosis and better prognosis. Homocysteine (Hcy) has been reported as a tumour marker in various cancers such as breast cancer, colorectal cancer, lung cancer, cervical cancer. To study the levels of serum Hcy in oral squamous cell carcinoma (OSCC) patients. To assess the clinical utility of serum Hcy as a potential tumour marker for OSCC cases. Serum Hcy levels were studied and compared between patients with OSCC and healthy individuals. Serum Hcy levels were higher in patients having OSCC. Serum Hcy levels could be utilized as a biological marker in the diagnosis and the prognosis of OSCC patients.

Role of Nidogen-2 in diagnosis and prognosis of head and neck squamous cell carcinoma A systematic review.

Nidogen-2 ( A systematic search was performed across multiple databases to identify studies pertaining to analysis of expression or methylation of Four studies were identified after a systematic search of literature. The studies analysed Data from the reviewed studies indicate that hypermethylation of

Proliferation, apoptosis and invasion of human lung cancer cells are associated with NFATc1.

The expression of nuclear factor of activated T cells c1 (NFATc1) is closely associated with the progression of numerous types of cancer. When NFATc1 expression becomes dysregulated in some types of cancer, this alteration can promote malignant transformation and thereby progression of cancer. NFATc1 expression has been demonstrated to be upregulated in lung cancer cells. This suggests that knockdown of NFATc1 in lung cancer cells may be a therapeutic marker for the treatment of cancer. In the present study, the effects of NFATc1 on the proliferation, apoptosis, invasion and migration of NCI-H1299 and A549 lung cancer cell lines were explored. Lentivirus infection was used to establish a cell model of NFATc1 knockdown in A549 and NCI-H1299 lung cancer cells. Reverse transcription-quantitative PCR was subsequently performed to detect NFATc1 expression in these human lung cancer cells. MTT, wound healing, colony formation and Transwell invasion assays, and flow cytometry were then performed to measure the proliferation, invasion, apoptosis and cell cycle of the cells. Finally, western blot analysis was performed to investigate the mechanism underlying the involvement of NFATc1 in these processes. NFATc1 knockdown was found to significantly inhibit the proliferation, clone formation, migration and invasion of the cells. Furthermore, the cell cycle was arrested at the G

A novel diagnostic model for predicting immune microenvironment subclass based on costimulatory molecules in lung squamous carcinoma.

There is still no ideal predictive biomarker for immunotherapy response among patients with non-small cell lung cancer. Costimulatory molecules play a role in anti-tumor immune response. Hence, they can be a potential biomarker for immunotherapy response. The current study comprehensively investigated the expression of costimulatory molecules in lung squamous carcinoma (LUSC) and identified diagnostic biomarkers for immunotherapy response. The costimulatory molecule gene expression profiles of 627 patients were obtained from the The Cancer Genome Atlas, GSE73403, and GSE37745 datasets. Patients were divided into different clusters using the k-means clustering method and were further classified into two discrepant tumor microenvironment (TIME) subclasses (hot and cold tumors) according to the immune score of the ESTIMATE algorithm. A high proportion of activated immune cells, including activated memory CD4 T cells, CD8 T cells, and M1 macrophages. Five CMGs (FAS, TNFRSF14, TNFRSF17, TNFRSF1B, and TNFSF13B) were considered as diagnostic markers using the Least Absolute Shrinkage and Selection Operator and the Support Vector Machine-Recursive Feature Elimination machine learning algorithms. Based on the five CMGs, a diagnostic nomogram for predicting individual tumor immune microenvironment subclasses in the TCGA dataset was developed, and its predictive performance was validated using GSE73403 and GSE37745 datasets. The predictive accuracy of the diagnostic nomogram was satisfactory in all three datasets. Therefore, it can be used to identify patients who may benefit more from immunotherapy.

Association of lncRNA H19 polymorphisms with cancer susceptibility An updated meta-analysis based on 53 studies.

The association between polymorphisms in lncRNA H19 and cancer susceptibility remains to be inconsistent. This study aimed to provide a more precise estimation of the relationship between lncRNA H19 polymorphisms and the risk of cancer based on all available published studies. 53 studies encompassing 32,376 cases and 43,659 controls were included in our meta-analysis by searching the Pubmed, Embase, Web of Science, WanFang, and China National Knowledge Infrastructure databases. Pooled ORs and their 95% CIs were used to estimate the strength between the SNPs in H19 (rs217727, rs2839698, rs2107425, rs3024270, rs2735971, rs3741216, and rs3741219) and cancer susceptibility. The results showed that H19 rs2839698 polymorphism was associated with increased cancer risk in all participants under three genetic models. However, no significant association was identified between the other six SNPs as well as an overall cancer risk. Stratification by ethnicity showed that rs2839698 mutation indicated to be an important hazardous factor for the Asian population. While rs2107425 mutation had a protective effect on the Caucasian population. Stratification by cancer type identified that rs217727 mutation was linked to increased susceptibility to oral squamous cell carcinoma, lung cancer, and hepatocellular carcinoma whereas rs2839698 mutation was associated with an elevated risk of hematological tumor and digestive system tumor (

Deep learning-based multi-drug synergy prediction model for individually tailored anti-cancer therapies.

While synergistic drug combinations are more effective at fighting tumors with complex pathophysiology, preference compensating mechanisms, and drug resistance, the identification of novel synergistic drug combinations, especially complex higher-order combinations, remains challenging due to the size of combination space. Even though certain computational methods have been used to identify synergistic drug combinations

ASK120067 potently suppresses B-cell or T-cell malignancies

Hyperactivation of Brutons tyrosine kinase (BTK) or interleukin-2-inducible T cell kinase (ITK) has been attributed to the pathogenesis of B-cell lymphoma or T-cell leukemia, respectively, which suggests that Brutons tyrosine kinase and interleukin-2-inducible T cell kinase are critical targets for the treatment of hematological malignancies. We identified a novel third-generation epidermal growth factor receptor (EGFR) inhibitor, ASK120067 (limertinib) in our previous research, which has been applied as a new drug application against non-small cell lung cancer in China. In this work, we found that ASK120067 displayed potent

Prevalence of polypharmacy and potentially inappropriate medication use in older lung cancer patients A systematic review and meta-analysis.

Correlation of

Sambit K. Mohanty

Prognostic Impact of Baseline Liver Metastasis in ALK Fusion-Positive Metastatic Lung Cancer A Retrospective Review.

Akhil Kapoor