Genomic characterization of peritoneal lavage cytology-positive gastric cancer

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives

BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.

LungPoint导航联合吲哚菁绿荧光成像在Ⅰa期非小细胞肺癌淋巴结采样中的应用价值

目的:寻找一种准确定位Ⅰa期非小细胞肺癌患者(NSCLC)前哨淋巴结(SLN)的方法,验证SLN作为淋巴结取样样本的合理性。方法:采用前瞻性研究方法,参照入组标准纳入2021年1月至2023年12月在山东省公共卫生临床中心胸外科临床分期为Ⅰa期NSCLC住院患者50例,术前借助LungPoint导航气管镜下肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像完成SLN定位,并对包括SLN在内的区域淋巴结行病理学检查,使用该方法对SLN的识别率、准确率与假阴性率等验证其作为淋巴结取样样本的合理性。结果:50例患者中,41例检测到SLN,识别率为82.0%(41/50),经病理检测发现3例共计9枚SLN有淋巴结转移(阳性),其中1例亦检出非前哨淋巴结(N-SLN)阳性2枚。9例患者未检测到SLN,清扫淋巴结54枚,未发现转移淋巴结,故SLN准确率为100.0%(41/41),假阴性率为0(0/3)。结论:借助LungPoint气管镜在肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像探寻SLN技术具有较高的区域淋巴结转移预测性,有望成为指导Ⅰa期NSCLC系统性淋巴结采样的依据。

Application Analysis of High Risk HPV Detection Combined with Cervical Cytology, Colposcopy and Pathology in Cervical Lesions of Women in Tiandeng County

Purpose: To understand the application of high-risk HPV detection combined with cervical cytology, colposcopy and pathology in cervical lesions of women in Tiandeng County. Method: Women in the outpatient and inpatient departments of our hospital from January 2021 to October 2022 were collected for high-risk HPV testing, TCT, colposcopy and pathological examination according to their personal wishes, to understand the application of relevant examinations in cervical lesions. Result: In 2021, the number of patients was 5801, among whom 1743 patients had received cervical cancer examination in the past, accounting for 30.05% of the total number of patients, and 5795 who had volunteered for TCT examination this time, accounting for 99.90% of the total;A total of 289 cases of atypical squamous cells with unclear significance (ASC-US) were detected, excluding 11 cases of high-grade squamous intraepithelial lesions (ASC-H), 122 cases of low-grade squamous intraepithelial lesions (LSIL), 16 cases of high-grade squamous intraepithelial lesions (HSIL), 2 cases of squamous cell carcinoma (SCC), and 4 cases of atypical adenocyte (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of people who volunteered for high-risk HPV testing was 4237, and the number of positive cases was 740, accounting for 17.47% of the screening population;Among 740 HPV-positive patients, 488 high-risk HPV-positive patients were selected for TCT examination, and 87 patients were found to be TCT positive;From 401 high-risk HPV-positive and TCT negative patients, 287 patients with possible lesions were screened out for colposcopy;The results showed that 60 patients may have certain cervical lesions and need further pathological examination and the results showed that 28 patients had CTN1 and 18 patients had CIN2 - 3. In 2022, 8840 patients received medical treatment, among which 3188 patients had received cervical cancer examination in the past, accounting for 36.06% of the total number of patients, and 8314 patients voluntarily underwent TCT examination, accounting for 94.05% of the total number of patients. 434 cases of atypical squamous cells with ambiguous meaning (ASC-US) were detected, excluding 13 cases of high-grade squamous intraepithelial lesions (ASC-H), 217 cases of low-grade squamous intraepithelial lesions (LSIL), 35 cases of high-grade squamous intraepithelial lesions (HSIL), 1 case of squamous cell carcinoma, and 4 cases of atypical adenocarcinoma (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of volunteers for high-risk HPV testing was 3871 cases, and the number of positive cases was 654 cases, accounting for 16.89% of the screening number. 527 high-risk HPV-positive patients were selected from 654 HPV-positive patients for TCT examination, and the number of TCT-positive patients was found to be 49. From 478 high-risk HPV-positive patients with TCT negative, 276 patients with possible lesions were screened out for colposcopy;The results showed that 66 patients may have certain cervical lesions and need further pathological examination;and then the results showed that 31 cases of CTN1 and 6 cases of CIN2 - 3. Conclusion: Gynecological high-risk HPV examination can provide better etiological sources for cervical cancer screening;Cervical cytology examination has high sensitivity;Colposcopy examination has high specificity;Pathological examination can be used as an effective supplement for cervical cytology examination and colposcopy;So high-risk HPV combined with cytology examination, colposcopy examination and pathological examination has high clinical application value;It is worth popularizing and applying.

Pulmonary rehabilitation protocols in urgent lung transplantation patients

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

Five-Year Survivors of Non-Small Cell Lung Cancer Patients with Positive Pleural Lavage Cytology

Background: The pleural lavage cytology (PLC) for non-small cell lung cancer (NSCLC) patients has been reported as a significant prognostic factor. The aim of this study is to clarify the clinicopathological characteristics of 5-year survivors of patients with positive PLC. Methods: Among 401 resected NSCLC patients, 30 (7.48%) patients with positive PLC were reviewed retrospectively. Results: Only 7 of 30 patients (23.3%) survived more than 5-year. There were no differences in age, gender, histology, pT status and pN status between 5-year survivors and non-survivors. On the other hand, the serum carcinoembryonic antigen (CEA) level was significantly higher in non-survivors. Among these 5-year survivors, 4 of 7 patients died of NSCLC recurrences more than 5 years after surgery. Remaining 3 patients survived without cancer recurrences. Interestingly these 3 survivors had not received any adjuvant therapies after surgery. Conclusion: None of the 5-year survivor with positive PLC had high serum CEA level. Furthermore 5-year survival did not equal to cure in NSCLC patients with positive PLC.

First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.

Primary biliary cholangitis presenting with granulomatous lung disease misdiagnosed as lung cancer:A case report

BACKGROUND There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis(PBC).No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported.CASE SUMMARY A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography.She underwent left lobectomy,and the pathology of the nodules showed granulomatous inflammation,which was then treated with antibiotics.However,a new nodule appeared.Further investigation with lung biopsy and liver serology led to the diagnosis of PBC,and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid.CONCLUSION Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

Effect of Climate Change on Lung Cancer

This research paper aims to draw a relationship between lung cancer and climate change. With the rise of climate change in the last few decades, many organizations and people are concerned about the future of the world. Climate change has many side effects, such as air pollution, which can increase the incidence and death rates of lung and bronchus cancer. This paper aims to draw the relationship between climate change factors and lung cancer incidence and mortality rates. The main finding of this analysis was that there is a positive relationship between lung cancer incidence, death rates, and climate change indicators. The findings from this study have the potential to inform targeted public health interventions and policies, emphasizing the need for proactive strategies in mitigating the health impacts of a changing climate. Section 2 of this paper is a literature review and focuses on the findings of other scholars in this field. Section 3 of this paper is Methods and Processes and will highlight the steps used to create the program and get the results. Section 4 of this paper is Results and Analysis, and will go over the results produced by the machine learning algorithm, and will present graphs and visualizations regarding the relationship of the dependent and independent variables. The final section, Section 5, is Limitations and Conclusion, in which we will discuss possible limitations to both my dataset and my model, and will conclude the paper by presenting a big-picture view of these problems in our society.

Empowering Diagnosis: Cutting-Edge Segmentation and Classification in Lung Cancer Analysis

Lung cancer is a leading cause of global mortality rates.Early detection of pulmonary tumors can significantly enhance the survival rate of patients.Recently,various Computer-Aided Diagnostic(CAD)methods have been developed to enhance the detection of pulmonary nodules with high accuracy.Nevertheless,the existing method-ologies cannot obtain a high level of specificity and sensitivity.The present study introduces a novel model for Lung Cancer Segmentation and Classification(LCSC),which incorporates two improved architectures,namely the improved U-Net architecture and the improved AlexNet architecture.The LCSC model comprises two distinct stages.The first stage involves the utilization of an improved U-Net architecture to segment candidate nodules extracted from the lung lobes.Subsequently,an improved AlexNet architecture is employed to classify lung cancer.During the first stage,the proposed model demonstrates a dice accuracy of 0.855,a precision of 0.933,and a recall of 0.789 for the segmentation of candidate nodules.The suggested improved AlexNet architecture attains 97.06%accuracy,a true positive rate of 96.36%,a true negative rate of 97.77%,a positive predictive value of 97.74%,and a negative predictive value of 96.41%for classifying pulmonary cancer as either benign or malignant.The proposed LCSC model is tested and evaluated employing the publically available dataset furnished by the Lung Image Database Consortium and Image Database Resource Initiative(LIDC-IDRI).This proposed technique exhibits remarkable performance compared to the existing methods by using various evaluation parameters.

Retraction: Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial-Mesenchymal Transition Process by Upregulation of MicroRNA-1284

Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.The authors were contacted and invited to comment on the concerns raised and to provide the original,unmodified figures,but did not respond.The Editors-in-Chief therefore no longer have confidence in the integrity of the data in this article and decided to retract this article.

Lung adenocarcinoma with initial binocular symptoms

Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.

miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Hepatoid adenocarcinoma of the lung:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.

Cancer-educated neutrophils promote lung cancer progression via PARP-1-ALOX5-mediated MMP-9 expression

Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been established.Methods:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients.The effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor model.Gene knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated neutrophils.Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with PARP-1.Co-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression.Results:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(P<0.001).Neutrophil activation promoted lung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in vivo.Mechanistically,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth.Conclusion:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer progression.

Multilevel Attention Unet Segmentation Algorithmfor Lung Cancer Based on CT Images

Lung cancer is a malady of the lungs that gravely jeopardizes human health.Therefore,early detection and treatment are paramount for the preservation of human life.Lung computed tomography(CT)image sequences can explicitly delineate the pathological condition of the lungs.To meet the imperative for accurate diagnosis by physicians,expeditious segmentation of the region harboring lung cancer is of utmost significance.We utilize computer-aided methods to emulate the diagnostic process in which physicians concentrate on lung cancer in a sequential manner,erect an interpretable model,and attain segmentation of lung cancer.The specific advancements can be encapsulated as follows:1)Concentration on the lung parenchyma region:Based on 16-bit CT image capturing and the luminance characteristics of lung cancer,we proffer an intercept histogram algorithm.2)Focus on the specific locus of lung malignancy:Utilizing the spatial interrelation of lung cancer,we propose a memory-based Unet architecture and incorporate skip connections.3)Data Imbalance:In accordance with the prevalent situation of an overabundance of negative samples and a paucity of positive samples,we scrutinize the existing loss function and suggest a mixed loss function.Experimental results with pre-existing publicly available datasets and assembled datasets demonstrate that the segmentation efficacy,measured as Area Overlap Measure(AOM)is superior to 0.81,which markedly ameliorates in comparison with conventional algorithms,thereby facilitating physicians in diagnosis.

The Mechanism of Celastrol in the Treatment of Metastatic Lung Adenocarcinoma Revealed by Network Pharmacology and Molecular Docking

Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.

TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

Lung cancer has the highest mortality rate among all cancers,in part because it readily metastasizes.The tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and invasion.TAMs secrete several cytokines,including interleukin(IL)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several carcinomas.Tonicityresponsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and invasion.However,the mechanisms by which it increases lung cancer migration remain unclear.Therefore,in this study,we aimed to elucidate the mechanisms by which IL-1βand TonEBP affect lung cancer cell migration and invasion.We found that A549 cocultured-MΦ-secreted IL-1βinduced A549 cell migration and invasion via the PAK1 pathway.TonEBP deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1β–induced migration and invasion.PAK1 phosphorylation,which was promoted by IL-1β,was reduced when TonEBP was depleted.These results suggest that TonEBP plays an important role in IL-1βinduction and invasiveness of A549 cells via the PAK1 pathway.These findings could be valuable in identifying potential targets for lung cancer treatment.

MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.