Bronchial Lung Cancer Research Articles

Association of Bronchial Asthma with Lung Cancer: A Systematic Review and Meta-analysis

The purpose of this study was to systematically examine the association between bronchial asthma and lung cancer. Research on the correlation between bronchial asthma and lung cancer was retrieved from the database. Literature was screened based on inclusion and exclusion criteria, and the number of patients in the included studies was extracted and analyzed. This study used Stata statistical software version 16.0 and Cochrane Review Manager version 5.4 for meta-analysis. In our study, 19 articles were selected. Without considering other influencing factors, the risk of lung cancer in asthma patients was relative risk (RR)=1.40 (95% CI: 1.17-1.67, I2=55.7%), and after correcting for risk factors such as smoking and age, it was found that the risk of small-cell lung cancer in asthma patients was RR=2.11 (95% CI: 1.45-3.24). Asthma may increase the risk of developing lung cancer, with an even higher likelihood for small cell lung cancer.

Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Prevalence and risk factors for anxiety in patients with early- and middle-stage lung cancer: a cross-sectional study.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide, with patients frequently experiencing significant psychological distress, particularly anxiety. Despite the high prevalence of anxiety in patients with cancer, there is limited comprehensive research focusing on the specific factors influencing anxiety in patients with early- and middle-stage lung cancer within the context of Chinese medicine hospitals. Therefore, we aimed to investigate the epidemiology and factors influencing anxiety disorders in patients with early- and middle-stage primary bronchial lung cancer through a cross-sectional study. A total of 340 patients with early and middle-stage lung cancer admitted to the outpatient ward of the oncology department at Guang'anmen Hospital from June 2023 to December 2023 were included in this study. Survey data, including the patients' general condition questionnaire, Generalized Anxiety Scale (GAD-7), Hospital Anxiety and Depression Scale (HADS), and Mental Toughness Scale (CD-RISC-10), were collected and recorded in a database using a two-person input format. Data analysis was performed using SPSS 27.0 software. Out of the 340 patients with early- and middle-stage lung cancer included in this study, 133 had anxiety, resulting in an overall anxiety detection rate of 39.12%. The chi-square test showed that statistically significant differences in religion, marital status, surgical treatment, tobacco use, and alcohol history between the anxious and non-anxious groups (p < 0.05). Moreover, statistically significant differences were observed in per capita annual family income, pathological type, VAS score, targeted therapy, treatment stage, and mental toughness level (p < 0.001). Other factors were not significantly correlated with anxiety onset. Multivariate logistic regression analysis showed that higher per capita family income and completed treatment independently acted as protective factors against anxiety onset in patients with early- and middle-stage lung cancer. Conversely, rare pathological types, increased pain severity, and lower levels of mental toughness were identified as independent risk factors for anxiety onset in these patients. Anxiety was prevalent in patients with early- and middle-stage lung cancers. Rare pathological types, increased pain severity, and lower levels of mental toughness were independent risk factors for anxiety. Therefore, clinicians and psychologists should pay more attention to patients with rare types of tumors, actively manage their pain symptoms, and consider implementing mental resilience training to improve patients' mental toughness.

Progress in the Prevention of Complications of Interventional Therapy in Patients with Lung Cancer Hemoptysis

Lung cancer is the malignant tumor with the highest incidence and mortality in our country and even in the world. The radical rate of conventional therapy, such as simple radiotherapy, chemotherapy, operation, traditional Chinese medicine treatment is low and the effect is not ideal. Bronchial lung cancer is one of the most common causes of massive hemoptysis. Vascular interventional therapy has become the first choice in clinical treatment of acute massive hemoptysis. Interventional therapy for lung cancer patients, as a safe, efficient, minimally invasive and economical treatment, has been widely used at home and abroad. However, due to inadequate patient assessment, equipment may not be advanced enough, and treatment techniques need to be developed, more or less postoperative complications associated with interventional therapy may occur. This article reviews the research status of interventional therapy and complication prevention in patients with lung cancer hemoptysis as follows.

Control of Mitochondrial Electron Transport Chain Flux and Apoptosis by Retinoic Acid: Raman Imaging In Vitro Human Bronchial and Lung Cancerous Cells.

The multiple functions of cytochrome c (cyt c) and their regulation in life and death decisions of the mammalian cell go beyond respiration, apoptosis, ROS scavenging, and oxidation of cardiolipine. It has become increasingly evident that cyt c is involved in the propagation of mitogenic signals. It has been proposed that the mitogenic signals occur via the PKCδ-retinoic acid signal complex comprising the protein kinase Cδ, the adapter protein Src homologous collagen homolog (p66Shc), and cyt c. We showed the importance of retinoic acid in regulating cellular processes monitored by the Raman bands of cyt c. To understand the role of retinoids in regulating redox status of cyt c, we recorded the Raman spectra and images of cells receiving redox stimuli by retinoic acid at in vitro cell cultures. For these purposes, we incubated bronchial normal epithelial lung (BEpC) and lung cancer cells (A549) with retinoic acid at concentrations of 1, 10, and 50 µM for 24 and 48 h of incubations. The new role of retinoic acid in a change of the redox status of iron ion in the heme group of cyt c from oxidized Fe3+ to reduced Fe2+ form may have serious consequences on ATPase effectiveness and aborting the activation of the conventional mitochondrial signaling protein-dependent pathways, lack of triggering programmed cell death through apoptosis, and lack of cytokine induction. To explain the effect of retinoids on the redox status of cyt c in the electron transfer chain, we used the quantum chemistry models of retinoid biology. It has been proposed that retinol catalyzes resonance energy transfer (RET) reactions in cyt c. The paper suggests that RET is pivotally important for mitochondrial energy homeostasis by controlling oxidative phosphorylation by switching between activation and inactivation of glycolysis and regulation of electron flux in the electron transport chain. The key role in this process is played by protein kinase C δ (PKCδ), which triggers a signal to the pyruvate dehydrogenase complex. The PKCδ-retinoic acid complex reversibly (at normal physiological conditions) or irreversibly (cancer) responds to the redox potential of cyt c that changes with the electron transfer chain flux.

Changing profile of lung cancer clinical characteristics in China: Over 8-year population-based study.

Although examinations and therapies for bronchial lung cancer, also called lung cancer (LC), have become more effective and precise, the morbidity and mortality of LC remain high worldwide. Describing the changing profile of LC characteristics over time is indispensable. This study aimed to understand the changes in real-world settings of LC and its characteristics in China. In this study, 119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital. The patients' medical records were extracted from the hospital's database. Demographic characteristics, general clinicopathological information, and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis, Nemenyi, chi-squared, and Bonferroni tests. Changes in demographic characteristics during the 8-year study period, namely dynamic changes among different stages and different pathological types, were evaluated. The percentages of female (from 38.50% [323/839] in 2012 to 48.29% [5112/10,585] in 2020) and non-smoking LC (from 69.34% [475/685] to 80.48% [8055/10,009]) patients increased significantly during the study period, with a trend toward a younger age at diagnosis (from 3.58% [30/839] to 8.99% [952/10,585]). Over the study period, the proportion and absolute number of lung adenocarcinoma cases increased (from 67.97% [433/637] to 76.31% [6606/8657]) while the proportion of lung squamous cell carcinoma decreased (from 21.19% [135/637] to 12.08% [1046/8657]). Comprehensive driver gene mutation examination became more common, and epidermal growth factor receptor (EGFR) mutation occurred more frequently in female vs. male (62.03% [12793/20625] vs. 29.90% [8207/27,447]) and non-smoking vs. smoking (53.54% [17,203/32,134] vs. 23.73% [3322/13,997]) patients (both P<0.001). The distribution of the common driver genes differed among different stages of LC. EGFR mutation was detected most frequently at each stage, and other driver gene alterations were more common in advanced stages (P<0.001). The combination of chemotherapy, targeted therapy, and immunotherapy, as a comprehensive management regimen, gradually became predominant over the study period (P<0.001). A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion, indicated by significantly elevated levels of d-dimer, fibrinogen, and fibrinogen degradation products. This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration: ClinicalTrials.gov, NCT05423236.

Retracted: Efficacy Analysis of DSA-Guided Bronchial Arterial Chemoembolization Interventional Therapy in Patients with Middle-Advanced Primary Bronchial Lung Cancer.

[This retracts the article DOI: 10.1155/2022/3722703.].

Retracted: Study on Serum miR-204 Expression Levels in Patients with Severe Pneumonia and Patients with Primary Bronchial Lung Cancer and Its Diagnostic Value.

[This retracts the article DOI: 10.1155/2021/6034413.].

Effect of Chromium on Human-Health: A Review

This review presents the health effects of chromium on the living organism based on previous studies. Chromium (Cr) belongs to the d-block element in the modern periodic table. Chromium has a wide range of oxidation states ranging from -2 to +6. Chromium mostly exists in the environment as trivalent (Cr3+) and hexavalent (Cr6+) states. Both trivalent and hexavalent states of chromiums are derived from the industrial effluents. Ingestion, dermal contact, and inhalation are the most common routes through which chromium enters the human body. Ion chromatography inductively coupled plasmamass spectrometry (IC-ICP-MS) is mostly used for the speciation analysis of metals. Hexavalent chromium is highly soluble and mobile in alkaline and slightly acidic soils, whereas trivalent chromium is less soluble, adheres to the coarse material on the soil, and precipitates as Cr(III) hydroxide. Hexavalent chromium is more detrimental as compared to trivalent chromium. The detrimental effects of chromium are bronchial asthma, lung cancer, nasal ulcers, skin allergies, carcinogenicity, and genotoxicity. To protect from these adverse effects, WHO has suggested a provisional guideline value of chromium as 0.05 mg/L until further information is available and revalued.

Needs of cancer patients during the SARS-CoV-2 Omicron lockdown: A population-based survey in Shanghai, China.

The aim of this study was to investigate the medical and healthcare needs of cancer patients during the Shanghai lockdown due to the SARS-CoV-2 Omicron pandemic. From April 15 to April 21, 2022, 4,195 cancer patients from every district in Shanghai were surveyed using quota sampling via an online platform. The questionnaire consisted of three main parts: demographic and sociological data, disease diagnosis, and different dimensions of patients' needs. Correlation analysis was used to examine the relationship between participants' need scores in each dimension, and generalized linear regression models were used to analyze the factors influencing patients' need scores. The mean age of participants was 63.23 years (SD: 7.43 years), with more female than male participants (80.38% vs. 19.62%). Among participants, the three leading groups of patients were those with breast cancer (39.02%), colorectal cancer (12.82%), or tracheal and bronchial lung cancer (10.23%). Social support, dietary/nutritional support, and psychological counselling ranked as the top three needs of cancer patients. In addition, vaccination against SARS-CoV-2 may reduce psychological anxiety in cancer patients. Compared to participants who had never received the SARS-CoV-2 vaccine, participants who had received one, two, or three doses of the vaccine were respectively 36% (odds ratio (OR): 0.64, 95% confidence interval (CI): 0.56-0.73), 38% (OR: 0.62, 95% CI: 0.59-0.54), and 37% (OR: 0.63, 95% CI: 0.60-0.66) less likely to have an increased need for psychological counseling. In light of constraints on offline medical resources for cancer patients during the lockdown, the current authors have begun to re-examine the universal accessibility and spread of telemedicine in the future. In addition, immune barriers can be established for cancer patients and vaccination guidelines for different disease stages, tumor types, and treatment regimens can be explored in detail.

Abstract 3055: Field cancerization and microbiome in lung cancer

Abstract Lung Cancer carcinogenesis is the outcome of a field of premalignant changes that occur in the bronchial tree leading to the overt emergence of the malignant lung cancer. We sought to study the proteome of the microbiome associated with the premalignant bronchial mucosa epithelia. The overall goal is the identify functional relationships between the bronchial mucosa microbiome and the risk of developing lung cancer. We evaluated the proteome of the microbiome using mass spectrometry and specialized microbiome authentication software. This method was applied to a case-control study of plasma samples donors of physician health study who donated plasma at different times prior to the onset of Non-Small Cell Lung Cancer. We also examined bronchial mucosa tissue samples near to, and distant from, the tumor harvested from surgical lobectomy specimens. Highly significant protein biomarker differences were found in the plasma and in the tissue samples that were blindly associated with cancer. These included specific proteins from the mucosal microbiome that may have functional role in the carcinogenic process. These key diagnostic risk markers were shared between the premalignant bronchial mucosa tissue and the plasma, supporting the concept that risk markers of bronchial mucosa lung cancer carcinogenesis can be detected in the peripheral circulation. Citation Format: Rayan I. Alhammad, Ngoc B. Vuong, Weidong Zhou, Claudius Mueller, Donald J Johann Jr, Amith R. Katta, Monique V. Hoek, Fahad M. Alsaab, Alessandra Luchini, Lance Liotta. Field cancerization and microbiome in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3055.

Efficacy Analysis of DSA-Guided Bronchial Arterial Chemoembolization Interventional Therapy in Patients with Middle-Advanced Primary Bronchial Lung Cancer.

Objective To investigate the clinical efficacy of digital subtraction angiography- (DSA-) guided bronchial arterial chemoembolization (BACE) in patients with primary bronchial lung cancer. Methods A total of 178 patients with primary intermediate and advanced bronchial lung cancer admitted to our hospital from February 2019 to March 2020 were selected as the subjects, and they were divided into control group (84 cases) and observation group (94 cases) according to the different chemotherapy regimens adopted by the patients. The control group was treated with traditional perfusion chemotherapy, and the observation group was treated with DSA-guided BACE interventional therapy, treated for 4 cycles, and followed up until the end of June 2021. The short-term clinical efficacy, hemoptysis remission, and incidence of adverse reactions were compared between the two groups. The mortality and recurrence rates between the two groups from treatment to the end of follow-up were counted, and the quality of life after treatment and 1 year after treatment were compared. Results The short-term remission rate (73.40% vs. 58.33%), disease control rate (93.62% vs. 84.52%), hemoptysis remission rate (75.00% vs. 41.51%), the quality of life after chemotherapy cycle (90.86 ± 2.55 vs. 78.04 ± 2.21), and the quality of life after 1 year of follow-up (85.68 ± 2.23 vs. 70.27 ± 1.72) in the observation group were significantly higher than those in the control group, and the difference was statistically significant (P < 0.05). The incidence of adverse reactions (9.57% vs. 20.24%), mortality (10.64% vs. 21.43%), and recurrence rate (11.70% vs. 27.38%) during the follow-up period in the observation group were significantly lower than those in control group, and the differences were statistically significant (P < 0.05). Conclusion DSA-guided BACE interventional therapy for patients with primary middle-advanced bronchial lung cancer has significant efficacy, which can not only reduce the mortality and recurrence rate of patients but also improve the quality of life of patients, with fewer adverse reactions and high safety, which is worthy of promotion.

Effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer cells by targeting the miR-7-5p/ADAM10 axis

To explore the effect of circ-SFMBT2 on the biological behavior of non-small cell lung cancer (NSCLC) cells and its regulatory role on the miR-7-5p/ADAM10 axis. qRT-PCR and Western blotting were used to determine the expression of circ-SFMBT2, miR-7-5p, and ADAM10 in NSCLC tissues and adjacent tissues. Pearson analysis was used to analyze the correlation between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. In vitro cultured human bronchial epithelial-like cells (HBE) and lung cancer cell lines H1650, H460, A549, H1299. CCK-8 and EdU methods were used to assess the ability of cell proliferation. Plate experiment was used to detect the clone formation ability. Flow cytometry was used to detect the apoptosis rate. Transwell experiment was used to detect cell invasion ability. Dual luciferase reporter experiment detects the targeting relationship between circ-SFMBT2 and miR-7-5p, and between miR-7-5p and ADAM10. Transplanted tumor experiment in nude mice assessed the effect of knocking down circ-SFMBT2 on the growth of transplanted tumor. Immunohistochemical experiments were performed to detect the positive rates of ADAM10 and Ki67 proteins in transplanted tumor tissues. The expression levels of circ-SFMBT2 and ADAM10 were increased in NSCLC tissues and cell lines, while decreased the expression of miR-7-5p. circ-SFMBT2 was negatively correlated with miR-7-5p, while miR-7-5p was negatively correlated with ADAM10. Silencing the overexpression of circ-SFMBT2 and miR-7-5p could inhibit cell proliferation, clone formation and invasion, and also promote apoptosis. circ-SFMBT2 could target miR-7-5p, and ADAM10 was the target gene of miR-7-5p. The combined effect of silencing circ-SFMBT2 and inhibition of miR-7-5p, as well as miR-7-5p overexpression and ADAM10 overexpression could promote cell proliferation, clone formation and invasion, and also suppress cell apoptosis. Silencing circ-SFMBT2 could inhibit the growth of transplanted tumors. Silencing circ-SFMBT2 can suppress the proliferation, clone formation, invasion ability and induce apoptosis of NSCLC cells by regulating the miR-7-5p/ADAM10 axis.

Salidroside prevents PM2.5-induced BEAS-2B cell apoptosis via SIRT1-dependent regulation of ROS and mitochondrial function

PM2.5 is a harmful air pollutant currently threatening public health. It has been closely linked to increased morbidity of bronchial asthma and lung cancer worldwide. Salidroside (Sal), an active component extracted from Rhodiola rosea, has been reported to ameliorate the progression of asthma. However, there are few studies on the protective effect of salidroside on PM2.5-induced bronchial epithelial cell injury, and the related molecular mechanism is not clear. Here, we aimed to explore the protective effect and related mechanism of Sal on PM2.5 bronchial injury. We chose 50 μg/mL PM2.5 for 24 h as a PM2.5-induced cell damage model. After that BEAS-2B cells were pretreated with 40, 80, 160 µM Sal for 24 h and then exposed to 50 μg/mL PM2.5 for 24 h. We found that Sal pretreatment significantly inhibited the decrease of cell viability induced by PM2.5. Sal was effective in preventing PM2.5-induced apoptotic features, including Ca2+ overload, the cleavages of caspase 3, and the increases in levels of caspase 9 and Bcl-2-associated X protein (Bax), ultimately, Sal significantly inhibited PM2.5-induced apoptosis. Sal improved mitochondrial membrane potential, inhibited the release of cytochrome c from the mitochondria to cytoplasm. Sal alleviated ROS production, decreased the level of MDA, prevented the reduction of CAT, SOD and GSH-Px and increased the expression of NF-E2-related factor 2 (Nrf2), HO-1 and superoxide dismutase 1 (SOD1) in cells exposed to PM2.5. Furthermore, Sal improved the decrease of SIRT1 and PGC-1 α expression levels caused by PM2.5. In addition, inhibition of SIRT1 by EX527 (SIRT1 inhibitor) reversed the protective effects of Sal, including the decrease of ROS level, the increase of membrane potential level and the decrease of apoptosis level. Thus, Sal may be regarded as a potential drug to prevent PM2.5-induced apoptosis of bronchial epithelial cells and other diseases with similar pathological mechanisms.

Study on Serum miR-204 Expression Levels in Patients with Severe Pneumonia and Patients with Primary Bronchial Lung Cancer and Its Diagnostic Value

Objective. To analyze the expression and clinical significance of miR-204 in the serum of patients with severe pneumonia (SP) and primary bronchial lung cancer (LC). Methods. 65 SP patients and 43 primary bronchial LC patients who were treated in the hospital from January 2017 to December 2018 were randomly selected as the SP group and LC group. At the same time, healthy patients from the physical examination department of the hospital were selected. 65 cases were the control group. QRT-PCR detected serum miR-204 expression and compared the differences between groups. The pathological data of patients were collected, and the relationship between serum miR-204 and the patient’s pathological data was compared; the area under the ROC curve and Kaplan–Meier curve were used to evaluate the diagnostic value of serum miR-204 for the two conditions and to explore the relationship between serum miR-204 and prognosis. Results. The serum miR-204 of the SP group was (0.43 ± 0.09), the serum miR-204 of the LC group was (0.40 ± 0.10), the serum miR-204 of the control group was (1.00 ± 0.09), and the miR-204 level of was significantly higher than that of the control group, and the difference between the groups was statistically significant ( P &lt; 0.05). There was no significant difference in serum miR-204 levels between the SP group and the LC group ( P &gt; 0.05). Serum miR-204 levels in SP patients with cumulative organs ≥3 were higher than those with cumulative organs &lt;3, and the difference was statistically significant ( P &lt; 0.001). In the LC group, in patients with stage III to IV and low and undifferentiated patients, the level of miR-204 was higher than that of stage I∼II and high and moderately differentiated patients, and the difference was statistically significant ( P &lt; 0.001). The level of miR-204 in the two groups of patients (0.89 ± 0.10, 0.83 ± 0.13) who died of illness was significantly higher than that of the surviving patients (1.00 ± 0.11, 1.00 ± 0.10), and the difference was statistically significant ( P &lt; 0.05); the survival rate of patients with high expression of miR-204 was higher than that of patients with low expression. The AUC of serum miR-204 level to SP and LC was 0.766 and 0.818, respectively. Conclusion. The level of miR-204 in the serum of SP patients and patients with primary bronchial LC was significantly lower than that of healthy people, and patients who died were lower than those who survived; the miR-204 in serum has a good diagnostic value for SP and LC and is related to the survival and prognosis of patients.

Abstract 2434: Transcriptional crosstalk between YAP, TEAD and TP63 is associated with early lung carcinogenesis

Abstract Introduction: The Hippo pathway effector YAP contributes to carcinogenesis by directing stem cell activity, cell proliferation and cell survival signals. In the lung, aberrant nuclear YAP activity promotes bronchial epithelial growth, which in animal models can drive pathology that resembles lung premalignant lesions (PMLs). However, the molecular mechanisms by which YAP contributes to aberrant lung epithelial pathology are poorly understood. In this project, we investigated the DNA binding pattern and gene expression program regulated by YAP and associated TEAD and TP63 transcriptional factors in primary normal human bronchial epithelial cells (HBECs) and lung cancer cell lines. Methods: RNA-seq experiments were conducted using HBEC, H2170 and SW900 cells transfected with siRNA targeting YAP, TEADs or TP63, and expression profiles were compared to corresponded controls to derive gene signatures. In parallel, ChIP-seq experiments were carried out using antibodies specific for the respective proteins to identify genome binding peaks. Direct target genes were inferred with Binding and Expression Target Analysis (BETA) using gene signature and peak profile of each factor in each cell line respectively. The metagene score for target genes in longitudinally collected endobronchial biopsies from patients with PMLs was calculated using GSVA and the association with PML phenotypes was tested with a mixed-effects model adjusting for batch and patient as random effect (GSE109743). Results: Chromatin binding analyses revealed that YAP co-occupies genomic regions with TEAD and TP63 in normal bronchial epithelial cells aligning with H3K27ac chromatin modifications. Integrating genomic binding and gene expression profiling, we identified large overlaps in target genes directly regulated by YAP, TEAD and TP63 in HBECs, demonstrating cooperation between these factors in the control of bronchial epithelial transcription. YAP-TEAD-TP63 induced targets in HBECs are enriched for genes involved in cell proliferation and extracellular matrix alteration, while repressed targets are enriched for genes involved in cell fate specification. Notably, cooperatively regulated genes are strongly associated with gene expression profile identified in progressive PML, and in particular with genes linked to early immune responses that are observed with PML pathology progression. Similar analyses of YAP, TEAD and TP63 in lung cancer cells revealed an altered transcriptional program for YAP with a divergence of YAP-TEAD away from TP63, suggesting contextual changes in YAP activity with cancer progression. Conclusion: We found that YAP, TP63 and TEADs co-regulate lung epithelial gene expression related to PML pathology progression. These findings provide insight into potential YAP function in the early stages of lung carcinogenesis and offer potential new avenues to develop lung cancer interception strategies. Citation Format: Boting Ning, Andrew Tilston-Lunel, Julia Hicks-Berthet, Sarah A. Mazzilli, Jennifer E. Beane, Xaralabos Varelas, Marc E. Lenburg. Transcriptional crosstalk between YAP, TEAD and TP63 is associated with early lung carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2434.

Bronchial Asthma and Lung Cancer

Aim: The aim of the study was to present existing evidence regarding the association between bronchial asthma and lung cancer risk, the impact of lung cancer treatment on asthma control as well as the impact of pre-existing asthma on lung cancer survival. Methods: A narrative review of all the relevant published literature has been conducted. Results: Published evidence suggests that patients with bronchial asthma are at a higher risk of developing lung cancer with an estimated odds ratio for squamous and small cell lung carcinoma at 1.69 and 1.71, respectively, within 2 years of asthma diagnosis. Interestingly, regular use of inhaled corticosteroids may protect asthmatics against lung cancer. Chemotherapy may temporarily relieve asthma symptoms. Pneumonitis is a common adverse reaction in asthmatics receiving immunotherapy for lung cancer treatment. Lung radiotherapy in asthma patients predisposes to eosinophilic alveolitis and pneumonia. Asthmatics are considered high-risk candidates for invasive surgical procedures because they carry a high risk of perioperative airway hyper responsiveness. Asthma is associated with a reduced lung cancer survival compared to other pulmonary co-morbidities. Conclusion: Literature shows that bronchial asthma is associated with increased lung cancer risk and worse survival rates. Chemotherapy may relieve asthma symptoms. However, asthmatics are prone to complications related to lung cancer surgery or radiotherapy treatment. Μore randomised controlled studies are required to strengthen the positive association between bronchial asthma and lung cancer, taking into consideration that there may be confounders that may influence the results. Finally, further studies must be conducted to investigate the impact of immunotherapy and specific radiotherapy modalities on asthma control.

ETV6-NTRK3 translocation-associated low-grade mucinous bronchial adenocarcinoma: A novel bronchial salivary gland-type non-small cell lung cancer subtype

IntroductionNTRK fusion genes have been found in several solid tumors, among which NSCLC and sarcoma. Novel NTRK translocation-related tumors are still being discovered. MethodsWe report a 49-year-old patient with a mass in the left lower lung lobe that was resected. This specimen was analyzed and sequenced using targeted DNA next generation sequencing (NGS) and anchored-multiplex-PCR (AMP) targeted RNA NGS. ResultsOn pathological evaluation, a peribronchial mucinous neoplasm with a unique morphology was found. RNA NGS analysis showed anETV6-NTRK3 translocation in a low-grade mucinous bronchial adenocarcinoma. ConclusionsThis entity represents a novel subtype of non-small cell lung cancer, which we would like to term ‘ETV6-NTRK3 translocation-associated low-grade mucinous bronchial adenocarcinoma’.

Effects of stomatin protein expression on proliferation and apoptosis of lung cancer cells

Objective: To investigate the effect of stomatin protein expression on the proliferation and apoptosis of lung cancer cells. Methods: The expressions of stomatin mRNA in human bronchial epithelial cells (HBE) and lung cancer cells (H520, A549, 95D, H460, Glc-82, 973 and H1299) were detected by Real-time PCR. Immunohistochemistry (IHC) was used to detect stomatin protein expression in 4 lung cancer tissue microarrays with 259 cases of lung cancer and adjacent normal tissues. After knocking down the expression of stomatin in A549 cells, the proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, the apoptosis was detected by flow cytometry, the expression levels of total protein kinase B (AKT) and phosphorylated AKT at Ser473 were detected by Western blot. BALB/c nude mice were used to detect the tumorigenic ability of stomatin downregulated A549 cells (3 mice) and control cells (3 mice), and the protein expressions of stomatin, Ki67 and CD31 in tumor tissues were detected by IHC. Results: The M (range) of stomatin mRNA expression level in H520, A549, 95D, H460, Glc-82, 973, H1299 and HBE cells were 2.71 (2.66), 3.55 (3.16), 0.26 (0.22), 2.08 (1.98), 0.87 (0.35), 1.72 (2.53), 1.10 (1.82) and 0.01 (0.02), respectively. The mRNA expression levels of stomatin in H520, A549 and H460 cells were higher than that of HBE cells (all P<0.05), whereas there was no statistical difference among 95D, Glc-82, 973, H1299 and HBE cells (all P>0.05). IHC of lung tissue microarrays showed that the positive rate of stomatin expression in human lung cancer tissues was 34.7% (90/259), which was significantly higher than that in adjacent normal tissues [1.9% (5/259)] (P<0.05). In stomatin positive lung cancer tissues, the M (IQR) of tumor size for lower stomatin expression tissues (67 cases) was [41.22 (2 761.50) cm], which was smaller than that of higher stomatin expression tissues [(23 cases, 57.98(1 333.50) cm) (P<0.05). After knocking down stomatin expression, the fourth day absorbance value of stomatin-downregulated A549 cells was 0.55±0.07, which was lower than that of control cells (0.79±0.16) (P=0.012). The proportion of early apoptotic cells of stomatin-downregulated A549 cells [8.83 (53.00)] was higher than that of control cells [4.17 (25.00)] (P=0.026). The Ser473 phosphorylated AKT protein expression level in stomatin-downregulated A549 cells was 0.68±0.16, which was decreased compared with control cells (1.16±0.39) (P<0.05). The M (IQR) of total AKT expression level in stomatin-downregulated A549 cells was 4.25 (17.00), without statistically significant difference from control cells [4.75 (19.00)] (P>0.05). After inoculation of stomatin-downregulated A549 cells in nude mice for 43 days, the tumor volume was (37.93±3.12) mm(3), which was significantly smaller than that of the control group [(454.04±32.39) mm(3)] (P<0.001). And the expression levels of stomatin, nuclear proliferation antigen Ki67, and platelet-endothelial cell adhesion molecule CD31 were 1.78±0.69, 5.19±3.84, and 10.77±1.67, respectively, which were all decreased compared with control group (17.52±8.76, 54.14±41.02, and 19.72±6.97, respectively) (all P<0.05). Conclusion: Stomatin promotes lung cancer cell proliferation and inhibits cell early apoptosis by regulating AKT signaling pathway.

Analysis of the short-term effect of photodynamic therapy on primary bronchial lung cancer

To analyze the short-term clinical effect of photodynamic therapy on bronchial lung cancer and provide relevant practical experience for its better application in clinical practice. Twenty patients with bronchial lung cancer diagnosed by pathology were treated with photodynamic therapy or interventional tumor reduction combined with photodynamic therapy. Follow-up at 3 months after treatment, the chest CT and bronchoscopy were reexamined. The lesions were observed under a microscope, and the pathological specimens of living tissues were stained with HE and TUNEL to evaluate the short-term clinical effect. The volume of the tumor in the trachea or bronchus was smaller than before and the obstruction improved after the PDT from the chest CT. We could conclude that after PDT, the tumor volume was reduced and the pathological tissue appeared necrotic, the surface was pale, and the blood vessels were fewer while compared with before, and less likely to bleed when touched from the results of the bronchoscopy. HE staining showed that before treatment, there were a large number of tumor cells, closely arranged and disordered, or agglomerated and distributed unevenly. The cell morphology was not clear and the sizes were various with large and deeply stained nucleus, and the intercellular substance was less. After treatment, the number of tumor cells decreased significantly compared with before and the arrangement was relatively loose and orderly. The cells were roughly the same size; the intercellular substance increased obviously and showed uniform staining. The nuclei morphology was incomplete and fragmented, and tumor cells were evenly distributed among the intercellular substance. TUNEL staining showed that the number of cells was large and the nucleus morphology was regular before treatment; the nuclear membrane was clear and only a small number of apoptotic cells could be seen. However, the number of cells decreased and arranged loosely after treatment, with evenly stained cytoplasm. The nuclear morphology was irregular and the nuclear membrane cannot be seen clearly. Apoptotic cells with typical characteristics such as karyopyknosis, karyorrhexis, and karyolysis were common. Photodynamic therapy for bronchial lung cancer can achieve a satisfactory short-term clinical treatment effect and improve the life quality of patients, but the long-term clinical effect remains to be further studied.