Displaying publications 1 - 20 of 99 in total

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  1. Too CW, Fong KY, Hang G, Sato T, Nyam CQ, Leong SH, et al.
    J Vasc Interv Radiol, 2024 May;35(5):780-789.e1.
    PMID: 38355040 DOI: 10.1016/j.jvir.2024.02.006
    PURPOSE: To validate the sensitivity and specificity of a 3-dimensional (3D) convolutional neural network (CNN) artificial intelligence (AI) software for lung lesion detection and to establish concordance between AI-generated needle paths and those used in actual biopsy procedures.

    MATERIALS AND METHODS: This was a retrospective study using computed tomography (CT) scans from 3 hospitals. Inclusion criteria were scans with 1-5 nodules of diameter ≥5 mm; exclusion criteria were poor-quality scans or those with nodules measuring <5mm in diameter. In the lesion detection phase, 2,147 nodules from 219 scans were used to develop and train the deep learning 3D-CNN to detect lesions. The 3D-CNN was validated with 235 scans (354 lesions) for sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) analysis. In the path planning phase, Bayesian optimization was used to propose possible needle trajectories for lesion biopsy while avoiding vital structures. Software-proposed needle trajectories were compared with actual biopsy path trajectories from intraprocedural CT scans in 150 patients, with a match defined as an angular deviation of <5° between the 2 trajectories.

    RESULTS: The model achieved an overall AUC of 97.4% (95% CI, 96.3%-98.2%) for lesion detection, with mean sensitivity of 93.5% and mean specificity of 93.2%. Among the software-proposed needle trajectories, 85.3% were feasible, with 82% matching actual paths and similar performance between supine and prone/oblique patient orientations (P = .311). The mean angular deviation between matching trajectories was 2.30° (SD ± 1.22); the mean path deviation was 2.94 mm (SD ± 1.60).

    CONCLUSIONS: Segmentation, lesion detection, and path planning for CT-guided lung biopsy using an AI-guided software showed promising results. Future integration with automated robotic systems may pave the way toward fully automated biopsy procedures.

    Matched MeSH terms: Lung/pathology
  2. Bhat AA, Afzal M, Goyal A, Gupta G, Thapa R, Almalki WH, et al.
    Chem Biol Interact, 2024 May 01;394:111002.
    PMID: 38604395 DOI: 10.1016/j.cbi.2024.111002
    Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.
    Matched MeSH terms: Lung/pathology
  3. Ng BH, Low HJ, Nuratiqah NA, Soo CI, Imree A, Mas FMJ, et al.
    Med J Malaysia, 2023 Dec;78(7):897-900.
    PMID: 38159925
    INTRODUCTION: Fluoroscopic-guided transbronchial lung biopsy (FG-TBLB) is routinely performed via bronchoscopy to diagnose focal peripheral lesions and diffuse lung disease. Identifying the risk factors of FG-TBLB-related pneumothorax can assist the operator in taking pre-emptive measures to prepare for this potential complication.

    MATERIALS AND METHODS: We retrospectively analysed data from 157 patients who underwent FG-TBLB, with the primary outcome being procedure-related pneumothorax. We assessed several risk factors for pneumothorax following FG-TBLB: patient characteristics, location of biopsy, number of biopsies and computed tomography pattern. Univariate and multivariate logistic regression analyses were performed.

    RESULTS: One-hundred fifty-seven patients were included [mean (SD) age 57.9 (16.2) years; 60.5% male]. The most common location for FG-TBLB was the right upper lobe (n=45, 28.7%). The mean (SD) number of biopsy samples was 6.7 (2.1). Radiographic evidence of pneumothorax was reported in 12 (7.6%) patients, with 11 of those requiring intercostal chest tube intervention (mean air leak time: 5.7 days and 1 had persistent air leak requiring autologous blood patch pleurodesis. None experienced pneumothorax recurrence. Female gender and upper lobe location of the biopsy were identified as predisposing factors for pneumothorax. In the multivariable analysis, upper lobe biopsies were associated with a higher risk of pneumothorax (OR 0.120; 95% CI 0.015-0.963; p = 0.046).

    CONCLUSION: The overall rate of pneumothorax is low. We recognise the increased risk of pneumothorax associated with upper lobe biopsy. These findings suggest that clinicians should exercise caution when performing FGTBLB in this region and consider alternative biopsy locations whenever feasible. We suggest adequate planning and preparation should be implemented to minimise the risk of pneumothorax following FG-TBLB.

    Matched MeSH terms: Lung/pathology
  4. Ismail IN, Alaga A
    Med J Malaysia, 2023 Nov;78(6):751-755.
    PMID: 38031216
    INTRODUCTION: Ultrasound guided lung biopsy (USLB) is a minimally invasive diagnostic tool with short examination time and real-time monitoring conducted bedside for accurate diagnosis in order to provide the best treatment. However, it is not widely performed by pulmonologists. We aim to explicate the efficacy and safety of USLB led by pulmonologists. The objective of this study is to assess safety and efficacy of USLB performed by pulmonologists in an outpatient setting.

    MATERIALS AND METHODS: We retrospectively enrolled patients who underwent the procedure from January 2018 to April 2022. Under real time ultrasound (Hitachi Medical ProSound F37), thoracic lesions adjacent to the chest wall were sampled with a full-core biopsy needle (CT Core Single Action Biopsy Device, 18G × 15 cm, Vigeo, Italy). Chest x-ray was performed 30 minutes post procedure ruling out pneumothorax. Patients were discharged home 1-2 hours post biopsy. Data was analysed using Microsoft Excel 2010 and Statistical Package for Social Science (SPSS) Version 26.

    RESULTS: A total of 18 patients (14 males, 4 females) underwent USLB for lung tumours. Biopsies were histologically deemed adequate with an overall diagnostic yield of 77.8% (14/18). A total of 57% were positive for thoracic malignancy (21% squamous cell carcinoma, 21% adenocarcinoma, 15% small cell carcinoma) and another 43% were positive for extra thoracic malignancy (1 hepatocellular carcinoma, 2 DLBCL, 1 Hodgkin's lymphoma, 1 seminoma, 1 thymoma). Four patients had inconclusive results but managed to get positive results from surgical or lymph node biopsy (thymoma and adenocarcinoma). Statistical analysis showed more than two passes are needed to achieve a positive HPE yield (p value<0.05). There were nil complications to all the cases done.

    CONCLUSIONS: USLB can safely and effectively be performed by trained pulmonologists with excellent accuracy and low complication rate in outpatients.

    Matched MeSH terms: Lung/pathology
  5. Kho SS, Chai CS, Ho RL, Ismail AM, Tie ST
    Lancet, 2023 Oct 14;402(10410):1356.
    PMID: 37838440 DOI: 10.1016/S0140-6736(23)01906-2
    Matched MeSH terms: Lung/pathology
  6. Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, et al.
    Lancet Oncol, 2023 Sep;24(9):989-1001.
    PMID: 37591293 DOI: 10.1016/S1470-2045(23)00329-7
    BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.

    METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.

    FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.

    FUNDING: Regeneron Pharmaceuticals and Sanofi.

    Matched MeSH terms: Lung/pathology
  7. Kho SS, Nyanti LE, Chai CS, Kho SK, Ismail AM, Voon PJ, et al.
    Respir Investig, 2023 Jul;61(4):473-477.
    PMID: 37182371 DOI: 10.1016/j.resinv.2023.04.003
    Peripheral transbronchial needle aspiration (pTBNA) allows the access of pulmonary nodules without bronchus sign but is limited to cytological examination. A 39-year-old man with left parotid carcinoma presented with an incidental lung nodule. Target localisation was performed with manual airway mapping, virtual bronchoscopic navigation, and pTBNA. Direct target validation using radial endobronchial ultrasound (rEBUS) was performed through the puncture defect. Targeted pinpoint biopsy with a 1.1 mm cryoprobe through the pTBNA puncture defect confirmed metastatic adenoid cystic carcinoma. Guided pTBNA with rEBUS validation followed by cryobiopsy of lung nodules without bronchus sign is potentially feasible for histological and molecular analyses.
    Matched MeSH terms: Lung/pathology
  8. Di J, Xiong Y, Li D, Li X, Wang W, Cheng Y, et al.
    Malays J Pathol, 2022 Dec;44(3):509-516.
    PMID: 36591718
    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 AE1/AE3, 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 didn't metastasise during follow-up 36 months. Case two is alive without disease after lobectomy during follow-up 14 months.
    Matched MeSH terms: Lung/pathology
  9. Wang S, Tan KS, Beng H, Liu F, Huang J, Kuai Y, et al.
    Pharmacol Res, 2021 Oct;172:105781.
    PMID: 34302975 DOI: 10.1016/j.phrs.2021.105781
    Sepsis is a severe inflammatory disorder that can lead to multiple organ injury. Isosteviol sodium (STV-Na) is a terpenoid derived from stevioside that exerts anti-inflammatory, antioxidant and antiapoptotic activities. However, the influence of STV-Na on sepsis remains unknown. Here, we assessed the potential effects of STV-Na on sepsis and multiple organ injury induced by lipopolysaccharide (LPS). We found that STV-Na increased the survival rate of mice treat with LPS, significantly improved the functions of the heart, lung, liver, and kidney, reduced the production of inflammatory cytokines and decreased macrophage infiltration. Moreover, Multiorgan metabolomics analysis demonstrated that glutathione metabolism, purine metabolism, glycerophospholipid metabolism and pantothenate and CoA biosynthesis, were significantly altered by STV-Na. This study provides novel insights into the metabolite changes of multiple organ injury in septic mice, which may help characterize the underlying mechanism and provide an improved understanding of the therapeutic effects of STV-Na on sepsis.
    Matched MeSH terms: Lung/pathology
  10. Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299042 DOI: 10.3390/ijms22147424
    Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology*
  11. Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology
  12. Heng WS, Kruyt FAE, Cheah SC
    Int J Mol Sci, 2021 May 27;22(11).
    PMID: 34071790 DOI: 10.3390/ijms22115697
    Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells-the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.
    Matched MeSH terms: Lung/pathology
  13. Shafi G, Desai S, Srinivasan K, Ramesh A, Chaturvedi R, Uttarwar M
    Mol Genet Genomics, 2021 May;296(3):501-511.
    PMID: 33743061 DOI: 10.1007/s00438-021-01774-1
    Coronavirus disease 2019 (COVID-19), a recent viral pandemic that first began in December 2019, in Hunan wildlife market, Wuhan, China. The infection is caused by a coronavirus, SARS-CoV-2 and clinically characterized by common symptoms including fever, dry cough, loss of taste/smell, myalgia and pneumonia in severe cases. With overwhelming spikes in infection and death, its pathogenesis yet remains elusive. Since the infection spread rapidly, its healthcare demands are overwhelming with uncontrollable emergencies. Although laboratory testing and analysis are developing at an enormous pace, the high momentum of severe cases demand more rapid strategies for initial screening and patient stratification. Several molecular biomarkers like C-reactive protein, interleukin-6 (IL6), eosinophils and cytokines, and artificial intelligence (AI) based screening approaches have been developed by various studies to assist this vast medical demand. This review is an attempt to collate the outcomes of such studies, thus highlighting the utility of AI in rapid screening of molecular markers along with chest X-rays and other COVID-19 symptoms to enable faster diagnosis and patient stratification. By doing so, we also found that molecular markers such as C-reactive protein, IL-6 eosinophils, etc. showed significant differences between severe and non-severe cases of COVID-19 patients. CT findings in the lungs also showed different patterns like lung consolidation significantly higher in patients with poor recovery and lung lesions and fibrosis being higher in patients with good recovery. Thus, from these evidences we perceive that an initial rapid screening using integrated AI approach could be a way forward in efficient patient stratification.
    Matched MeSH terms: Lung/pathology
  14. Liau CS, Mogan P, Thomas W
    J Steroid Biochem Mol Biol, 2021 04;208:105786.
    PMID: 33189851 DOI: 10.1016/j.jsbmb.2020.105786
    Lung cancer is increasing in incidence particularly among women, associated with a global change in smoking habits. Steroid hormones, particularly oestrogen exert an influence on tumour progression in tissues where their target receptor is expressed. Oestrogen receptor, particularly ERβ is highly expressed in the lung and becomes more highly expressed in lung carcinogenesis. Genes involved in the process of lung carcinoma progression and signalling cascades linked to invasion and angiogenesis are modulated by oestrogen receptors. This review intends to collate recently published evidence identifying a role for oestrogen in the initiation and progression of lung carcinoma and how these two processes are differentially affected by circulating oestrogens both in women and in men. Circulating oestrogens may be a significant risk factor in women's susceptibility to lung carcinoma and also provide an additional approach for more targeted therapy.
    Matched MeSH terms: Lung/pathology
  15. Abdul Satar N, Ismail MN, Yahaya BH
    Molecules, 2021 Feb 18;26(4).
    PMID: 33670440 DOI: 10.3390/molecules26041056
    Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/pathology*
  16. Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
    Matched MeSH terms: Lung/pathology
  17. Abbasian Ardakani A, Acharya UR, Habibollahi S, Mohammadi A
    Eur Radiol, 2021 Jan;31(1):121-130.
    PMID: 32740817 DOI: 10.1007/s00330-020-07087-y
    OBJECTIVES: CT findings of COVID-19 look similar to other atypical and viral (non-COVID-19) pneumonia diseases. This study proposes a clinical computer-aided diagnosis (CAD) system using CT features to automatically discriminate COVID-19 from non-COVID-19 pneumonia patients.

    METHODS: Overall, 612 patients (306 COVID-19 and 306 non-COVID-19 pneumonia) were recruited. Twenty radiological features were extracted from CT images to evaluate the pattern, location, and distribution of lesions of patients in both groups. All significant CT features were fed in five classifiers namely decision tree, K-nearest neighbor, naïve Bayes, support vector machine, and ensemble to evaluate the best performing CAD system in classifying COVID-19 and non-COVID-19 cases.

    RESULTS: Location and distribution pattern of involvement, number of the lesion, ground-glass opacity (GGO) and crazy-paving, consolidation, reticular, bronchial wall thickening, nodule, air bronchogram, cavity, pleural effusion, pleural thickening, and lymphadenopathy are the significant features to classify COVID-19 from non-COVID-19 groups. Our proposed CAD system obtained the sensitivity, specificity, and accuracy of 0.965, 93.54%, 90.32%, and 91.94%, respectively, using ensemble (COVIDiag) classifier.

    CONCLUSIONS: This study proposed a COVIDiag model obtained promising results using CT radiological routine features. It can be considered an adjunct tool by the radiologists during the current COVID-19 pandemic to make an accurate diagnosis.

    KEY POINTS: • Location and distribution of involvement, number of lesions, GGO and crazy-paving, consolidation, reticular, bronchial wall thickening, nodule, air bronchogram, cavity, pleural effusion, pleural thickening, and lymphadenopathy are the significant features between COVID-19 from non-COVID-19 groups. • The proposed CAD system, COVIDiag, could diagnose COVID-19 pneumonia cases with an AUC of 0.965 (sensitivity = 93.54%; specificity = 90.32%; and accuracy = 91.94%). • The AUC, sensitivity, specificity, and accuracy obtained by radiologist diagnosis are 0.879, 87.10%, 88.71%, and 87.90%, respectively.

    Matched MeSH terms: Lung/pathology
  18. Khajotia R
    Pan Afr Med J, 2021;40:169.
    PMID: 34970411 DOI: 10.11604/pamj.2021.40.169.31223
    Twenty months into the COVID-19 pandemic, we are still learning about the various long-term consequences of COVID-19 infection. While many patients do recover with minimal long-term consequences, some patients develop irreversible parenchymal and interstitial lung damage leading to diffuse pulmonary fibrosis. Unfortunately, these are some of the consequences of post-SARS-CoV-2 infection which thousands more people around the world will experience and which will outlast the pandemic for a long time to come. It is now being observed at various leading medical centres around the world that lung transplantation may be the only meaningful treatment available to a select group of patients experiencing serious lung damage and non-resolving COVID-19-associated respiratory failure, resulting from the triad of coronavirus infection, a hyper-inflammatory immune response to it and the inability of the human body to repair that injury.
    Matched MeSH terms: Lung/pathology
  19. Mok PL, Anandasayanam ANK, Oscar David HM, Tong J, Farhana A, Khan MSA, et al.
    PLoS One, 2021;16(4):e0250552.
    PMID: 33914777 DOI: 10.1371/journal.pone.0250552
    Multiple matrix metalloproteinases have significant roles in tissue organization during lung development, and repair. Imbalance of proteinases may lead to chronic inflammation, changes in tissue structure, and are also highly associated to cancer development. The role of MMP20 is not well studied in lung organogenesis, however, it was previously shown to be present at high level in lung adenocarcinoma. The current study aimed to identify the functional properties of MMP20 on cell proliferation and motility in a lung adenocarcinoma in vitro cell model, and relate the interaction of MMP20 with other molecular signalling pathways in the lung cells after gaining tumoral properties. In this study, two different single guide RNA (sgRNAs) that specifically targeted on MMP20 sites were transfected into human lung adenocarcinoma A549 cells by using CRISPR-Cas method. Following that, the changes of PI3-K, survivin, and MAP-K mRNA gene expression were determined by Real-Time Polymerase Chain Reaction (RT-PCR). The occurrence of cell death was also examined by Acridine Orange/Propidium Iodide double staining. Meanwhile, the motility of the transfected cells was evaluated by wound healing assay. All the data were compared with non-transfected cells as a control group. Our results demonstrated that the transfection of the individual sgRNAs significantly disrupted the proliferation of the A549 cell line through suppression in the gene expression of PI3-K, survivin, and MAP-K. When compared to non-transfected cells, both experimental cell groups showed reduction in the migration rate, as reflected by the wider gaps in the wound healing assay. The current study provided preliminary evidence that MMP20 could have regulatory role on stemness and proliferative genes in the lung tissues and affect the cell motility. It also supports the notion that targeting MMP20 could be a potential treatment mode for halting cancer progression.
    Matched MeSH terms: Lung/pathology
  20. Surien O, Ghazali AR, Masre SF
    Histol Histopathol, 2020 Oct;35(10):1159-1170.
    PMID: 32893871 DOI: 10.14670/HH-18-247
    BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, and squamous cell carcinoma (SCC) is one of the most common types of lung cancer. Chemoprevention of lung cancer has gained increasing popularity as an alternative to treatment in reducing the burden of lung cancer. Pterostilbene (PS) may be developed as a chemopreventive agent due to its pharmacological activities, such as anti-proliferative, anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of PS on the development of lung SCC in the mouse model.

    METHODS: A total of 24 seven-week-old female Balb/C mice were randomly categorised into four groups, including two control groups comprising the N-nitroso-trischloroethylurea (NTCU)-induced lung SCC and vehicle control (VC) groups and two treatment groups comprising the 10mg/kg PS (PS10) and 50mg/kg PS (PS50) groups. All lung organs were harvested at week 26 for histopathological analysis.

    RESULTS: All PS treatment groups showed chemopreventive activity by inhibiting the progression of lung SCC formation with PS10, resulting in mild hyperplasia, and PS50 was completely reversed in the normal bronchial epithelium layer compared with the VC group. PS treatment also reduced the expression of cytokeratin 5/6 in the bronchial epithelium layer. Both PS10 and PS50 significantly reduced the epithelium thickness compared to the NTCU group (p<0.05). PS is a potential chemopreventive agent against lung SCC growth by suppressing the progression of pre-malignant lesions and reducing the thickness of the bronchial epithelium.

    CONCLUSIONS: The underlying molecular mechanisms of PS in lung SCC should be further studied.

    Matched MeSH terms: Lung/pathology
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