Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations

Schwalk, Audra; Ost, David; Saltijeral, Sahara N.; Garza, Henriette De La; Casal, Roberto F.; Jiménez, Carlos A.; Eapen, Georgie A.; Lewis, Jeff; Rinsurongkawong, Waree; Rinsurongkawong, Vadeerat; Lee, John; Elamin, Yasir Y.; Zhang, Jianjun; Roth, Jack A.; Swisher, Stephen G.; Heymach, John V.; Grosu, Horiana B.

doi:10.1016/j.chest.2020.10.081

Cited by 16 publications

(13 citation statements)

References 17 publications

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“… 1 Undergoing surgery for early-stage patients and performing adjuvant treatments according to the conditions of the patient are recommended, but about 30–50% of early-stage lung cancer patients would die within 5 years of recurrent diseases. 2 The pathogenesis of LUAD recurrence is closely related to lipid metabolism alterations, 3 immune infiltration, 4 , 5 gene mutations, 6 , 7 cell proliferation, 5 enhanced stemness, DNA repair deficiency, bacterial microbiome 8 and angiogenesis. 9 , 10 It is worth mentioning that the role of sphingolipid metabolism in tumor growth has attracted more and more attention in recent years.…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology and Experimental Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Liu¹,

Lin²,

Li³

et al. 2022

DDDT

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Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by "nourishing yin and clearing heat". In this study, the mechanism of YHT in LUAD recurrence was investigated. Methods: Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways. Results: There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway. Conclusion:The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Network Pharmacology and Experimental Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Liu¹,

Lin²,

Li³

et al. 2022

DDDT

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“…(Fariha, et al 2016). Studies showed that patients with MPE are typical patients with lung cancer of the NSCLC type accompanied by Epidermal Growth Factor Receptor (EGFR) mutations (Schwalk et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The goals of MPE treatment are to relieve symptoms, minimize unnecessary pleural procedures, reduce the incidence of hospitalization, and improve the quality of life of sufferers (Schwalk et al, 2020). There are several options for the management of MPE.…”

Section: Introductionmentioning

confidence: 99%

“…Current recommendations for managing pleural effusions in patients with malignancy suggest that therapeutic thoracentesis be performed first to evaluate the drainage effect in patients with shortness of breath and determine the type of effusion. Treatment in the form of thoracentesis or pleural puncture only provides a temporary effect, definitive therapy is the installation of a thoracostomy Indwelling Pleural Catheter (IPC), installation of Water Sealed Drainage (WSD), and pleurodesis (Verma et al, 2016;Schwalk et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Risk factors of repetitive thoracentesis of malignant pleural effusion in naive non-small cell lung carcinoma

Sujana

Kusumawardani

Candrawati

et al. 2022

ijhs

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Almost 40% of Non Small Cell Lung (NSCLC) patients develop Malignant Pleural Effusion (MPE). Nowadays, clinicians prefer to perform a repetitive thoracentesis rather than a definitive procedure, which causes pleural loculations and inflammation. This study aimed to identify risk factors of repeated thoracentesis MPE in NSCLC. This was an observational analytic study with a retrospective cohort design held at Prof.Dr. I.G.N.G Ngoerah General Hospital from January 2018 to June 2022. There were 95 subjects who participated in this study. The median time of repetitive thoracentesis MPE in NSCLC is 3 days (95% CI 1,9-4). The difference in location tumor in the peripheral was 3 days (2.25-3.74) while in the central was 7 days (4.24-9.75), p=0.21. The difference in histology type, Adenocarcinoma was 3 days (1.86-4.13) while squamous cell carcinoma was 4 days (2.53-5.46), p=0.69. Pleural fluid cytology positive was 6 days (2.78-9.22) while negative was 3 days (1.83-4.16), p=0.51. The EGFR mutation positive was 4 days (2.48-5.52) while negative 3 days (1.68-4.31), p=0.78. LDH levels ≥821 IU/L was 3 days (1.49-4.50) while <821 IU/L was 4 days (2.32-5.67), p=0.81. The size of pleural effusion massive was 3 days (1.88-4.11) while non-massive was 4 days (0.93-7.06), p=0.49.

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“…Undergoing surgery for early-stage patients and performing adjuvant treatments according to the conditions of the patient are recommended, but about 30-50% of early-stage lung cancer patients would die within 5 years of recurrent diseases [2]. The pathogenesis of LUAD recurrence is closely related to lipid metabolism alterations [3], immune in ltration [4,5], gene mutations [6,7], cell proliferation [5], enhanced stemness, DNA repair de ciency, bacterial microbiome [8] and angiogenesis [9,10]. In the theory of traditional Chinese medicine (TCM), LUAD belongs to the category of "lung obstruction", which can be treated by "nourishing yin and clearing heat".…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Liu

Lin

et al. 2021

Preprint

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BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

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Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations

Cited by 16 publications

References 17 publications

Network Pharmacology and Experimental Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Network Pharmacology and Experimental Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Risk factors of repetitive thoracentesis of malignant pleural effusion in naive non-small cell lung carcinoma

Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

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