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Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells.

ABSTRACT: In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C-C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation.

SUBMITTER: Wu CY

PROVIDER: S-EPMC5710895 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells.

Wu Ching-Yuan CY Cherng Jong-Yuh JY Yang Yao-Hsu YH Lin Chun-Liang CL Kuan Feng-Che FC Lin Yin-Yin YY Lin Yu-Shih YS Shu Li-Hsin LH Cheng Yu-Ching YC Liu Hung Te HT Lu Ming-Chu MC Lung Jthau J Chen Pau-Chung PC Lin Hui Kuan HK Lee Kuan-Der KD Tsai Ying-Huang YH

Oncotarget 20170628 53

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the <i>in vivo</i> protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed <i>in vitro</i> that dihydroisotanshinone I (DT), a bioactive compound in dansh ...[more]

PMID: 29207614

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Project description:IntroductionAmong those with advanced illness, higher levels of hope may offer physiological benefits. Yet, greater levels of hope may also encourage aggressive treatments. Therefore, higher levels of hope may lead to greater healthcare utilization, higher expenditure, and longer survival. We test these hypotheses among patients with advanced cancer.MethodsA secondary data analysis from a cross-sectional survey of 195 advanced cancer patients with high mortality risk linked to subsequent healthcare utilization (outpatient, day surgeries, non-emergency admissions), health expenditures, and death records. The survey collected data on hope, measured generally by the Herth Hope Index (HHI) and more narrowly by two questions on illness-related hope. Generalized linear regression and Cox models were used to test our hypotheses.Results142 (78%) survey participants died during the period of analysis, with close to half (46%) doing so within a year of the survey. Contrary to expectation, HHI scores did not have a significant association with healthcare utilization, expenditure or survival. Yet, illness-related hope, defined as those who expected to live at least 2 years, as opposed to the likely prognosis of 1 year or less as determined by the primary treating oncologist, had 6.6 more planned hospital encounters (95% CI 0.90 to 12.30) in the 12-months following the survey and 41% lower mortality risk (hazard ratio: 0.59, 95% CI 0.36 to 0.99) compared to those who were less optimistic. Secondary analysis among decedents showed that patients who believed that the primary intent of their treatment is curative, had higher total expenditure (S$30,712; 95% CI S$3,143 to S$58,282) in the last 12 months of life than those who did not have this belief.ConclusionWe find no evidence of a relationship between a general measure of hope and healthcare utilization, expenditure, or survival among advanced cancer patients. However, greater illness-related hope is positively associated with these outcomes.

Project description:IntroductionAlternative predictive end points for overall survival (OS), such as tumor response and progression-free survival (PFS), are useful in the early detection of drug efficacy; however, they have not been fully investigated in patients with advanced NSCLC treated with anti-programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies.MethodsIn a systematic review of the reported prospective clinical trials, data for response rate, median PFS, and median OS were extracted from 12 arms in 10 reported clinical trials using anti-PD-1/PD-L1 antibody, and their correlation was investigated. In a retrospective analysis at our institution, OS was compared according to tumor response on 5- to 9-week computed tomography scans and status of being progression-free at 8, 16, and 24 weeks by landmark analysis in 71 patients with advanced NSCLC treated with anti-PD-1/PD-L1 antibodies between 2013 and 2015.ResultsIn a systematic review, moderate correlations between median OS and median PFS (p = 0.120, r = 0.473) and between median OS and response rate (p = 0.141, r = 0.452) were identified using the Spearman correlation coefficient, although these correlations were not statistically significant. In a retrospective analysis of patients treated at our institution, disease control (partial response [PR]/stable disease versus progressive disease/not evaluable), and progression-free status at 8, 16, and 24 weeks significantly predicted OS (Cox proportional hazards model, PR/stable disease versus progressive disease/not evaluable, p = 0.0104, HR = 3.041; 8-week progression-free yes versus no, p = 0.0183, HR = 2.684; 16-week progression-free yes versus no, p = 0.0036, HR = 4.009; and 24-week progression-free yes versus no, p = 0.0002, HR = 12.726).ConclusionsBoth disease control (PR plus stable disease status) and landmark progression-free survival were correlated with OS, with the longer interval landmark PFS being the best predictor of survival in patients with NSCLC treated with anti-PD-1/PD-L1 antibodies.

Dataset Information

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells.

Publications

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells.

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