The association between IDO activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic body radiotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21054-e21054
Author(s):  
Yaoyao Zhu ◽  
Min Hu ◽  
Qinghua Xu ◽  
Yaping Xu

e21054 Background: Immunity affects the efficacy of radiotherapy of lung cancer patients. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that converts tryptophan (T) into heparin (K), which can promote immune suppression and assist tumor cells in immune evasion. The purpose of this study was to quantitatively analyze the immune activity of IDO in serum before and after SBRT, and to explore the changes in immune activity of IDO mediated by SBRT and its relationship with patient's survival. Methods: High-performance liquid chromatography and mass spectrometry were used to determine serum K and T in 30 patients with early non-small cell lung cancer before and after SBRT treatment. K: T stands for IDO activity. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Cox proportional hazards model was used for univariate and multivariate analyses. Results: The median follow-up time was 37.4 months. The median PFS was 37.5 (95% CI, 31.0-44.0) months. The median survival was not reached. In all patients, lower post/pre kynurenine ratio correlated significantly with better PFS (HR = 0.31, 95% CI = 0.11-0.90, P = 0.032). The lower K: T ratio at post-RT received longer OS (HR = 0.27, 95% CI = 0.079-0.95, P = 0.042). In multivariate analysis, smoking < 30 packs / year (P = 0.030), higher BED (P < 0.001), and lower post/pre kynurenine (P = 0.043) were associated with better PFS. Lower K: T ratio post-RT (P = 0.040) and higher BED (P < 0.001) were significantly associated with better OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. The lower level of post/pre kynurenine ratio was significantly related with better PFS. The lower K: T ratio at post-RT was related with better OS. This study shows that IDO is a potentially valuable biomarker for monitoring the immune status and predicting survival in early NSCLC patients after SBRT.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sile Liu ◽  
Hongjing Zang ◽  
Hongmei Zheng ◽  
Weiyuan Wang ◽  
Qiuyuan Wen ◽  
...  

Oncogene ◽  
2021 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Chia-Chan Hsu ◽  
Hsiang-Lin Song ◽  
Yu-Chi Huang ◽  
Chun-Wei Kuo ◽  
...  

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 257-261
Author(s):  
Masahiro Yamasaki ◽  
Kunihiko Funaishi ◽  
Naomi Saito ◽  
Ken-ichi Sakamoto ◽  
Sayaka Ishiyama ◽  
...  

Background: Small-cell lung cancer (SCLC) rarely coexists with pulmonary Mycobacterium avium intracellular complex (MAC) infection. The key drug for SCLC treatment is etoposide, which is metabolized by cytochrome P-450 (CYP) 3A4. Meanwhile, the key drugs for pulmonary MAC infection are clarithromycin (CAM) and rifampicin (RFP), and their metabolism influences CYP3A4. Therefore, treatment of concurrent SCLC and pulmonary MAC infection is difficult, and to the best of our knowledge, no report of treatments for concurrent SCLC and pulmonary MAC infection has been published. Patient Concerns and Diagnoses: A 65-year-old man presented to our hospital with abnormal findings of chest computed tomography: (1) a hilar region nodule in the left lung and mediastinal lymphadenopathy and (2) a thick-walled cavity lesion in the right upper lobe of the lung. After further examinations, the former lesions were diagnosed as SCLC, cT4N3M0, stage IIIC and the latter as pulmonary MAC infection, fibrocavitary disease. Interventions and Outcomes: Concurrent treatment was conducted with discontinuation of CAM and RFP before and after etoposide administration. Specifically, intravenous cisplatin and etoposide were administered on day 1 and days 1–3, respectively, and CAM, RFP, and ethambutol (EB) were administered orally on days 6–22 every 4 weeks. Concurrent radiotherapy was added to the drug administration on days 1–27 of the first cycle. The chemotherapy was continued for 4 cycles, followed by continuation of CAM and RFP administration. EB was discontinued because of optic nerve disorder. The treatments were conducted completely and safely, and both of the SCLC lesions and the MAC lesion were improved. Conclusions: Treatments for concurrent SCLC and pulmonary MAC infection may be successfully conducted with discontinuation of CAM and RFP before and after etoposide administration.


Author(s):  
Ming Li ◽  
Wulin Shan ◽  
Yan Hua ◽  
Fengmei Chao ◽  
Yayun Cui ◽  
...  

Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: MicroRNAs are noncoding RNAs that regulate cellular processes during the progression of tumors. Among various microRNAs, MicroRNA-154 (miR-154) has been reported to be involved in many critical processes of human malignancies. This study aimed to evaluate the significance and prognostic value of miR-154 in human non-small cell lung cancer (NSCLC).Methods: A total of 144 NSCLC tissues samples and matched non-tumor adjacent tissues specimens were obtained from NSCLC patients and the quantitative real-time PCR (qRT-PCR) was performed to investigate expression levels of miR-154. The correlation between miR-154 expression and survival outcomes of NSCLC patients was performed by Kaplan-Meier analysis, univariate and multivariate analysis.Results: MiR-154 expression was significantly decreased in NSCLC tissues compared with that in matched non-tumor adjacent tissues (P<0.001). In addition, low expression of miR-154 was demonstrated to be associated with tumors size, TNM stages and distant metastasis of NSCLC patients Survival analysis revealed that patients with low expression of miR-154 showed significantly lower survival rate for OS, DFS and RFS, respectively (all, log rank test, P<0.001) and miR-154 could be an independent prognostic indicator for NSCLC patients.Conclusion: The results suggest that miR-154 has the clinical significance in the progression of NSCLC and could be a potential prognostic biomarker for NSCLC patients.


2000 ◽  
Vol 18 (12) ◽  
pp. 2354-2362 ◽  
Author(s):  
Frank V. Fossella ◽  
Russell DeVore ◽  
Ronald N. Kerr ◽  
Jeffrey Crawford ◽  
Ronald R. Natale ◽  
...  

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m2 (D100) or 75 mg/m2 (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P = .001 and P = .036, respectively). Patients who received docetaxel had a longer time to progression (P = .046, by log-rank test) and a greater progression-free survival at 26 weeks (P = .005, by χ2 test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P = .025, by χ2 test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.


2018 ◽  
Vol 71 (7) ◽  
pp. 642-647 ◽  
Author(s):  
Liuwei Gao ◽  
Hua Zhang ◽  
Bin Zhang ◽  
Jinfang Zhu ◽  
Chen Chen ◽  
...  

ObjectiveThe aim of this study was to evaluate the expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) in non-small cell lung cancer (NSCLC) patients and to investigate the relevance of B3GNT3 expression in tumour prognosis.MethodsIn this study, B3GNT3 expression was examined in five pairs of resectable NSCLC tissue by Western blot and in 42 pairs of resectable NSCLC tissue by quantitative real-time PCR (qRT-PCR). Immunohistochemistry and statistical analysis were performed to assess the relationship between B3GNT3 expression scores and clinicopathological parameters, as well as clinical prognosis in a retrospective cohort of 176 NSCLC patients.ResultsBoth B3GNT3 mRNA and protein expression levels were significantly higher in NSCLC tissue than in adjacent normal tissue. In the 176 NSCLC cases, a high B3GNT3 expression level was positively correlated with lymph node metastasis (P<0.001) and advanced TNM stage (P=0.043). Kaplan-Meier analysis indicated that patients with high B3GNT3 expression had significantly lower disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001) than those with low B3GNT3 expression. Moreover, in the multivariate analyses, B3GNT3 expression was an independent prognostic factor for DFS (HR 0.329, 95% CI 0.213 to 0.508, P<0.001) and OS (HR 0.383, 95% CI 0.249 to 0.588, P<0.001).ConclusionsOur study demonstrated that high expression of B3GNT3 was associated with unfavourable DFS and OS in NSCLC patients, suggesting that B3GNT3 might be a potential prognostic biomarker for NSCLC.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sumin Shin ◽  
Yong Soo Choi ◽  
Jae Jun Jung ◽  
Yunjoo Im ◽  
Sun Hye Shin ◽  
...  

Abstract Background and objective This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. Methods We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco < 80% predicted and DLco < 60% predicted, respectively. Results On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36–3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68–8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. Conclusions The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.


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