Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway

Ruan, Hao; Lv, Ziwei; Liu, Shuaishuai; Zhang, Liang; Huang, Kai; Gao, Shaoyan; Gan, Wenhua; Liu, Xiaowei; Zhang, Shanshan; Helian, Kaiyue; Li, Xiaohe; Yang, Cheng

doi:10.1111/jphp.13183

Cited by 53 publications

(31 citation statements)

References 37 publications

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“…Anti-angiogenesis of anlotinib could contribute to the regulation of tumor microenvironment and in ammation in tumors [24,25]. In our study, concentration of plasma VEGFA and CCL11 were signi cantly increased at PD, and level of PD-L2 and CCL5 were signi cantly decreased.…”

Section: Discussionsupporting

confidence: 50%

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

Sun

Zhou

Zhang

et al. 2021

Preprint

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Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12mg/day, Day1–14, three weeks per cycle). The primary endpoint was 12-week progression free survival (PFS) rate. Relationship between series plasma cytokine level and efficacy of anlotinib was analyzed.Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% (95% confidence interval [CI]; 59.8%–91.5%) and median time to progression (TTP) was 5.9 months (95% CI; 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI; 48.7%–86.6%) and 4.6 months (95% CI; 2.7–10.0), respectively. The median TTP on patients with baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significant longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for efficacy of anlotinib.

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Section: Discussionsupporting

confidence: 50%

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

Sun

Zhou

Zhang

et al. 2021

Preprint

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“…Besides, nintedanib and bevacizumab have been shown to reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer (Shimizu et al, 2014;Enomoto et al, 2015;Hamada et al, 2019). Anlotinib, a new anti-angiogenesis agent approved globally in 2018, has been proven attenuating bleomycin-induced pulmonary fibrosis in mice via the TGF-β1 signaling pathway (Ruan et al, 2020). Recombinant human endostatin and apatinib have not been evaluated to reduce AE in patients with ILD.…”

Section: Discussionmentioning

confidence: 99%

Management and Prognosis of Interstitial Lung Disease With Lung Cancer (ILD-LC): A Real-World Cohort From Three Medical Centers in China

Xie

Wang

et al. 2021

Front. Mol. Biosci.

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Background and ObjectiveInterstitial lung disease with lung cancer (ILD-LC) is rare and its management has not been fully described. This study aimed to investigate the management and prognosis of ILD-LC patients in China.MethodsThe present analysis is a retrospective real-world cohort study. Clinical data of ILD-LC patients were obtained from 3 hospitals in China. The overall survival (OS) of patients was analyzed. Univariate and multivariate regression analyses were performed.ResultsOne hundred eighty-four ILD-LC patients included were biased toward male (85.3%), smokers (75.5%), idiopathic pulmonary fibrosis (IPF) (58.2%) patients with comorbidities (67.9%) and ECOG-PS score of 1 (65.2%). Most patients were advanced peripheral non-small cell lung cancer. The initial anti-cancer regimen for ILD-LC is mainly chemotherapy, and patients with early-stage LC prefer surgery. In the anti-cancer cohort, the number of ILD-LC patients who underwent the 2nd and 3rd or more anti-cancer regimens were 78 (55.7%) and 32 (22.8%), respectively. In the non-anticancer cohort, the median OS was 3.5 months. In the early-stage cohort, the median OS was 14.2 months in the systematic therapy group; however, the median OS was not reached in the surgery group. In the advanced-stage cohort with systematic therapy, the median OS was 7.2 months. Interstitial pneumonia (IIP) and anti-angiogenesis were associated with OS in the univariate analysis, whereas anti-angiogenesis was an independent protective factor for advanced LC with ILD.ConclusionPatients with ILD-LC have very poor prognosis. Appropriate anti-tumor treatment can prolong the survival time of patients who can tolerate it. Targeted therapy and immunotherapy are alternative treatments for LC patients with mild ILD. For ILD patients with advanced LC, antiangiogenic regimens significantly improve the prognosis of the disease.

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“…The probability of EGFR ‐sensitive mutations in Chinese patients with advanced lung adenocarcinoma is about 50%. On one hand, antiangiogenic drugs target specific monoclonal antibodies against VEGFR, such as bevacizumab and cetuximab, which have high target specificity and require genetic testing before application, and on the other, they inhibit the VEGFR domain of small‐molecule tyrosine kinase inhibitors, such as apatinib and sorafenib, which are multitargeted drugs 10,11 . There are no monoclonal targeting agents that specifically target SqCLC targets.…”

Section: Discussionmentioning

confidence: 99%

In vitro studies of H520 cell cycle and apoptosis by anlotinib combined with radiotherapy

et al. 2021

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Background To study in vitro the effects of anlotinib combined with radiotherapy on the lung cancer H520 cell cycle and apoptosis. Methods The log growth period H520 cells were divided into the control group, anlotinib group (A group), radiotherapy group (RT group) and combined group (A + RT group). Cell cycle and apoptosis were detected by flow cytometry and changes in H520 cell cycle and apoptosis were analyzed in each group. Results Anlotinib was determined to significantly inhibit cell growth in all groups, both alone, or in combination with radiotherapy. After receiving corresponding treatments, the proportions of G2/M‐phase cells in the control group, A group, RT group and A + RT group were different, and statistically significant (F = 32.086, P < 0.001). The apoptotic cell statistics of H520 cells in the control group, A group, RT group and A + RT group were significantly different (F = 44.537, P < 0.01). The relative expression of CDK1 in each group of cells was 0.04 ± 0.02, 0.07 ± 0.12, 0.81 ± 0.11, and 0.56 ± 0.16, respectively. There were differences between the groups by analysis of variance which were statistically significant (F = 58.36, P < 0.0001). The relative expression of cycle B in each group of cells was 0.27 ± 0.05, 0.40 ± 0.16, 0.65 ± 0.14, and 0.57 ± 0.13, respectively. There were differences between the groups by analysis of variance which were statistically significant (F = 10.77, P = 0.0002). Conclusions Anlotinib had an inhibitory effect on lung cancer H520 cell proliferation. A higher rate of apoptosis and G2/M phase block was observed in the anlotinib‐radiotherapy combined group. Anlotinib combined with radiotherapy was able to synergistically inhibit tumor cell growth. Key points Anrotinib combined with radiotherapy can synergistically inhibit tumor cell growth.

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Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway

Cited by 53 publications

References 37 publications

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

Management and Prognosis of Interstitial Lung Disease With Lung Cancer (ILD-LC): A Real-World Cohort From Three Medical Centers in China

In vitro studies of H520 cell cycle and apoptosis by anlotinib combined with radiotherapy

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