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BLI images and 3D BLT reconstruction of orthotopic liver tumors (n = 5). a BLI signals of orthotopic HepG2-Red-fLuc cell-derived tumorbearing mice on days 0, 3, 6, 9, 12, 15, and 18 post-drug treatment. b BLI signal intensity of mice. (*) P < 0.05, (**) P < 0.01 vs. the control group. c Body weight of mice. (*) P < 0.05, day 6 vs. day 0 in the sorafenib group. d The 3D BLT reconstruction in the control and sorafenib and apatinib treatment groups on day 20 post-drug treatment
Source publication
Researchers have combined different sophisticated imaging techniques to assess the safety and efficacy of liver cancer therapy in animal models. Many hepatocellular carcinoma (HCC) patients respond to sorafenib, but this drug is expensive and may cause severe side-effects. Qian Liang at China’s Institute of Automation, Beijing, and colleagues have...
Contexts in source publication
Context 1
... orthotopic HCC mouse model is a reliable and reproducible tool for investigating tumorigenesis 19,20 . We established this model to simulate the natural tumor microenvironment and monitored orthotopic liver tumor growth during drug treatment by BLI (Fig. 3a, b). Apatinib treatment inhibited tumor growth to a degree similar to sorafenib. In addition, although sorafenibtreated mice showed a statistically significant reduction in body weight on day 6 (16.25 ± 0.2217 g) and a numerical reduction on days 12 (16.58 ± 0.3065 g) and 18 (16.65 ± 0.3884 g) post-treatment compared with day 0 (17.58 ± ...
Context 2
... although sorafenibtreated mice showed a statistically significant reduction in body weight on day 6 (16.25 ± 0.2217 g) and a numerical reduction on days 12 (16.58 ± 0.3065 g) and 18 (16.65 ± 0.3884 g) post-treatment compared with day 0 (17.58 ± 0.3198 g), there were no evident changes in apatinib-treated and control mice during treatment (Fig. ...
Context 3
... 21 . However, two-dimensional planar BLI provides limited information; detection of a 3D BLI signal can better reveal tumor location and distribution in living animals. Therefore, following drug treatment, we used the sparsity adaptive subspace pursuit reconstruction method 22 to generate a 3D image of liver tumors based on μCT/BLI signals (Fig. 3d). Tumors were detected in the liver lobes, and the 3D reconstruction confirmed that the tumor volumes were reduced by apatinib and sorafenib treatment, which was consistent with the BLI ...
Context 4
... that the drugs caused some degree of liver damage. H&E staining of major organs showed no visible tissue damage in the heart, spleen, lung, or kidney caused by drug treatment. However, some damage was observed in the livers of apatinib-treated and sorafenib-treated mice, but this was more severe in the latter group than in the former group (Fig. ...
Citations
... Apatinib is a new oral small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), which is convenient, economical and efficient. It selectively competes for the ATP binding site of VEGFR-2 in cells, blocks the downstream signal transduction and inhibits angiogenesis in tumor tissues, thereby exerting its anti-tumor effect (9). Apatinib is the first small-molecule anti-angiogenic targeted drug worldwide proven to be safe and effective and has achieved gratifying results in treating advanced gastric cancer (10). ...
Recurrent high-grade glioma is a refractory disease, and its prognosis is poor. Although the treatment of apatinib combined with temozolomide provides improved efficacy and is able to prolong survival, this conclusion has been based on small samples. In order to clarify this treatment's efficacy, a meta-analysis was performed in the present study. Different databases were screened and finally, 10 studies were included, comprising 357 patients with recurrent high-grade gliomas. The efficacy and prognosis were analyzed using Stata software. The results indicated that the overall objective response rate (ORR) and disease control rate (DCR) of apatinib combined with temozolomide were 0.36 (95% CI, 0.26-0.46) and 0.86 (95% CI, 0.82-0.89), respectively. Subgroup analysis indicated that the overall ORR was 0.43 (95% CI, 0.29-0.57) and 0.26 (95% CI, 0.14-0.38), and the DCR was 0.89 (95% CI, 0.85-0.93) and 0.76 (95% CI, 0.69-0.84) in the treatment of apatinib with temozolomide dose-dense group and the conventional-dose group (5/28 regimen), respectively. Further prognostic analysis indicated that the median overall survival of patients with high-grade glioma treated with apatinib combined with temozolomide was 8.21 months (95% CI, 7.20-9.22 months) and the median progression-free survival was 5.45 months (95% CI, 4.53-6.37). Analysis of the publication bias of the effect size revealed that there was bias in the DCR, while no bias was found in the remaining effect size (ORR, median overall survival and median progression-free survival). After correction by the trim-and-fill method, bias was indicated to have no significant impact on the results. In conclusion, apatinib combined with temozolomide has the effect that, compared with traditional Bevacizumab treatment, it can improve the efficacy in the treatment of recurrent high-grade glioma and improve prognosis. When combining with dose-dense temozolomide, the effect may be better than that of the conventional 5/28 regimen.
... Apatinib is a novel small-molecule tyrosine kinase inhibitor that exerts antitumor efficacy because of its high selectivity for vascular endothelial growth factor receptor (VEGFR)-2 (Li et al. 2022a). Several previous studies have shown the benefit of apatinib in patients with various solid tumors such as gastric cancer, liver cancer, breast cancer, and others (Liang et al. 2019;Li et al. 2013Li et al. , 2022bZhang et al. 2022). A phase III clinical trial showed that median OS was significantly improved and median progression-free survival (PFS) was significantly prolonged in the apatinib arm compared with the placebo arm (Li et al. 2016). ...
Purpose
Lymphocyte-monocyte ratio (LMR) has previously been used as a prognostic predictor in various solid tumors. This research aims in comparing the prognostic predictive Please check and conability of several inflammatory parameters and clinical parameters to validate further the excellent prognostic value of LMR in patients with gastric cancer treated with apatinib.
Methods
Monitor inflammatory, nutritional parameters and tumor markers. Cutoff values of the parameters concerned were identified with the X-tile program. Subgroup analysis was made via Kaplan–Meier curves, and univariate and multivariate Cox regression analyses were used to find independent prognostic factors. The nomogram of logistic regression models was constructed according to the results.
Results
A total of 192 patients (115 divided into training group and 77 into validation group) who received the second- or later-line regimen of apatinib were retrospectively analyzed. The optimal cutoff value for LMR was 1.33. Patients with high LMR (LMR-H) were significantly longer than those with low LMR (LMR-L) in progression-free survival (median 121.0 days vs. median 44.5 days, P < 0.001). The predictive value of LMR was generally uniform across subgroups. Meanwhile, LMR and CA19-9 were the only hematological parameters with significant prognostic value in multivariate analysis. The area under the LMR curve (0.60) was greatest for all inflammatory indices. Adding LMR to the base model significantly enhanced the predictive power of the 6-month probability of disease progression (PD). The LMR-based nomogram showed good predictive power and discrimination in external validation.
Conclusion
LMR is a simple but effective predictor of prognosis for patients treated with apatinib.
... Apatinib has been demonstrated to have direct anti-tumor effect and anti-angiogenic effect in pre-clinical studies. The mechanisms of direct anti-tumor effect of apatinib may involve the inhibition of activating AKT and ERK1/2, and enhancing anti-tumor effect by inducing production of 3-hydroxybutyric acid, which is a class I histone deacetylase inhibitor, via activating proliferator-activated receptor α (41)(42)(43). In the setting of anti-angiogenesis, apatinib selectively inhibits the kinase activity VEGFR-2, which play pivotal roles in the migration of endothelial cell and tube formation, truncating the blood supply in intratumor environment (18). ...
Background:
A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC.
Methods:
In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964.
Results:
From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed.
Conclusions:
Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.
... Apatinib was approved in China for the treatment of advanced or metastatic gastric cancer [18]. Additionally, apatinib exhibited better effects against HCC than sorafenib, both in vivo and in vitro [19]. e efficacy of inhibiting HCC growth and angiogenesis by apatinib was comparable to that of sorafenib but was associated with fewer adverse effects. ...
Background:
The treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains controversial due to the limited effect of sorafenib. The aim of the study was to investigate whether apatinib could improve the efficacy of transarterial chemoembolization (TACE) for patients with HCC complicated by PVTT.
Methods:
The study included 109 patients with HCC and PVTT who received TACE combined with apatinib (TACE + apatinib) (53 patients) or TACE alone (56 patients) between June 2015 and January 2019. Propensity score matching (PSM) analysis was used to reduce the potential selection bias. Overall survival time (OS) and time to progression (TTP) were used to evaluate the efficacy of TACE + apatinib and TACE alone.
Results:
Before PSM, TACE + apatinib significantly improved median TTP (7.0 vs. 3.0 months, P < 0.001) and median OS (15.0 vs. 7.0 months, P < 0.001) when compared with TACE alone. After PSM, the median TTP was significantly longer in the TACE + apatinib group, 6.0 months, than in the TACE alone group, 3.0 months (P < 0.001), and the median OS was significantly longer in the TACE + apatinib group, 14.0 months, than in the TACE alone group, 7.0 months (P < 0.001). Subgroup analysis revealed that, except for patients with Child-Pugh class B, the patients with or without extrahepatic metastases and with Child-Pugh class A had longer TTP and OS after the combined TACE + apatinib treatment than after TACE alone.
Conclusion:
The combination of TACE + apatinib might be an effective and safe treatment for HCC patients with PVTT.
... Angiogenesis is closely associated with the occurrence, development, and metastasis of malignant tumors. Tumor cells can produce a variety of molecules to induce angiogenesis, the new blood vessels can provide nutrients necessary for tumor growth and excrete metabolites [50,51]. Additionally, tumor cells are mainly transferred to other parts of the body through vascular dissemination [18]. ...
Background
The timely and effective treatments are vital to the prognosis of patients with hepatocellular carcinoma, and the role of Apatinib combined with TACE in the treatment of hepatocellular carcinoma remains unclear. Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of Apatinib combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma.
Methods
We searched for randomized controlled trials (RCTs) on Apatinib and TACE use in the treatment of hepatocellular carcinoma. Cochrane Central Register of Controlled Trials, Embase, PubMed, China Biomedical Literature Database, China Knowledge Network, Wanfang Database, and Weipu Chinese Science and Technology Journal Database were searched up to 16 April 2021. Two researchers independently screened the literature and extracted data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-6-0047/).
Results
A total of 14 RCTs involving 936 hepatocellular carcinoma patients were included. The objective remission rate (OR = 2.93, 95% CI 2.17–3.95), 1-year survival (OR = 2.47, 95% CI 1.65–3.68), 2-year survival (OR = 2.67, 95% CI 1.41–5.04), the incidence of hand-foot syndrome (OR = 32.09, 95% CI 10.87–94.74) and the incidence of proteinuria (OR = 14.79, 95% CI 6.07–36.06) of the Apatinib + TACE group was significantly higher than that of the TACE group (all P < 0.05). There were no significant differences in the incidence of myelosuppression (OR = 1.01, 95% CI 0.61–1.67), the incidence of hypertension (OR = 7.56, 95% CI 0.95–1.67, P = 60.17) between Apatinib + TACE and TACE group (all P > 0.05).
Conclusions
Apatinib combined with TACE is more effective than TACE alone in the treatment of hepatocellular carcinoma, but it has certain adverse reactions.
... A series of studies [7][8][9] found that apatinib has encouraging antitumor properties and is toxicologically tolerable in several malignant tumor cases. Furthermore, another study [10] found that apatinib has similar antitumorigenic and antiangiogenic efficacy to sorafenib in HCC with less toxicity in vitro and in vivo. These findings provide preclinical evidence supporting the potential application of apatinib to the treatment of HCC. ...
Objectives: To develop and validate radiomics nomograms for the pretreatment predictions of overall survival (OS) and time to progression (TTP) in the patients with advanced hepatocellular carcinoma (HCC) treated with apatinib plus transarterial chemoembolization (TACE), and to assess the incremental value of the clinical-radiomics nomograms for estimating individual OS and TTP.
Methods: A total of 60 patients with advanced HCC (BCLC stage C) treated with apatinib plus TACE were divided into a training set (n=48) and a validation set (n=12). The predictors identified from the clinical variables and the radiomics signature constructed from the computed tomography images, such as ɑ-fetoprotein level (AFP), formfactor, the grey level co-occurrence matrix, the gray level size zone matrix, and the gray level run-length matrix, were used to build the clinical-radiomics nomograms and the radiomics nomograms for the prediction of OS and TTP.
Results: Apatinib plus TACE benefited the patients with advanced HCC, with a 579-day median OS and a 270-day median TTP. The nomograms were built with the radiomics signature and AFP, and achieved favorable prediction efficacy with acceptable calibration curves. Decision curve analyses demonstrated that the clinical-radiomics nomograms outperformed the radiomics nomograms for the predictions of OS and TTP.
Conclusions: Apatinib plus TACE may improve OS and prolonged TTP in the patients with advanced HCC. The clinical-radiomics nomograms, a noninvasive pretreatment prediction tool that incorporate radiomics signature and AFP, demonstrated good prediction accuracy for OS and TTP in these patients. These results indicate that the clinical-radiomics nomograms may provide novel insight for precise personalized medicine approaches in the patients with advanced HCC.
... (Shanghai, China), [25] is a typical representative anti-angiogenesis agent with antineoplastic functions. It could induce apoptosis and suppress tumor proliferation across a variety of advanced solid malignancies with proven efficacy and safety for solid tumors, [26][27][28][29][30][31] even TC. [32,33] Of note, previous studies from our hospital also found that apatinib had better efficacy, a more manageable safety profile and faster therapeutic responses. ...
Rationale:
Though the majority of differentiated thyroid cancer (DTC) patients have a good prognosis after careful and standardized therapy, approximately 13% to 15% of DTC cases show surprisingly aggressive behavior and invasion of the surrounding structures, and a few progress to unresectable diseases. In this study, we report a case of an inoperable locally advanced DTC patient who underwent a curative operation after treatment of preoperative monotherapy of apatinib in a short time.
Patient concerns:
A 64-year-old woman complained of dysphagia due to large cervical mass, which severely invaded the left esophagus at the junction of the neck and thorax.
Diagnoses:
The female patient was diagnosed with locally advanced papillary thyroid cancer (PTC) by cytopathology and it was difficult to perform a safe and complete removal.
Interventions:
Apatinib (500 mg orally once a day) was initially used to treat this patient as a neoadjuvant therapy.
Outcomes:
Six weeks later, the tumor dramatically shrunk from 56 × 37 mm to 29 × 26 mm with well-controlled mild hypertension. After a 10-day interval of apatinib withdrawal, complete tumor excision was accomplished through cervical incision without esophageal fistula. Postoperative thyroid stimulating hormone suppression and radioiodine 131I ablation therapy were performed. At the 1-year follow-up evaluation, no tumor recurrence or metastasis was observed.
Lessons:
Preoperative short term targeted treatment with apatinib for locally advanced inoperable DTC may become a promising neoadjuvant therapy that, can reduce the tumor size and decrease stage, thus making the complete and safe removal of the lesion feasible.
... Apatinib, a selective vascular endothelial growth factor receptor 2-TKI, has been approved as a third-line treatment for patients with metastatic gastric cancer [14], and has shown promising therapeutic effects against diverse tumor types, including HCC [15][16][17]. In addition, preliminary results of a phase Ib clinical trial of SHR-1210 (a clinically available αPD-1 antibody) in combination with apatinib have shown promising efficacy in patients with advanced HCC [18]. ...
Apatinib, a selective vascular endothelial growth factor receptor 2-tyrosine kinase inhibitor, has demonstrated activity against a wide range of solid tumors, including advanced hepatocellular carcinoma (HCC). Preclinical and preliminary clinical results have confirmed the synergistic antitumor effects of apatinib in combination with anti-programmed death-1 (PD-1) blockade. However, the immunologic mechanism of this combination therapy remains unclear. Here, using a syngeneic HCC mouse model, we demonstrated that treatment with apatinib resulted in attenuation of tumor growth and increased tumor vessel normalization. Moreover, our results indicated that natural killer cells, but not CD4⁺ or CD8⁺ T cells mediated the therapeutic efficacy of apatinib in HCC mouse models. As expected, the combined administration of apatinib and anti-PD-1 antibody into tumor-bearing mice generated potent immune responses resulting in a remarkable reduction of tumor growth. Furthermore, increased interferon-γ and decreased tumor necrosis factor-α and interleukin-6 levels were observed, suggesting the potential benefits of combination therapy with PD-1 blockade and apatinib in HCC.
... Apatinib, a small molecule VEGFR TKI targeting VEGFR2 and other receptor tyrosine kinases, such as c-kit, RET, and c-src, is a first generation oral antiangiogenesis agent developed in China (25). The efficacy of apatinib monotherapy has been demonstrated in various cancer types, such as gastric cancer (26), liver cancer (27), lung cancer (28,29), and thyroid cancer (30). Our study demonstrated that low dose apatinib combined with pemetrexed could provide beneficial clinical outcomes and a favorable safety profile in advanced NSCLC patients. ...
Background:
The outcomes of advanced non-small cell lung cancer (NSCLC) patients after first- or second-line therapy are still discouraging due to a lack of effective treatment strategies. As a novel oral anti-angiogenesis drug, apatinib, approved by the National Medical Products Administration of China only for advanced gastric cancer, has been increasingly used in off-label treatment across various cancer types in recent years, especially advanced NSCLC. It has shown strong anti-tumor efficacy and acceptable safety.
Methods:
This prospective study (NCT02974933) was conducted in patients with advanced NSCLC, who had suffered disease progression from the first- or second-line treatment, in Hubei Cancer Hospital. Eligible patients were enrolled and administrated with apatinib mesylate (500 mg qd) in combination with pemetrexed (500 mg/m2, every 4 weeks). The primary endpoint was progression-free survival (PFS).
Results:
From September 2016 to September 2019, a total of 21 advanced NSCLC patients were enrolled in Hubei Cancer Hospital. As of January 2021, treatment was discontinued in all patients, with 1 still in follow-up. There were 7/21 (33.3%) patients who achieved objective response. The median PFS and median overall survival (OS) were 7.0 months (95% CI: 6.15-7.85 months) and 13.0 months (95% CI: 7.39-18.6 months), respectively. Toxicities were tolerable or could be clinically managed. The most common grade 3-4 adverse events (AEs) were hypertension (14.3%, 3/21), hand-foot syndrome (4.7%, 1/21), and proteinuria (4.7%, 1/21). Hematological toxicities were moderate, with rare occurrences of grade 3/4 toxicities. During the period of treatment, there was no occurrence of treatment-related death.
Conclusions:
Apatinib plus pemetrexed demonstrated promising efficacy and a high level of safety profile in previously heavily-treated NSCLC patients. More definitive studies on the combination of apatinib and pemetrexed are warranted.
... Apatinib inhibits cell invasion and migration by inhibiting the RET/SRC signaling pathway, suggesting a potential role in treating KIF5B-RET-driven tumors [30] . Apatinib can also promote the apoptosis of tumor cells of extrahepatic bile duct cancer [31] , esophageal cancer [32] , colon cancer [33] , osteosarcoma and glioma [34] , and B and T cell acute lymphoblastic leukemia [33] . ...
Angiogenesis plays an important role in the occurrence and development of tumors. Registered tyrosine kinase inhibitors targeting vascular endothelial growth factor reduce angiogenesis. Apatinib, a tyrosine kinase inhibitor, can specifically inhibit vascular endothelial growth factor receptor 2, showing encouraging anti-tumor effects in a variety of tumors including advanced hepatocellular carcinoma (HCC). This article intends to review the clinical research and application prospects of apatinib in the field of HCC.
