Acute cardiac tamponade after Endostar treatment of non-small cell lung cancer: A case report.

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.

Pre-clinical Efficacy and Safety Pharmacology of PEGylated Recombinant Human Endostatin.

INTRODUCTION: This study aimed to outline the pre-clinical efficacy and safety pharmacology of PEGylated recombinant human endostatin (M2ES) according to the requirements of new drug application. METHODS: The purity of M2ES was evaluated by using silver staining. Transwell migration assay was applied to detect the bioactivity of M2ES in vitro. The antitumor efficacy of M2ES was evaluated in an athymic nude mouse xenograft model of pancreatic cancer (Panc-1) and gastric cancer (MNK45). BALB/C mice were treated with different doses of M2ES (6, 12 and 24 mg/kg) intravenously, both autonomic activity and cooperative sleep were monitored before and after drug administration. RESULTS: The apparent molecular weight of M2ES was about 50 kDa, and the purity was greater than 98%. Compared with the control group, M2ES significantly inhibits human micro-vascular endothelial cells (HMECs) migration in vitro. Notably, weekly administration of M2ES showed a significant antitumor efficacy when compared with the control group. Treatment of M2ES (24mg/kg or below) showed no obvious effect on both autonomic activity and hypnosis. CONCLUSION: On the basis of the pre-clinical efficacy and safety pharmacology data of M2ES, M2ES can be authorized to carry out further clinical studies.

Plasmid co-expressing siRNA-PD-1 and Endostatin carried by attenuated Salmonella enhanced the anti-melanoma effect via inhibiting the expression of PD-1 and VEGF on tumor-bearing mice.

Melanoma, the most perilous form of skin cancer, is known for its inherent resistance to chemotherapy. Even with advances in tumor immunotherapy, the survival of patients with advanced or recurrent melanomas remains poor. Over time, melanoma tumor cells may produce excessive angiogenic factors, necessitating the use of combinations of angiogenesis inhibitors, including broad-spectrum options, to combat melanoma. Among these inhibitors, Endostatin is one of the most broad-spectrum and least toxic angiogenesis inhibitors. We found Endostatin significantly increased the infiltration of CD8+ T cells and reduced the infiltration of M2 tumor-associated macrophages (TAMs) in the melanoma tumor microenvironment (TME). Interestingly, we also observed high expression levels of programmed death 1 (PD-1), an essential immune checkpoint molecule associated with tumor immune evasion, within the melanoma tumor microenvironment despite the use of Endostatin. To address this issue, we investigated the effects of a plasmid expressing Endostatin and PD-1 siRNA, wherein Endostatin was overexpressed while RNA interference (RNAi) targeted PD-1. These therapeutic agents were delivered using attenuated Salmonella in melanoma-bearing mice. Our results demonstrate that pEndostatin-siRNA-PD-1 therapy exhibits optimal therapeutic efficacy against melanoma. We found that pEndostatin-siRNA-PD-1 therapy promotes the infiltration of CD8+ T cells and the expression of granzyme B in melanoma tumors. Importantly, combined inhibition of angiogenesis and PD-1 significantly suppresses melanoma tumor progression compared with the inhibition of angiogenesis or PD-1 alone. Based on these findings, our study suggests that combining PD-1 inhibition with angiogenesis inhibitors holds promise as a clinical strategy for the treatment of melanoma.

Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status.

Angiogenesis is the physiological process that results in the formation of new blood vessels develop from pre-existing vasculature and plays a significant role in several physiological and pathological processes. Inhibiting angiogenesis, a crucial mechanism in the growth and metastasis of cancer, has been proposed as a potential anticancer therapy. Different studies showed the beneficial effects of angiogenesis inhibitors either in patients suffering from different cancers, alone or in combination with conventional therapies. Even though there are currently a number of efficient anti-angiogenic drugs, including monoclonal antibodies and kinase inhibitors, the associated toxicity profile and their affordability constraints are prompting researchers to search for a safe and affordable angiostatic agent for cancer treatment. Endostatin is one of the endogenous anti-angiogenic candidates that have been extensively pursued for the treatment of cancer, but even over three decades after its discovery, we have not made much advancement in employing it as an anticancer therapeutic despite of its remarkable anti-angiogenic effect with low toxicity profile. A recombinant human endostatin (rh-Es) variant for non-small cell lung cancer was approved by China in 2006 and has since been used effectively. Several other successful clinical trials related to endostatin for various malignancies are either ongoing or have already been completed with promising results. Thus, in this review, we have provided an overview of existing anti-angiogenic drugs developed for cancer therapy, with a summary of tumour angiogenesis in the context of Endostatin, and clinical status of rh-Es in cancer treatment. Furthermore, we briefly discuss the various strategies to improve endostatin features (poor pharmacokinetic properties) for developing rh-Es as a safe and effective agent for cancer treatment.

Canagliflozin improves coronary microvascular vasodilation and increases absolute blood flow to the myocardium independent of angiogenesis.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitor, canagliflozin, improves myocardial perfusion to ischemic territory without accompanying changes in vascular density. We aimed to (1) characterize effects on angiogenic pathways, (2) use multiomics to identify gene expression and metabolite profiles relevant to regulation of myocardial blood flow, and (3) investigate drug effect on coronary microvascular reactivity. METHODS: A nondiabetic swine model of chronic myocardial ischemia and nondiabetic rat model were used to study functional and molecular effects of canagliflozin on myocardium and in vitro microvascular reactivity. RESULTS: Canagliflozin resulted in increased coronary microvascular vasodilation and decreased vasoconstriction (P < .05) without changes in microvascular density (P > .3). Expression of the angiogenic modulator, endostatin, increased (P = .008), along with its precursor, collagen 18 (P < .001), and factors that increase its production, including cathepsin L (P = .004). Endostatin and collagen 18 levels trended toward an inverse correlation with blood flow to ischemic territory at rest. Proangiogenic fibroblast growth factor receptor was increased (P = .03) and matrix metalloproteinase-9 was decreased (P < .001) with canagliflozin treatment. Proangiogenic vascular endothelial growth factor A (P = .13), Tie-2 (P = .10), and Ras (P = .18) were not significantly altered. Gene expression related to the cardiac renin-angiotensin system was significantly decreased. CONCLUSIONS: In chronic myocardial ischemia, canagliflozin increased absolute blood flow to the myocardium without robustly increasing vascular density or proangiogenic signaling. Canagliflozin resulted in altered coronary microvascular reactivity to favor vasodilation, likely through direct effect on vascular smooth muscle. Downregulation of cardiac renin-angiotensin system demonstrated local regulation of perfusion. VIDEO ABSTRACT.

Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway.

BACKGROUND: A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. OBJECTIVE: To explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. METHODS: Chemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. RESULTS: Seven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. CONCLUSIONS: DDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.

Efficacy of concurrent chemoradiotherapy plus Endostar compared with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: To retrospectively analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) plus recombinant human endostatin (Endostar, CCRT + E) versus CCRT alone in locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A retrospective analysis of patients initially treated for LANPC from November 2016 to March 2019 was performed: trial group received CCRT + E and control group received CCRT. Prognoses and adverse effects were evaluated. RESULTS: Eighty-eight patients were included: 43 received CCRT + E and 45 received CCRT. The median follow-up time was 54.0 (range: 8.0-64.0) months. The survival data of the CCRT + E and CCRT groups were as follows: 3-year progression-free survival (PFS) rates, 81.4% and 63.6% (hazard ratio [HR] 0.418, 95%CI 0.181-0.963, P = 0.034); 3-year distant metastasis-free survival (DMFS) rates, 88.3% and 77.3% (HR 0.370, 95%CI 0.132-1.039, P = 0.049); 3-year overall survival rates, 88.2% and 81.9% (HR 0.437, 95%CI 0.151-1.260, P = 0.114); and 3-year locoregional failure-free survival rates, 87.8% and 86.9% (HR 0.795, 95%CI 0.242-2.616, P = 0.705). Three months after radiotherapy, the complete response (CR) rates of cervical lymph node regression were 97.7% and 82.2% for the CCRT + E and CCRT groups (P = 0.041). The corresponding CR rates were 100% and 80.0% for lymph node necrosis (P = 0.001) and 100% and 85.2% for extranodal extension (P = 0.041). The CCRT + E group had higher incidence of grade 3/4 leukopenia (32.6% vs. 13.3%, P = 0.031), with similar results for late toxicity. CONCLUSIONS: CCRT + E significantly prolonged 3-year PFS and DMFS in LANPC, and patients had better lymph node regression.

The Treatment Combining Antiangiogenesis with Chemoradiotherapy Impinges on the Peripheral Circulation Vascular Endothelial Cells and Therapeutic Effect in the Patients with Locally Advanced Nasopharyngeal Carcinoma.

This study was implemented for the evaluation on the circulating endothelial cells' (CECs) clinical significance in the locally advanced nasopharyngeal carcinoma treatment with endostatin-combined chemoradiotherapy. This study enrolled 47 patients with locally advanced nasopharyngeal carcinoma who were hospitalized from May 9, 2012 to March 10, 2013. These patients were split up into the observation group (25 patients) and control group (22 patients). Patients in the observation group received the endostatin combined with induction chemotherapy and subsequently with concurrent chemoradiotherapy with endostatin. Patients in the control group were treated with inductive chemotherapy followed by concurrent chemoradiotherapy. CECs in peripheral blood were conducted separately before or after inductive chemotherapy and additionally in the end of concurrent chemoradiotherapy. The CEC values of the observation group showed significant statistical differences (p < 0.05) before or after different therapies, whereas those data in the control group were not statistically different. And, the mostly importantly, the CEC values in the observation group and control group turned out a statistical difference. The combination of endostatin and chemoradiotherapy significantly reduced parameters of peripheral blood CECs in these patients. According to the CEC parameters' variety that we observed in the combined therapies, this study demonstrated that the CECs might be a clinical clue to evaluate this antiangiogenic chemoradiotherapy. And the clinical value of CECs will be further determined along with increasing comparative studies and clinical long-term efficacy observation.

Efficacy and safety of recombinant human endostatin combined with whole-brain radiation therapy in patients with brain metastases from non-small cell lung cancer.

BACKGROUND AND PURPOSE: Brain metastasis (BM) is the leading cause of poor prognosis in non-small cell lung cancer (NSCLC) patients. To date, whole-brain radiation therapy (WBRT) is a standard treatment for patients with multiple BMs, while its effectiveness is currently unsatisfactory. This study aimed to investigate the effects of Rh-endostatin combined with WBRT on NSCLC patients with BMs. MATERIALS AND METHODS: A total of 43 patients with BM were randomly divided into two groups. The Rh-endostatin combination group (n = 19) received Rh-endostatin combined with WBRT, and the radiation group (n = 24) received WBRT only. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were intracranial progressionfree survival (iPFS), overall survival (OS), objective response rate (ORR), and changes in the cerebral blood volume (CBV) and cerebral blood flow (CBF). RESULTS: Median PFS (mPFS) was 8.1 months in the Rh-endostatin combination group and 4.9 months in the radiation group (95%CI 0.2612-0.9583, p = 0.0428). Besides, the median iPFS was 11.6 months in the Rh-endostatin combination group and 4.8 months in the radiation group (95%CI 0.2530-0.9504, p = 0.0437). OS was 14.2 months in the Rh-endostatin combination group and 6.4 months in the radiation group (95%CI 0.2508-1.026, p = 0.0688). CBV and CBF in the Rh-endostatin combination group were better improved than that in the radiation group, which indicated that Rh-endostatin might improve local blood supply and microcirculation. CONCLUSION: Rh-endostatin showed better survival and improved cerebral perfusion parameters, which may provide further insights into the application of Rh-endostatin for NSCLC patients with BMs.

Real-world treatment pattern and comprehensive comparative effectiveness of Endostar plus different chemotherapy in advanced patients with non-small cell lung cancer.

Recombinant human endostatin (Endostar) plus vinorelbine/cisplatin (NP) had been approved for the treatment of non-small cell lung cancers (NSCLC). But the real-world treatment pattern and effectiveness of Endostar plus other combination chemotherapy, namely docetaxel/platinum (DP), gemcitabine/platinum (GP), pemetrexed/platinum (PP), and paclitaxel/platinum (TP) in both treatment-naïve and re-treatment patients with advanced NSCLC were still unclear. A retrospective observational study was conducted based on the electronic medical record (EMR) system and advanced patients with NSCLC were identified from 7 cancer hospitals in China from 2012 to 2019. These patients were divided into five groups, Endostar plus NP, Endostar plus DP, Endostar plus GP, Endostar plus PP, and Endostar plus TP groups. The disease control rate (DCR), overall response rate (ORR), and the progression-free survival (PFS) were evaluated. Of the eligible 512 advanced patients with NSCLC, 10.35% were in Endostar plus NP group, while the numbers were 15.43%, 32.42%, 26.56%, 15.23% in Endostar plus DP group, Endostar plus GP group, Endostar plus PP group, and Endostar plus TP group, respectively. The ORRs were 31%, 28%, 22%, 41% and 27%, and the DCRs were 71%, 72%, 57%, 72% and 76%, respectively. The median of PFSs for the above groups were 7.9, 6.8, 5.6, 13.7, and 5.4 months. Compared with Endostar plus NP group, the hazard ratios (HRs) and 95%CIs of Endostar plus other chemotherapy were 1.86 (0.75-4.61), 2.15 (0.83-5.60), 1.33 (0.51-3.44), and 2.42 (0.86-6.81). This real-world study found the effectiveness of Endostar plus DP, Endostar plus GP, Endostar plus PP, and Endostar plus TP were of no statistically significant differences compared with Endostar plus NP and reflected the good effectiveness of Endostar plus different chemotherapy in advanced patients with NSCLC.

Systematic Evaluation Meta-Analysis of the Efficacy of Recombinant Human Endostatin Combined with Gemcitabine and Cisplatin in Non-Small-Cell Lung Cancer.

Objective: To evaluate the efficacy of recombinant human endostatin combined with gemcitabine and cisplatin in the treatment of non-small-cell lung cancer (NSCLC). Methods: The databases of Cochrane Library, Embase, ClinicalTrials, PubMed, HowNet, Wanfang, and VIP were searched to collect randomized controlled trials (RCTs) of recombinant human endostatin combined with gemcitabine and cisplatin (experimental group) and gemcitabine combined with cisplatin (control group) for comparative study. The quality of literature was evaluated by bias risk assessment tools and related scales, and then meta-analysis was performed. Results: A total of 27 RCTs (1646 patients) were included. The results of meta-analysis showed that the effective rate (P < 0.000 01) and benefit rate (P < 0.000 01) of the experimental group were significantly higher than those of the control group, the incidence of leucopenia (P = 0.79), thrombocytopenia (P = 0.39), and gastrointestinal reaction (P = 0.85) were not statistically significant. Conclusion: The combination of recombinant human endostatin, gemcitabine, and cisplatin can increase the efficacy and safety of NSCLC patients.

Analysis of cardio-cerebrovascular adverse events in patients with brain metastasis from lung cancer treated with antiangiogenic drugs.

To observe the occurrence of cardio-cerebrovascular adverse events in patients with brain metastases from lung cancer treated with antiangiogenic drugs. A total of 182 patients with brain metastases from lung cancer were selected as the research objects. They were divided into patients receiving antiangiogenic drugs and those not receiving antiangiogenic drugs. The incidence of cardio-cerebrovascular adverse events was observed. The incidence of low-grade hypertension, cerebral haemorrhage, cerebrovascular accident, cerebrovascular arrhythmia and other cardio-cerebrovascular adverse events in patients with brain metastases from lung cancer after receiving antiangiogenic therapy was higher than in the group that did not receive anti-vascular therapy (P<0.05). The incidence of low-grade hypertension increased in patients with a previous history of hypertension after they received antiangiogenic drugs (P< 0.05). There were no statistically significant differences between cardio-cerebrovascular adverse event rates in patients treated with three different antiangiogenic drugs (P>0.05). Head radiotherapy did not increase the rate of cardio-cerebrovascular adverse events among patients treated with antiangiogenic drugs (P< 0.05), and the incidence of adverse events was lowest in the endost group combined with radiotherapy. The incidence of cardio-cerebrovascular adverse events in the combined gemcitabine + platinum (GP) and irinotecan + platinum (IP) regimen group was higher than that in the other combined chemotherapy regimen groups. Treatment of brain metastases from lung cancer using antiangiogenic drugs increases the incidence of low-grade cardio-cerebrovascular adverse events, but these drugs are safe and controllable and are worthy of clinical application.

Efficacy and safety of recombinant human endostatin during peri-radiotherapy period in advanced non-small-cell lung cancer.

Background: This study aimed to retrospectively investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with radiotherapy in advanced non-small-cell lung cancer (NSCLC). Methods: Patients with unresectable stage III and IV NSCLC who treated with radiotherapy were enrolled. Patients who received Rh-endostatin infusion throughout the whole peri-radiotherapy period formed the Endostar group, and those who received no Rh-endostatin infusion were the control group. Results: The median progression-free survival was 8.0 and 4.4 months (hazard ratio: 0.53; 95% CI: 0.32-0.90; p = 0.019) and median overall survival was 40.0 and 13.1 months (hazard ratio: 0.53; 95% CI: 0.28-0.98; p = 0.045) for the Endostar and control groups, respectively. The Endostar group exhibited a numerically lower rate of radiation pneumonitis relapse, radiation pneumonitis death and pulmonary fibrosis. Conclusion: Rh-endostatin infusion throughout the peri-radiotherapy period enhanced radiosensitivity and showed better survival outcomes and a tendency toward fewer radiation-related pulmonary events in patients with NSCLC.

Recombinant human endostatin (Rh-endostatin/Endostar) combined with chemotherapy has been approved as first-line standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) in China. This study aimed to retrospectively investigate the efficacy and safety of Rh-endostatin combined with radiotherapy in advanced NSCLC. Patients with unresectable stage III and IV NSCLC who treated with radiotherapy were enrolled. Patients who received Rh-endostatin infusion throughout the whole peri-radiotherapy period were the Endostar group, and those receiving no Rh-endostatin infusion were the control group. Results showed that the median progression-free survival was 8.0 and 4.4 months, and median overall survival was 40.0 and 13.1 months, for the Endostar and control groups, respectively. The Endostar group had a lower rate of radiation pneumonitis relapse, radiation pneumonitis death and pulmonary fibrosis. In conclusion, Rh-endostatin infusion throughout the peri-radiotherapy period enhanced radiosensitivity and showed better survival outcomes and a tendency toward fewer radiation-related pulmonary events in patients with NSCLC.

Bronchoscopic intratumoral injections of cisplatin and endostar as concomitants of standard chemotherapy to treat malignant central airway obstruction.

STUDY PURPOSE: Malignant central airway obstruction (CAO) in non-small cell lung cancer (NSCLC) is associated with high morbidity and requires endobronchial palliative treatment to re-establish a free air passage. We investigate intratumoral therapy combining anti-angiogenic and cytotoxic as a feasible therapeutic modality to treat malignant CAO. STUDY DESIGN: Ten NSCLC subjects with symptomatic malignant CAO underwent endobronchial intratumoral cisplatin and Endostar co-injection after tumour debulking next to systemic cisplatin-based chemotherapy. Injection was performed immediately after debulking surgery and was then carried out on day 2, day 6 and day 10 past systemic chemotherapy. Nine subjects of control group constantly received traditional cisplatin-based chemotherapy. Bronchoscopy, CT scanning, histology, FEV1/FVC ratio, Karnofsky performance (KPS) and shortness of breath scores were analysed to assess therapeutic efficacy. RESULTS: All 10 subjects benefited from the intratumoral cisplatin and endostar co-injection and systemic chemotherapy combination therapy. Bronchoscopy and CT scanning analyses showed a massive airway widening after treatment. Increased KPS and reduced shortness of breath score were also observed. A substantial improvement of lung function was further confirmed by increased FEV1/FVC ratio. For subjects of control group, the improvement was moderate and obviously not as optimal as the 10 subjects with intratumoral injection. CONCLUSIONS: We have shown that the intratumoral injection of cytotoxic cisplatin plus anti-angiogenic Endostar is an effective and safe adjuvant therapeutic option to treat malignant CAO in clinical practice. This time-staggered local and systemic treatment combination improves quality of life and clinical parameters, thus may provide a feasible therapeutic option for symptomatic CAO.

Efficacy and safety of endostar combined with cisplatin in treatment of non-small cell lung cancer with malignant pleural effusion: A meta-analysis.

BACKGROUND: Although there are new treatments for non-small cell lung cancer with malignant pleural effusion, these therapies are prone to recurrent pleural effusion and poor in efficacy. And recombinant human endostatin is a new type of anti-tumor angiogenesis drug independently developed in my country. It has the effect of inhibiting tumor angiogenesis, inhibiting tumor proliferation and differentiation, and effectively inhibiting the formation and recurrence of malignant pleural effusion. Therefore, this study is aim to systematically review the efficacy and safety of intrapleural injection of endostar combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC) with malignant pleural effusion. METHODS: Databases including Cochrane Library, PubMed, CBM, Embase, CNKI, and WanFang Data were searched to collect randomized controlled trials about endostar combined with cisplatin for NSCLC with malignant pleural effusion from inception to April 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in included studies. Finally, the meta-analysis was made by using RevMan 5.4.1 software. RESULTS: A total of 11 randomized controlled trials involving 814 patients were finally included. The results of the meta-analysis showed that: The overall response rate and the improvement rate of quality of life in the endostar combined with cisplatin group were higher than that of the cisplatin alone group (relative risk = 1.58, 95% confidence interval = 1.42-1.76, P < .00001; relative risk = 1.63, 95% confidence interval = 1.38-1.93, P < .00001, respectively). Meanwhile, there were no significant differences between the 2 groups in the incidence of gastrointestinal reaction, the incidence of leucopenia, the incidence of thrombocytopenia, and the incidence of hypodynamia (all P values > .05). CONCLUSION: Compared with cisplatin, intrapleural injection of endostar combined with cisplatin could improve the overall response rate and the quality of life of NSCLC patients with malignant pleural effusion. Due to the limited quality and quantity of included studies, more high-quality studies are needed to verify the above conclusion.

Rh-endostatin combined with chemotherapy in patients with advanced or recurrent mucosal melanoma: retrospective analysis of real-world data.

BACKGROUND: Mucosal melanoma is rare and has distinct clinical and genetic features. Even with advances in targeted and immune therapies, the survival of patients with advanced or recurrent mucosal melanomas remains poor. The standard treatment remains controversial and we conducted this real-world study aimed to explore continuous intravenous recombinant human endostatin (Rh-endostatin) infusion plus chemotherapy in this population in the first-line setting. METHODS: Overall, 43 patients with advanced or recurrent mucosal melanoma treated at Fudan University Shanghai Cancer Center between April 2017 and August 2020 were retrospectively included. Patients received dacarbazine plus cisplatin or temozolomide plus cisplatin per the investigators' preference. Rh-endostatin (105 mg/m2) was administered with continuous infusion for 168 h (Civ 168 h). RESULTS: Of the 43 patients, 72.1% had metastatic disease, and the most common primary site was the gastrointestinal tract (51.2%). The most commonly observed mutations were NRAS (23.1%), BRAF (7.7%) and CKIT mutations (5.1%). An objective response was observed in 12 (30.0%) of the 40 evaluable patients, and disease control was achieved in 31 (77.5%) patients. With a median follow-up of 17.6 months, the median progression-free survival (PFS) and overall survival (OS) were 4.9 and 15.3 months, respectively. Additionally, high lymphocyte-to-monocyte ratio (LMR) (p = 0.023, HR 0.29, 95% CI: 0.10-0.84) and BRAF/KIT/RAS mutation (p = 0.028, HR 0.24, 95% CI: 0.07-0.86) were independently correlated with prolonged OS. Toxicity was manageable overall. CONCLUSION: Continuous Rh-endostatin infusion plus chemotherapy was effective and safe for the treatment of advanced or recurrent mucosal melanoma. High LMR was correlated with favorable PFS and OS in this patient population.

Endostar, an Antiangiogenesis Inhibitor, Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer.

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

Synergistic Effect of Baculovirus-Mediated Endostatin and Angiostatin Combined with Gemcitabine in Hepatocellular Carcinoma.

Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous studies have shown that the BDS-hEA, a baculovirus long-term expressing the fusion protein of human endostatin and angiostatin, has a favorable effect in inhibiting the growth and angiogenesis of hepatocellular carcinoma. The purpose of this study was to further investigate its synergistic antitumor efficiency in combination with low-dose chemotherapeutic gemcitabine (GEM) on the subcutaneous hepatocellular carcinoma xenograft model in nude mice. The results showed that the combined group significantly inhibited (p < 0.05 or p < 0.01 or p < 0.001) the growth of tumor weight and volume, reduced the expression of ki67 (cell proliferation marker), CD31 (angiogenic marker) and Matrix metalloproteinase 9 (MMP-9, tumor invasion and metastasis marker) and increased the apoptosis of tumor cells compared with the monotherapy and control groups, respectively. Synergistic index results showed that BDS-hEA combined with GEM had a synergistic effect in inhibiting tumor volume, proliferation, microvessel density, metastasis and promoting tumor apoptosis. Furthermore, there were no metastatic nodules and obvious pathological changes in liver tissue of the combined group, and the serum liver function indicators aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) were significantly reduced (p < 0.05 or p < 0.01 or p < 0.001) in the BDS-hEA or GEM groups compared with the control group. Notably, the combined therapy showed lower levels of liver function indicators than the GEM group. These data support the view that the combination of BDS-hEA and GEM has a synergistic anti-tumor properties and can reduce the damage of liver to certain extent.

rh-ES and Chemotherapy in Advanced Gastrointestinal Cancer in China: A Meta-analysis.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of recombinant human endostatin (rh-ES) combined with chemotherapy in advanced gastrointestinal tumors in China. METHODS: A literature search was performed in PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang, and China National Knowledge Infrastructure (CNKI), with the last report through September 2019. The included research was scored using a modified Jadad scale, and a meta-analysis was performed using RevMan 5.3 software. RESULTS: Twenty articles including 905 participants (experimental group [rh-ES combined with chemotherapy] 459; control group [chemotherapy alone] 446) were considered. The total effective rate for the experimental group in advanced gastrointestinal tumors was higher than that of the control group (P<0.05). No significant difference in adverse reactions was seen between the two groups (P>0.05). CONCLUSIONS: The short-term efficacy of rh-ES combined with chemotherapy for advanced gastrointestinal tumors was better, with fewer adverse reactions.

Study on the clinical effects of targeted therapy on elderly patients with gastric cancer.

To explore the clinical effects of targeted drug therapy on elderly patients with gastric cancer. Totally 200 metastatic gastric cancer patients who came to our hospital from January 2017 to January 2020 were selected and randomized into four groups, with 50 patients in each group. Bevacizumab (Group I), apatinib (Group II), and recombinant human endostatin (Group III) adopted respectively. While the control group received no targeted drug. Clinical data and clinical effect was collected and compared. After the therapy, the vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-2 (sVEGFR2) and human epithelial growth factor receptor-2 (HER2) positive detection of Group I, Group II, and Group III were better than the control group (P<0.05). In addition, the therapeutic effects of Group I, Group II, and Group III were higher and the incidence of adverse reactions was lower than the control group (P<0.05). Targeted drugs have obvious clinical effects in gastric cancer. It can effectively inhibit tumor growth and reduce the occurrence of complications, which is worthy of extensive clinical application and promotion.