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Wu F, Lu Z, Que J, Ma S, Jiang L, Tang X, Zheng C, Zhou L, Huang Q, Zhang Y. The safety of combining Endostar with concurrent chemoradiotherapy for the treatment of locally advanced cervical cancer and the evaluation of its anti-angiogenic effects via transrectal contrast-enhanced ultrasound. Front Oncol 2025; 15:1514425. [PMID: 40406255 PMCID: PMC12095288 DOI: 10.3389/fonc.2025.1514425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 04/14/2025] [Indexed: 05/26/2025] Open
Abstract
Background In recent years, exploring the addition of angiogenesis inhibitors to chemoradiotherapy for locally advanced cervical cancer (LACC) has gained research interest. This study assessed the safety and anti-angiogenic effects of combining Endostar with concurrent chemoradiotherapy (CCRT) via transrectal contrast-enhanced ultrasound. Methods A total of 120 patients with locally advanced cervical cancer (LACC) were randomly allocated to two groups: CCRT combined with Endostar (CRT+E group, n = 60) and CCRT alone (CRT group, n = 60). Endostar was administered intravenously before radiotherapy and repeated for four cycles. All patients received platinum-based CCRT. Adverse events were monitored, and transrectal contrast-enhanced ultrasonography (CEUS) was conducted before, during, and after radiotherapy. Vascular malformation (VM) rates were calculated from tumor cross-sectional images, and quantitative analysis software measured peak intensity (PI), time to peak (TTP), and mean transit time (MTT) of tumor vessels. Results No significant differences were observed in hematological, hepatic, renal, gastrointestinal, or cardiac adverse reactions between the two groups (all P>0.05). In the CRT+E group, VM rates, TTP, and MTT significantly differed at three time points (with P values of 0.003, 0.002, and P<0.001, respectively), whereas the CRT group showed no significant changes (all P>0.05). Post-radiotherapy, statistically significant differences emerged between the CRT+E and CRT groups for VM rates (P = 0.027), MTT (P = 0.027), and TTP (P < 0.001), while PI showed no significant difference (65.67 ± 36.53 vs. 74.69 ± 61.21, P = 0.598). Conclusion The combination of Endostar with CCRT for locally advanced cervical cancer (LACC) demonstrated favorable safety and tolerability. Transrectal contrast-enhanced ultrasound (CEUS) effectively assessed tumor vascular normalization induced by Endostar during CCRT. Specifically, Endostar significantly reduced VM rates and shortened MTT, suggesting its potential to normalize tumor vasculature.
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Affiliation(s)
- Fang Wu
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Zhouxue Lu
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Jinting Que
- Department of Oncology, The First People’s Hospital of Qinzhou, Qinzhou, Guangxi, China
| | - Shanshan Ma
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Li Jiang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Xiaobi Tang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Chengshan Zheng
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Li Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Qiufeng Huang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
| | - Yong Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China
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Liu Y, Liu HG, Zhao C. Intraperitoneal perfusion of endostatin improves the effectiveness and prolongs the prognosis of patients with gastric cancer. World J Gastrointest Oncol 2025; 17:103131. [PMID: 40235905 PMCID: PMC11995351 DOI: 10.4251/wjgo.v17.i4.103131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/02/2025] [Accepted: 02/18/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Studies on the application of recombinant human endostatin (RH-endostatin) intraperitoneal perfusion in gastric cancer (GC) with malignant ascites are limited. AIM To explore the effectiveness, prognosis, and safety of intraperitoneal RH-endostatin perfusion in treating patients with GC and malignant ascites. METHODS Patients with GC and malignant ascites were divided into the cisplatin intraperitoneal perfusion (control group) group and the cisplatin combined with RH-endostatin intraperitoneal perfusion group (RH-endostatin group). Efficient ascites control, overall survival (OS), quality of life, and adverse events were observed, and possible influencing factors on prognosis outcomes analyzed. RESULTS We identified no significant differences in baseline characteristics between the control and RH-endostatin groups. The latter group had higher ascites control rates than the control group. Treatment methods were identified as an independent OS factor. Clinically, RH-endostatin-treated patients had significantly improved OS rates when compared with control patients, particularly in those with small and moderate ascites volumes. Quality of life improvements in control patients were significantly lower when compared with RH-endostatin patients. Adverse events were balanced between the groups. CONCLUSION Overall, intraperitoneal RH-endostatin improved treatment efficacy and prolonged prognosis in patients with GC and malignant ascites. This approach may benefit further clinical applications for treating GC.
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Affiliation(s)
- Yong Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300000, China
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300000, China
- Tianjin Key Laboratory of Digestive Cancer, Tianjin Clinical Research Center for Cancer, Tianjin 300000, China
| | - Hong-Gen Liu
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin Cancer Institute of Traditional Chinese Medicine, Tianjin 300380, China
| | - Cheng Zhao
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin Cancer Institute of Traditional Chinese Medicine, Tianjin 300380, China
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Luo Y, Teng J, Wang Z, Hong Q, Zou H, Li L, Zhang N, Wang H. Clinical Characteristics, Treatment and Prognosis of Primary Tracheal Adenoid Cystic Carcinoma: A Multicenter Retrospective Study. Cancer Med 2025; 14:e70877. [PMID: 40249221 PMCID: PMC12007181 DOI: 10.1002/cam4.70877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 03/09/2025] [Accepted: 04/04/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Tracheal adenoid cystic carcinoma (TACC) is a rare salivary gland malignant tumor. Previous studies mainly focused on surgery, radiation, and chemotherapy. The purpose of this study is to describe more clinical characteristics, treatments, and overall survival (OS) of TACC. METHODS Retrospectively analyzed TACC patients from two medical institutions and the SEER database from January 2010 to December 2021. Survival curves were drawn using the Kaplan-Meier method, and the effects of prognosis were analyzed by multivariate COX regression and AFT. The endpoint of the study was overall survival (OS). RESULTS One hundred fifty TACC patients were enrolled (DZM 11, EG 64, SEER 75), and the 5- and 10-year survival rate was 70.62% and 35.80%, with a median survival time of 98 months. Lymph node status (yes) is an independent risk factor for TACC (HR = 3.020, 95% CI = 1.419-6.426, p = 0.004), and surgery is an independent protective factor (HR = 0.293, 95% CI = 0.146-0.587, p = 0.001). The AFT yielded similar results. In subgroup analysis of 63 non-surgical patients, lymph node status (Yes) (HR = 3.511, 95% CI = 1.498-8.229, p = 0.004), and tumor longitudinal diameter range (TLDR) > 1 (HR = 2.975, 95% CI = 1.360-6.506, p = 0.006) are independent risk factors, while Targeted Therapy (HR = 0.248, 95% CI = 0.096-0.637, p = 0.004) is an independent protective factor. CONCLUSION Lymph node status and TLDR are prognostic factors of TACC. Surgery is associated with prolonged survival of TACC. Targeted therapy may be associated with improved survival among non-surgical TACC patients. TRIAL REGISTRATION ChiCTR2400083551.
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Affiliation(s)
- Yi Luo
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
- Beijing University of Chinese MedicineChaoyangBeijingChina
| | - Jun Teng
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
- Beijing University of Chinese MedicineChaoyangBeijingChina
| | - Zhina Wang
- Department of OncologyBeijing Emergency General HospitalChaoyangBeijingChina
- Department of Pulmonary and Critical Care Medicine IIBeijing Emergency General HospitalChaoyangBeijingChina
| | - Qinyan Hong
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
- Beijing University of Chinese MedicineChaoyangBeijingChina
| | - Hang Zou
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
| | - Lei Li
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
| | - Nan Zhang
- Department of OncologyBeijing Emergency General HospitalChaoyangBeijingChina
- Department of Pulmonary and Critical Care Medicine IIBeijing Emergency General HospitalChaoyangBeijingChina
| | - Hongwu Wang
- Respiratory Disease Center, Dongzhimen HospitalBeijing University of Chinese MedicineTongzhouBeijingChina
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Anakha J, Prasad YR, Pande AH. Endostatin in disease modulation: From cancer to beyond. Vascul Pharmacol 2025; 158:107459. [PMID: 39708990 DOI: 10.1016/j.vph.2024.107459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/04/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.
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Affiliation(s)
- J Anakha
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
| | - Yenisetti Rajendra Prasad
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India
| | - Abhay H Pande
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
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Tian Q, Tian C, Lu Y, Yan B, Zhang K, Wu C. RETRACTED: Poly (lactic-co-glycolic acid)-encapsulated Endostar-loaded calcium phosphate cement as anti-tumor bone cement for the treatment of bone metastasis in lung cancer. ENVIRONMENTAL TOXICOLOGY 2025; 40:E17-E30. [PMID: 38400521 DOI: 10.1002/tox.24166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 01/14/2024] [Accepted: 01/20/2024] [Indexed: 02/25/2024]
Abstract
Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-β1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.
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Affiliation(s)
- QingHua Tian
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cong Tian
- Department of Oncology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - YingYing Lu
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - BiCong Yan
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kaixian Zhang
- Department of Oncology, Tengzhou Central People's Hospital Affiliated to Jining Medical College, Tengzhou, China
| | - ChunGen Wu
- Department of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Vierra MA, Morgan RB, Bhutiani N, White MG, Eng OS. Contemporary Management of Malignant Ascites. J Surg Res 2025; 307:157-175. [PMID: 40037156 DOI: 10.1016/j.jss.2025.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/26/2025] [Indexed: 03/06/2025]
Abstract
INTRODUCTION Malignant ascites (MA) develops when malignant disease of the peritoneum causes excess fluid to accumulate in the abdominal cavity. It portends a poor prognosis and is associated with debilitating symptoms. While several palliative therapies exist, none have proven curative or free from side effects and complications. This review article describes experimental therapies on the horizon and the contemporary management of MA. MATERIALS AND METHODS A literature review was performed using MEDLINE/PubMed, in which studies of emerging or experimental therapies under investigation for the management of MA were reviewed. Current therapies were also reviewed to provide important context. Data, including study design, sample size, primary and secondary outcomes, and side effects were recorded and described. Studies were then categorized into distinct sections and subsections, with tables corresponding to each section. RESULTS Five current therapies, including paracentesis, diuretics, peritoneovenous shunting, permanent catheters, and intraperitoneal chemotherapy, are described. Their limitations in effectively managing MA are highlighted. The "Experimental therapies" section is subsectioned into several categories, with the major studies corresponding to each section thoroughly described regarding methods, results, and validity. A final section describes treatments for mucinous ascites, which has distinct characteristics. CONCLUSIONS While each of the experimental therapies described offers unique benefits and has demonstrated some promise in managing MA, they all have limitations that have thus far prevented any one of them from being routinely used in practice. MA remains a challenging condition to treat, warranting further research into novel therapies.
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Affiliation(s)
- Mason A Vierra
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
| | - Ryan B Morgan
- Department of Surgery, University of Chicago Medical Center, Chicago, Illinois
| | - Neal Bhutiani
- Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Michael G White
- Department of Colon & Rectal Surgery, MD Anderson Cancer Center, Houston, Texas
| | - Oliver S Eng
- Department of Surgery, University of California Irvine, Orange, California
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Htet H, Anaghan JRJ, Jaiprakash H, Burud IAS, Subramaniam T, Iezhitsa I, Agarwal R. Efficacy and safety of molecular targeted therapies in nasopharyngeal carcinoma: a network meta-analysis. BMC Cancer 2025; 25:110. [PMID: 39838362 PMCID: PMC11748561 DOI: 10.1186/s12885-025-13528-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 01/15/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) is one of the most common head and neck cancers worldwide. The majority of the new cases were from Asia and are the leading cause of cancer in China. The main treatment is surgery and radiotherapy with chemotherapy for advanced cases. With the advancement of targeted therapies, the objective of this study was to investigate the efficacy and safety of targeted therapies in NPC. METHODS Databases were searched from inception to Aug 2023, comparing molecular targeted therapies (MTT) with conventional chemotherapy, chemotherapy or surgery. Study screening, data extraction, and data analysis were conducted independently by two investigators. The Cochrane Risk of Bias tool 1.0 was used for the quality of the studies. RESULTS There was a total of ten eligible studies with 471 participants in the treatment arm and 469 participants in the control arm. Most studies had an unclear risk of bias assessment. Upon network meta-analysis, cetuximab was found to be the most effective regimen for complete response (CR), bevacizumab was found to be the most effective regimen for partial response (PR), nimotuzumab was found to be the most effective regimen for overall survival rate (OS) and progression-free survival (PFS). Pairwise meta-analysis showed that MTT had a significantly better response than conventional therapies in complete response. GRADE analysis reported low certainty of evidence for CR and very low certainty of evidence for other efficacy outcomes. There was a higher chance of bleeding with MTT and was statistically significant. CONCLUSION It was observed that targeted therapies were found to be a promising strategy for NPC especially recurrent and/or metastatic NPC, but the most appropriate therapy still needs to be evaluated. TRIAL REGISTRATION This study was registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) with a registration number of INPLASY202380024.
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Affiliation(s)
- Htet Htet
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia.
| | - Jwala Rebacca James Anaghan
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
| | - Heethal Jaiprakash
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
| | - Ismail Abdul Sattar Burud
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
| | - Thiruselvi Subramaniam
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
| | - Igor Iezhitsa
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
| | - Renu Agarwal
- School of Medicine, IMU University (Formerly Known as the International Medical University), Kuala Lumpur, Malaysia
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Song C, Xiong DD, He RQ, Yong XZ, Huang ZG, Dang YW, Chen G, Pang YY, Zhao CY, Qu N, Wei DM. Bibliometric study of the application of the chicken embryo chorioallantoic membrane model in cancer research: the top 100 most cited articles. J Comp Pathol 2024; 213:59-72. [PMID: 39116802 DOI: 10.1016/j.jcpa.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/26/2024] [Accepted: 07/07/2024] [Indexed: 08/10/2024]
Abstract
The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.
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Affiliation(s)
- Chang Song
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Dan-Dan Xiong
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Xiang-Zhi Yong
- Department of Periodontal and Oral Medicine, College of Stomatology, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Zhi-Guang Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Yi-Wu Dang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Yu-Yan Pang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Chun-Yan Zhao
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Ning Qu
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
| | - Dan-Ming Wei
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
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Kang Q, He L, Zhang Y, Zhong Z, Tan W. Immune-inflammatory modulation by natural products derived from edible and medicinal herbs used in Chinese classical prescriptions. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155684. [PMID: 38788391 DOI: 10.1016/j.phymed.2024.155684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/29/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Edible and medicinal herbs1 (EMHs) refer to a class of substances with dual attribution of food and medicine. These substances are traditionally used as food and also listed in many international pharmacopoeias, including the European Pharmacopoeia, the United States Pharmacopoeia, and the Chinese Pharmacopoeia. Some classical formulas that are widely used in traditional Chinese medicine include a series of EMHs, which have been shown to be effective with obvious characteristics and advantages. Notably, these EMHs and Chinese classical prescriptions2 (CCPs) have also attracted attention in international herbal medicine research because of their low toxicity and high efficiency as well as the rich body of experience for their long-term clinical use. PURPOSE Our purpose is to explore the potential therapeutic effect of EMHs with immune-inflammatory modulation for the study of modern cancer drugs. STUDY DESIGN In the present study, we present a detailed account of some EMHs used in CCPs that have shown considerable research potential in studies exploring modern drugs with immune-inflammatory modulation. METHODS Approximately 500 publications in the past 30 years were collected from PubMed, Web of Science and ScienceDirect using the keywords, such as natural products, edible and medicinal herbs, Chinese medicine, classical prescription, immune-inflammatory, tumor microenvironment and some related synonyms. The active ingredients instead of herbal extracts or botanical mixtures were focused on and the research conducted over the past decade were discussed emphatically and analyzed comprehensively. RESULTS More than ten natural products derived from EMHs used in CCPs are discussed and their immune-inflammatory modulation activities, including enhancing antitumor immunity, regulating inflammatory signaling pathways, lowering the proportion of immunosuppressive cells, inhibiting the secretion of proinflammatory cytokines, immunosuppressive factors, and inflammatory mediators, are summarized. CONCLUSION Our findings demonstrate the immune-inflammatory modulating role of those EMHs used in CCPs and provide new ideas for cancer treatment in clinical settings.
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Affiliation(s)
- Qianming Kang
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Luying He
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Yang Zhang
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Zhangfeng Zhong
- Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
| | - Wen Tan
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
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Liu X, Guo Z, Su L, Zuo A, Gao M, Ji X, Lu J, Yang S, Jiang Y, Lu D. The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer. Invest New Drugs 2024; 42:309-317. [PMID: 38700579 PMCID: PMC11164818 DOI: 10.1007/s10637-024-01439-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 04/19/2024] [Indexed: 06/11/2024]
Abstract
BACKGROUND Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS GOV: NCT05574998.
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Affiliation(s)
- Xinyi Liu
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Zihan Guo
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Lin Su
- Department of Respiratory, Jinan Fourth People's Hospital, 250000, Jinan, Shandong, P.R. China
| | - Anli Zuo
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Min Gao
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Xiang Ji
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Jiameng Lu
- School of Microelectronics, Shandong University, 250100, Jinan, Shandong, China
| | - Shuran Yang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Yunxiu Jiang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China
| | - Degan Lu
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, The First Affiliated Hospital of Shandong First Medical University, 250014, Jinan, Shandong, P.R. China.
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Song JM, Mo N, Lv YQ, Huang LL, Wen YJ, Liu T, Li ZR, Wang RS, Zhang TT. Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study. J Cancer Res Clin Oncol 2024; 150:232. [PMID: 38703186 PMCID: PMC11069474 DOI: 10.1007/s00432-024-05762-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 04/23/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND AND PURPOSE To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.
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Affiliation(s)
- Jun-Mei Song
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Oncology Department, Nanchong Central Hospital, The Second Clinical Institute of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Ning Mo
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Yu-Qing Lv
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Lu-Lu Huang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Ya-Jing Wen
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ting Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Zhi-Ru Li
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Ren-Sheng Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
| | - Ting-Ting Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
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Wang Y, Ren H. Multi-omics sequencing revealed endostar combined with cisplatin treated non small cell lung cancer via anti-angiogenesis. BMC Cancer 2024; 24:187. [PMID: 38331776 PMCID: PMC10854066 DOI: 10.1186/s12885-023-11665-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 11/21/2023] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND Endostar, an anti-angiogenic drug, has been approved for treating non-small cell lung cancer (NSCLC). At present, endostar combined with radiotherapy or chemotherapy has achieved ideal results in the treatment of some tumors, but there is a lack of application and study in NSCLC. This study investigated the therapeutic effect and potential mechanism of endostar combined with cisplatin (EC) in NSCLC. METHODS HE staining, TUNEL staining, immunofluorescence, colony formation ability, and cell migration ability were used to evaluate the anti-tumor activity of EC. The expressions of FMOD, VEGF, FGF-2, and PDGF-B were detected by western blotting and qPCR. The target of combination therapy was analyzed by m6A sequencing and RNA sequencing. METTL3 knockdown and overexpressed A549 cells were constructed and co-cultured with HUVECs to further evaluate the effect of METLL3 on combination therapy. RESULTS Combination therapy significantly reduced the colony formation and migration ability of NSCLC cells, induced cell apoptosis, and inhibited the tube formation ability of HUVECs. The results of m6A sequencing and RNA sequencing showed that the EC could down-regulate the expression level of FMOD in tumor tissues, which might be related to the reduction of its m6A methylation modification regulatory enzyme METTL3. Restricting FMOD expression could reduce the expression of FGF2, TGF-β1, VEGF and PDGF-B. Moreover, overexpression of METTLE almost abolished the anti-tumor effect of EC and promoted angiogenesis. CONCLUSIONS Endostar combined with cisplatin might exert anti-tumor effects by down-regulating the expression of METTL3 and FMOD.
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Affiliation(s)
- Yufei Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, 710061, Shanxi, Xi'an, Shanxi, P.R. China
- Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, 010050, Hohhot, Inner Mongolia, P.R. China
| | - Hong Ren
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, 710061, Shanxi, Xi'an, Shanxi, P.R. China.
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Ying H, Zhou C, Hang Q, Fang M. The Preventive Effect of Endostar on Radiation-induced Pulmonary Fibrosis. Curr Mol Med 2024; 24:610-619. [PMID: 37038709 DOI: 10.2174/1566524023666230406134640] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 12/14/2022] [Accepted: 01/09/2023] [Indexed: 04/12/2023]
Abstract
BACKGROUND Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy without effective treatment available. OBJECTIVE This study aimed to establish a RIPF mouse model and explore the therapeutic effects and mechanisms of recombinant human endostatin (Endostar). METHODS C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks. RESULTS Radiation-induced body weight loss was partially attenuated by Endostar (P<0.05). Endostar significantly reduced alveolar inflammation (P<0.05) and pulmonary fibrosis (P<0.001), as indicated by a decrease in the expression levels of collagen I and collagen IV in lung tissue (both P<0.001). Angiogenesis (as shown by CD31 immunohistochemistry) was also decreased (P<0.01). In irradiated mice, Endostar inhibited the transforming growth factor-β1 (TGF-β1)/drosophila mothers against the decapentaplegic 3 (Smad3)/extracellular regulated protein kinases (ERK) signaling pathway (all P<0.05). In vitro, Endostar treatment decreased the radiation-induced expression of TGF-β1, vascular endothelial growth factor (VEGF), p-Smad3, and p-ERK in alveolar epithelial cells and vascular endothelial cells (all P<0.05). CONCLUSION Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-β1/Smad3/ERK pathway.
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Affiliation(s)
- Hangjie Ying
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
| | - Cheng Zhou
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Qingqing Hang
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
| | - Min Fang
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
- The Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China
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Peng S, Huang H, Chen J, Ding X, Zhu X, Liu Y, Chen L, Lu Z. Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer. Technol Cancer Res Treat 2024; 23:15330338241248573. [PMID: 38656242 PMCID: PMC11044805 DOI: 10.1177/15330338241248573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024] Open
Abstract
Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.
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Affiliation(s)
- Sujuan Peng
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Hongxiang Huang
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Jinhong Chen
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Xinjing Ding
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Xie Zhu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Yangyang Liu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Li Chen
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Zhihui Lu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Jiangxi, China
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Cao F, Ding S, Gu C, Zhou Y, Hong W, Jin Y. Efficacy and outcome analysis: Combination of Endostar and chemotherapy as a neoadjuvant treatment of stage IIIA/IIIB squamous cell lung cancer. Oncol Lett 2024; 27:23. [PMID: 38058468 PMCID: PMC10696629 DOI: 10.3892/ol.2023.14156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 10/20/2023] [Indexed: 12/08/2023] Open
Abstract
Patients with stage IIIA/IIIB squamous non-small cell lung cancer (SqCLC) are particularly challenging to treat with a poor 5-year survival rate and new treatment strategies are needed. In the present study, a retrospective, single-center study was conducted to explore the efficacy and safety of Endostar combined with chemotherapy as the neoadjuvant treatment in patients with stage IIIA/IIIB SqCLC. A total of 27 patients with locally advanced SqCLC treated with Endostar combined with chemotherapy as neoadjuvant therapy from January 1, 2017 to December 31, 2019 at the Zhejiang Cancer Hospital (Hangzhou, China) were included. Short-term efficacy, rate of surgical resection, long-term outcome and adverse events were analyzed. After treatment with Endostar combined with chemotherapy, 37% of the patients underwent surgery and the radical resection rate was 90%. The objective response rate was 63% for the total population and 80% for patients who received surgery. Of note, 100% of the patients achieved disease control after treatment with Endostar combined with chemotherapy. In patients who underwent surgical resection, postoperative pathology showed that 100% of the patients achieved pathological downstaging. Furthermore, 1 (10%) patient showed a pathological complete response after surgery. The median progression-free survival was 13.5 months and overall survival was 27.9 months for the total cohort. The most common adverse events (AEs) were anemia (69.4% of patients), followed by hypertension (29.6% of patients). Most of the AEs were grade 1-2 and only 4 patients (14.8%) developed grade 3-4 AEs. Endostar combined with chemotherapy was well-tolerated and showed promising efficacy in patients with stage IIIA/IIIB SqCLC. Further prospective studies are warranted to explore its value as a neoadjuvant therapy.
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Affiliation(s)
- Feiyi Cao
- Department of Medical Oncology, Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, P.R. China
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
| | - Sijie Ding
- Department of Tumor Radiotherapy and Chemotherapy, Lishui Central Hospital, Lishui, Zhejiang 323000, P.R. China
| | - Cuiping Gu
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
| | - Yao Zhou
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
| | - Wei Hong
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
| | - Ying Jin
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China
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Han B, Kang Y, Wang H, Wang J, Shen R, Liu S, Lu L, Sun Z, Zhang N. A retrospective study on the efficacy and safety of Endostar with chemotherapy in EGFR-TKI-resistant NSCLC. BMC Pulm Med 2023; 23:437. [PMID: 37951898 PMCID: PMC10638772 DOI: 10.1186/s12890-023-02705-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 10/11/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Endostar is a strong angiogenesis inhibitor that is effective in treating non-small cell lung cancer (NSCLC), but the effect of Endostar in the treatment of patients with EGFR-TKI-resistant NSCLC remains unclear. We evaluated the clinical efficacy and safety of Endostar in EGFR-mutant NSCLC patients resistant to EGFR inhibition treatment. METHODS From January 1, 2016 to June 30, 2018, 68 patients were selected from the 4 institutions for the study. Patients with NSCLC received Endostar plus chemotherapy every 21-day cycle. Chemotherapy types included platinum-containing dual drugs and platinum-free single drugs. Endostar was administered by intermittent intravenous infusion or continuous microinfusion pump infusion. The overall response rate (ORR), disease control rate (DCR) and adverse events were analyzed. Survival of patients was also evaluated. RESULTS For all patients, the median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 14.2 months. PFS and OS in the Endostar pump continuous group were better than those in the Endostar intravenous infusion group. The disease control rate (DCR) was 79.4%. A total of 28 (41.2%) patients experienced varying grades of adverse events during treatment. No treatment-associated deaths were observed. The grade 3 treatment-emergent adverse events (TEAEs) were myelosuppression, weakness, and nausea/vomiting. CONCLUSIONS Endostar was effective and well tolerated in advanced NSCLC patients. Endostar treatment showed promising survival results in EGFR-mutant NSCLC patients.
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Affiliation(s)
- Bing Han
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong, 250013, China
| | - Yanrong Kang
- Department of Breast Center, Central Hospital, Shandong First Medical University, Jinan, Shandong, 250013, China
- Department of Oncology, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong, 264001, China
| | - Haiji Wang
- Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China
| | - Jian Wang
- Department of Medical Oncology, Qilu Hospital of Shandong University, Shandong, 250013, China
| | - Rong Shen
- Department of Chemotherapy, Shandong Provincial Hospital, Shandong First Medical University, Shandong, 250021, China
| | - Shuai Liu
- Department of Breast Center, Central Hospital, Shandong First Medical University, Jinan, Shandong, 250013, China
| | - Lu Lu
- Department of Breast Center, Central Hospital, Shandong First Medical University, Jinan, Shandong, 250013, China
| | - Zhigang Sun
- Department of Thoracic Surgery, Central Hospital, Shandong First Medical University, Jinan, Shandong, 250013, China.
| | - Nan Zhang
- Department of Breast Center, Central Hospital, Shandong First Medical University, Jinan, Shandong, 250013, China.
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Cheng M, Xin Q, Ma S, Ge M, Wang F, Yan X, Jiang B. Advances in the Theranostics of Oesophageal Squamous Carcinoma. ADVANCED THERAPEUTICS 2023; 6. [DOI: 10.1002/adtp.202200251] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Indexed: 01/04/2025]
Abstract
AbstractOesophageal squamous carcinoma (ESCC) is one of the most lethal human malignancies, and it is a more aggressive form of oesophageal cancer (EC) that comprises over 90% of all EC cases in China compared with oesophageal adenocarcinoma (EAC). The high mortality of ESCC is attributed to the late‐stage diagnosis, chemoradiotherapy resistance, and lack of appropriate therapeutic targets and corresponding therapeutic formulations. Recently, emerging clinical and translational investigations have involved genome analyses, diagnostic biomarkers, and targeted therapy for ESCC, and these studies provide a new horizon for improving the clinical outcomes of patients with ESCC. Here, the latest research advances in the theranostics of ESCC are reviewed and the unique features of ESCC (including differences from EAC, genomic alterations, and microbe infections), tissue and circulating biomarkers, chemoradiotherapy resistance, clinical targeted therapy for ESCC, identification of novel therapeutic targets, and designation of nanotherapeutic systems for ESCC are particularly focused on. Finally, the perspectives for future clinical and translational theranostic research of ESCC are discussed and the obstacles that must be overcome in ESCC theranostics are described.
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Affiliation(s)
- Miaomiao Cheng
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Qi Xin
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Saiyu Ma
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Mengyue Ge
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
| | - Feng Wang
- Oncology Department The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450000 China
| | - Xiyun Yan
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
- CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China
| | - Bing Jiang
- Nanozyme Medical Center School of Basic Medical Sciences Zhengzhou University Zhengzhou 450001 China
- State Key Laboratory of Esophageal Cancer Prevention &Treatment Zhengzhou Henan 450001 China
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Popov A, Kozlovskaya E, Rutckova T, Styshova O, Vakhrushev A, Kupera E, Tekutyeva L. Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application. Int J Mol Sci 2023; 24:ijms24119502. [PMID: 37298452 DOI: 10.3390/ijms24119502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) are used for various biomedical purposes. Due to the absence of toxic side effects, low species specificity, relatively small size, and presence of various targets at the cell membranes, MKs often exhibit antitumor properties and, therefore, are promising agents for antitumor combination therapy. This review summarizes and analyzes the current data on the antitumor activity of MKs of different origins, discusses the problems and prospects for their therapeutic use, and evaluates the experimental results of studying the antitumor properties of MKs from different echinoderm species generated with the help of a complex of proteolytic enzymes from red king crab Paralithodes camtschatica. Special attention is paid to the analysis of possible mechanisms of the antitumor action of various functionally active MKs, products of the enzymatic activity of various MMPs, and the existing problems for their use in antitumor therapy.
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Affiliation(s)
- Aleksandr Popov
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Emma Kozlovskaya
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Tatyana Rutckova
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Olga Styshova
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Aleksey Vakhrushev
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Elena Kupera
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-Letiya Vladivostoka, Vladivostok 690022, Russia
| | - Ludmila Tekutyeva
- Department of Bioeconomy and Food Security, School of Economics and Management, Far Eastern Federal University, Vladivostok 690922, Russia
- ARNIKA, Territory of PDA Nadezhdinskaya, Volno-Nadezhdinskoye 692481, Russia
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19
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Tan XR, Li J, Chen HW, Luo W, Jiang N, Wang ZB, Wang S. Successful multidisciplinary therapy for a patient with liver metastasis from ascending colon adenocarcinoma: A case report and review of literature. World J Clin Cases 2023; 11:1498-1505. [PMID: 36926405 PMCID: PMC10011996 DOI: 10.12998/wjcc.v11.i7.1498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 01/07/2023] [Accepted: 02/10/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer, and the only possible curative treatment for patients with colorectal liver metastases (CRLM) is hepatectomy. However, approximately 25% of patients with CRLM have indications for liver resection at the initial diagnosis. Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.
CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases. Due to the huge lesion size and compression of the right portal vein, the liver metastases were initially diagnosed as unresectable lesions. The patient was treated with preoperative transcatheter arterial chemoembolization (TACE) consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®. After four courses, radical right-sided colectomy and ileum transverse colon anastomosis were performed. Postoperatively, the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins. Thereafter, S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy. Pathological examination of the resected specimen revealed a pathologically complete response (pCR). Intrahepatic recurrence was detected more than two months after the operation, and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®. Subsequently, the patient was treated with a γ-knife to enhance local control. Notably, a pCR was reached, and the patient's overall survival time was > 9 years.
CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.
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Affiliation(s)
- Xiao-Rong Tan
- Oncological Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, School/Hospital of Stomatology Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
| | - Juan Li
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Hua-Wei Chen
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Wei Luo
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Nan Jiang
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Zheng-Bo Wang
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Shuai Wang
- Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China
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20
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Correlation between hypoxia and HGF/c-MET expression in the management of pancreatic cancer. Biochim Biophys Acta Rev Cancer 2023; 1878:188869. [PMID: 36842767 DOI: 10.1016/j.bbcan.2023.188869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/16/2023] [Accepted: 02/07/2023] [Indexed: 02/28/2023]
Abstract
Pancreatic cancer (PC) is very deadly and difficult to treat. The presence of hypoxia has been shown to increase the probability of cancer developing and spreading. Pancreatic ductal adenocarcinoma (PDAC/PC) has traditionally viewed a highly lethal form of cancer due to its high occurrence of early metastases. Desmoplasia/stroma is often thick and collagenous, with pancreatic stellate cells as the primary source (PSCs). Cancer cells and other stromal cells interact with PSCs, promoting disease development. The hepatocyte growth factor (HGF)/c-MET pathway have been proposed as a growth factor mechanism mediating this interaction. Human growth factor (HGF) is secreted by pancreatic stellate cells (PSCs), and its receptor, c-MET, is generated by pancreatic cancer cells and endothelial cells. Hypoxia is frequent in malignant tumors, particularly pancreatic (PC). Hypoxia results from limitless tumor development and promotes survival, progression, and invasion. Hypoxic is becoming a critical driver and therapeutic target of pancreatic cancer as its hypoxia microenvironment is defined. Recent breakthroughs in cancer biology show that hypoxia promotes tumor proliferation, aggressiveness, and therapeutic resistance. Hypoxia-inducible factors (HIFs) stabilize hypoxia signaling. Hypoxia cMet is a key component of pancreatic tumor microenvironments, which also have a fibrotic response, that hypoxia, promotes and modulates. c-Met is a tyrosine-protein kinase. As describe it simply, the MET gene in humans' codes for a protein called hepatocyte growth factor receptor (HGFR). Most cancerous tumors and pancreatic cancer in particular, suffer from a lack of oxygen (PC). Due to unrestrained tumor development, hypoxia develops, actively contributing to tumor survival, progression, and invasion. As the processes by which hypoxia signaling promotes invasion and metastasis become clear, c-MET has emerged as an important determinant of pancreatic cancer malignancy and a potential pharmacological target. This manuscript provides the most current findings on the role of hypoxia and HGF/c-MET expression in the treatment of pancreatic cancer.
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21
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Fu S, Huang H, Shang K, Tu G, Zhong P, Li S, Zhu X, Peng S, Liu Y, Lu Z, Chen L. Efficacy and safety of immune checkpoint inhibitors combined with recombinant human endostatin and chemotherapy as the first-line treatment of advanced non-small-cell lung cancer. Future Oncol 2023; 19:147-158. [PMID: 36779488 DOI: 10.2217/fon-2022-0861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2023] Open
Abstract
Background: To assess the efficacy and safety of combination of PD-1 inhibitors, recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC were retrospectively reviewed and analyzed (58 in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy; 42 in the group receiving Rh-endostatin and chemotherapy). The primary end point was progression-free survival. Results: Patients in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy had significantly improved progression-free survival (10.2 vs 6.5 months; p < 0.001) and objective response rate (67.2 vs 42.9%; p = 0.015), with acceptable toxicity. Conclusion: Our study showed the superiority of combination therapy of PD-1 inhibitors and Rh-endostatin as first-line treatment for advanced NSCLC.
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Affiliation(s)
- Silv Fu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.,Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang, 330029, China
| | - Hongxiang Huang
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Kai Shang
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Ganjie Tu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.,Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang, 330029, China
| | - Peiyuan Zhong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Siling Li
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Xie Zhu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Sujuan Peng
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Yangyang Liu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Zhihui Lu
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Li Chen
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
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22
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Li Y, Liu W, Xu Y, Guo LY, Weng YL, Huang ZW, Chen XC, Lin T, Lu J, Qiu SF. Impact of Radiotherapy Combined With Chemotherapy on Long-Term Outcomes of Patients With Recurrent Nasopharyngeal Carcinoma. Technol Cancer Res Treat 2023; 22:15330338231155721. [PMID: 36762400 PMCID: PMC9926007 DOI: 10.1177/15330338231155721] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023] Open
Abstract
Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019 were included in this study. Overall survival (OS) was the primary outcome. Kaplan-Meier method was employed to detect the prognostic difference with Log-rank tests. The Cox regression analysis was performed to explore the potential prognostic factors while the multivariate Cox analysis was used to identify candidate variables for the prognostic model of OS. Results: The 5-year actuarial rates of OS, progression-free survival, loco-regional progression-free survival, and distant metastases-free survival did not show significant difference between the IMRT and RCT groups (P > .05). Age at recurrence and rT category were found to be the independent prognostic factors for OS. We found that rNPC patients suffered poor OS in the high-risk group (patients with higher age at recurrence and advanced rT category) (high-risk vs low-risk, HR = 1.87, 95% CI: 1.36-2.57, P < .001). Salvage RT alone may be superior to RCT for patients in the low-risk group (RCT group vs RT group, HR = 1.89, 95% CI: 1.11-3.20, P = .038). Conclusion: Salvage RT combined with chemotherapy cannot improve survival outcomes for rNPC. More novel clinical trials should be explored to develop individualized strategies to improve survival and minimize toxicities.
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Affiliation(s)
- Ying Li
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Wei Liu
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Yun Xu
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Lan-Yan Guo
- Fujian Medical
University Union Hospital, Fujian,
China
| | - You-Liang Weng
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Zong-Wei Huang
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Xiao-Chuan Chen
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Ting Lin
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China
| | - Jun Lu
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China,Jun Lu, Clinical Oncology School of Fujian
Medical University, Fujian Cancer Hospital, Fuma Road 420, Jinan District,
Fuzhou 350014, Fujian, China.
| | - Su-Fang Qiu
- Clinical Oncology School of Fujian Medical University,
Fujian Cancer
Hospital, Fujian, China,Fujian Key Laboratory of Translational Cancer Medicine, Fujian,
China,Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian,
China,Sufang Qiu, Clinical Oncology School of
Fujian Medical University, Fujian Cancer Hospital, Fuma Road 420, Jinan
District, Fuzhou 350014, Fujian, China.
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23
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Cunningham C, Bolcaen J, Bisio A, Genis A, Strijdom H, Vandevoorde C. Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer. Pharmaceuticals (Basel) 2023; 16:219. [PMID: 37259367 PMCID: PMC9961924 DOI: 10.3390/ph16020219] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/22/2023] [Accepted: 01/24/2023] [Indexed: 11/03/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, which is the leading cause of cancer-related deaths worldwide. Over the past decades, tumour angiogenesis has been intensely studied in the treatment of NSCLC due to its fundamental role in cancer progression. Several anti-angiogenic drugs, such as recombinant endostatin (RE), have been evaluated in several preclinical and clinical trials, with mixed and often disappointing results. However, there is currently an emerging interest in RE due to its ability to create a vascular normalization window, which could further improve treatment efficacy of the standard NSCLC treatment. This review provides an overview of preclinical and clinical studies that combined RE and radiotherapy for NSCLC treatment. Furthermore, it highlights the ongoing challenges that have to be overcome in order to maximize the benefit; as well as the potential advantage of combinations with particle therapy and immunotherapy, which are rapidly gaining momentum in the treatment landscape of NSCLC. Different angiogenic and immunosuppressive effects are observed between particle therapy and conventional X-ray radiotherapy. The combination of RE, particle therapy and immunotherapy presents a promising future therapeutic triad for NSCLC.
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Affiliation(s)
- Charnay Cunningham
- Centre for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Stellenbosch University, Cape Town 7602, South Africa
- Radiation Biophysics Division, SSC Laboratory, NRF Ithemba LABS, Cape Town 7131, South Africa
| | - Julie Bolcaen
- Radiation Biophysics Division, SSC Laboratory, NRF Ithemba LABS, Cape Town 7131, South Africa
| | - Alessandra Bisio
- Department of Cellular, Computational and Integrative Biology—CIBIO, University of Trento, 38123 Trento, Italy
| | - Amanda Genis
- Centre for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Stellenbosch University, Cape Town 7602, South Africa
| | - Hans Strijdom
- Centre for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Stellenbosch University, Cape Town 7602, South Africa
| | - Charlot Vandevoorde
- Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Planckstr. 1, 64291 Darmstadt, Germany
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MCPIP1 Suppresses the NF-κB Signaling Pathway Through Negative Regulation of K63-Linked Ubiquitylation of TRAF6 in Colorectal Cancer. Cancer Gene Ther 2023; 30:96-107. [PMID: 36076064 DOI: 10.1038/s41417-022-00528-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 08/10/2022] [Accepted: 08/24/2022] [Indexed: 01/19/2023]
Abstract
The abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is an important precipitating factor for the inception and development of colorectal cancer (CRC), one of the most common tumors worldwide. As a pro-apoptotic transcription factor, monocyte chemotactic protein-induced protein 1 (MCPIP1) has been closely associated with many tumor types. In the present study, the expression of MCPIP1 was firstly discovered reduced in CRC tissues and correlated with poor patient prognosis. The decreased expression was caused by promoter hypermethylation. Overexpressed MCPIP1 was found to inhibit the proliferative and migratory abilities of CRC cells, whereas knockdown of MCPIP1 produced the opposite result. The subsequent investigation demonstrated that MCPIP1 exerted its "anti-cancer" effect by suppression of the NF-κB signaling pathway through negative regulation of K63-linked ubiquitylation of TNF receptor associated factor 6 (TRAF6). Therefore, our results indicate a prognostic marker for CRC and a theoretical basis for MCPIP1 as a treatment.
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25
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Yuan B, Upton Z, Leavesley D, Fan C, Wang XQ. Vascular and Collagen Target: A Rational Approach to Hypertrophic Scar Management. Adv Wound Care (New Rochelle) 2023; 12:38-55. [PMID: 34328823 PMCID: PMC9595647 DOI: 10.1089/wound.2020.1348] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Significance: Hypertrophic scarring is a challenging issue for patients and clinicians. The prevalence of hypertrophic scarring can be up to 70% after burns, and patients suffer from pain, itching, and loss of joint mobility. To date, the exact mechanisms underlying hypertrophic scar formation are unclear, and clinical options remain limited. Recent Advances: Several studies have demonstrated that pathological scars are a type of hyperactive vascular response to wounding. Scar regression has been found to be accompanied by microvessel occlusion, which causes severe hypoxia, malnutrition, and endothelial dysfunction, suggesting the essential roles of microvessels in scar regression. Therefore, interventions that target the vasculature, such as intense pulsed light, pulsed dye lasers, vascular endothelial growth factor antibodies, and Endostar, represent potential treatments. In addition, the mass of scar-associated collagen is usually not considered by current treatments. However, collagen-targeted therapies such as fractional CO2 laser and collagenase have shown promising outcomes in scar treatment. Critical Issues: Traditional modalities used in current clinical practice only partially target scar-associated microvessels or collagen. As a result, the effectiveness of current treatments is limited and is too often accompanied by undesirable side effects. The formation of scars in the early stage is mainly affected by microvessels, whereas the scars in later stages are mostly composed of residual collagen. Traditional therapies do not utilize specific targets for scars at different stages. Therefore, more precise treatment strategies are needed. Future Directions: Scars should be classified as either "vascular-dominant" or "collagen-dominant" before selecting a treatment. In this way, strategies that are vascular-targeted, collagen-targeted, or a combination thereof could be recommended to treat scars at different stages.
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Affiliation(s)
- Bo Yuan
- Burns and Plastic Surgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Zee Upton
- Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - David Leavesley
- Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Chen Fan
- Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China
- Correspondence: Chen Fan, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China
| | - Xi-Qiao Wang
- Burns and Plastic Surgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
- Correspondence: Xi-Qiao Wang, Burns and Plastic Surgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, P.R. China
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26
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Chu XD, Bao H, Lin YJ, Chen RX, Zhang YR, Huang T, He JS, Huangfu SC, Pan YL, Ding H. Endostatin induces normalization of blood vessels in colorectal cancer and promotes infiltration of CD8+ T cells to improve anti-PD-L1 immunotherapy. Front Immunol 2022; 13:965492. [PMID: 36389685 PMCID: PMC9644205 DOI: 10.3389/fimmu.2022.965492] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/30/2022] [Indexed: 11/03/2023] Open
Abstract
INTRODUCTION The purpose of this study was to evaluate recombinant human endostatin (rHE)-induced normalization of the tumor vasculature in colorectal cancer (CRC) and to evaluate the therapeutic effects of combined treatment with rHE and a programmed death ligand-1 (PD-L1) inhibitor. METHODS A mouse subcutaneous tumorigenesis model was established to evaluate the antitumor effects of endostatin combined with a PD-L1 inhibitor on CRC. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DW MRI) was used to evaluate changes in the intratumor microcirculation in response to combined treatment with endostatin and a PD-L1 inhibitor. The infiltration density and function of CD8+ T cells in tumors were evaluated using flow cytometry. Finally, clinical specimens were used to evaluate the expression area of tumor vascular pericytes and CD8+ T cells in tumor tissues. RESULTS The antitumor effects of endostatin combined with a PD-L1 inhibitor were significantly greater than those of endostatin or a PD-L1 inhibitor alone. On the ninth day of intervention, the endostatin group showed significantly higher pseudo diffusion parameter (D*) and microvascular volume fraction (F) values in tumors than those in the control group or PD-L1 group. After 27 days of intervention, the endostatin groups showed significantly lower levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β than those in the control group. Treatment of CD8+ T cells with endostatin for 24 h did not alter the expression levels of markers of reduced T-cell activity. However, endostatin reversed the VEGF-mediated inhibition of the secretion of interferon (IFN)-γ from T cells. The results in CRC clinical samples showed that treatment with endostatin induced significantly higher infiltration of CD8+ T cells compared with treatment that did not include endostatin. Furthermore, the expression area of pericytes was significantly positively related to the infiltration density of CD8+ T cells and overall survival time. CONCLUSION Endostatin improved the antitumor effects of PD-L1 inhibitors on CRC, significantly increased the activity of CD8+ T cells, and synergistically improved the tumor treatment effect of the two inhibitors.
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Affiliation(s)
- Xiao-Dong Chu
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Hui Bao
- Department of Plastic Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yu-Jian Lin
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ruo-Xi Chen
- Department of Plastic Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yi-Ran Zhang
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ting Huang
- Department of Clinical Pathology, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jia-Shuai He
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Shu-Chen Huangfu
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yun-Long Pan
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Hui Ding
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, China
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27
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Yin Y, Zhou Z, Li Z, Shen M, Qin Y, Yang C, Wang R, Kang M. Efficacy of concurrent chemoradiotherapy plus Endostar compared with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study. Radiat Oncol 2022; 17:135. [PMID: 35906636 PMCID: PMC9338543 DOI: 10.1186/s13014-022-02104-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 07/15/2022] [Indexed: 12/02/2022] Open
Abstract
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.
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Affiliation(s)
- Yuanxiu Yin
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China.,Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, 530021, Guangxi, China
| | - Ziyan Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China.,Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, 530021, Guangxi, China
| | - Zhiru Li
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China
| | - Mingjun Shen
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China
| | - Yating Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China
| | - Chaolin Yang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China
| | - Rensheng Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China.,Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, 530021, Guangxi, China
| | - Min Kang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China. .,Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China. .,Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, 530021, Guangxi, China.
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Zhu J, Xu Y, Huang WC, Ji T, Ai GP, Gao YH. Case Report: Recombinant Human Endostatin Plus Chemotherapy for Epidermal Growth Factor Receptor-Negative Miliary Lung Adenocarcinoma. Front Oncol 2022; 12:922076. [PMID: 35860549 PMCID: PMC9293051 DOI: 10.3389/fonc.2022.922076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 05/20/2022] [Indexed: 11/23/2022] Open
Abstract
Except for the traditional chemotherapy, few treatments strategy about miliary intrapulmonary carcinomatosis (MIPC) have been reported in the existing literature. In this report, we primarily discussed the possible etiology and the potentially effective treatment options for a patient with MIPC who benefited from combined treatment. A nonsmoking woman was diagnosed with MIPC at an advanced stage. Gene detection showed an EGFR negative status. She accepted first-line chemotherapy with pemetrexed and cisplatin, and the tumor progressed. Next, PD-1 inhibitors plus pemetrexed and cisplatin were administered, and the tumor remained uncontrolled. After two cycles of recombinant human endostatin plus second-line chemotherapy, the numerous pulmonary nodules had all nearly completely disappeared, while an accentuated decrease in the primary tumor volume was observed. Moreover, biochemical markers, including the patient’s tumor markers, also trended toward normal. This report describes the first case of a MIPC patient who significantly responded to antiangiogenic therapy combined with chemotherapy. Anti-angiogenic therapy may be a possible strategy for the EGFR-negative lung adenocarcinoma population.
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Affiliation(s)
- Jian Zhu
- Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
| | - Ya Xu
- Department of Respiratory Medicine, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
| | - Wen-Cai Huang
- Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
| | - Tao Ji
- Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
| | - Guo-Ping Ai
- Department of Radiology, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
- *Correspondence: Guo-Ping Ai, ; Yan-Hong Gao,
| | - Yan-Hong Gao
- Department of Ultrasound, General Hospital of Central Theater Command of the People’s Liberation Army, Wuhan, China
- *Correspondence: Guo-Ping Ai, ; Yan-Hong Gao,
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Chen L, Tong F, Peng L, Huang Y, Yin P, Feng Y, Cheng S, Wang J, Dong X. Efficacy and safety of recombinant human endostatin combined with whole-brain radiation therapy in patients with brain metastases from non-small cell lung cancer. Radiother Oncol 2022; 174:44-51. [PMID: 35788355 DOI: 10.1016/j.radonc.2022.06.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 06/11/2022] [Accepted: 06/24/2022] [Indexed: 11/29/2022]
Abstract
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 progression free 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.
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Affiliation(s)
- Lingjuan Chen
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Fang Tong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Ling Peng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Yu Huang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Ping Yin
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Yue Feng
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Shishi Cheng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jing Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
| | - Xiaorong Dong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Jiang W, Sun W, Li W, Gao J, Wang H, Zhou W, Liang J, Aa L, Wang L. Real-world treatment pattern and comprehensive comparative effectiveness of Endostar plus different chemotherapy in advanced patients with non-small cell lung cancer. Sci Rep 2022; 12:10841. [PMID: 35761010 PMCID: PMC9237081 DOI: 10.1038/s41598-022-14222-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 06/02/2022] [Indexed: 11/21/2022] Open
Abstract
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.
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Affiliation(s)
- Wei Jiang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, Guangdong, China
| | - Wei Sun
- Department of Thoracic Surgery, The Third Clinical College of Xinjiang Medical University, Urumqi, 830000, Xinjiang, China
| | - Wenhui Li
- Department of Radiation Oncology, Yunnan Cancer Hospital, Kunming, 650106, Yunnan, China
| | - Jin Gao
- Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, 230031, Anhui, China
| | - Hui Wang
- Department of Radiation Oncology, Hunan Cancer Hospital, Changsha, 410013, Hunan, China
| | - Wei Zhou
- Department of Radiation Oncology, Chongqing Cancer Hospital, Chongqing, 400030, China
| | - Jing Liang
- Department of Radiation Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, 710061, Shaanxi, China
| | - Lixiang Aa
- The State Key Laboratory of Translational Medicine and Innovative Drug Development, Nanjing, 210042, Jiangsu, China
| | - Luhua Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, Guangdong, China.
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Mo WF, Tong YL. Hepatic epithelioid hemangioendothelioma after thirteen years’ follow-up: A case report and review of literature. World J Clin Cases 2022; 10:6119-6127. [PMID: 35949854 PMCID: PMC9254202 DOI: 10.12998/wjcc.v10.i18.6119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/24/2022] [Accepted: 04/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial cell tumor of the liver, consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. Immunohistochemistry is usually positive for vascular markers, such as factor VIII-related antigen, CD31, and CD34. Hepatic EHE can have a varied clinical course; treatment includes liver transplantation, liver resection, chemotherapy, and radiation therapy.
CASE SUMMARY A 46-year-old woman with abdominal discomfort and elevated serum carcinoembryonic antigen was found to have multiple low-density lesions in the liver and lung on computed tomography (CT) evaluation. An ultrasound-guided fine needle aspiration biopsy revealed a fibrous stroma with dendritic cells, containing intracellular vacuoles. Immunohistochemical staining found that the tumor cells were positive for CD34, CD31, and factor VIII-related antigen. The patient received four courses of combined chemotherapy and was followed-up for 13 years, at which time the patient was in stable condition without disease progression and a confined neoplasm, as evidenced by CT scans.
CONCLUSION The histology and immunohistochemical characteristics of hepatic EHE are well described. Chemotherapy may be effective in patients with extrahepatic lesions.
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Affiliation(s)
- Wei-Fang Mo
- Department of General Practice, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, Zhejiang Province,China
| | - Yu-Ling Tong
- Department of General Practice, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, Zhejiang Province,China
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Role of Anti-Angiogenic Factors in the Pathogenesis of Breast Cancer: A Review of Therapeutic Potential. Pathol Res Pract 2022; 236:153956. [DOI: 10.1016/j.prp.2022.153956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 05/06/2022] [Accepted: 05/25/2022] [Indexed: 11/23/2022]
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Dituri F, Gigante G, Scialpi R, Mancarella S, Fabregat I, Giannelli G. Proteoglycans in Cancer: Friends or Enemies? A Special Focus on Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14081902. [PMID: 35454809 PMCID: PMC9024587 DOI: 10.3390/cancers14081902] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/04/2022] [Accepted: 04/08/2022] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Proteoglycans affect multiple molecular and cellular processes during the progression of solid tumors with a highly desmoplastic stroma, such as HCC. Due to their role in enhancing or limiting the traits of cancer cells underlying their aggressiveness, such as proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and stemness, these macromolecules could be exploited as molecular targets or therapeutic agents. Proteoglycans, such as biglycan, versican, syndecan-1, glypican-3, and agrin, promote HCC cell proliferation, EMT, and angiogenesis, while endostatin and proteoglycan 4 were shown to impair cancer neovascularization or to enhance the sensitivity of HCC cells to drugs, such as sorafenib and regorafenib. Based on this evidence, interventional strategies involving the use of humanized monoclonal antibodies, T cells engineered with chimeric antigen receptors, or recombinant proteins mimicking potentially curative proteoglycans, are being employed or may be adopted in the near future for the treatment of HCC. Abstract Proteoglycans are a class of highly glycosylated proteins expressed in virtually all tissues, which are localized within membranes, but more often in the pericellular space and extracellular matrix (ECM), and are involved in tissue homeostasis and remodeling of the stromal microenvironment during physiological and pathological processes, such as tissue regeneration, angiogenesis, and cancer. In general, proteoglycans can perform signaling activities and influence a range of physical, chemical, and biological tissue properties, including the diffusivity of small electrolytes and nutrients and the bioavailability of growth factors. While the dysregulated expression of some proteoglycans is observed in many cancers, whether they act as supporters or limiters of neoplastic progression is still a matter of controversy, as the tumor promoting or suppressive function of some proteoglycans is context dependent. The participation of multiple proteoglycans in organ regeneration (as demonstrated for the liver in hepatectomy mouse models) and in cancer suggests that these molecules actively influence cell growth and motility, thus contributing to key events that characterize neoplastic progression. In this review, we outline the main roles of proteoglycans in the physiology and pathology of cancers, with a special mention to hepatocellular carcinoma (HCC), highlighting the translational potential of proteoglycans as targets or therapeutic agents for the treatment of this disease.
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Affiliation(s)
- Francesco Dituri
- National Institute of Gastroenterology Saverio de Bellis, IRCCS Research Hospital, Castellana Grotte, 70013 Bari, Italy; (G.G.); (R.S.); (S.M.); (G.G.)
- Correspondence:
| | - Gianluigi Gigante
- National Institute of Gastroenterology Saverio de Bellis, IRCCS Research Hospital, Castellana Grotte, 70013 Bari, Italy; (G.G.); (R.S.); (S.M.); (G.G.)
| | - Rosanna Scialpi
- National Institute of Gastroenterology Saverio de Bellis, IRCCS Research Hospital, Castellana Grotte, 70013 Bari, Italy; (G.G.); (R.S.); (S.M.); (G.G.)
| | - Serena Mancarella
- National Institute of Gastroenterology Saverio de Bellis, IRCCS Research Hospital, Castellana Grotte, 70013 Bari, Italy; (G.G.); (R.S.); (S.M.); (G.G.)
| | - Isabel Fabregat
- Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), CIBEREHD and University of Barcelona, L’Hospitalet de Llobregat, 08908 Barcelona, Spain;
| | - Gianluigi Giannelli
- National Institute of Gastroenterology Saverio de Bellis, IRCCS Research Hospital, Castellana Grotte, 70013 Bari, Italy; (G.G.); (R.S.); (S.M.); (G.G.)
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Ouyang W, Fu S, Zhao X, Su S, Zhang J, Luo D, Liu L, Ding W, Cao D, Liu L, He Z, Lu B. Recombinant human endostatin combined with radiotherapy promotes cardiomyocyte apoptosis in rats via TGFβ1/Smads/CTGF signaling pathway. BMC Cardiovasc Disord 2022; 22:97. [PMID: 35279096 PMCID: PMC8917752 DOI: 10.1186/s12872-022-02499-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 02/03/2022] [Indexed: 11/21/2022] Open
Abstract
PURPOSE The aim of the present study was to investigate the efficacy of recombinant human endostatin (ES) (rh-ES) combined with radiation on rat cardiomyocyte apoptosis and the regulatory mechanism of transforming growth factor beta1 (TGF-β1)/Sma and Mad-related protein 3 (Smad3)/connective tissue growth factor (CTGF) signaling. METHOD The primary cardiomyocytes were isolated from neonatal Sprague-Dawley rats for culture in vitro and divided into blank control group (without treatment), 10 Gy radiation + siTGF-β1 siRNA (gene silencing) group, ES + siTGF-β1 siRNA group, and 10 Gy radiation + ES + siTGF-β1 siRNA group. Methyl thiazolyl tetrazolium assay was used to calculate the half-maximal inhibitory concentration (IC50) of rh-ES on cardiomyocytes. Adenoviral vector was constructed for virus packaging to silence TGF-β1 expression in cardiomyocytes. Quantitative real-time polymerase chain reaction and Western blot were carried out to analyze TGF-β1, Smad2, Smad3 and CTGF expression at both gene and protein levels. Flow cytometry and electron microscope were used to examine cell apoptosis. RESULTS ES had a dose-dependent inhibitory effect on the proliferation of primary rat cardiomyocytes. ES combined with radiotherapy significantly inhibited cardiomyocyte proliferation and promoted cell apoptosis (P < 0.01). The gene and protein expression of TGF-β1, Smad2, Smad3 and CTGF were significantly up-regulated in primary cardiomyocytes transfected with TGF-β1 gene (P < 0.05). CONCLUSION The combination therapy with rh-ES and radiation can promote cardiomyocyte apoptosis and aggravate myocardial cell damage via TGF-β1/Smad3/CTGF signaling pathway.
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Affiliation(s)
- Weiwei Ouyang
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Shimei Fu
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Xing Zhao
- Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang, 550025, China
| | - Shengfa Su
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Jun Zhang
- Department of Pathology, The Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Daxian Luo
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Lina Liu
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Wenjin Ding
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Dongdong Cao
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Likun Liu
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China
| | - Zhixu He
- Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang, 550025, China
| | - Bing Lu
- Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and The Affiliated Cancer Hospital of Guizhou Medical University, No. 1 Beijing Road West, Guiyang, 550004, China.
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Zhan Z, Wang X, Yu J, Zheng J, Zeng Y, Sun M, Peng L, Guo Z, Chen B. Intraperitoneal infusion of recombinant human indentation improves prognosis in gastric cancer ascites. Future Oncol 2022; 18:1259-1271. [PMID: 35114805 DOI: 10.2217/fon-2021-0896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human indentation in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human indentation improved efficacy and survival for gastric cancer with ascites.
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Affiliation(s)
- Zhouwei Zhan
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Xiaojie Wang
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Jiami Yu
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Jingxian Zheng
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Yi Zeng
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Mingyao Sun
- Department of Clinical Nutrition, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
| | - Li Peng
- Department of Diagnostic Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Zengqing Guo
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Bijuan Chen
- Department of Radiotherapy, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
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Lu H, Wu Y, Liu X, Huang H, Jiang H, Zhu C, Man Y, Chen Z, Long X, Pang Q, Peng L, Li X, Gu J, Deng S, Xing L. Endostar, an Antiangiogenesis Inhibitor, Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer. Oncol Res 2022; 28:929-944. [PMID: 34544526 PMCID: PMC8790112 DOI: 10.3727/096504021x16318716607908] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
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.
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Affiliation(s)
- Heming Lu
- *Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, P.R. China
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Yuying Wu
- ‡Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Xu Liu
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Huixian Huang
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Hailan Jiang
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Chaohua Zhu
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Yuping Man
- §Department of Radiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Zhaohong Chen
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Xianfeng Long
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Qiang Pang
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Luxing Peng
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Xianglong Li
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Junzhao Gu
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Shan Deng
- †Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, P.R. China
| | - Ligang Xing
- *Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, P.R. China
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Liao Z, Zhang C, Yang T, Liu H, Yang S, Li T, Xing R, Teng S, Yang Y, Zhao J, Zhao G, Bai X, Zhu L, Yang J. Chemotherapy Combined With Recombinant Human Endostatin (Endostar) Significantly Improves the Progression-Free Survival of Stage IV Soft Tissue Sarcomas. Front Oncol 2022; 11:778774. [PMID: 35047396 PMCID: PMC8761904 DOI: 10.3389/fonc.2021.778774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/08/2021] [Indexed: 11/13/2022] Open
Abstract
Purpose Our previously study showed that recombinant human endostatin (Endostar) combined with chemotherapy had significant activity to increase the mPFS in patients with advanced sarcomas with tolerable side effects. However, the small cohort size and short follow-up time made it difficult to screen sensitive sarcoma subtypes and determine whether there is an overall survival benefit. With the largest sarcoma cohort to our knowledge, we try to confirm the efficacy and safety of chemotherapy combined with Endostar in stage IV sarcomas, with the specific purpose of finding out the sensitive sarcoma types for this combined treatment. Methods After the exclusion of ineligible patients, 156 patients with stage IV bone and soft tissue sarcomas were included in this study according to the inclusion criteria. Results By the end of follow-up, the ORR was 10.7% (9/84) vs 1.4% (1/72) (p=0.041), the DCR was 26.2% (22/84) vs 5.6% (4/72) (p=0.001) in the combined group and chemotherapy group, respectively. The mPFS of combined group was significantly longer than the chemotherapy group (10.42 vs 6.87 months, p=0.003). The mOS were 26.84 months and 23.56 months, without significant difference (p= 0.481). In osteogenic sarcoma, there was no statistically significant difference in the mPFS between the two groups (p=0.59), while in the soft tissue sarcoma, the mPFS in the combined group was significantly higher than that of the chemotherapy group (11.27 vs 8.05 months, p=0.004). Specifically, undifferentiated polymorphic sarcoma (UPS) was the possible sarcoma subtypes that benefited from the combined therapy. For the 38 UPS patients (28 patients in the combined group and 10 patients in the chemotherapy group), the mPFS in the combined group was up to 14.88 months, while it was only 7.1 months in the chemotherapy group, with a significant difference (p=0.006). The most common adverse events in the combined group were myelosuppression, gastrointestinal reactions and abnormal liver function, without significant difference in two groups. Conclusion Chemotherapy plus Endostar could prolong mPFS and improve ORR and DCR in patients with stage IV soft tissue sarcoma, suggesting that the combined therapy could improve the patient prognosis in soft tissue sarcomas, especially the UPS patients.
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Affiliation(s)
- Zhichao Liao
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Chao Zhang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tielong Yang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Haotian Liu
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Songwei Yang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Departments of Bone and Soft Tissue Tumor, Chongqing University Cancer Hospital, Chongqing, China
| | - Ting Li
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ruwei Xing
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Sheng Teng
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yun Yang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jun Zhao
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Gang Zhao
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xu Bai
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Lei Zhu
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,Department of Molecular Imaging and Nuclear Medicine, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jilong Yang
- Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.,National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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Zhou J, Xie Z. Endostatin Inhibits Blood-Retinal Barrier Breakdown in Diabetic Rats by Increasing the Expression of ICAM-1 and VCAM-1 and Decreasing the Expression of VEGF. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:5105866. [PMID: 37795476 PMCID: PMC10547573 DOI: 10.1155/2022/5105866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 12/16/2021] [Accepted: 12/20/2021] [Indexed: 10/06/2023]
Abstract
Objective Endostatin has become the strongest endogenous angiogenesis inhibitor due to suppressing VEGF expression. The purpose of this study was to assess the impact of endostatin on the blood-retinal barrier (BRB) in diabetic rats. Methods SD rats were induced to develop diabetes by streptozotocin, and endostatin was administrated by intravitreal injection. The body weight, the level of blood glucose, the expressions of C-reactive protein (CRP), adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), junction proteins (occludin, claudin-5, and zonula occluden-1), and VEGF were measured in rats' retinas of diabetes. The BRB breakdown was evaluated using Evans blue. Results The level of CRP and adhesion molecules (ICAM-1 and VCAM-1) was increased in retinas of diabetic rats, while endostatin significantly inhibited the upregulation of these. Diabetes increased the BRB permeability and retinal thickness. Diabetes also decreased the levels of occludin, claudin-5, and ZO-1 in retinals. These changes were inhibited by endostatin treatment. Upregulation of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and protein kinase C- (PKC-) β2 was also reversed by endostatin in retinas of diabetic rats. Conclusions Endostatin provides protection against diabetic retinopathy, which may involve its barrier-enhancing effects.
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Affiliation(s)
- Jinhua Zhou
- Department of Ophthalmology, Yizheng Hospital, Nanjing Drum Tower Hospital Group, Yangzhou 211400, China
| | - Zhenggao Xie
- Department of Ophthalmology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, China
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Jin X, Dong C, Zheng K, Shi X, Liu Y, Huo L, Wang F, Li F. Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD 2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo. Front Oncol 2021; 11:792431. [PMID: 35769548 PMCID: PMC9236135 DOI: 10.3389/fonc.2021.792431] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 11/22/2021] [Indexed: 01/14/2023] Open
Abstract
Background Molecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models. Methods The pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups. Results Tumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002). Conclusion With 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.
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Affiliation(s)
- Xiaona Jin
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
| | | | - Kun Zheng
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
| | - Ximin Shi
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
| | - Yu Liu
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
| | - Li Huo
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
| | - Fan Wang
- Medical Isotopes Research Center, Peking University,
Beijing, China
| | - Fang Li
- Department of Nuclear Medicine, Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in
Nuclear Medicine, Beijing,
China
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Xiao C, Xu F, Wang R, Liang Q, Shen K, Xu J, Liu L. Endostar Plus Apatinib Successfully Achieved Long Term Progression-Free Survival in Refractory Ovarian Cancer: A Case Report and Literature Review. Onco Targets Ther 2021; 14:5363-5372. [PMID: 34880628 PMCID: PMC8646866 DOI: 10.2147/ott.s335139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/10/2021] [Indexed: 12/18/2022] Open
Abstract
Background Ovarian cancer (OC) is a common malignancy in the gynecological tumor. Standard treatment for ovarian cancer is surgery and chemotherapy based on paclitaxel and platinum. However, traditional chemotherapy for ovarian cancer is limited by drug resistance and systemic side effects. It is imperative to explore effective treatment options for refractory ovarian cancer. Case Presentation A 52-year-old female initially presented with lower abdominal distension and migratory pain. After the laparoscopic exploration and biopsy, immunohistochemistry showed poorly differentiated adenocarcinoma originated from ovarian (cT3NxM1, stage IV, peritoneal and abdominal wall metastasis). The next generation sequence detected ERRFI1 (T187A, exon4) mutation. Results The patient received first-line chemotherapy (paclitaxel, nedaplatin plus avastin), followed by maintenance therapy with gefitinib, achieving a 15-month progression-free survival (PFS). After disease progression and second-line treatment failure, endostar plus apatinib was administered for 14 cycles and she obtained a PFS of 14 months without long-term adverse events. Conclusion We believe that the ERRFI1 gene may be a potential target of gefitinib. Importantly, endostar combined with apatinib is worth recommending for maintenance treatment in refractory ovarian cancer.
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Affiliation(s)
- Chunmei Xiao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Fangye Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Rong Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Qi Liang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Kai Shen
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Jiali Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Lianke Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
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Yuan M, Zhai Y, Men Y, Wang J, Deng L, Wang W, Bao Y, Yang X, Sun S, Ma Z, Liu Y, Wang J, Zhu H, Hui Z. Endostar (rh-endostatin) improves efficacy of concurrent chemoradiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis. Thorac Cancer 2021; 12:3208-3215. [PMID: 34676669 PMCID: PMC8636201 DOI: 10.1111/1759-7714.14188] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 09/25/2021] [Accepted: 09/29/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND We aimed to clarify the benefits of the addition of rh-endostatin into concurrent chemoradiotherapy (CCRT) versus CCRT alone for locally advanced non-small cell lung cancer (NSCLC) by a meta-analysis. METHODS PubMed, Embase, Cochrane Central Register of Controlled Trials, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically screened from inception to November 2020 using the prespecified terms. Prospective trials (evaluating or) comparing the efficacy of endostar combined with CCRT and CCRT for locally advanced NSCLC were included. The primary endpoints were risk ratios (RRs) for objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were RRs for overall survival (OS) and adverse events (AEs). RESULTS Ten studies with 716 patients were included in this meta-analysis. Endostar combined with CCRT significantly improved ORR and DCR compared with CCRT. The RRs of ORR and DCR for endostar combined with CCRT versus CCRT were 1.263 (95% CI: 1.137-1.403, p < 0.001) and 1.274 (95% CI: 1.124-1.444, p < 0.001), respectively. Endostar combined with CCRT significantly improved one-year survival rate compared with CCRT with pooled RR = 1.113 (95% CI: 1.006-1.231, p = 0.038). Endostar combination treatments had similar incidences of main adverse events compared with CCRT (p > 0.05). CONCLUSION Endostar combined with CCRT is associated with significantly higher ORR, DCR and survival rate than CCRT with similar incidences of main adverse events in NSCLC.
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Affiliation(s)
- Meng Yuan
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yirui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Men
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianyang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongxing Bao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Yang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuang Sun
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zeliang Ma
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunsong Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Zhouguang Hui
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Shu H, Dong Y, Xu Z, Luo W, Xu L, Zhu H, Cheng L, Lv Y. The Efficacy and Safety of Continuous Intravenous Endostar Treatment Combined With Concurrent Chemoradiotherapy in Patients With Locally Advanced Cervical Squamous Cell Carcinoma: A Randomized Controlled Trial. Front Oncol 2021; 11:723193. [PMID: 34485157 PMCID: PMC8414882 DOI: 10.3389/fonc.2021.723193] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/30/2021] [Indexed: 12/23/2022] Open
Abstract
Objective To investigate the short-term efficacy and safety of Endostar combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical squamous cell carcinoma (LACSC). Methods A total of 91 patients with LACSC admitted to the First Affiliated Hospital of Anhui Medical University from June 2019 to December 2020 were randomly assigned to either the experimental group (n = 48) or control group (n = 43). The control group received radiotherapy for cervical cancer and paclitaxel combined with platinum chemotherapy (CCRT), and the experimental group received Endostar continuous intravenous infusion of anti-angiogenic therapy plus CCRT. The short-term efficacy, common clinical indicators, tumor indicators, changes in serum vascular endothelial growth factor-A (VEGF-A), and the occurrence of adverse events (AEs) were explored after treatment. Results Compared with the control group, the complete response (CR) rate in the experimental group was significantly increased (83.33% vs 65.12%, P < 0.05). Both routine indicators and tumor indicators in the two groups were significantly decreased compared to before treatment. Compared with the control group, patients in the experimental group had higher incidences of neutropenia, hypertension, and infection, but lower incidence of nausea. After treatment, the serological expression of VEGF-A was significantly decreased in both groups. Conclusion Endostar combined with CCRT in the treatment of LACSC can further improve the efficacy of CR rate and significantly reduce serum tumor indicators and VEGF-A levels, with mild and controllable AEs. Endostar combined with CCRT is expected to be a new treatment regimen for LACSC.
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Affiliation(s)
- Hang Shu
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yaqin Dong
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhonghua Xu
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Weiwei Luo
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Lei Xu
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Haochen Zhu
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Linghui Cheng
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Yin Lv
- Department of Oncology Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Liu Y, Huang N, Liao S, Rothzerg E, Yao F, Li Y, Wood D, Xu J. Current research progress in targeted anti-angiogenesis therapy for osteosarcoma. Cell Prolif 2021; 54:e13102. [PMID: 34309110 PMCID: PMC8450128 DOI: 10.1111/cpr.13102] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 07/05/2021] [Accepted: 07/12/2021] [Indexed: 12/12/2022] Open
Abstract
Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.
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Affiliation(s)
- Yun Liu
- Department of Spine and Osteopathic SurgeryFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
- Research Centre for Regenerative MedicineGuangxi Key Laboratory of Regenerative MedicineGuangxi Medical UniversityNanningChina
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
| | - Nenggan Huang
- Department of Trauma Orthopedic and Hand SurgeryFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Shijie Liao
- Department of Spine and Osteopathic SurgeryFirst Affiliated Hospital of Guangxi Medical UniversityNanningChina
- Research Centre for Regenerative MedicineGuangxi Key Laboratory of Regenerative MedicineGuangxi Medical UniversityNanningChina
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
| | - Emel Rothzerg
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
- Perron Institute for Neurological and Translational ScienceOEII Medical CentreNedlandsWAAustralia
| | - Felix Yao
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
| | - Yihe Li
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
| | - David Wood
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
| | - Jiake Xu
- Division of Regenerative BiologySchool of Biomedical SciencesUniversity of Western AustraliaPerthWAAustralia
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McMahon JT, Faraj RR, Adamson DC. Emerging and investigational targeted chemotherapy and immunotherapy agents for metastatic brain tumors. Expert Opin Investig Drugs 2020; 29:1389-1406. [PMID: 33040640 DOI: 10.1080/13543784.2020.1836154] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients. AREAS COVERED This study reviews novel drug regimens that are under investigation in phase 1 and 2 clinical trials. To identify relevant therapies under clinical investigation, a search was performed on http://clinicaltrials.gov and Pubmed with the keywords brain metastasis, Phase I clinical trial, and Phase II clinical trial from 2016 to 2020. The authors detail the mechanisms of action of all trial agents, outline evidence for their utility, and summarize the current state of the field. EXPERT OPINION Current advancements in the medical management of brain metastases can be categorized into targeted therapies, methods of overcoming treatment resistance, novel combinations of therapies, and modulation of the tumor microenvironment with a specific focus on immunotherapy. Each of these realms holds great promise for the field going forward. A more streamlined structure for enrollment into clinical trials will be a crucial step in accelerating progress in this area.
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Affiliation(s)
| | - Razan R Faraj
- Department of Neurosurgery, Emory University , Atlanta, GA, USA
| | - David Cory Adamson
- Department of Neurosurgery, Emory University , Atlanta, GA, USA.,Department of Neurosurgery, Atlanta VA Medical Center , Decatur, GA
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Wang B, Xu L, Li Q, Man S, Jin C, Liu L, Zhan S, Ning Y. Endostar continuous versus intermittent intravenous infusion combined with chemotherapy for advanced NSCLC: a systematic review and meta-analysis including non-randomized studies. BMC Cancer 2020; 20:1021. [PMID: 33087103 PMCID: PMC7579986 DOI: 10.1186/s12885-020-07527-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 10/14/2020] [Indexed: 01/10/2023] Open
Abstract
Background Both intermittent intravenous (IIV) infusion and continuous intravenous (CIV) infusion of Endostar are widely used for NSCLC in China. We aimed to compare the efficacy and safety of CIV of Endostar versus IIV in combination with first-line chemotherapy for patients with advanced NSCLC. Methods RCTs, NRCTs and cohort studies which compared CIV of Endostar with IIV in advanced NSCLC patients and reported efficacy or safety outcomes were eligible. Two reviewers independently screened records, extracted data and assessed risk of bias. Pooled risk ratios (RRs) with 95% confidence intervals were calculated using random effects meta-analysis for short-term efficacy and safety outcomes, and hazard ratios (HRs) for survival outcomes. Results Finally nine studies involving 597 patients were included, containing two RCTs, three NRCTs and four cohort studies. For short-term efficacy, moderate quality of evidence showed that there were no significant differences between CIV of Endostar and IIV in objective response rate (ORR; RR 1.34, 95% CI 0.91–1.98, P = 0.14) and disease control rate (DCR; RR 1.11, 95% CI 0.94–1.30, P = 0.21). Very low quality of evidence indicated that CIV of Endostar significantly improved both overall survival (OS; HR 0.69, 95% CI 0.48–0.99, P = 0.046) and progression-free survival (PFS; HR 0.71, 95% CI 0.55–0.93, P = 0.01) compared with IIV. As for safety outcomes, moderate quality of evidence found that CIV of Endostar significantly reduced the risk of myelosuppression (RR 0.55, 95% CI 0.32–0.96, P = 0.03) and cardiovascular toxicity (RR 0.21, 95% CI 0.06–0.78, P = 0.02) compared with IIV. Conclusions In advanced NSCLC, compared with IIV, CIV of Endostar had similar short-term efficacy, and substantially lower risk of myelosuppression and cardiovascular toxicity. Although very low quality of evidence supported the survival benefit of CIV compared with IIV, large RCTs with long-term follow-up are needed to demonstrate survival benefits. Caution should be given for off-label use of CIV of Endostar. Supplementary information The online version contains supplementary material available at 10.1186/s12885-020-07527-4.
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Affiliation(s)
- Bo Wang
- Department of Epidemiology, Meinian Institute of Health, Beijing, China
| | - Lu Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Qihuan Li
- Department of Epidemiology, Meinian Institute of Health, Beijing, China
| | - Sailimai Man
- Department of Epidemiology, Meinian Institute of Health, Beijing, China.,Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Cheng Jin
- Department of Biostatistics, Meinian Institute of Health, Beijing, China
| | - Lian Liu
- State Key Laboratory of Translational Medicine and Innovative Drug Development, Nanjing, Jiangsu, China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. .,Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
| | - Yi Ning
- Department of Epidemiology, Meinian Institute of Health, Beijing, China.
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Peng C, Cohen DJ. Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma. Expert Opin Pharmacother 2020; 22:93-107. [PMID: 33034212 DOI: 10.1080/14656566.2020.1813278] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Esophageal squamous cancer remains an important cause of mortality worldwide with two new immunotherapy drugs recently approved for metastatic disease. AREAS COVERED The authors review the epidemiology and genomics of esophageal squamous cell carcinoma. They also examine prior trials involving targeted agents under investigation as well immunotherapies that have been approved and novel combinations. EXPERT OPINION Great advances have been made in characterizing the molecular changes in esophageal carcinoma. However, relatively few drugs have shown benefit in this disease. Targeted therapies have not shown to improve survival although many of these trials did not explore potential biomarkers. Pembrolizumab and nivolumab are now approved for esophageal squamous carcinoma but much more data are needed to understand how these agents may be used in non-metastatic settings. Novel treatments are still required as overall prognosis remains poor.
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Affiliation(s)
| | - Deirdre J Cohen
- Department of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai Health , New York, NY, USA
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Yang YM, Hong P, Xu WW, He QY, Li B. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther 2020; 5:229. [PMID: 33028804 PMCID: PMC7542465 DOI: 10.1038/s41392-020-00323-3] [Citation(s) in RCA: 304] [Impact Index Per Article: 60.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/09/2020] [Accepted: 09/10/2020] [Indexed: 12/13/2022] Open
Abstract
Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.
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Affiliation(s)
- Yan-Ming Yang
- MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China
| | - Pan Hong
- MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China
| | - Wen Wen Xu
- MOE Key Laboratory of Tumor Molecular Biology and Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
| | - Qing-Yu He
- MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.
| | - Bin Li
- MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.
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Masoumi J, Jafarzadeh A, Khorramdelazad H, Abbasloui M, Abdolalizadeh J, Jamali N. Role of Apelin/APJ axis in cancer development and progression. Adv Med Sci 2020; 65:202-213. [PMID: 32087570 DOI: 10.1016/j.advms.2020.02.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/26/2019] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
Apelin is an endogenous peptide, which is expressed in a vast board of organs such as the brain, placenta, heart, lungs, kidneys, pancreas, testis, prostate and adipose tissues. The apelin receptor, called angiotensin-like-receptor 1 (APJ), is also expressed in the brain, spleen, placenta, heart, liver, intestine, prostate, thymus, testis, ovary, lungs, kidneys, stomach, and adipose tissue. The apelin/APJ axis is involved in a number of physiological and pathological processes. The apelin expression is increased in various kinds of cancer and the apelin/APJ axis plays a key role in the development of tumors through enhancing angiogenesis, metastasis, cell proliferation and also through the development of cancer stem cells and drug resistance. The apelin also stops the apoptosis of cancer cells. The apelin/APJ axis was considered in this review as an attractive therapeutic target for cancer treatment.
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Ge JJ, Li C, Qi SP, Xue FJ, Gao ZM, Yu CJ, Zhang JP. Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study. BMC Cancer 2020; 20:24. [PMID: 31914946 PMCID: PMC6950828 DOI: 10.1186/s12885-019-6467-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 12/15/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.
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Affiliation(s)
- Jing-Jing Ge
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China
| | - Cheng Li
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China
| | - Shao-Pei Qi
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China
| | - Feng-Jun Xue
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China
| | - Zhi-Meng Gao
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China
| | - Chun-Jiang Yu
- Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China
| | - Jun-Ping Zhang
- Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University, No. 50, Yi-Ke-Song Road, Haidian District, Beijing, 100093, People's Republic of China.
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Ma C, Zhou J, Xu X, Wang L, Qin S, Hu C, Nie L, Tu Y. The Construction of a Radiation-Induced Brain Injury Model and Preliminary Study on the Effect of Human Recombinant Endostatin in Treating Radiation-Induced Brain Injury. Med Sci Monit 2019; 25:9392-9401. [PMID: 31816619 PMCID: PMC6921694 DOI: 10.12659/msm.917537] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background The aim of this study was to construct a radiation-induced brain injury (RBI) model and assess the effects of human recombinant endostatin in the treatment of RBI. Material/Methods In this study, the RBI model was used. Real-time quantitative polymerase chain reaction, immunohistochemistry, hematoxylin and eosin staining were conducted to detect the mRNA and protein expression of vascular endothelial growth factor (VEGF) and assess the effects of human recombinant endostatin in the treatment of RBI. Results In this study, we successfully constructed a RBI model. VEGF mRNA expression was decreased after human recombinant endostatin treatment; however, VEGF protein secretion was increased in brain endothelial cells, and the secretion of VEGF protein was decreased in glial cells and nerve cells. Body weight changes indicated that human recombinant endostatin can increase the risk of weight loss. Brain water content results showed that human recombinant endostatin might aggravate cerebral edema in the acute stage of RBI, but it can reduce the progression of cerebral edema in the early delayed stage. Survival analysis showed that human recombinant endostatin improved the survival rate only in the early stage of RBI. Conclusions Radiation can induce vasogenic edema and is associated with the RBI occurrence and development. VEGF protein is highly relevant to the induction of edema and thrombosis in the acute phase of RBI and in the early delayed phase of RBI, including vascular repair and regeneration, thrombus ablation and other events. Human recombinant endostatin can reduce the progression of cerebral edema during the early onset of RBI.
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Affiliation(s)
- Chenying Ma
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Juying Zhou
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Xiaoting Xu
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Lili Wang
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Songbin Qin
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Chao Hu
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Liangqin Nie
- Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)
| | - Yu Tu
- School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu, China (mainland)
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