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Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence

《化学科学与工程前沿（英文）》 2022年 第16卷 第4期   页码 536-545 doi: 10.1007/s11705-021-2067-5

摘要： Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells, but the outcomes have been limited. More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs. A biodegradable wafer containing the chemotherapeutics carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU) was the only local drug delivery system approved for clinical glioblastoma treatment, but with a prolonged survival time of only two months and frequent side effects. In this study, to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection, both free BCNU and BCNU- poly (lactic-co-glycolic acid) (the ratio of lactic acid groups to glycolic acid groups is 75/25) nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels. The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model. Free drugs were released instantly to kill the residual tumor cells, while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days. These combined actions effectively restricted tumor growth in rats. Thus, this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.

关键词： BCNU     glioblastoma recurrence     tumor resection     nanoparticles     hydrogel    

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Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

《医学前沿（英文）》 2021年 第15卷 第4期   页码 551-561 doi: 10.1007/s11684-020-0760-2

摘要： Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5–10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.

关键词： glioma     evolution mechanism     strategies     tumor heterogeneity     secondary glioma    

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肝内区域免疫对肝移植后肿瘤复发的影响 Review

刘江, 卢宠茂, 万钧

《工程（英文）》 2022年 第10卷 第3期   页码 57-64 doi: 10.1016/j.eng.2021.11.012

摘要：

肝脏恶性肿瘤是肝移植的一个主要适应症，但是肝移植后肿瘤复发却是影响受体长期生存的一个严峻临床挑战。肿瘤生物学特征、分期和移植后的免疫抑制状态一直被认为是肝癌复发的危险因素。而越来越多的证据表明，肝脏缺血再灌注（IR）对同种异体移植物的损伤则为肝移植后的肿瘤细胞侵袭性、转移性
提供了有利的免疫微环境。在活体肝移植中，边缘移植物（如小体积或脂肪移植物）的严重损伤与较低的无复发生存率之间的相关性，证实了IR 损伤与肿瘤复发之间的关联。IR 可引起肝内免疫微环境重构，包括恶化移植物损伤的促炎反应和加快组织修复的抗炎反应。然而，肝内区域免疫对移植后肿瘤复发的作
用尚不清晰。本文详述了IR 损伤诱导的肝内体液微环境和调节性区域免疫微环境，以及它们如何影响肝移植后肿瘤复发的最新研究进展。综合理解移植后肝内区域免疫，将为移植后肿瘤复发提供精准诊断、治疗和预后预测的新策略。

关键词： 肝移植     肝癌     复发     免疫学    

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meta-analysis of randomized trials of maintenance bacillus Calmette-Guerin instillation efficacy against recurrence

PAN Jiangang, ZHOU Xing, CHEN Zhiguang, HAN Ruifa

《医学前沿（英文）》 2008年 第2卷 第3期   页码 259-263 doi: 10.1007/s11684-008-0049-3

摘要： Meta-analysis was used to determine whether maintenance intravesical bacillus Calmette-Guerin (BCG) could reduce recurrence after transurethral resection of tumor 1 grade 3 (T1G3) superficial bladder cancer. All available published data of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment on the treatment results in patients with superficial bladder cancer of T1G3 were selected for analysis. Both the fixed effects model and random effects model were applied, and the odds ratio () with its 95% confidence interval (CI) was used as the effect size estimate. Sensitivity analysis and publication bias determination were performed by funnel plots and comparing s of different models. Within the follow-up period, 375 of 915 (41.0%) BCG-treated patients and 332 of 733 (45.3%) non-BCG-treated patients developed tumor recurrence. In the combined results, a statistically significant difference in the s for tumor recurrence between the two treatment groups was found (randomized model combined effect 0.58, 95% CI 0.41 to 0.83, = 0.003). The stratified meta-analysis did not show any statistically significant confounding effects on the results when stratified by BCG strains. The randomized model combined effect of Pasteur F and other strains were 0.50 (95% CI 0.26 to 0.95, = 0.04) and 0.63 (95% CI 0.40 to 0.99, = 0.04), respectively. Therefore, we came to the conclusion that adjuvant maintenance instillation BCG combined with transurethral resection of bladder tumor (TURBT) is an effective conservative treatment for preventing recurrence of T1G3 bladder cancer.
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Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with non-muscle invasive bladder

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 241-249 doi: 10.1007/s11684-014-0328-0

摘要：

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer (NMIBC). NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guérin (BCG) instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

关键词： non-muscle invasive bladder cancer     bacillus Calmette-Guérin (BCG)     meta-analysis    

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Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast

Jiayi Wu, Weiqi Gao, Xiaosong Chen, Chunxiao Fei, Lin Lin, Weiguo Chen, Ou Huang, Siji Zhu, Jianrong He, Yafen Li, Li Zhu, Kunwei Shen

《医学前沿（英文）》 2021年 第15卷 第4期   页码 621-628 doi: 10.1007/s11684-020-0738-0

摘要： Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER ), human epidermal growth factor receptor 2-negative (HER2 ) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0–69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR= 2.450, 95% CI 1.017–5.902, = 0.046; DDFS: HR= 2.829, 95% CI 1.013–7.901, = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292–5.297, = 0.768; high vs. low: HR= 2.933, 95% CI 0.759–11.327, = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010–1.047, = 0.002), DDFS (HR= 1.030, 95% CI 1.010–1.051, = 0.003), and OS (HR= 1.034, 95% CI 1.007–1.063, = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER /HER2 breast cancer with N0 or N1 disease.

关键词： early breast cancer     21-gene assay     recurrence score     prognosis    

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Adjuvant treatment strategy after curative resection for hepatocellular carcinoma

Wei Zhang, Bixiang Zhang, Xiao-ping Chen

《医学前沿（英文）》 2021年 第15卷 第2期   页码 155-169 doi: 10.1007/s11684-021-0848-3

摘要： Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.

关键词： hepatocellular carcinoma     adjuvant treatment     hepatic resection     recurrence    

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Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field

Jianpeng Liu, Xinhua Chen, Shusen Zheng

《医学前沿（英文）》 2021年 第15卷 第2期   页码 170-177 doi: 10.1007/s11684-020-0747-z

摘要： Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

关键词： nanosecond pulsed electric fields (nsPEF)     hepatocellular carcinoma (HCC)     immune response     recurrence     metastasis    

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迈入新世纪的硼中子俘获疗法（BNCT）

周永茂

《中国工程科学》 2012年 第14卷 第8期   页码 4-13

摘要：

扼要叙述进入21世纪之际，硼中子俘获疗法（boron neutorn capture therapy，BNCT）在国际范围内的一些显著进展，包括BNCT的临床定位、肿瘤复发的探索、硼浓度的定量探测、靶向掺硼药物的开发以及我国医院中子照射器的问世。这些BNCT长期开发中的瓶颈趋于缓解，预示了BNCT个性化与例行化的前景更为清晰。

关键词： 中子俘获疗法     临床试治     肿瘤复发     硼浓度探测     靶向药物     医院中子照射器    

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The first year follow-up after colorectal adenoma polypectomy is important: A multiple-center study in symptomatic hospital-based individuals in China

Qin-Yan GAO, Hui-Min CHEN, Jing-Yuan FANG, Jian-Qiu SHENG, Ping ZHENG, Cheng-Gong YU, Bo JIANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 436-442 doi: 10.1007/s11684-010-0200-9

摘要： The recurrence of colorectal adenoma (CRA) is high. Although there are guidelines for colonoscopy surveillance after polypectomy in other countries, little is known about its recurrence rate and recurrence peak, especially in China. The aim of the present research is to investigate how long after polypectomy follow-up should take and to analyze risk factors of recurrence. 1208 patients who received polypectomies from five clinical research centers in four regions of China (Shanghai, Guangzhou, Nanjing and Beijing) were included. They were divided into 4 groups: group A (follow-up≤1 year after polypectomy), group B (follow-up 2–3 years after polypectomy), group C (follow-up 4–5 years after polypectomy), and group D (follow-up>5 years after polypectomy). The sex, age, adenoma location, size, number, and pathological characteristics were compared. On the whole, the recurrence rate was 59.46% in group A, 61.09% in group B, 78.07% in group C, and 87.12% in group D, which indicated an increased tendency with a prolonged follow-up duration. There was a significant difference between group A and C or D, and between group B and C or D (<0.01), but there was no statistical difference between group A and B. Additionally, the recurrent patients in the first year had a recurrence rate of 97.33% in the first three years (59.46/61.09), which means that the peak of recurrence was almost entirely concentrated in the first year. The recurrence rate was higher in males and the elder. The risk factors included multiple numbers, villous feature, high-grade dysplasia of medium or smaller size and location in the distal colon. In conclusion, the peak of recurrence was almost totally concentrated in the first year; meanwhile, the first year follow-up is of critical importance in China. It may not be necessary to do the follow-up examination during the second and third years, but after three years, another colonoscopy should be undertaken.

关键词： colorectal adenoma     polypectomy     follow-up     recurrence     risk factor    

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标题 作者 时间 类型 操作

Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence

期刊论文

Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

期刊论文

肝内区域免疫对肝移植后肿瘤复发的影响

刘江, 卢宠茂, 万钧

期刊论文

meta-analysis of randomized trials of maintenance bacillus Calmette-Guerin instillation efficacy against recurrence

PAN Jiangang, ZHOU Xing, CHEN Zhiguang, HAN Ruifa

期刊论文

Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with non-muscle invasive bladder

null

期刊论文

Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast

Jiayi Wu, Weiqi Gao, Xiaosong Chen, Chunxiao Fei, Lin Lin, Weiguo Chen, Ou Huang, Siji Zhu, Jianrong He, Yafen Li, Li Zhu, Kunwei Shen

期刊论文

Adjuvant treatment strategy after curative resection for hepatocellular carcinoma

Wei Zhang, Bixiang Zhang, Xiao-ping Chen

期刊论文

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field

Jianpeng Liu, Xinhua Chen, Shusen Zheng

期刊论文

迈入新世纪的硼中子俘获疗法（BNCT）

周永茂

期刊论文

The first year follow-up after colorectal adenoma polypectomy is important: A multiple-center study in symptomatic hospital-based individuals in China

Qin-Yan GAO, Hui-Min CHEN, Jing-Yuan FANG, Jian-Qiu SHENG, Ping ZHENG, Cheng-Gong YU, Bo JIANG,

期刊论文