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Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 104-110 doi: 10.1007/s11684-016-0432-4

摘要：

Advances in next-generation sequencing and bioinformatics have begun to reveal the complex genetic landscape in human cancer genomes, including oral squamous cell carcinoma (OSCC). Sophisticated preclinical models that fully represent intra- and inter-tumoral heterogeneity are required to understand the molecular diversity of cancer and achieve the goal of personalized therapies. Patient-derived xenograft (PDX) models generated from human tumor samples that can retain the histological and genetic features of their donor tumors have been shown to be the preferred preclinical tool in translational cancer research compared with other conventional preclinical models. Specifically, genetically well-defined PDX models can be applied to accelerate targeted antitumor drug development and biomarker discovery. Recently, we have successfully established and characterized an OSCC PDX panel as part of our tumor bio-bank for translational cancer research. In this paper, we discuss the establishment, characterization, and preclinical applications of the PDX models. In particular, we focus on the classification and applications of the PDX models based on validated annotations, including clinicopathological features, genomic profiles, and pharmacological testing information. We also explore the translational value of this well-annotated PDX panel in the development of co-clinical trials for patient stratification and treatment optimization in the near future. Although various limitations still exist, this preclinical approach should be further tested and improved.

关键词： patient-derived xenograft models     personalized medicine     co-clinical trial     patient stratification     oral squamous cell carcinoma    

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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

《医学前沿（英文）》 2023年 第17卷 第2期   页码 290-303 doi: 10.1007/s11684-022-0956-8

摘要： Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine     cyclin-dependent kinase 2     patient-derived xenograft     esophageal squamous cell carcinoma    

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肿瘤特异性环状RNA来源抗原肽被证实存在于肝胆肿瘤中 Article

王文闻, 马莉丽 , 邢政, 苑廷淦, 包金霞, 朱妍静, 赵晓芳, 赵燕, 宗雅丽, 张雅妮, 莘似韵, 邱辛瑶, 杨帅, 王红阳, 高栋, 王鹏, 陈磊

《工程（英文）》 2023年 第22卷 第3期   页码 159-170 doi: 10.1016/j.eng.2022.06.008

摘要：

由于缺乏经证实具备免疫原性的多肽，基于肿瘤抗原的免疫治疗应用受到限制。在本研究中，利用肝胆肿瘤类器官分析了环状RNA（circRNA）作为肿瘤抗原肽新来源的潜力。使用RNA测序（RNA-seq）和基于算法的评分工具，预测出27 个类器官中3950 个肿瘤特异性circRNA 可翻译18 971 条抗原肽。抗原图谱显示，11 个氨基酸长度（mer）的肽和人类白细胞抗原（HLA）-A结合肽的免疫原性相关评分最高。通过对5 个类器官进行基于质谱的免疫肽组学分析，直接证实其中三个类器官的13 条抗原肽为HLA-A、HLA-B 和HLA-C（HLA-ABC）结合肽。通过流式细胞仪和酶联免疫分析发现，HLA-ABC 呈递的cricRNA来源肿瘤特异性肽可以刺激CD8 T细胞，使其CD107a 和干扰素γ（IFNγ）共表达提高、IFNγ分泌增加。细胞杀伤实验证实，经circRNA 来源免疫原性肽活化的T 细胞可杀伤类器官细胞。值得注意的是，来自circTBC1D15 的抗原肽YGFNEILKK不仅可以被HLA-ABC呈递，还能活化T细胞，显著降低肿瘤类器官活率。本研究的发现提供了一种产生肿瘤抗原的重要来源，提示肿瘤特异性circRNA 可作为抗肿瘤靶点。

关键词： 肿瘤抗原     患者来源肝胆肿瘤类器官     环状RNA     基于质谱的免疫肽组学    

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基于人工智能的肺癌NOG/PDX模型驱动基因匹配预测 Article

何雅億, 郭皓越, 刁丽, 陈宇, 朱俊杰, Hiran C. Fernando, Diego Gonzalez Rivas, 祁辉, Chunlei Dai​​​​​​​, 汤旭蓁, 朱军, 戴家威, 何侃, Dan Chan, 杨洋

《工程（英文）》 2022年 第15卷 第8期   页码 102-114 doi: 10.1016/j.eng.2021.06.017

摘要：

患者源性肿瘤异种移植物（PDX）是癌症药物发现和筛查的有力工具。然而，目前的研究对PDX的基因型错配知之甚少，导致PDX使用过程中产生巨大的经济损失。在此，本研究建立了53 例肺癌患者的PDX模型，基因型匹配率为79.2%（42/53）。此外，检查了17 个临床病理学特征，并基于最低赤池信息量准则（AIC）、最小绝对收缩和选择算子（LASSO）-逻辑回归（LR）、支持向量机（SVM）递归特征消除（SVM-RFE）、极端梯度增强（XGBoost）、梯度增强和分类特征（CatBoost），以及合成少数过采样技术（SMOTE）输入逐步逻辑回归模型。最后，通过100 个试验组的准确度、受试者工作特征曲线下面积（AUC）和F1 评分评价所有模型的性能。两个多变量 LR 模型显示，年龄、驱动基因突变的数量、表皮生长因子受体（EGFR）基因突变、既往化疗的类型、既往酪氨酸激酶抑制剂（TKI）治疗和样本来源是强有力的预测因素。此外，CatBoost （平均精度= 0.960；平均AUC = 0.939；平均F1 分数= 0.908）和八特征SVM-RFE（平均精度= 0.950；平均AUC = 0.934；平均F1 分数= 0.903）在算法中表现出最好的性能。同时，除CatBoost 外，SMOTE的应用提高了大多数模型的预测能力。基于SMOTE，单一模型的集成分类器达到了最高的准确度（平均值= 0.975）、AUC（平均值= 0.949）和F1 评分（平均值= 0.938）。总之，本文建立了一个最佳预测模型来筛选肺癌患者的NOD/Shi-scid白细胞介素-2受体（IL-2R） γnull（NOG）/PDX模型，并为建立预测模型提供了一种通用方法。

关键词： 机器学习     患者源性肿瘤异种移植物     NOG小鼠    

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Effect of atorvastatin on tumor growth and metastasis in a breast cancer cell xenograft model and its

Liu LIU MD, PhD, Yaogui NING MM, Chen CHEN MD, Daowen WANG MD, PhD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 443-446 doi: 10.1007/s11684-009-0079-5

摘要： This paper aims to evaluate the effects and the possible mechanisms of atorvastatin on tumor growth and metastasis in a xenograft tumor model. Twenty-four female athymic BALB/C mice with MDA-MB-435 xenograft tumors were randomly assigned to three groups: a control group, a low-dose atorvastatin treatment group, and a high-dose atorvastatin treatment group. The mice in the treatment groups began to be administered with atorvastatin (10 or 20 mg/kg per day) when the xenograft tumors reached 1 cm in diameter. At the end of the experiment, the tumor volume and weight and the lung metastasis colonies of each mouse were measured. Western blotting was applied to detect phosphorylation of protein kinase B (PKB, Akt), extracellular signal regulated kinase (ERK), c-Jun N-terminal Kinase (JNK), and the expression of cytochrome P450 (CYP) subtype CYP2J2. Atorvastatin suppressed xenograft tumor growth and metastasis both in the low-dose and the high-dose treatment groups ( < 0.05). Atorvastatin also decreased the phosphorylated Akt (p-Akt) and p-ERK but increased p-JNK expression. However, atorvastatin did not alter the expression of CYP2J2 in tumor tissue. This suggests that atorvastatin has the efficacy of suppressing tumor growth and metastasis . These effects were not dependent on down-regulation of CYP2J2 expression.

关键词： atorvastatin     xenograft tumor     metastasis     CYP2J2    

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Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 284-286 doi: 10.1007/s11684-017-0514-y

摘要：

Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.

关键词： arsenic trioxide     APL     rhabdomyolysis    

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An investigation on patient dose in screen-film diagnostic radiology in Lhasa City, Xizang Autonomous

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 506-509 doi: 10.1007/s11684-013-0294-y

摘要：

This study aimed to investigate patient dose in diagnostic screen-film radiographic examinations in the city of Lhasa, China. Seven out of the twenty-six hospitals registered with the Lhasa Health Bureau were included in the investigation. The entrance surface air Kerma (ESAK) of seven conventional screen-film radiology X-ray equipment in these hospitals was measured with a QA dosimeter in September 2012. The X-ray examinations were divided into three categories: PA (posterior-anterior) chest, upper/lower limb, and AP (anterior-posterior) lumbar spine. For each category, ESAKs were calculated and analyzed. The mean ESAK was 0.6 mGy for PA chest, 0.3 mGy for upper/lower limb, and 1.8 mGy for AP lumbar spine. In addition, the mean ESAK value recorded for PA chest X-ray examinations exceeded the corresponding value recommended by the International Atomic Energy Agency (0.4 mGy).

关键词： radiation dosage     radiology     radiation protection     radiography/statistics & numerical data    

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Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

《医学前沿（英文）》 2022年 第16卷 第1期   页码 150-155 doi: 10.1007/s11684-021-0846-5

摘要： Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G>A, p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C>G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C>G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

关键词： cystic fibrosis     CFTR     splicing mutation     minigene    

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年 第16卷 第4期   页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint     Siglec10     kidney renal clear cell carcinoma    

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Xingnao Kaiqiao acupuncture combined with Angong Niuhuang Wan for a patient under persistent vegetative

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 334-339 doi: 10.1007/s11684-017-0539-2

摘要：

Persistent vegetative state (PVS) is a clinical condition wherein the cerebral cortex loses its function although brain stem function remains relatively intact. It has high mortality and disability rates. Although treatment for PVS is extensively studied in developed countries, little breakthrough has been made. In China, many PVS patients who were treated with traditional Chinese medicine (TCM) and acupuncture therapy were reported to have regained consciousness. In our department, we have been investigating TCM diagnosis and treatment methods for PVS for many years and have summarized a set of curative programs. Our patient is a male and 5 years and 3 months of age. He had traumatic brain injury and had been unconscious for three months on admission. Considering his condition, we adopted Xingnao Kaiqiao acupuncture, oral Angong Niuhuang Wan, and Xingnaojing intravenous drip. After the 50-day treatment, his health significantly improved and is nearly similar to that of a healthy child, indicating that the treatment is effective for PVS. Therefore, we decided to report the case and treatment methods.

关键词： PVS     stubborn disease     Xingnao Kaiqiao     Angong Niuhuang Wan     TCM     acupuncture    

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Ventricular tachycardia in a disseminated MDR-TB patient: a case report and brief review of literature

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 259-263 doi: 10.1007/s11684-014-0321-7

摘要：

Although significant breakthroughs have been achieved in tuberculosis management, we still encounter numerous difficulties in diagnosis and treatment of the disease. Additionally, a new challenge, multidrug-resistant tuberculosis (MDR-TB) with unspecific clinical presentation, often results in delayed diagnosis. In this paper, we reported a case of disseminated tuberculosis with rare presentation of ventricular fibrillation, which proved resistant to both isoniazid and rifampicin. A review of literature showed that ventricular fibrillation or tachycardia in tuberculosis patients with pericarditis or myocarditis has been sporadically reported in the past, but none has been conducted involving patients with MDR-TB infections.

关键词： tuberculosis     MDR-TB     ventricular tachycardia    

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Tuning porosity of coal-derived activated carbons for CO2 adsorption

《化学科学与工程前沿（英文）》 2022年 第16卷 第9期   页码 1345-1354 doi: 10.1007/s11705-022-2155-1

摘要： A simple method was developed to tune the porosity of coal-derived activated carbons, which provided a model adsorbent system to investigate the volumetric CO2 adsorption performance. Specifically, the method involved the variation of the activation temperature in a K2CO3 induced chemical activation process which could yield activated carbons with defined microporous (< 2 nm, including ultra-microporous < 1 nm) and meso-micro-porous structures. CO2 adsorption isotherms revealed that the microporous activated carbon has the highest measured CO2 adsorption capacity (6.0 mmol∙g–1 at 0 °C and 4.1 mmol∙g–1 at 25 °C), whilst ultra-microporous activated carbon with a high packing density exhibited the highest normalized capacity with respect to packing volume (1.8 mmol∙cm−3 at 0 °C and 1.3 mmol∙cm–3 at 25 °C), which is significant. Both experimental correlation analysis and molecular dynamics simulation demonstrated that (i) volumetric CO2 adsorption capacity is directly proportional to the ultra-micropore volume, and (ii) an increase in micropore sizes is beneficial to improve the volumetric capacity, but may lead a low CO2 adsorption density and thus low pore space utilization efficiency. The adsorption experiments on the activated carbons established the criterion for designing CO2 adsorbents with high volumetric adsorption capacity.

关键词： coal-derived activated carbons     porosity     CO2 adsorption     molecular dynamics    

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Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 250-253 doi: 10.1007/s11684-014-0333-3

摘要：

The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.

关键词： acute-on-chronic liver failure     submassive necrosis     viral hepatitis B     esophageal variceal bleeding     liver transplantation    

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Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

《医学前沿（英文）》 2023年 第17卷 第3期   页码 534-548 doi: 10.1007/s11684-022-0953-y

摘要： Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

关键词： autoimmune hepatitis (AIH)     concanavalin A (Con A)     human menstrual blood-derived stem cells (MenSCs)     apoptosis     mitogen-activated protein kinase (MAPK)    

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Microorganism-derived biological macromolecules for tissue engineering

《医学前沿（英文）》 2022年 第16卷 第3期   页码 358-377 doi: 10.1007/s11684-021-0903-0

摘要： According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

关键词： biological macromolecules     regenerative medicine     tissue engineering     exopolysaccharide     carbohydrate    

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标题 作者 时间 类型 操作

Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

null

期刊论文

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

期刊论文

肿瘤特异性环状RNA来源抗原肽被证实存在于肝胆肿瘤中

王文闻, 马莉丽 , 邢政, 苑廷淦, 包金霞, 朱妍静, 赵晓芳, 赵燕, 宗雅丽, 张雅妮, 莘似韵, 邱辛瑶, 杨帅, 王红阳, 高栋, 王鹏, 陈磊

期刊论文

基于人工智能的肺癌NOG/PDX模型驱动基因匹配预测

何雅億, 郭皓越, 刁丽, 陈宇, 朱俊杰, Hiran C. Fernando, Diego Gonzalez Rivas, 祁辉, Chunlei Dai​​​​​​​, 汤旭蓁, 朱军, 戴家威, 何侃, Dan Chan, 杨洋

期刊论文

Effect of atorvastatin on tumor growth and metastasis in a breast cancer cell xenograft model and its

Liu LIU MD, PhD, Yaogui NING MM, Chen CHEN MD, Daowen WANG MD, PhD,

期刊论文

Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report

null

期刊论文

An investigation on patient dose in screen-film diagnostic radiology in Lhasa City, Xizang Autonomous

null

期刊论文

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

期刊论文

Xingnao Kaiqiao acupuncture combined with Angong Niuhuang Wan for a patient under persistent vegetative

null

期刊论文

Ventricular tachycardia in a disseminated MDR-TB patient: a case report and brief review of literature

null

期刊论文

Tuning porosity of coal-derived activated carbons for CO2 adsorption

期刊论文

Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

null

期刊论文

Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

期刊论文

Microorganism-derived biological macromolecules for tissue engineering

期刊论文