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p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 412-418 doi: 10.1007/s11684-010-0260-x

摘要： mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type or the functional activation of mutant-type might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant and KYSE 150 with wild-type , p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type , KYSE 70 with mutant , and EC9706 with unknown genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the genotype.

关键词： p53     esophageal squamous cell carcinoma     DNA damage    

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Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

《医学前沿（英文）》 doi: 10.1007/s11684-023-1016-8

摘要： p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation     triple-negative breast cancer     decitabine     DNMT1     IRF7     innate immune response    

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Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

Wei Wang,Bhavitavya Nijampatnam,Sadanandan E. Velu,Ruiwen Zhang

《化学科学与工程前沿（英文）》 2016年 第10卷 第1期   页码 1-15 doi: 10.1007/s11705-016-1562-6

摘要： Natural products and their derivatives represent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have been shown to be effective agents in the clinic or in preclinical settings. In the present review, we present a story of discovery, synthesis and evaluation of three synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs as cancer therapeutic agents. Chemical synthesis of these compounds (BA-TPQ, TBA-TPQ, and TCBA-TPQ) has been accomplished and the mechanisms of action (MOA) and structure-activity relationships (SAR) have been investigated. In the past, the complexity of chemical synthesis and the lack of well-defined MOA have dampened the enthusiasm for the development of some makaluvamines. Recent discovery of novel molecular targets for these alkaloids (unrelated to inhibition of Topoisomerase II) warrant further consideration as clinical candidates in the future. In addition to the establishment of novel synthetic approaches and demonstration of and anticancer activities, we have successfully demonstrated that these makaluvamines attack several key molecular targets, including the MDM2-p53 pathway, providing ample opportunities of modulating the compound structure based on SAR and the use of such compounds in combination therapy in the future.

关键词： synthesis     marine drugs     tricyclic pyrroloquinone alkaloid     cancer therapy     MDM2     p53    

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Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

《医学前沿（英文）》 2009年 第3卷 第1期   页码 41-44 doi: 10.1007/s11684-009-0009-6

摘要： This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues ( = 0.000). The Syk expression was positively correlated withthe p53 expression in NSCLC specimens ( = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

关键词： Syk kinase     carcinoma     non-small-cell lung     tumor suppressor protein p53    

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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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Mutation profiling of 16 candidate genes in

Yang Zhang, Fang Wang, Xue Chen, Wenjing Liu, Jiancheng Fang, Mingyu Wang, Wen Teng, Panxiang Cao, Hongxing Liu

《医学前沿（英文）》 2019年 第13卷 第2期   页码 229-237 doi: 10.1007/s11684-018-0616-1

摘要： This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing. We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. was the most common mutated gene (16.2%, 42/259), followed by (15.1%, 39/259), (14.7%, 38/259), and (13.5%, 35/259). Concurrence was observed in 97.1% of the mutated cases and in 29.6% of the double mutated cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the gene: mutations were associated with and/or mutations, whereas mutations co-occurred with mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.

关键词： leukemia     myeloid     acute     gene     mutation    

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P2P energy trading via public power networks: Practical challenges, emerging solutions, and the way forward

《能源前沿（英文）》 2023年 第17卷 第2期   页码 189-197 doi: 10.1007/s11708-023-0873-9

摘要： Peer-to-peer (P2P) energy trading is an emerging energy supply paradigm where customers with distributed energy resources (DERs) are allowed to directly trade and share electricity with each other. P2P energy trading can facilitate local power and energy balance, thus being a potential way to manage the rapidly increasing number of DERs in net zero transition. It is of great importance to explore P2P energy trading via public power networks, to which most DERs are connected. Despite the extensive research on P2P energy trading, there has been little large-scale commercial deployment in practice across the world. In this paper, the practical challenges of conducting P2P energy trading via public power networks are identified and presented, based on the analysis of a practical Local Virtual Private Networks (LVPNs) case in North Wales, UK. The ongoing efforts and emerging solutions to tackling the challenges are then summarized and critically reviewed. Finally, the way forward for facilitating P2P energy trading via public power networks is proposed.

关键词： distribution network     local virtual private network     network charges     peer-to-peer (P2P) energy trading     practical implementation.    

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Solomon P Wasser：蕈菌的药用（2019年9月19日）

Solomon P Wasser(高级职称)

2021年01月20日

关键词： 农业科学    

面向服务的P2P网络体系结构层次参考模型研究

刘业,刘林峰,庄艳艳

《中国工程科学》 2007年 第9卷 第9期   页码 72-77

摘要： <p style="text-align: justify;">提出了一种基于交互、 面向服务的P2P网络体系结构框 架模型ISPNA，同时结合P2P网络 松耦合、自组织、可缩放等特点， 对P2P网络技术中增强其可用性需从P2P网络体系结构的研究角度出发， 将增强P2P网络可用性所需要考虑的 多方面因素放置在P2P网络的不同 层次予以解决，有利于从宏观上 把握需要解决的问题。p>

关键词： P2P网络     体系结构     层次参考模型     资源     服务    

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Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

《化学科学与工程前沿（英文）》 2023年 第17卷 第2期   页码 123-138 doi: 10.1007/s11705-022-2194-7

摘要： The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many tissues. NAD(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most cancers. Therefore, it could be a target for cancer therapy. Because it is a quinone reductase, many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose tumours. Its expression is higher in tumours than in normal tissues, and using target drugs such as β-lapachone to reduce side effects in normal tissues can help. However, the physicochemical properties of β-lapachone limit its application. The problem can be solved by using nanosystems to deliver β-lapachone. This mini-review summarizes quinone-based fluorescent, near-infrared and two-photon fluorescent probes, as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drug β-lapachone. This review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

关键词： NAD(P)H:quinone oxidoreductase 1     cancer therapy     target     probe     nanosystem    

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Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia

《医学前沿（英文）》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

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Fine-grained P2P traffic classification by simply counting flows

Jie HE,Yue-xiang YANG,Yong QIAO,Wen-ping DENG

《信息与电子工程前沿（英文）》 2015年 第16卷 第5期   页码 391-403 doi: 10.1631/FITEE.1400267

摘要： The continuous emerging of peer-to-peer (P2P) applications enriches resource sharing by networks, but it also brings about many challenges to network management. Therefore, P2P applications monitoring, in particular, P2P traffic classification, is becoming increasingly important. In this paper, we propose a novel approach for accurate P2P traffic classification at a fine-grained level. Our approach relies only on counting some special flows that are appearing frequently and steadily in the traffic generated by specific P2P applications. In contrast to existing methods, the main contribution of our approach can be summarized as the following two aspects. Firstly, it can achieve a high classification accuracy by exploiting only several generic properties of flows rather than complicated features and sophisticated techniques. Secondly, it can work well even if the classification target is running with other high bandwidth-consuming applications, outperforming most existing host-based approaches, which are incapable of dealing with this situation. We evaluated the performance of our approach on a real-world trace. Experimental results show that P2P applications can be classified with a true positive rate higher than 97.22% and a false positive rate lower than 2.78%.

关键词： Traffic classification     Peer-to-peer (P2P)     Fine-grained     Host-based    

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背包问题的混合粒子群优化算法

高尚,杨静宇

《中国工程科学》 2006年 第8卷 第11期   页码 94-98

摘要： <p>经典的粒子群是一个有效的寻找连续函数极值的方法，结合遗传算法的思想提出的混合粒子群算法来解决背包问题，经过比较测试，6种混合粒子群算法的效果都比较好，特别交叉策略A和变异策略C的混合粒子群算法是最好的且简单有效的算法p>

关键词： 粒子群算法     背包问题     遗传算法     变异    

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》   页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10     mice     motile cilia     mutation     primary ciliary dyskinesia    

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标题 作者 时间 类型 操作

p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

期刊论文

Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

期刊论文

Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

Wei Wang,Bhavitavya Nijampatnam,Sadanandan E. Velu,Ruiwen Zhang

期刊论文

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

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

Mutation profiling of 16 candidate genes in

Yang Zhang, Fang Wang, Xue Chen, Wenjing Liu, Jiancheng Fang, Mingyu Wang, Wen Teng, Panxiang Cao, Hongxing Liu

期刊论文

construction integration technology in Brazil’s superlarge deep-water offshore oil and gas unit project (FPSO P67/P70)

期刊论文

P2P energy trading via public power networks: Practical challenges, emerging solutions, and the way forward

期刊论文

Solomon P Wasser：蕈菌的药用（2019年9月19日）

Solomon P Wasser(高级职称)

2021年01月20日

会议视频

面向服务的P2P网络体系结构层次参考模型研究

刘业,刘林峰,庄艳艳

期刊论文

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1: a mini-review

期刊论文

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia

期刊论文

Fine-grained P2P traffic classification by simply counting flows

Jie HE,Yue-xiang YANG,Yong QIAO,Wen-ping DENG

期刊论文

背包问题的混合粒子群优化算法

高尚,杨静宇

期刊论文

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

期刊论文