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MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

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Protein & Cell 2014年第11期5卷 851-861页

作者： Mingxu Song Yuan Yin Jiwei Zhang Binbin Zhang Zehua Bian Chao Quan Leyuan Zhou Yaling Hu Qifeng Wang Shujuan Ni Bojian Fei Weili Wang Xiang Du Dong Hua Zhaohui Huang Wuxi oncology Institute the Affiliated Hospital of Jiangnan University Wuxi 214062 China Department of Surgical oncology the Affiliated Hospital of Jiangnan University Wuxi 214062 China Department of radiation oncology the Affiliated Hospital of Jiangnan University Wuxi 214062 China Department of Pathology Fudan University Shanghai Cancer Center Shanghai 200032 China

MicroRNAs （miRNAs） that exert function by posttran- scriptional suppression have recently brought insight in our understanding of the role of non.protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer （CRC） and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues （NCTs）, and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phe- nocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potentialtumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

关键词： miR-139-5p AMFR NOTCH1 colorectalcancer metastasis prognosis

Detecting the epidermal growth factor receptors status in non-small cell lung cancer

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Chinese Medical Journal 2011年第24期124卷 4324-4329页

作者： MENG Xue YU Jin-ming Department of radiation oncology Key Laboratory of RadiationOncology of Shandong Province Shandong Cancer Hospital andInstitute Jinan Shandong 250117 China

Non-small cell lung cancer is one of the leading causes of all cancer deaths, but despite years of research, it is still difficult to predict the response and clinical outcome of the disease. In recent years, new treatment strategies targeting the epidermal growth factor receptors （EGFR） have been developed. EGFR is one of the most frequently over expressed proteins in various cancers, including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, EGFR has become an attractive target for various treatment strategies. However, it is important to note that not all patients with lung cancer are suitable for targeted treatment, and that patients should be selected for this treatment. Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with, and predict the likelihood of response to EGFR targeted therapy. There are many standard techniques to be used for the detection of EGFR. This overview summarizes the ongoing and future investigations to determine the status of the EGFR.

关键词： lung cancer epidermal growth factor receptors molecular imaging

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Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin:Analysis of 1,085 WHO classified cases in a single institution in China

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Chinese Journal of Cancer Research 2019年第1期31卷 152-161页

作者： Yuankai Shi Ying Han Jianliang Yang Peng Liu Xiaohui He Changgong Zhang Shengyu Zhou Liqiang Zhou Yan Qin Yongwen Song Yueping Liu Shulian Wang Jing Jin Lin Gui Yan Sun Department of Medical oncology Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Departement of radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

关键词： Diffuse large B-cell lymphoma(DLBCL) distribution nodal extranodal

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Role of YES1 signaling in tumor therapy resistance

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Cancer Innovation 2023年第3期2卷 210-218页

作者： Hai Zhou Dantong Sun Junyan Tao Mingjin Xu Xiaochun Zhang Helei Hou Precision Medicine Center of oncology The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Department of Medical oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Qingdao Sixth People's Hospital QingdaoShandongChina Department of radiation oncology The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina

YES proto-oncogene 1(YES1)is an SRC family kinase(SFK)that plays a key role in cancer cell proliferation,adhesion,invasion,survival,and angiogenesis during tumorigenesis and tumor development.Reports suggest that YES1 amplification is associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors(TKIs)in human malignancies.However,the mechanisms of drug resistance have not been fully elucidated.In this article,we review the literature on YES1 and discuss the implications of YES1 signaling for targeted therapy and chemotherapy resistance in malignancies.Moreover,recent advances in targeted therapy for YES1-amplified malignancies are summarized.Finally,we conclude that targeting YES1 may reverse drug resistance and serve as a valuable tumor treatment strategy.

关键词： YES1-amplified malignancies chemotherapy resistance molecular mechanisms EGFR-TKIs

高热生物学与肿瘤治疗：对“Lance Armstrong效果”的假设

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美国医学会杂志（中文版） 2007年第6期26卷 368-371页

作者： Donald S. Coffey Robea H. Getzenberg Theodore L DeWeese 彭楠（译）蒋彦勇（译） Departments of Urology Johns Hopkins University School of Medicine Baltimore Md. radiation oncology and molecular radiation Sciences Sidney Kinunel Comprehensive Cancer Center 不详

在肿瘤研究中，可能没有比懂得大多数睾丸癌患者能被非常有效地治疗的分子机理更为重要的了。例如，Lance Armstrong被诊断为晚期睾丸癌并发生转移，但是其治疗非常成功，以致随后他能赢得多项极限环法旅行比赛。尽管对此类晚期睾丸癌... 详细信息

在肿瘤研究中，可能没有比懂得大多数睾丸癌患者能被非常有效地治疗的分子机理更为重要的了。例如，Lance Armstrong被诊断为晚期睾丸癌并发生转移，但是其治疗非常成功，以致随后他能赢得多项极限环法旅行比赛。尽管对此类晚期睾丸癌治疗成功目前已属平常，但是大多数其他类型晚期实体肿瘤仍无法达到这样的效果。如何解释睾丸癌治疗令人惊奇的疗效，能否于细胞和分子水平对其结果做出解释？了解Lance Armstrong疗效的基础可以为其他采用现行最佳系统治疗难以控制的晚期实体肿瘤的治愈提供治疗目标。

关键词：肿瘤治疗热生物学晚期实体肿瘤睾丸癌分子机理分子水平系统治疗癌患者

Amino acid transporter SLC7A11/ xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer

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Cancer Communications 2018年第1期38卷 145-157页

作者： Pranavi Koppula Yilei Zhang Li Zhuang Boyi Gan Department of Experimental radiation oncology The University of Texas MD Anderson Cancer Center1515 Holcombe BlvdHoustonTX 77030USA The University of Texas Graduate School of Biomedical Sciences 6767 Bertner Ave.HoustonTX 77030USA Department of molecular and Cellular oncology The University of Texas MD

Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.

关键词： SLC7A11 xCT System xc− Cystine Glutamate Ferroptosis Oxidative stress Nutrient dependency Cancer metabolism

Role of PLC-PIP2 and cAMP-PKA Signal Pathways in radiation-induced Immune-suppressing Effect

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Biomedical and Environmental Sciences 2014年第1期27卷 27-34页

作者： DONG Juan Cong CHENG Guang Hui SHAN Yu Xing WU Ning SHAO Ming Long LI Peng Wu JIN Shun Zi Ministry of Health Key Laboratory of Radiobiology Jilin University Department of radiation oncology China-Japan Union Hospital of Jilin University Department of Orthopedics First Hospital of Jilin University

Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line （EL-4 cells） was used. The expressions of CD4, CD25, Nrpl, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-131, IL-10, PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation, the expression of Nrpl increased significantly in 4.0 Gy group, compared with sham-irradiation group （P〈0.05） in the spleen and thymus, respectively, when ICR mice received whole-body irradiation （WBI）. Meanwhile the synthesis of Interleukin 10 （IL-20） and transforming growth factor-β1 （TGF-β1） increased significantly after high dose irradiation （HDR）（〉 or = 1.0 Gy）. In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4＋CD25＋Nrpl＋Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4＋CD25＋Nrpl＋Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.

关键词： Ionizing radiation Neuropilin-1 （Nrpl） Regulatory T cells Signal molecule

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A disease-relevant mutation of SPOP highlights functional significance of ATM-mediated DNA damage response

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Signal Transduction and Targeted Therapy 2021年第2期6卷 235-237页

作者： Mingming Xiao Joshua S.Fried Jinlu Ma Yang Su Rebecca J.Boohaker Qinghua Zeng Yaqi Mo Fanbiao Meng Rong Xiang Bo Xu Department of Biochemistry and molecular Biology Key Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China Department of oncology Southern Research InstituteBirminghamAL 35205USA Cell Biology Program University of Alabama at BirminghamBirminghamAL 35205USA Department of radiation oncology First Afliated HospitalXian Jiaotong UniversityXi'anChina Department of Biochemistry and molecular Biology Nankai University School of MedicineTianjinChina Center for Itelligent oncology Chongqing University Cancer HospitalChongqing University School of MedicineChongqing 400030China

Dear Editor,Accumulating evidence supports that,as a critical genome guardian mechanism,the DNA damage response(DDR)is a barrier to early tumorigenesis.As a crucial DDR pathway,Ataxia Telangiectasia Mutated(ATM)-mediated phosphorylation of downstream targets is essential for activation of cell cycle checkpoints,DNA repair,and programed cell death in the presence of DNA damage.Despite extensive biochemical and cellular studies on ATM phosphorylation,these phosphorylation sites are rarely mutated in cancers,challenging the pathophysio-logical relevance of ATM-mediated phosphorylation in the disease setting.

关键词： damage DDR ATM

Rapid Purification of a New Humanized Single-chain Fv Antibody/Human Interleukin-2 Fusion Protein Reactive against HER2 Receptor

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 707-712页

作者： Tak-Chun YIP Cheuk-Sang KWOK Department of Clinical oncology Queen Elizabeth Hospital Hong Kong China Division of radiation oncology City of Hope National Medical Center Duarte CA91010 USA

Human embryonic kidney 293 cells were transfected with plasmid pcDNA-H520C9scFv-rhIL- 2 containing a chimeric cDNA encoding the humanized 520C9 scFv/recombinant human IL-2 fusion protein (H520C9scFv-rhIL-2). The transfected cells in plateau growing phase were cultured in serum-free medium for three days. The supernatant was collected, concentrated and purified using an affinity column packed with CNBr-activated Sepharose 4B coupled with anti-rhIL-2 mouse monoclonal antibody. The purified fusion protein was analyzed by ELISA, SDS-PAGE and Western blot. The fusion protein showed only one band in both silver stained electrophoresis gel and Western blot developed by ECL chemiluminescence system. Its molecular weight was confirmed to be about 45 kD. This fusion protein possessed binding specificity against p185 positive SKOV3 and B16/neu cells, and it might stimulate IL-2-dependent CTLL-2 cell prolifera- tion as well.

关键词： single-chain Fv antibody IL-2 fusion protein human embryonic kidney 293 cells affinity chromatography