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      • KCI등재
      • KCI등재

        Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations

        Xinyi Zhu,Tian Tian,Miao Ruan,Jia Rao,Wentao Yang,Xu Cai,Menghong Sun,Guangqi Qin,Zhonghua Zhao,Jiong Wu,Zhimin Shao,Ruohong Shui,Zhen Hu 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3

        Purpose: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. Methods: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. Results: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. Conclusion: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.

      • KCI등재

        MicroRNA-576-3p Inhibits Proliferation in Bladder Cancer Cells by Targeting Cyclin D1

        Liang, Zhen,Li, Shiqi,Xu, Xin,Xu, Xianglai,Wang, Xiao,Wu, Jian,Zhu, Yi,Hu, Zhenghui,Lin, Yiwei,Mao, Yeqing,Chen, Hong,Luo, Jindan,Liu, Ben,Zheng, Xiangyi,Xie, Liping Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.2

        MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3'-UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3'-UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.

      • KCI등재

        Estrogen weakens muscle endurance via estrogen receptor-p38 MAPK-mediated orosomucoid (ORM) suppression

        Yang Sun,Zhen Qin,Jing-jing Wan,Peng-yuan Wang,Yi-Li Yang,Jian-Guang Yu,Bo-Han Hu,Ding-Feng Su,Zhu-Min Luo,Xia Liu 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

        Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.

      • KCI등재

        Three new diphenylpropanes from Celastrus hindsii

        Xian Qing Hu,Wei Han,Zhu Zhen Han,Qing Xin Liu,Xi-Ke Xu,Peng Fu,Hui-Liang Li 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.11

        Three new diphenylpropanes, HindsiipropaneA–C (1–3), together with one known arylpropyl quinoneGriffithane D (4), were isolated from Celastrus hindsii. Their structures were established by 1D and 2D nuclearmagnetic resonance spectroscopic analysis, and massspectroscopy. Compound 4 was firstly obtained in thisgenus. All the isolated compounds were evaluated in vitrofor cytotoxicity against four human tumor cell lines (A549,HCT116, MDA-MB-231, BEL7404) by the MTT assay.

      • KCI등재

        MicroRNA-576-3p Inhibits Proliferation in Bladder Cancer Cells by Targeting Cyclin D1

        Liping Xie,Zhen Liang,Shiqi Li,Xin Xu,Xianglai Xu,Xiao Wang,Jian Wu,Yi Zhu,Zhenghui Hu,Yiwei Lin,Yeqing Mao,Hong Chen,Jindan Luo,Ben Liu,Xiangyi Zheng 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.2

        MicroRNAs (miRNAs) are small, endogenous RNAs that play important gene-regulatory roles by binding to the imperfectly complementary sequences at the 3 -UTR of mRNAs and directing their gene expression. Here, we first discovered that miR-576-3p was down-regulated in human bladder cancer cell lines compared with the non-malignant cell line. To better characterize the role of miR-576-3p in bladder cancer cells, we over-expressed or down-regulated miR-576-3p in bladder cancer cells by transfecting with chemically synthesized mimic or inhibitor. The overexpression of miR-576-3p remarkably inhibited cell proliferation via G1-phase arrest, and decreased both mRNA and protein levels of cyclin D1 which played a key role in G1/S phase transition. The knock-down of miR-576-3p significantly promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression of cyclin D1. Moreover, the dual-luciferase reporter assays indicated that miR-576-3p could directly target cyclin D1 through binding its 3 -UTR. All the results demonstrated that miR-576-3p might be a novel suppressor of bladder cancer cell proliferation through targeting cyclin D1.

      • Cryptotanshinone Induces Inhibition of Breast Tumor Growth by Cytotoxic CD4+ T Cells through the JAK2/STAT4/ Perforin Pathway

        Zhou, Jun,Xu, Xiao-Zhen,Hu, Yao-Ren,Hu, Ai-Rong,Zhu, Cheng-Liang,Gao, Guo-Sheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

        Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

      • Prognostic Values of Various Clinical Factors and Genetic Subtypes for Diffuse Large B-cell lymphoma Patients: A Retrospective Analysis of 227 Cases

        Zhou, De,Xie, Wan-Zhuo,Hu, Ke-Yue,Huang, Wei-Jia,Wei, Guo-Qing,He, Jing-Song,Shi, Ji-Min,Luo, Yi,Li, Li,Zhu, Jing-Jing,Zhang, Jie,Lin, Mao-Fang,Ye, Xiu-Jin,Cai, Zhen,Huang, He Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

        Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-cell lymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectively reviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), ${\beta}2$-microglobulin (${\beta}2$-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predicting the prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-cell-like (GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOP management, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%, P=0.288). Conclusion: Elevated LDH and ${\beta}2$-M levels, positive B symptoms, Ann Arbor stage III/IV, and primary nodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have a better prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment with the addition of rituximab can improve the prognosis of patients with DLBCL.

      • Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

        Piao, Yong-Rui,Piao, Long-Zhen,Zhu, Lian-Hua,Jin, Zhe-Hu,Dong, Xiu-Zhe Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

        Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. Conclusions: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our resutlts indicate that TIM-3 is a potential prognostic marker in prostate cancer.

      • KCI등재

        Biodegrading of Pyrene by a Newly Isolated Pseudomonas putida PL2

        Lifeng Ping,Chunrong Zhang,Yahong Zhu,Min Wu,Xiuqing Hu,Zhen Li,Hua Zhao 한국생물공학회 2011 Biotechnology and Bioprocess Engineering Vol.16 No.5

        Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic compounds derived from natural sources and anthropogenic processes, which have been recommended as priority pollutants. Degradation of PAHs in the environment is becoming more necessary and urgent. In the current study, strain PL2, which is capable of growing aerobically on pyrene (PYR) as the sole carbon source, was isolated from hydrocarbons-contaminated soil and then identified as Pseudomonas putida by morphological and physiological characteristics as well as 16S rDNA sequence. The strain PL2 was able to degrade 50.0%of the pyrene at 28°C within 6 days in the presence of 50mg/L pyrene, while the strain PL2 degraded 50.0% of the pyrene within 2 days when a solution of 50 mg/L pyrene and 50 mg/L phenanthrene was used. In addition, phenanthrene was shown to increase the biodegradation efficiency of pyrene by the strain PL2. The order of degradation by the strain PL2 was pH 6.0 > pH 7.0 > pH 5.0 > pH 8.0. The degradation rate of PYR in the soil by the strain PL2reached 70.0% at the 10^th day. The dynamics of PYR degradation in soil by PL2 was fit to the first order model and the strain PL2 was shown to efficiently degrade PYR in soil. The current study showed that P. putida PL2 was a novel bacterium that could degrade pyrene and holds great promise for use in PAHs bioremediation in soil.

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