2.A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth.
Fang-Fang LAI ; Xiao-Yu LIU ; Fei NIU ; Li-Wei LANG ; Ping XIE ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(5):622-626
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals
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Antineoplastic Agents
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pharmacology
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Breast Neoplasms
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metabolism
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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Heterografts
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Humans
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Hypoxia-Inducible Factor 1
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metabolism
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Lignans
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pharmacology
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Mice, Nude
3.Female bladder ectopic skene glands: one case report and literature review
Yashi RUAN ; Wei GUO ; Tianli NIU ; Wei XIAO ; Hong YU ; Min BIAN
Chinese Journal of Urology 2015;36(2):131-134
Objective To investigate the pathological and immunohistochemical characteristics of female bladder ectopic skene glands.Methods A female with bladder tumor was treated in our hospital in May 2013.Preoperative so(n)graphy revealed a 0.9 cm×0.6 cm round solid mass in the bottom of bladder wall.Mass was hypoechoic homogeneous with regular shape,blood flow within the mass was noted.The tumor was treated with transurethral resection.Routine pathological examination suggested bladder ectopic Skene glands.Immunohistochemical stains for prostate specific antigen (PSA),prostate spectific acid phosphatase (PSAP),androgen receptor (AR),estrogen receptor (ER),CD10,cytokeratin 14 (CK14),cytokeratin 18 (CK18),P63,high molecular weight cytokeratin (34βE12),α-methylacyl-CoA racemase (AMACR/p504s) were further performed.Results Routine pathological examination showed prostate glands composed of prostate gland epithelial cells and basal cells in a submucosal location.Immunohistochemical stains showed:PSA-,PSAP +,AR +,ER-,CD10+,CK18 +,CK14-,P63 +,34βE12 +,AMACR-.Conclusions Routine pathological examination combined with immunohistochemical stains such as PSA,PSAP,and others,can be used to diagnose ectopic Skene glands disease.Female bladder ectopic Skene glands is a benign lesion,and the prognosis is good.
4.On Key issues of Public Hospitals Reform
Haichao LEI ; Guang SHI ; Ying WU ; Hongli NIU ; Xiao WEI ; Xiaoyuan ZHOU ; Zhongyuan LI ; Chunyan XIE
Chinese Journal of Hospital Administration 2010;26(4):241-243
Public hospital reform pilots have been initiated recently and it is necessary to clarify some key issues. To this end, thispaper touches upon six fundamental issues, discussing the generality and value for the existence of public hospitals, differences between reforms of public hospital and those of state-owned enterprise, the public financing for and regulation on public hospitals, relationship with the private sector, as well as service and function positioning of public hospitals.
6.Research advance of preoperative assessment in patients with auto liver transplantation
Qi XIAO ; Qifa YE ; Wei WANG ; Zhiping XIA ; Yingzi MING ; Yanfeng WANG ; Ying NIU
Chinese Journal of Hepatobiliary Surgery 2016;22(2):141-144
Auto liver transplantation (ALT) is a treatment option for patients with liver space-occupying lesion that could not be removed by conventional surgery and severe liver trauma,which also helps alleviate the shortage of donor liver.But many problems like the preoperative assessment,the tolerance of patients to surgery and anesthesia,delayed postoperative recovery of the liver function,primary non-function,liver failure and hepatic encephalopathy and even death still need to be addressed.Thus,it is particularly important to evaluate the operative indication,completely and accurately assess the preoperative liver function and liver function reserve,and reduce the perioperative mortality and complication in order to improve the prognosis of ALT.Combined with literalure and the experience in our center,this paper summarized the research advance of preoperative assessment in patients with ALT.
7.Isolation and identification of cancer stem cells from human osteosarcom by serum-free three-dimensional culture combined with anticancer drugs.
Song, ZHOU ; Feng, LI ; Jun, XIAO ; Wei, XIONG ; Zhong, FANG ; Wenjian, CHEN ; Pengyan, NIU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(1):81-4
The cancer stem cells (CSCs) from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified. The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension, and mixed homogeneously into 1.2% alginate gel. Single-cell alginate gel was cultured with serum-free DMEM/F12 medium. Epirubicin (0.8 mug/mL) was added to the medium to enrich CSCs. After cultured conventionally for 7 to 10 days, most of cells suspended in alginate gel were killed by epirubicin. But few cells survived and some single-cell cloning spheres formed. Immunofluorescent staining for Oct3/4 and Nanog was implemented to find cells with properties of self-renewal and multi-potential differentiation. Cells from cloning spheres were transplanted into BALB/c mice to detect the tumorigenicity in vivo. The results showed that some cells positive for Oct3/4 (TRITC) and Nanog (TRITC) were found in single-cell cloning spheres, and most of positive cells were concentrated in the core of sphere. Cells from spheres could form osteosarcoma in the body of mice. It was concluded that cells from single-cell cloning spheres had the properties of the expression of parts of stem cell genes (Oct3/4 and Nanog), resisting anti-cancer drugs, and tumorigenicity in vivo. To sum up, it is believed that cells obtained from osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs are cancer stem cells.
8.Application of early cleavage embryo in combination with embryo growth rate and morphology scoring in embryo selection
Yi-juan, SUN ; Ai-jun, ZHANG ; Xiao-wei, LU ; Zhi-hong, NIU ; Qian, CHEN ; Yun, FENG
Journal of Shanghai Jiaotong University(Medical Science) 2009;29(6):719-721
Objective To evaluate the role of early cleavage embryo in combination with embryo growth rate and morphology scoring in embryo selection in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods Six hundred and ten IVF/ICSI cycles were randomly assigned to group A(269 cycles) and group B(341 cycles). In group A, transferred embryos were chosen according to embryo growth rate and morphology scoring by 72 h(D3) after fertilization, while early cleavage embryo was added to the selecting system in group B. The pregnancy rate and implantation rate were compared between two groups, and the clinic outcomes were compared between transfers with early cleavage embryos and without early cleavage embryos in group B. Results The pregnancy rate and implantation rate in group B were significantly higher than those in group A (P < 0.05). Transfers with early cleavage embryos also achieved much higher pregnancy rate and implantation rate in group B (P < 0.01). Conclusion Compared with embryo growth rate and morphology scoring, early cleavage embryo in combination with embryo growth rate and morphology scoring can improve the clinical outcomes in IVF/ICSI cycles.
9.Expression of manganese superoxide dismutase in colorectal carcinoma and its relationship with clinicopathological findings.
Xiao LI ; Zi-Qin SUN ; Zhi WEI ; Jing NIU ; Xiao-Feng LIU ; Wei WANG
Acta Academiae Medicinae Sinicae 2011;33(6):670-674
OBJECTIVETo explore the expression of manganese superoxide dismutase (MnSOD) in colorectal carcinoma and its relationship with the clinicopathological findings.
METHODSThe expressions of MnSOD in colorectal carcinoma, adenoma, and adjacent corresponding intestinal mucosal tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between MnSOD expression level in colorectal adenoma and clinical parameters was analyzed.
RESULTSThe expression of MnSOD was negative in adjacent corresponding colorectal tissues. The positive expression rate of MnSOD was 44% (11/25) in colorectal adenoma and 76% (19/25) in colorectal carcinoma (P < 0.05 when compared with the colorectal adenoma and its adjacent tissues). The expression of MnSOD was positively correlated with histopathological grades (P < 0.05) but not with other clinicopathological findings (P > 0.05).
CONCLUSIONThe expression of MnSOD may be associated with the carcinogenesis and progression of colorectal carcinoma, and therefore may be used as a new biomarker.
Adult ; Aged ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Superoxide Dismutase ; metabolism
10.Affinity maturation of a single chain antibody against VEGFR2 by hydrophilic shuffling.
Hai-di QI ; Xiao-niu MIAO ; Juan ZHANG ; Kai GU ; Si-wei ZHANG ; Min WANG
Acta Pharmaceutica Sinica 2012;47(10):1323-1328
Abstract: This study is to improve the affinity of scFv-AK404R against VEGFR2. The secondary mutational library was constructed by hydrophilic shuffling in CDR3 region of the heavy chain. VEGFR2-specific screening was performed by phage display technology and the protein of mutants was expressed in periplasm of E.coli HB2151 and purified by affinity chromatography. The affinity constant of scFvs was measured by competitive ELISA, and the structure of scFvs was analyzed by bioinformatics. The result showed that a library with 6.4x10(5) scFv members was established by electro-transformation. Two mutated clones with high absorbance value were isolated after screening. After purification by affinity chromatography, electrophoretically pure scFv proteins were obtained. The competitive ELISA showed that the affinities of WZ01 and WZ02 were three times higher than that of the parental AK404R, and bioinformatics analysis showed that the enlarged contact surface and fitted closely with KDR3 surface may be the reasons for improved affinity. These results suggest that introducing hydrophilic amino acids to the heavy chain CDR3 region is an effective approach to improve the affinity of scFv.
Amino Acid Sequence
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Antibody Affinity
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Chromatography, Affinity
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Computational Biology
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Enzyme-Linked Immunosorbent Assay
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Escherichia coli
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metabolism
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Hydrophobic and Hydrophilic Interactions
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Peptide Library
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Single-Chain Antibodies
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genetics
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immunology
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isolation & purification
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Vascular Endothelial Growth Factor Receptor-2
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genetics
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immunology
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metabolism