2.The mechanisms of apoptosis induced by curcumin in gastric cancer cells
Xiao-Ping TAN ; San-Ping XU ; Chang-Hua HE ; Yan-Ni ZHU ; Hong-An WU ; Bo HU
Cancer Research and Clinic 2001;0(04):-
Objective To study the mechanisms of Curcumin-induced apoptosis on human gastric cancer cell line SGC-7901.Methods SC,C-7901 cells were treated with various concentrations of Curcumin and the growth inhibition rates of it were accessed by MTT method.Apoptosis of gastric cancer cells were in- spected by flow cytometry.The expression of Fas and survivin in gastric cancer cells were evaluated by west- ern blot.Results Curcumin could effectively inhibit the growth of gastric cancer cells in dose-dependent and time-dependent manners,the sub-peak appeared and the apoptotic rate was increased.The expressions of Fas was higher in Western blot,meanwhile,the expressions of survivin was decreased.Conclusion Curcumin could significantly inhibit the growth and induce apoptosis of gastric cancer cells(SGC-7901),Curcumin could probably through up-regulating Fas and down-regulating surviving to induce apoptosis.
3.Association between Dopamine Receptor D4 Gene Polymorphism and Obsessive-Compulsive Disorder
yong, XU ; zhen, WANG ; ze-ping, XIAO ; dong-xiang, WAN ; yi-ping, QIANG ; san-duo, JIANG
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(04):-
0.05). After dividing the patients into early-onset and late-onset subgroups, there were significant differences of DRD4 genotype and allele frequency between early-onset patients and controls (P0.05). Conclusion The results suggested that the polymorphism of DRD4 receptor gene may be associated with early-onset OCD. The 3/4 genetype may be the risk factor of early-onset OCD. Early-onset and late-onset OCD may have different etiology.
4.Combination with SN-38 on human colon cancer LoVo cells.
Yan WANG ; Jian-ming XU ; Qin-zhi XU ; Ping-kun ZHOU ; San-tai SONG
Chinese Journal of Oncology 2009;31(10):746-851
OBJECTIVETo observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.
METHODSHuman colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay. The drug modulation on HIF-1alpha, VEGF, ERK and AKT were assessed by the following assays. The mRNA expression of HIF-1alpha and VEGF were measured by RT-PCR. The protein expression of HIF-1alpha, ERK and AKT were evaluated by Western blot analysis, and VEGF by ELISA assay.
RESULTSAmong different combination schedules, Bevacizumab given after SN-38 show most synergistic anti-proliferation effect. Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF. Moreover, the MAP kinase pathway was involved in the drug modulation of HIF-1alpha and VEGF.
CONCLUSIONThese findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.
Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Phytogenic ; pharmacology ; Bevacizumab ; Camptothecin ; analogs & derivatives ; pharmacology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; Drug Synergism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; Time Factors ; Vascular Endothelial Growth Factor A ; genetics ; metabolism
5.Lactic acid levels and related influencing factors in type 2 diabetes with normal renal function
fang, LIU ; jun-xi, LU ; jun-ling, TANG ; xu-hong, HOU ; jing, WANG ; jue, LI ; wei-ping, JIA ; kun-san, XIANG
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(07):-
0.05),while hyperlactacidemia existed in 21 patients(4.62%).LA levels increased with the creatinine levels,especially in those with Cr more than 90 ?mol/L.However,LA levels increased with the reduction of GFR,especially in those with GFR less than 80 mL/min.It was revealed by correlation analysis that LA level was positively correlated with Cr,ALT and BMI.The optimal cutoff of Cr inducing the lactic acidemia was 95.35 ?mol/L.Conclusion The baseline LA levels of patients with T2DM are similar to those of healthy adults,and LA levels are mainly influenced by BMI and renal and hepatic function.Hyperlactacidemia may be induced when Cr reaches a level more than 95 ?mol/L.
6.Silencing Filamin A Inhibits the Invasion and Migration of Breast Cancer Cells by Up-regulating 14-3-3σ
Zhi-Min JI ; Li-Li YANG ; Juan NI ; San-Peng XU ; Cheng YANG ; Pei DUAN ; Li-Ping LOU ; Qiu-Rong RUAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2018;38(3):461-466
Filamin A and 14-3-3-σ are closely associated with the development of breast cancer.However,the exact relationship between them is still unknown.The present study aimed to examine the interaction of filamin A with 14-3-3-σ in the invasion and migration of breast cancer.RNA interference technology was employed to silence filamin A in MDA-MB-231 cells.Real-time PCR and Western blotting were used to detect the expression of filamin A and 14-3-3-σ at mRNA and protein levels,respectively.Double immunofluorescence was applied to show their colocalization morphologically.Wound healing assay and Trans-well assay were used to testify the migration and invasion of MDA-MB-231 cells in filamin A-silenced cells.The results showed that silencing filamin A significantly increased the mRNA and protein levels of 14-3-3σ.In addition,double immunofluorescence displayed that filamin A and 14-3-3σ were predominantly colocalized in the cytoplasm of MDA-MB-231 cells.Silencing filamin A led to the enhanced fluorescence of 14-3-3σ.Furthermore,cell functional experiments showed that silencing filamin A inhibited the migration and invasion of MDA-MB-231 cells in vitro.In conclusion,silencing filamin A may inhibit the invasion and migration of breast cancer cells by upregulating 14-3-3σ.
7.Screening and structure analysis of nucleic acid aptamers binding to surface of CD33(+)/CD34(+) cells from patients with acute myeloid leukemia subtype M₂.
Shu-Qin ZHANG ; Guang-Ping WANG ; Ping ZHU ; Jia-Jia LIANG ; Ya-Jing XU ; Min-Yuan PENG ; Yan CHEN ; San-Qin TAN ; Fang-Ping CHEN
Journal of Experimental Hematology 2011;19(3):561-565
A little is known about the specific marker on the surface of acute leukemia cells, leading to the lack of the specific diagnosis method for acute leukemia. Therefore, in this study, cell-systematic evolution of ligands by exponential enrichment (cSELEX) was performed to screen the aptamers binding to CD33(+)/CD34(+) cells from the patients with acute myeloblastic leukemia (AML) of M(2) subtype (AML-M₂) so as to provide the basis for finding the specific marker on the surface of AML-M(2) CD33(+)/CD34(+) cells. Firstly, AML-M₂ CD33(+)/CD34(+) cells were sorted and used as targeted cells, and normal CD33(+)/CD34(+)cells were used as counter-targeted cells; the aptamers binding to CD33(+)/CD34(+) cells from patients with AML-M₂ were screened from the single strand deoxyribonucleic acid (ssDNA) library by cSELEX. Subsequently, each aptamer structure was analyzed after cloning and sequencing. The results indicated that after 13 round of screenings, the enrichment of aptamers in the ssDNA library was ranged from 0.7% to 52.9%, and reached steady state at 13th round screening. Sequence analysis for 30 aptamers showed that most of the aptamers born one of the three conserved sequences of CCCCT, CTCTC, and CTCAC. Secondary structure analysis indicated that three different secondary structures existed in these aptamers. It is concluded that the aptamers binding to the AML-M(2) CD33(+)/CD34(+) cells are successfully screened, which lay the basis for further looking for the specific marker on the surface of AML-M₂ CD33(+)/CD34(+) cells, and the molecular diagnosis of the AML-M₂ leukemia.
Antigens, CD
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genetics
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immunology
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Antigens, CD34
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genetics
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immunology
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Antigens, Differentiation, Myelomonocytic
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genetics
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immunology
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Aptamers, Nucleotide
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metabolism
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Biomarkers
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Flow Cytometry
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Humans
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Immunophenotyping
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Leukemia, Myeloid, Acute
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genetics
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immunology
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Nucleic Acid Conformation
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SELEX Aptamer Technique
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Sialic Acid Binding Ig-like Lectin 3
8.Screening and expression of CD34(+) cell-specific microRNA in acute myelogenous leukemia.
Guang-ping WANG ; Shu-qin ZHANG ; Ping ZHU ; Min-yuan PENG ; San-qin TAN ; Hui YIN ; Ya-jing XU ; Yan CHEN ; Fang-ping CHEN
Chinese Journal of Hematology 2012;33(7):541-545
OBJECTIVETo screen and analyze CD34(+) cell specific microRNAs (miRNAs) from the patients with acute myelogenous leukemia (AML) and their expression.
METHODSCD34(+) cells were sorted from AML patients or the mobilized peripheral blood of the donors of hematopoietic stem cell transplantation (normal control subjects) and followed by the extraction of the cell total RNAs. The differentially expressed microRNAs (miRNAs, miR) were selected after hybridizing with miRNA microarray, real time polymerase chain reaction (real-time PCR) was subsequently applied to confirm the expression of the selected miRs, and PCR products were further cloned and sequenced to check their specificity.
RESULTSOf the differentially expressed miRNAs, 191 were found to be at least one-fold change in the CD34(+) cells between the AML patients and the normal control subjects. Of the 191 miRNAs, the expression difference of 94 was significant (P < 0.05). Among these 94 miRNAs, the expression of 44 miRNAs was increased and the other 50 miRNAs was decreased in the CD34(+) cells from the bone marrow of AML patients compared with the CD34(+) cells from the mobilized peripheral blood of the normal control subjects. Real time PCR verified that the expression level of miR-10a and miR-220c in the CD34(+) cells from the bone marrow of AML patients was 19.6% and 19.0% of that of CD34(+) cells from mobilized peripheral blood of the normal control subjects. DNA sequencing and BLAST DNA database searching results indicated that the PCR products were really miR-10a and miR-220c.
CONCLUSIONA variety of differentially expressed-miRNAs are existed between AML and normal control subjects CD34(+) cells, the expression of miR-10a and miR-220c was significantly down-regulated in the CD34(+) cells from the bone marrow of AML patients.
Antigens, CD34 ; metabolism ; Female ; Hematopoietic Stem Cells ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Oligonucleotide Array Sequence Analysis
9.No association of vascular endothelial growth factor A gene rs9369425 polymorphism with glucose metabolism in Chinese Han population.
Rong ZHANG ; Cheng HU ; Cong-rong WANG ; Jing XU ; Xiao-jing MA ; Kun-san XIANG ; Wei-ping JIA
Chinese Journal of Medical Genetics 2010;27(4):457-459
OBJECTIVETo investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population.
METHODSOne thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform.
RESULTSThe frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes.
CONCLUSIONVEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.
Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; genetics ; Population Groups ; genetics ; Vascular Endothelial Growth Factor A ; genetics
10.Relationship of plasma creatinine and lactic acid in type 2 diabetic patients without renal dysfunction.
Fang LIU ; Jun-xi LU ; Jun-ling TANG ; Li LI ; Hui-juan LU ; Xu-hong HOU ; Wei-ping JIA ; Kun-san XIANG
Chinese Medical Journal 2009;122(21):2547-2553
BACKGROUNDAs one of most widely-used biguanides, metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low. However, lactic acidemia induced by metformin was reported in patients without renal dysfunction. It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors. This study aimed to clarify the influencing factors of lactic acid, and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function.
METHODSThe clinical data and venous blood samples of 1024 type 2 diabetic patients treated with (n = 426) or without metformin (n = 599) were collected. The lactic acid was assayed by enzyme-electrode method. The biochemical indexes included creatinine (Cr) and hepatase were measured with enzymatic procedures. The lactic acid concentrations of different Cr subgroups were compared, and the correlation and receiver operating characteristic curve analysis were used.
RESULTSThe mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group (P < 0.01), but no lactic acidosis was found in all patients. The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr, metformin, alanine transferase (ALT), body mass index (BMI), Urine albumin (Ualb), and blood urea nitrogen (BUN) in total patients; and Cr, ALT, BMI and BUN in non-metformin treated patients; Cr and ALT in metformin-group. The lactate concentration increased with the increment of Cr levels, and reached its peak at Cr 111-130 micromol/L, and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 micromol/L.
CONCLUSIONSMetformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction. Cr, ALT, and BMI are independent associated factors of blood lactic acid levels. There is low proportion of lactatemia in type 2 diabetics without metformin therapy, the optimal cutoff of Cr to predict lactatemia in these patients is 96.5 micromol/L.
Adult ; Aged ; Aged, 80 and over ; Creatinine ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Lactic Acid ; blood ; Male ; Metformin ; adverse effects ; therapeutic use ; Middle Aged ; Radioimmunoassay ; Young Adult