1.Expression of candidate tumor suppressor gene N-Myc downstream-regulated gene 2 in colon cancer.
Da-Ke CHU ; Jian ZHANG ; Hai SHI ; Guang-Long DONG ; Xin-Pin LIU ; Wei-Zhong WANG
Chinese Journal of Gastrointestinal Surgery 2008;11(4):354-357
OBJECTIVETo analyze the expression level of candidate tumor suppressor gene N-Myc downstream-regulated gene 2 (NDRG2) in human colon cancer.
METHODSThirty samples of colon cancer tissues with matched normal colon tissues were collected. The NDRG2 mRNA level was detected by semi-quantitive RT-PCR and the NDRG2 protein level was examined by Western blot and immunohistochemistry.
RESULTSTwelve samples of colon cancer tissues had low NDRG2 mRNA level and low protein level. The positive rates of NDRG2 in normal tissues and the tumorous colon tissues were 90.0%(27/30) and 53.3%(16/30) by immunohistochemistry respectively. There was a significant difference between two groups (P<0.05). The NDRG2 expression was not correlated with age, sex, metastasis of lymph node, depth of infiltration, as well as the Dukes staging(P>0.05), while it was correlated to the histology grading. The positive rate of NDRG2 in the well- and moderate-differentiation group was higher than that in the poor-differentiation group(P<0.05).
CONCLUSIONThe expression of NDRG2 is low in some colon cancer tissues, which indicates that the low level of NDRG2 expression may be engaged in the development of colon cancer.
Blotting, Western ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins ; genetics ; metabolism
3.Biological activity of the virulence factor cagA of Helicobacter pylori.
Yong-liang ZHU ; Shu ZHENG ; Ke-da QIAN ; Ping-chu FANG
Chinese Medical Journal 2004;117(9):1330-1333
BACKGROUNDChina is one of the countries with the highest incidence of H. pylori and more than 9090 isolates possessed the cagA gene. This study was to evaluate the biological activity of the H. pylori virulence factor cagA isolated from Chinese patients.
METHODScagA DNA fragments were amplified from the genomic DNA and subsequently cloned into the mammalian expression vector for cell transfection and DNA sequencing. cagA protein, phosphorylated-tyrosine cagA and the complex of cagA precipitated with SHP-2 were identified respectively by western blot in the crude cell lysate from conditionally immortalized gastric epithelial cells at 48 hours after transfection with cagA DNA. In addition, the ability of induction of scattering phenotype was examined after transient expression of cagA in AGS cells.
RESULTSThe C-terminal half of cagA contained only one repeated sequence and three tandem five-amino-acid motifs glutamic acid-proline-isoleucine-tyrosine-alanine (EPIYA). Moreover, the amino acid sequence of D2 region in repeated sequence was aspartic acid-phenylanaline-aspartic acid (D-F-D) which was significantly distinguished from the three repeated sequences and aspartic acid-aspartic adid-leucine (D-D-L) in the western standard strain NCTC11637. Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells. Transient expression of cagA in AGS cells showed that cagA was able to induce the elongation phenotype although to a lesser extent than western strains.
CONCLUSIONScagA perturbs cell signaling pathways by binding with SHP-2. However, significant difference exists in amino acid sequence and biological function of cagA in Chinese compared with those of western countries.
Amino Acid Sequence ; Antigens, Bacterial ; chemistry ; physiology ; Bacterial Proteins ; chemistry ; physiology ; Blotting, Western ; Cells, Cultured ; Gastric Mucosa ; Humans ; Intracellular Signaling Peptides and Proteins ; Molecular Sequence Data ; Phenotype ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatases ; metabolism ; Repetitive Sequences, Amino Acid ; Signal Transduction
4.Expression of NDRG1 gene in human glioma
Bo-Qian SUN ; Da-Ke CHU ; Wei LI ; Wei LIN ; Dun WEI
Chinese Journal of Neuromedicine 2009;8(9):881-883,888
Objective To analyze the expression of NDRG1 gene in human glioma tissues.Methods Eighty-three samples of glioma tissues(including 19 grade Ⅰ,22 grade Ⅱ,25 grade Ⅲ,and 17 grade Ⅳ gliomas)and 12 normal brain tissues were obtained from patients undergoing surgeries between February,2006 and June,2007.The mRNA and protein expression of NDRG1 in the tissues was detected using real-time PCR and Western blotting,respectively.Results NDRG1 expressions in the gliomas at both the mRNA and protein levels in comparison with those in normal brain tissues.PCR showed that the NDRG1 expression decreased as the upgrading of tumor from Ⅰto Ⅳ,except grade Ⅱ and grade Ⅲ.(P<0.05)Conclusion NDRG1 expression is reduced in glioma tissues in close correlation to the pathological grade,suggesting that NDRG1 may play an important role in the occurrence and progression of gliomas.
5.Expression and significance of new candidate tumor suppressor gene N-Myc downstream-regulated gene 2 in colorectal cancer.
Hai SHI ; Wei-Zhong WANG ; Li-Bo YAO ; Jian ZHANG ; Qin YIN ; Chun-Sheng XU ; Da-Ke CHU ; Guang-Long DONG ; Hong-Wei ZHANG ; Ji-Peng LI
Chinese Journal of Gastrointestinal Surgery 2009;12(3):281-284
OBJECTIVETo determine the expression of new candidate tumor suppressor gene N-Myc downstream-regulated gene 2(Ndrg2) in colorectal cancer with different differentiation, and analyze its clinical significance.
METHODSSpecimens of 50 colorectal cancer patients with different differentiation were collected. Immunohistochemistry and Western blot were used to examine the expression of Ndrg2. Colorectal cancer tissue array in large scale was applied to analyze the expression of Ndrg2 and the statistics analysis was performed referring to the patients information of the array.
RESULTSAmong 50 cases, Ndrg2 expression level of colorectal cancer was significantly lower in 32 cases as compared to adjacent and normal tissue of the same individual, while Ndrg2 expression of adjacent tissue was significantly lower than that of normal tissue. Ndrg2 protein levels increased from poor-differentiated to well-differentiated carcinomas(P=0.005).
CONCLUSIONSThe expression of Ndrg2 in different differentiated colorectal cancer tissues show a significant distinction. Ndrg2 may be involved in the regulation of differentiation in colorectal cancer.
Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Protein Array Analysis ; Tumor Suppressor Proteins ; metabolism ; Young Adult
7.Surgical therapy for massive deep skin and soft tissue injuries.
Zhao ZHENG ; Da-hai HU ; Ming-da XU ; Xiong-xiang ZHU ; Jun-tao HAN ; Mao-long DONG ; Ke TAO ; Hong-tao WANG ; Song-tao XIE ; Chu-yun JIANG ; Bi CHEN
Chinese Journal of Burns 2009;25(1):11-14
OBJECTIVETo explore the methods of repair of massive deep skin and soft tissue injuries.
METHODSFifty-six patients with deep skin and soft tissue injuries were hospitalized from July 2006 to January 2008. Among them, 23 cases were caused by burn, 17 cases by electric injury, 7 cases by hot crush injury, 6 cases by avulsion injury, and 3 cases due to other reasons (including traffic accident, crush injury, soft tissue infection respectively). Sixty-five skin flaps were raised to repair and reconstruct the injured tissues, including 21 local flaps, 18 distant pedicled skin flaps, and 26 free skin flaps. The area of skin flaps ranged from 1.5 cm x 1.0 cm to 39.0 cm x 23.0 cm.
RESULTSSixty skin flaps survived completely, partial necrosis occurred in 3 flaps, and complete necrosis in 2 flaps. There was no obvious difference in average survival rate among local skin flaps (95.2%), distant pedicled skin flaps (88.8%), and free skin flaps (92.3%, P > 0.05).
CONCLUSIONSSkin flap transposition can be still considered as the major effective method in repair of massive deep skin and soft tissue injury. On the premises of high survival rate, free skin flap transposition can be considered as the first choice.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Burns ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin ; injuries ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Young Adult
8.Incomplete protective effects of minocycline on traumatic brain injury in rats and mice.
Wen-wen SHENG ; Wei-ping ZHANG ; Meng-ling WANG ; Shi-hong ZHANG ; Hua HU ; Sheng-li CHU ; Yu ZHOU ; San-hua FANG ; Guo-liang YU ; Xiao-dong QIAN ; Ke-da CHEN ; Hui-min XU ; Lu-ying LIU ; Lei ZHANG ; Er-qing WEI
Journal of Zhejiang University. Medical sciences 2006;35(4):411-418
OBJECTIVETo evaluate protective effect of minocycline,a semisynthetic tetracycline derivative on different traumatic brain injuries in rats and mice.
METHODSThe opened brain trauma was induced in rats and the closed head injury and cold brain injury were induced in mice. In 3 brain trauma models, minocycline (45 mg/kg, ip) was administered twice daily for 2 d before the operation, at 30 min before and 1 h after the operation, and once daily for 2 d following the operation (totally 8 doses in 5 d). After the operation, the behavioral alteration was observed daily, lesion area and survival neuron density were measured at the end of the experiments (14 d after the injuries).
RESULTFor rat opened traumatic injury, minocycline promoted the recovery of hindlimb motor activity (inclined board angle), but did not alter other indexes. For mouse closed head traumatic injury, minocycline reduced the neuron loss, but did not improve behavioral dysfunction. For mouse cold injury-induced trauma, minocycline reduced death rate and lesion area, but did not remarkably improve behavior and neuron loss.
CONCLUSIONMinocycline only has an incomplete neuroprotective effect on different brain traumatic injuries in rats and mice.
Animals ; Brain Injuries ; drug therapy ; Male ; Mice ; Mice, Inbred ICR ; Minocycline ; therapeutic use ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley
9.Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer.
Jun-ling LI ; Beijing 100021, CHINA. ; Xiang-ru ZHANG ; Ji-wei LIU ; Zhong-yuan CHEN ; Ying-cheng LIN ; Yuan-dong WANG ; Qiang CHEN ; Ke-jun NAN ; Shu-ping SONG ; Fu-cai HAN ; Yun-zhong ZHU ; Long-yun LI ; Yu-hong ZHENG ; Da-Tong CHU
Chinese Journal of Oncology 2006;28(4):309-312
OBJECTIVEThe purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.
METHODSIn phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.
RESULTSIn the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.
CONCLUSIONWeekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Drug Administration Schedule ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Remission Induction ; Survival Rate ; Taxoids ; administration & dosage ; adverse effects ; Vomiting ; chemically induced
10.Shexiang Tongxin Dropping Pill () Protects against NaSO-Induced Hypoxia-Reoxygenation Injury in H9c2 Cells.
Shan LIN ; Jiu-Mao LIN ; Ling ZHANG ; Da-Xin CHEN ; Fei XIAO ; Hong-Wei CHEN ; You-Qin CHEN ; Yu-Ling ZHU ; Jian-Feng CHU ; Jun PENG
Chinese journal of integrative medicine 2019;25(6):439-445
OBJECTIVES:
To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STP) on NaSO-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells.
METHODS:
The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following NaSO-induced hypoxia using Hoechst staining, annexin V/propidium iodide (PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis.
RESULTS:
STP pretreatment significantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by NaSO treatment (P<0.05). In addition, STP pretreatment attenuated NaSO-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax, and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells (P<0.05).
CONCLUSIONS
STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis. These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.