Objective To evaluate the effect of three diamension-digital subtraction angiography (3D-DSA) or computed tomography angiography (CTA) on the patients with ruptured multiple intmcranial aneurysm (MIA). Methods A retrospective study on 21 patients with MIA was performed.After scanning with 3D-DSA or 3D-CTA, three-dimensional reconstruction of MIA was carried out by 3D workstation,then the diagnosis was decided and the treatment plan (endovascular treatment or microsurgery) was selected according to stereoscopic image of MIA. Results (1) 3D-DSA or CTA was performed in 21 patients with subarachnoid hemorrhage (SAH),it was revealed these patients carried with 48 aneurysms,including 35 small aneurysms (25 mm).Not only miero-aneurysms and small aneurysms could be precisely showed,also the size of aneurysmal neck,the relationship of the aneurysm and the parent vessel and contiguous branches by stereoscopic image.(2) According to the standard of classification,9 patients with MIA for gradeⅠ(42.9%),10 for gradeⅡ(47.6%),2 for gradeⅢ(9.5%),0 for gradeⅣ.Endovascular treatment was selected prior to microsargery for those high grade patients.In this group,17 patients with 40 aneurysms underwent endovascular embolotherapy with GDC coils.Twenty four anemysms were completely occlusioned,12 beyond 90%,4 were left without treatment because of their small size.In microsurgery group,3 aneurysrus were totally clipped,1 could not be found during operation.No any treatment was accepted in 2 patients with 4 aneurysms. Conclusions 3D-DSA or CTA,which is very useful for the diagnosis and treatment of MIA,could improve the accuracy of diagnosis of MIA and clearly show the stereoscopic image of MIA,also the relation of sac and parent artery.For those patients with high grade MIA,endovascular treatment was selected prior to microsurgery,pro re nata,used to combine with mierosurgery.

A recombinant immunotoxin named CEA/PE38/KDEL was constructed, which was composed of anti-CEA single-chain Fv and the truncated and modified form of Pseudomonas exotoxin (PE38/KDEL). The CEA/PE38/KDEL immunotoxin was expressed in the E. coli strain BL21 (DE3)-star as inclusion bodies. The denatured inclusion bodies were purified with Ni-NTA chelate agarose, then the constant gradient dialysis was used to perform the refolding of the CEA/PE38/KDEL immunotoxin. Results of FACS and MTT assay indicate that the refolded immunotoxins keep potent and specific cytotoxicity to tumor cells bearing CEA antigens.
ADP Ribose Transferases ; biosynthesis ; genetics ; pharmacology ; Antibodies ; genetics ; metabolism ; pharmacology ; Antineoplastic Agents ; metabolism ; pharmacology ; Bacterial Toxins ; biosynthesis ; genetics ; pharmacology ; Carcinoembryonic Antigen ; immunology ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Exotoxins ; biosynthesis ; genetics ; pharmacology ; Humans ; Immunoglobulin Fragments ; biosynthesis ; genetics ; Immunotoxins ; genetics ; isolation & purification ; metabolism ; pharmacology ; Protein Renaturation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology ; Virulence Factors ; biosynthesis ; genetics ; pharmacology

Adolescent ; Adult ; Biomarkers ; Female ; Hepatitis B, Chronic ; metabolism ; Humans ; Liver ; chemistry ; Liver Cirrhosis ; blood ; therapy ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; analysis ; Proto-Oncogene Proteins c-sis

Stress in medical education has been inevitable among medical students. However, the prevalence of stress among pre-clinical and clinical medical students differed by year of study. There were several stressors reported to affect medical students. Therefore, effective coping strategies were applied to manage the stress faced by medical students. The aim of this study was to determine the prevalence of stress, stressors and coping strategies comparing pre-clinical and clinical Universiti Tunku Abdul Rahman (UTAR) medical students, and the associated stressors and stress among them. This was a cross-sectional study with a study population of 223 medical students. Universal sampling was used. A self-administered questionnaire which included socio-demographic characteristics, the General Health Questionnaire (GHQ-12), the Medical Students Stressor Questionnaire (MSSQ) and the Brief COPE Inventory were used in this study. The overall prevalence of stress among medical students was 48.15%. Clinical students had a higher prevalence of stress (53.73%) compared to pre-clinical students (39.02%). Year 3 students had the highest prevalence of stress (64.58%) compared to other years of study. Nearly 1 out of 2 medical students were stressed (48.15%). Academic Related Stressor ranked the highest and Acceptance was the most practiced coping strategy. The only associated stressor with stress was Academic Related Stressor.

OBJECTIVETo explore the anti-tumor mechanism of the combination of cisplatin with DC vaccine in tumor-bearing mice.

METHODSB16 melanoma cells were treated with cisplatin at the final concentration of 20 µg/ml in vitro for 24 h. The expression of HMGB1, Hsp70 and TGF-β were detected by Western blot. B16 tumor-bearing mouse models were generated. The therapeutic effect of the combination of cisplatin (100 µg/mouse i.p., for sequential 3 days) and intratumoral injection of DC cells (3×10(6)/mouse, twice with a 7-day interval) in the tumor-bearing mouse models was evaluated. Expression of MHC II, ICAM-1 and CD86 was analyzed by flow cytometry. The mice were sacrificed at 28 days after tumor cell inoculation. The tumors were removed and weighed, and tissue samples were taken for pathological examination. Tumor infiltrating lymphocytes (TIL) were isolated by discontinuous gradient centrifugation. The distribution of T-reg and CD8(+) T cells in the TIL was analyzed by flow cytometry, and the ratio of CD8(+) T/T-reg was determined. The activity of cytotoxic lymphocytes (CTL) was determined by microcytotoxicity assay.

RESULTSCisplatin enhanced both the B16 cell apoptosis and HMGB1 expression. After loading with cisplatin-treated cell lysate, the expression of MHC II, ICAM-1 and CD86 on DC cells were (47.5 ± 8.8)%, (35.5 ± 8.3)% and (36.2 ± 9.2)%, respectively. At 28 days after tumor cell inoculation, the tumor weight of the control group was (2.1 ± 0.6) g, that of the cisplatin group was (0.3 ± 0.2) g and that of cisplatin + DC vaccine group was (0.5 ± 0.2) g, showing a significant inhibition of tumor growth (P < 0.01). Furthermore, the CD8(+) T/T-reg ratio and CTL activity in TIL were also significantly enhanced in the tumor-bearing mice treated with cisplatin + DC vaccine. When the effector-to-target ratio was 20:1, 10:1 and 5:1, the CTL activity in the cisplatin + DC vaccine treated mice was (25.0 ± 5.0)%, (22.0 ± 6.0)% and (14.0 ± 4.0)%, respectively, significantly higher than (8.2 ± 3.6)%, (6.7 ± 1.8)% and (3.6 ± 1.9)%, respectively, in the control group (all P < 0.01).

CONCLUSIONCisplatin promotes the anti-tumor effect of DC vaccine by down-regulating T-reg cells and enhancing the CTL activity in tumors.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; B7-2 Antigen ; metabolism ; CD8-Positive T-Lymphocytes ; pathology ; Cancer Vaccines ; pharmacology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Dendritic Cells ; immunology ; metabolism ; Female ; Genes, MHC Class II ; HMGB1 Protein ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Melanoma, Experimental ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; T-Lymphocytes, Cytotoxic ; immunology ; T-Lymphocytes, Regulatory ; pathology ; Tumor Burden ; drug effects

OBJECTIVETo investigate the efficacy and safety of adefovir dipivoxil (ADV, DAIDING) for Chinese chronic hepatitis B patients with lamivudine (LAM) resistance.

METHODSThis study was a multicenter, double-blind clinical trial. 209 chronic hepatitis B patients with LAM resistance were randomly put in an ADV, DAIDING or a LAM group. After 24 and 48-weeks of treatment, serum HBV DNA levels were measured by quantitative PCR and liver function tests; HBV serology and safety assessments were also conducted.

RESULTSThe mean reduction of HBV DNA from baseline at 24 and 48 weeks was significantly greater in the ADV group compared with that in the LAM group (2.40 log10 vs 0.94 log10, P < 0.01; 2.71 log10 vs 1.07 log10, P < 0.01). In the ADV group, the virological response and ALT normalization at 24 and 48 weeks were significantly higher than those in the LAM group. There was no significant difference between the two groups in the portion of HBeAg reduction, HBeAg seroconversion and incidence of adverse events. There was no severe adverse event related to the investigational product, DAIDING, in this trial.

CONCLUSIONDAIDING (ADV) is effective and safe for the treatment of chronic hepatitis B patients with LAM resistance.

Adenine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Resistance, Viral ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; pharmacology ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Young Adult

OBJECTIVESTo study the relationship between lymphangiogenesis and lymphatic metastasis in mice bearing hepatic carcinoma and analyze the mechanism of the lymphatic metastasis.

METHODSHepatic carcinoma cell lines of high and low potentialities of lymphatic metastasis were injected into the footpads of Balb/c mice. Their metastases to lymph nodes were examined. The tumor tissues of each group were stained with 5'-nucleotidase-ALP to observe the lymphoangiogenesis. The total RNA of high and low metastatic potential cell lines were extracted for metastasis gene DNA array. The vascular endothelial cell growth factor C (VEGF-C) and VEGF-D of each cell line were detected using semi-quantitative RT-PCR and were further quantatively analyzed using real time PCR.

RESULTSThe para-common iliac a. and renal hilar lymph nodes metastases of the high metastatic potential cells were significantly higher than in the controls (P>0.05). The quantity of lymphatic vessels in the high metastasis group was significantly larger than that of the control group (P<0.05). The expressions of CD44, E-cadherin, HER2/neu, H-Ras and VEGF-C in the high metastasis group were higher than those in the low metastasis group shown by the cDNA micro array experiment but the expressions of nm23A, nm23-E4, p16ink4a, CD61 were lower. The VEGF-C expression was higher and the VEGF-D was lower in the high metastasis group compared to those of the low metastasis group shown by semi-quantitative RT-PCR. The secretion of VEGF-D was significantly lower and the ratio of VEGF-C/VEGF-D was significantly higher in the high metastasis group than the low metastasis group (P<0.05).

CONCLUSIONSThe lymphatic metastasis of hepatic carcinoma is related to lymphoangiogenesis. The changes of VEGF-C and VEGF-D expressions might be a cause influencing the lymphoangiogenesis. VEGF-C/VEGF-D might be an effective parameter in affecting lymphatic metastases.

Animals ; Liver Neoplasms, Experimental ; pathology ; Lymph Nodes ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor D ; metabolism

OBJECTIVETo study the tumor cell killing function of T lymphocytes stimulated by dendritic cells (DC) and to analyze the differences of protein contents of exosomes in each type of cell.

METHODSThe exosomes of hepatic cell lines with high (P group) or low (F group) metastatic potentials were isolated by a process of four-step centrifugation and the collected exosomes were observed under an electron microscope (EM). The tumor cell killing experiment was performed by adding T lymphocytes activated by DC loaded with exosomes from corresponding P and F group cells and was studied using 3H-TdR experiments. The proteomic analysis was performed by surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF-MS ) on the exosomes of P and F group cells.

RESULTSThe density distribution and content of exosomes in the P group were not equal to those in the F group observed by EM. The CD80, CD86, MHC-I and MHC-II in the P group were 64.27+5.00, 44.89+10.11, 84.35+19.89 and 59.03+19.37, and those in the F group were 71.53+4.85, 50.01+9.50, 80.68+29.87 and 58.86+21.11, respectively (P>0.05, compared with the control group). The counts per minute value in the P group was 528.40+179.06 and 78.80+24.44 in the F group after being loaded with exosomes (P<0.01, compared with the control group). There were significant differences between the proteins in the exosomes of hepatic cancer cell lines with high or low metastatic potentials.

CONCLUSIONExosomes have potential values of application in immunotherapy and in biotherapy for recurrences and metastases of hepatic carcinomas.

Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Dendritic Cells ; immunology ; metabolism ; Exosomes ; Liver Neoplasms ; metabolism ; pathology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes ; immunology ; metabolism

OBJECTIVETo investigate the effectiveness of reconstruction of immunological functions of T cells on the degree of metastases of mouse hepatocarcinoma and the mechanisms of their functioning.

METHODSThe T cell model of immunological functions in Balb/c nu/nu mice was established and the effectiveness of the model was evaluated. The mice were divided into 4 groups. The immunological functions of T cells in experiment groups of Balb/c nu/nu mice were reconstructed. Metastases of the cancer in lymph nodes in each group were examined histologically. The formation time and growth rate of the tumors were calculated. The expression of MHCI and II of the tumor cell line and the difference of expression of immune associated gene were detected by Th1-Th2-Th3 gene array.

RESULTSThe ratio of CD3, CD4, CD8 and CD4/CD8 in the reconstructed group was higher than that in the control group. The average formation time was 7.7+/-0.6 days in Balb/c nu/nu mice and 11.5+/-1.3 days in Balb/c mice. The extent of metastases of the experiment group was lower than that of the control group (P < 0.05). The expression of MHCI of the high metastasis cell line was lower than that of the low metastasis cell line (P < 0.05). The expressions of Th1/Th2 associated genes in lymphocytes of high metastasis mice were lower than those of the low metastasis mice.

CONCLUSIONReconstruction of the immunological function of T cells can influence the metastasis of mouse hepatocarcinoma. The alteration of MHC molecule and low expression of Th1/Th2 correlated genes in lymphocytes may be a factor influencing the metastasis of liver cancer.

Animals ; CD4-CD8 Ratio ; Carcinoma, Hepatocellular ; immunology ; pathology ; Liver Neoplasms ; immunology ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; T-Lymphocytes ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Tumor Cells, Cultured

OBJECTIVESTo study the relationship between the expression level of DLC-1 mRNA (located in 8p) and the invasion/metastasis of human hepatocellular carcinoma (HCC).

METHODSFifty-one surgical specimens of human HCC were divided into high-invasive and low invasive groups according to their clinicopathological features. DLC-1 mRNA expression was studied in the 51 HCC specimens as well as 5 different metastasis potential cell lines using real-time quantitative PCR (RQ-PCR).

RESULTSThe expression level of DLC-1 mRNA in HCC specimens with high invasiveness was significantly lower than that with low invasiveness (P < 0.05). The expression levels of DLC-1 mRNA were significantly different between non-metastatic (Hep3B and HepG2) and metastatic (MHCC97-H, MHCC97-L and HCCLM3) cell lines (P < 0.05). From MHCC97-L to HCCLM3, with an increase of invasiveness and metastatic potentials, the expression level of DLC-1 decreased correspondingly, and its expression level in HCCLM3 was significantly lower than that in MHCC97-L (P < 0.01).

CONCLUSIONThe expression of DLC-1 mRNA may play an important role in inhibiting the invasiveness and metastasis of HCC.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; GTPase-Activating Proteins ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Mutagenesis, Site-Directed ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Suppressor Proteins ; biosynthesis ; genetics