Objective To investigate the expression of DNA methyltransferases (DNMTs) in liver cancer and its clinical significance. Methods The specimens of liver cancer tissues, adjacent tissues, cirrhotic tissues and chronic hepatitis tissues were collected from 50 patients who received radical resection at the First Affiliated Hospital of Sun Yat-Sen University from July 2007 to April 2008. The mRNA and protein expressions of DNMT1,DNMT3a and DNMT3b in liver cancer tissues, adjacent tissues, cirrhotic tissues and chronic hepatitis tissues were detected by real-time quantitative PCR and immunohistochemical staining. The mRNA expression of DNMTs in the liver cancer tissues was compared with those in the adjacent tissues, cirrhotic tissues and chronic hepatitis tissues by using t test and Mann-Whitney U test. The correlation between the protein expression of DNMTs in the liver cancer tissue and the clinicopathological features was analyzed by chi-square test or Fisher exact test, and the tumor-free survival time was analyzed by using Kaplan-Meier method and the difference in tumor-free survival rate between different patients was analyzed by Log-rank test. Results The mRNA expressions of DNMT1, DNMT3a and DNMT3b in the liver cancer tissue were 2.57, 2.29 and 4.86 times higher than those in the adjacent tissues (t = 3.94, 2. 72, 4. 06, P ＜ 0.05 ). The mRNA expressions of DNMT1, DNMT3a and DNMT3b were 2.38,2.14 and 4.66 times higher than those in the cirrhotic tissues, and 6.12, 4.58 and 12.99 times higher than those in the chronic hepatitis tissues. The mRNA expressions of DNMT1, DNMT3a and DNMT3b in the liver cancer tissue were significantly higher than those in the cirrhotic tissues and chronic hepatitis tissues ( U = 587.5,730. 0,562.5; 65.5, 64.5, 71.0, P ＜ 0.05). The protein expression of DNMT1 was correlated with the size, number,TNM stages and vascular invasion of tumors ( x2 = 4.08, 5.95, 4.08, P ＜ 0.05 ). The protein expression of DNMT3a was correlated with the size, number and TNM stages of tumors (x2 = 4.08, 5.95, 4.08, P ＜ 0.05 ).The mean tumor recurrence time of patients with low expressions of DNMT1 and DNMT3a were 9.4 and 8.7 months, which were significantly longer than 5.0 and 3.2 months of those with high expressions of DNMT1 and DNMT3a (x2 =3.89, 9.91, P＜0.05). Conclusions DNMTs play an important role in hepatocarcinogenesis.High expressions of DNMT1 and DNMT3a are correlated with the postoperative recurrence of liver cancer, which are valuable prognostic factors for liver cancer.

Objective To investigate the expression of DNA methyltransferases ( DNMTs) in hilar cholangiocarcinoma and its clinical significance.Methods A total of 150 samples of cholangetic tissues were collected from 111 patients with hilar cholangiocarcinoma ( cholangiocarcinoma group) and 39 patients with choledochocele ( control group) at the First Affiliated Hospital of Sun Yat-Sen University from April 1997 to March 2007.A tissue chip containing the samples of hilar cholangiocarcinoma and choledochocele was prepared.Expressions of DNMT1,DNMT3a and DNMT3b were detected by the immunohistochemical staining. Differences in the protein expressions of DNMTs in the cholangiocarcinoma group and the control group were compared,and the correlation between DNMTs protein expressions and clinicopathological features was analyzed.All data were analyzed by using the chi-square test or Fisher exact probability.The survival curve was drawn by using the Kaplan-Meier method and the survival rate was compared by using the Log-rank test.Results The rates of high protein expressions of DNMT1 and DNMT3b were 54.1％ (60/111) and 47.7％ (53/111) in the cholangiocarcinoma group, which were significantly higher than 28.2％ ( 11/39) and 23.1％ ( 9/39) in the control group　( x2 =7.740,7.240,P ＜0.05). The high protein expression of DNMT1 was correlated with-the Bismuth-Corlette classification and T staging of the tumor ( x2 =12.200, 17.800,P ＜0.05) ; there was no significant difference in the high protein expressions of DNMT3a in the cholangiocarcinoma group and the control group ( x2 =3.370.P ＞0.05 ) ; while the high protein expressions of DNMT3b was correlated with the Bismuth-Corlette classification (x2 =8.300,P ＜ 0.05 ),but not with the T staging. Sixty-six patients received hilar cholangiocarcinoma resection,and 42 of them were followed up.The median postoperative survival time of patients with low protein expression of DNMT1 was 23.9 months,which was significantly longer than 11.8 months of patients with high protein expression of DNMT1 (x2 =3.980,P ＜ 0.05).Conclusions DNMT1 and DNMT3b with high protein expression might play important roles in the carcinogenesis and development of hilar cholangiocarcinoma.There is an obvious relationship between the expression of DNMT1 and postoperative survival time of patients with hilar cholangiocarcinoma,and DNMT1 might be a valuable prognostic factor for hilar cholangiocarcinoma.

[ ABSTRACT ] AIM: To investigate the expression and clinical significance of bone morphogenetic protein 3 (BMP3) in hilar cholangiocarcinoma tissues.METHODS: Thirty cases of hilar cholangiocarcinoma specimens were col-lected.The expression of BMP3 at mRNA and protein levels in the tumor tissues and paracancerous tissues was detected by real-time PCR and Western blot.The hilar cholangiocarcinoma paraffin-embedded specimens (n=103) were collected. The protein expression of BMP3 was determined by immunohistochemical method, and the relationship of BMP3 protein ex-pression with clinical pathological characteristics was evaluated.RESULTS:In the 30 patients with hilar cholangiocarcino-ma, the expressions of BMP3 protein and mRNA in 22 cases of tumor tissues were significantly decreased compared with the adjacent normal tissues.The results of immunohistochemistry showed that 87 cases were negative and 16 cases were weakly positive in all 103 cases of hilar cholangiocarcinoma.The expression of BMP3 protein was associated with the tumor TNM staging, lymph node metastasis and tumor differentiation (P<0.05).CONCLUSION:BMP3 gene might be inhibited in human hilar cholangiocarcinoma.The down-regulation of BMP3 gene might be associated with the carcinogenesis and devel-opment of hilar cholangiocarcinoma.

OBJECTIVETo elucidate the relation between cytochrome P4502D6 (CYP2D6) gene polymorphism and the susceptibility of heroin spongiform leucoencephalopathy (HSLE).

METHODSWith polymerase chain reaction-restriction fragment length polymorphism technique, the cytochrome P4502D6 gene polymorphisms were analyzed in HSLE cases and control subjects.

RESULTSThe frequencies of CYP2D6 (CYP2D6/C188, CYP2D6/L2938, CYP2D6/G4268) gene mutations were higher in HSLE patients than in the controls.

CONCLUSIONThe CYP2D6 gene mutation is associated with a high risk of HSLE.

Adult ; Canavan Disease ; chemically induced ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Female ; Heroin ; adverse effects ; Heroin Dependence ; complications ; Humans ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; Young Adult

OBJECTIVETo summarize the clinical and radiographic characteristics of heroin spongiform leukoencephalopathy (HSLE).

METHODSA clinical analysis of 42 cases of HSLE was conducted.

RESULTSClinically, the patients with HSLE all had a positive history of inhalation of heated heroin vapor with acute or subacute onset in most cases, presenting initially cerebellar signs. Pyramidal tract lesion was frequently involved, but the sensory system usually remained normal. The consciousness disturbances may occur in the serious cases. Brain CT and magnetic resonance imaging (MRI) revealed extensive symmetric white matter lesions in the cerebrum and cerebellum, and in serious cases, the midbrain and pons could be damaged. Spongiform vacuoles degeneration of white matter characterized the predominant pathological changes.

CONCLUSIONSpongiform leukoencephalopathy should be considered in a patient who shows acute cerebellar signs and reports a history of inhaling heated heroin vapor, and a definite diagnosis of HSLE can be made in such a case upon the identification of typical CT or MRI findings.

Adult ; Brain ; pathology ; Female ; Heroin Dependence ; complications ; Humans ; Leukoencephalopathies ; chemically induced ; diagnosis ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo investigate the feasibility and therapeutic results of multiple organ resection in patients with tumor of the body and tail of pancreas.

METHODSThe clinical and pathological data were analysed in 16 consecutive patients with neoplasm of the body and tail of pancreas from 1999 to 2004 retrospectively.

RESULTSMultiple organ resection was performed in 6 cases of primary pancreatic adenocarcinoma of the body and tail (3 cases of pancreatic cancer, 2 cases of malignant glucagonoma, and 1 case of well-differentiated pancreatic stromal sarcoma) and 10 cases of extrapancreatic malignancy (4 cases of gastric cancer, 2 cases of gastric leiomyosarcoma, 1 case of duodenal cancer, and 3 cases of colon cancer of hepatic flexure). Distal pancreatectomy with splenectomy was performed in all cases. In addition, 10 patients received splenic flexure colectomy, 6 patients received distal gastrectomy, 3 patients received left nephrectomy, left colectomy, total gastrectomy, liver lobe resection, left adrenalectomy, and local diaphragma resection, and 2 patients received transverse colectomy, subtotal colectomy, proximal proctectomy, proximal gastrectomy, and duodenectomy. No perioperative death and severe complications were observed. Patients with primary pancreatic cancer or pancreatic stromal sarcoma died within 1 year. Two patients with malignant glucagonoma died 51 and 39 months later. The 3-year survival rate was 70% in 10 patients with extrapancreatic malignancy, among which 2 patients with enteric cancer have survived 37 and 48 months.

CONCLUSIONRadical combined multiple organ resection may be performed actively in appropriately selected patients.

Adenocarcinoma ; mortality ; pathology ; surgery ; Adult ; Aged ; Colectomy ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Pancreatectomy ; methods ; Pancreatic Neoplasms ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy ; Retrospective Studies ; Splenectomy ; Survival Rate ; Treatment Outcome

Objective To evaluate the reliability, validity and sensitivity of a Family Burden Scale (FBS) of disease used on schistosomiasis. Methods 224 schistosomiasis patients were investigated, using the FBS. Reliability was estimated by Cronbach's α coefficient and split-half reliability. Validity was tested by factor analysis. Sensitivity was evaluated by comparison of patients with different income levels. Results The Cronbach's α coefficient was 0.874 and split-half reliability was 0.939 for FBS, respectively. Most values of Cronbach's α and split-half reliability for each component of scale were above 0.70. Construct validity was appraised by factor analysis, and 6 factors were identified. These factors could explain 66.76 % of the total variance. Patients with different income levels showed significant difference in terms of family burden for schistosomiasis (P<0.001 ). Conclusion This FBS appeared to have satisfactory reliability, validity and sensitivity and could be used in evaluating family burden of schistosomiasis patients.

OBJECTIVETo detect changes of serum soluble Apo-1/Fas (sApo-1/Fas) in pancreatic cancer patients and to investigate its clinical value in assessing the effect of chemotherapy.

METHODSThe serum level of sApo-1/Fas in 30 normal control subjects and 58 pancreatic cancer patients were detected using enzyme-linked immunosorbent assay (ELISA), and the sApo-1/Fas level of 48 pancreatic cancer patients, before and after chemotherapy was compared.

RESULTSCompared with the level of the control group, the level of serum soluble Apo-1/Fas was significantly correlated with clinical stage but not with age, sex or pathologic type of pancreatic cancer. It was elevated gradually from stage II to IV (P < 0.01). However, it would obviously decrease in pancreatic cancer patients after chemotherapy (P < 0.01).

CONCLUSIONThe serum soluble Apo-1/Fas may be involved in the development of pancreatic cancer, and it may be used as one parameter to assess the disease status and prognosis of pancreatic cancer patient.

Adenocarcinoma, Mucinous ; blood ; drug therapy ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Pancreatic Ductal ; blood ; drug therapy ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms ; blood ; drug therapy ; Prognosis ; Remission Induction ; fas Receptor ; blood

OBJECTIVETo investigate the pathological characteristics of heroin spongiform leukoencephalopathy (HSLE).

METHODSCerebral tissue specimens were obtained from 15 patients with HSLE and the histological observations under optical and electron microscopes were carried out by HE, Bielschowsky's, and chromotrope 2R-brilliant green staining.

RESULTSHSLE was characterized primarily by spongiform vacuolar degeneration of the cerebral white matter. Neurons in the gray matter, Purkinje and granular cells in the cerebella remain intact in all the cases. Numerous vacuoles, which merged to form larger cavities, appeared in the damaged white matter, and the axons survived in the deep white matter. The myelin sheath in the cerebellar white matter sustained more severe damages than those in the cerebral white matter. No vacuoles or lymphocyte infiltration occurred in the small peripheral vessels.

CONCLUSIONHSLE is pathologically characterized by vacuolar degeneration due to primary damage of the myelin, and the spongiform vacuolar degeneration is closely associated with the severity of demyelination in the white matter.

Adult ; Autopsy ; Canavan Disease ; etiology ; pathology ; Cerebellum ; chemistry ; pathology ; ultrastructure ; Cerebral Cortex ; chemistry ; pathology ; ultrastructure ; Female ; Heroin Dependence ; complications ; Humans ; Male ; Microscopy, Electron ; Middle Aged ; Neurons ; chemistry ; pathology ; Purkinje Cells ; chemistry ; pathology ; Staining and Labeling ; methods ; Young Adult

OBJECTIVETo study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS).

METHODSOne hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants.

RESULTSThe incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05).

CONCLUSIONSTrace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.

Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glomerular Mesangium ; immunology ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulin M ; analysis ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Nephrosis, Lipoid ; drug therapy ; immunology ; Retrospective Studies