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Liang Wang

Publications and source records attributed to Liang Wang.

98 records · Page 6Linked to original sources
PubMed2002

Isolation and characterization of androgen receptor mutant, AR(M749L), with hypersensitivity to 17-beta estradiol treatment.

Estrogens, primarily 17beta-estradiol (E(2)), may play important roles in male physiology via the androgen receptor (AR). It has already been shown that E(2) modulates AR function in LNCaP prostate cancer cells and xenograft CWR22 prostate cancer tissues. Using a molecular model of E(2) bound-AR-ligand binding domain (LBD) and employing site-directed mutagenesis strategies, we screened several AR mutants that were mutated at E(2)-AR contact sites. We found a mutation at amino acid 749, AR(M749L), which confers AR hypersensitivity to E(2). The reporter assays demonstrate that E(2) can function, like androgen, to induce AR(M749L) transactivation. This E(2)-induced AR mutant transactivation is a direct effect of the AR(M749L), because the transactivation was blocked by antiandrogens. The hypersensitivity of AR(M749L) to E(2) is not due to increased affinity of AR(M749L) for E(2), rather it may be due to the existence of the proper conformation necessary to maintain E(2) binding to the AR-LBD long enough to result in E(2)-induced transactivation. AR(M749L) transactivation can be further enhanced in the presence of AR coregulators, such as ARA70 and SRC-1. Therefore, amino acid 749 may represent an important site within the AR-LBD that is involved in interaction with E(2) that, when mutated, allows E(2) induction of AR transactivation.

Animals↗
PubMed2002

Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase.

The androgen receptor (AR) controls several biological functions including prostate cell growth and apoptosis. However, the mechanism by which AR maintains its stability to function properly remains largely unknown. Here we show that Akt and Mdm2 form a complex with AR and promote phosphorylation-dependent AR ubiquitylation, resulting in AR degradation by the proteasome. The effect of Akt on AR ubiquitylation and degradation is markedly impaired in a Mdm2-null cell line compared with the wild-type cell line, suggesting that Mdm2 is involved in Akt-mediated AR ubiquitylation and degradation. Furthermore, we demonstrate that the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation. These results suggest that phosphorylation-dependent AR ubiquitylation and degradation by Akt require the involvement of Mdm2 E3 ligase activity, a novel mechanism that provides insight into how AR is targeted for degradation.

Animals↗
PubMed2002

Synthesis and cytotoxicity of 2alpha-amido docetaxel analogues.

Various 2-amido docetaxel analogues were prepared and evaluated for their cytotoxicities. Among them, m-methoxy and m-chlorobenzoylamido analogues were most active but not superior to docetaxel and paclitaxel, and D-seco analogues inactive. Change of 2-benzoate to 2-benzamide may not improve their activities to drug-resistant cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Analysis of the RNASEL gene in familial and sporadic prostate cancer.

The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (chi(2) trend test = 1.42; P=.23) or the Asp541 variant (chi2=1.52; P=.22). However, significant differences were detected for the Arg462Gln genotypes (chi2=5.20; P=.02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32-0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis </=64 years) (P=.0008; OR=0.29; 95% CI = 0.13-0.66), in node-negative patients (P=.01; OR=0.48; 95% CI 0.27-0.84), patients with stage T(1)/T(2) disease (P=.008; OR=0.39; 95% CI 0.2-0.75), and patients with low-grade disease (P=.01; OR=0.40; 95% CI 0.20-0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (chi2=4.82; P=.03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

Adult↗
PubMed2002

[Correlation of invasion, metastasis, and prognosis in low and middle rectal cancer].

BACKGROUND & OBJECTIVE: Several reports have showed that three histologic variables (venous invasion, regional lymph node status, and depth of primary tumor penetration) were associated with the prognosis of colorectal adenocarcinoma patients. Based on these variables, a new classification system has been recommended. This study was designed to evaluate prognostic significance and risk factors of neoplasm in low and middle rectal cancer. METHODS: Four hundreds and eighty-four consecutive patients with low and middle rectal cancer were treated by the abdominoperineal resection (APR) (356 patients) and the low anterior resection(LAR) (128 patients) between 1990 and 1996. To determine the independent prognostic variables, the variables were evaluated both univariately and multivariately from the perspectives of oncologic outcome. RESULTS: The 5-year survival rate for all patients was 71.1% (344/484), 63.5% (226/356) for APR and 92.2% (118/128) for LAR/SSR, respectively (P < 0.01). The resulting multivariate analysis using Cox regression showed that the three tumor variables were significantly associated with the 5-year survival (P < 0.01), the independent prognostic variables included venous invasion, tumor size, and TNM stages. CONCLUSIONS: The three tumor variables identified in multivariate analysis as bearing the strongest independent effect on the 5-year survival in low and middle rectal cancer were (in order to decrease prognostic impact) venous invasion, tumor size, and TNM stages. These three tumor variables may be used as important bases for a new classification system.

Adenocarcinoma↗
PubMed2002

[Study on low density lipoprotein receptor of adult Schistosoma japonicum].

OBJECTIVE: To provide a theoretical basis for the study of vaccines against Schistosoma japonicum, the receptor for human LDL in the tegument of adult Schistosoma japonicum was investigated. METHODS: Proteins existed in adult Schistosoma japonicum membrane were extracted by Triton X-100 and purified through reverse-phase high performance liquid chromatography (HPLC), and the main protein peaks were then collected separately. 125I-LDL of human plasma as the ligand, through the radioautography and radioligand binding assay, the protein which can bind human serum 125I-LDL specifically was identified. The molecular weight and IEF were detected by SDS-PAGE. RESULTS: According to the radioautography and radioligand binding assay, a protein with retention time of 10.5 min was proved to be able to bind human serum 125I-LDL specifically. SDS-PAGE revealed that the molecular weight of the purified protein is 60-65 kDa, and its IEF is 6.7. CONCLUSION: LDL binding protein may exist on the surface of both male and female adult Schistosoma japonicum with the function of obtaining cholesterol from host circulating system.

Animals↗
PubMed2002

Iatrogenic extrahepatic bile duct injury in 182 patients: causes and management.

OBJECTIVE: To describe the causes and treatment of iatrogenic bile duct injury caused by cholecystectomy. METHODS: 182 patients with iatrogenic extrahepatic bile duct injury from 4 university hospitals of China were reviewed. Details of primary cholecystectomy, biliary reconstruction as well as postoperative management were recorded. All patients were followed up for at least 6 months (6 months to 9 years, median 3.5 years). The adequacy of repair was assessed by regular evaluation of the patients' clinical status and liver function variables. Hepatobiliary B-ultrasonography was used routinely in the follow up of patients, and magnetic resonance cholangiopancreatography was applied in the patients suggestive of abnormality. RESULTS: In 152 patients, bile duct injury happened during open cholecystectomy, and in 30 patients during laparoscopic cholecystectomy. All the injuries developed during anterograde cholecystectomy (at the Calot's triangle). All the patients with these injuries underwent choledochocholedochostomy or Roux-en-Y choledochojejunostomy with good results (161 patients), recurrent stricture (11), and death (10). CONCLUSIONS: During cholecystectomy, the Calot's triangle should be identified anatomically, but retrograde cholecystectomy is the optimal choice. Bile duct injury should be discovered as soon as possible and be managed timely. Different operative methods are optional according to the degree of injury and the postoperative period.

Adult↗