Biomedical subjects

D Wan

Publications and source records attributed to D Wan.

At least 19 recordsLinked to original sources

PubMed2001

A novel growth suppressor gene on chromosome 17p13.3 with a high frequency of mutation in human hepatocellular carcinoma.

Previous studies have shown that there is a high frequency of loss of heterozygosity (LOH) on chromosome 17p13.3 in hepatocellular carcinoma [HCC (M. Fujimori et al., Cancer Res., 51: 89-93, 1991; H. Nagai et al., Oncogene, 14: 2927-2933, 1997; V. Boige et al., Cancer Res., 57: 1986-1990, 1997; Z. Piao et al., Int. J. Cancer, 75: 29-33, 1998; and B. Charroux et al., J. Cell Biol., 148: 1177-1186, 2000)]. The minimum region of LOH on chromosome 17p13.3 in HCC has been defined within the region between D17S643 and D17S1574. Moreover, D17S926 in the minimum region of LOH has the highest frequency of LOH, and its sequencing analysis has been accomplished. In this region, 6 of 13 novel genes have been characterized (X. Zhao, D. Wan, M. He, Yu. Ye, Yi. He, L. Han, M. Guo, Y. Huang, W. Qin, M-W. Wang, W. Chong, J. Chen, L. Zhang, N. Yang, B. Xu, M. Wu, L. Zuo, and J. Gu. A high frequency LOH region on chromosome 17p13.3 in human HCC with densely clustered genes identified, submitted for publication). Here we describe the cloning and characterization of one of these novel genes, designated HCC suppressor 1 (HCCS1), located at this region. HCCS1 had 18 exons, and its full-length cDNA was 2.0 kb. The protein expression product of HCCS1 was located in mitochondria. HCCS1 had a high frequency of mutations in HCC samples, whereas no alteration has been found in matched noncancerous liver tissues. Immunohistochemistry revealed a significantly higher expression of HCCS1 in the noncancerous liver tissues (33 of 35 samples) than in the HCC samples (2 of 35 samples). Transfection of HCCS1 cDNA into the HCC cell line remarkably reduced the efficiency of its colony formation and inhibited tumor growth in nude mice. Taken together, these findings strongly suggest a potential role of HCCS1 as a HCC putative suppressor gene.

3T3 Cells↗

PubMed2001

Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma.

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

Adult↗

PubMed2001

[Expression level of c-erbB-2 protein correlates with the prognosis of patients with colorectal cancer].

OBJECTIVE: To study the expression level of c-erbB-2 gene in colorectal cancer and its correlation to prognosis. METHODS: In 173 colorectal carcinoma patients, c-erbB-2 protein was examined immunohistochemically and patients' prognosis was evaluated by retrospective analysis combined with follow-up data. RESULTS: The immunohistochemical staining of c-erbB-2 protein was found in the cytoplasm and membrane with a positive rate of 52% in tumor tissue. The 1-, 3-, 5- and 10-year survival rate of patients with negative c-erbB-2 expression was 98.7%, 92.4%, 87.1% and 84.1% respectively; that of the patients with weakly positive c-erbB-2 expression was 94.5%, 76.1%, 72.3% and 68.3%, respectively. In contrast, that of patients with strongly positive c-erbB-2 expression was 91.0%, 43.5%, 36.8% and 23.4%, respectively. The survival rates among the three groups of patients were statistically different. Multivariate survival analysis by Cox regression model showed that c-erbB-2 expression level was a risky prognostic factor for colorectal cancer. CONCLUSION: The expression level of c-erbB-2 protein is an independent prognostic factor in colorectal carcinoma.

Adult↗

PubMed2001

[Distal intramural spread of rectal cancer studied on large slices].

OBJECTIVE: To study the length of distal intramural spread of rectal cancers, and provide evidence for anal-preserving operations. METHODS: Specimens of ninety-eight patients with rectal cancers who had been operated from August, 1996 to October, 1997, were collected and their large pathologic slices examined. The length of intramural spread distal to rectal cancers was measured under light microscope. The actual length of spread in live conditions was estimated according to equal proportional shrinkage. RESULTS: In 48 of the 98 patients, distal intramural spread of the tumor was observed. The length of spread varied from 0.1 cm to 2.5 cm. In 77% of the 48 patients, the length of tumor spread was < 0.5 cm. In only 5 patients was the distance of spread > or = 1.0 cm. Four different ways of tumor invasion were observed: contiguous, lymphatic, neural and venous invasion. Distal intramural spread could be via mucosa, submucosa, inner circular muscular layer, outer longitudinal muscular layer or serosa, either separately or concomitantly. CONCLUSION: Distal intramural spread of rectal cancers can be detected in about 1/2 of the specimens examined on large pathologic slice. In most of them the distance of spread is < 0.5 cm. Occasionally it may be > or = 1 cm. To set the edge of resection > or = 3 cm distal to the rectal cancers is relatively safe in anal-preserving operations.

Colorectal Neoplasms↗

PubMed2001

[Surgical management for colon cancer complicated with acute obstruction].

OBJECTIVE: To evaluate the feasibility of tumor resection and stage-I anastomosis for colon cancer complicated with acute obstruction. METHODS: Seventeen colon cancer patients complicated with acute obstruction admitted from 1994-1998 into our hospital, together with 1,872 cases collected from 40 reports published in the same interval in China, a total of 1,889 cases were analyzed as to the results of their surgical management. RESULTS: In the whole group, there was an incidence of 3.1% anastomotic leak, 6.6% wound infection and 1.1% pulmonary infection. Ninety-three patients died of operation with an operation mortality of 4.9%. Postoperative 5-year survival rate was 26.0%-48.0% in patients with stage-I operation. It was 20.0%-38.0% in staged operation. CONCLUSION: Tumor resection with stage-I anastomosis for colon cancer complicated with acute obstruction is acceptable giving relatively satisfactory results. Technique, bowel cleansing during the operation, rational use of antibiotics and adherence to proper indications are crucial for stage-I operation.

Acute Disease↗

PubMed2000

[Analysis on loss of heterozygosity of chromosome 17p13.3 in hepatocellular carcinoma and construction of genomic contig in the deleted region].

OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 17p13.3 in hepatocellular carcinoma (HCC) and determine a minimum region of LOH as well as construct genomic contig in LOH region. METHODS: Variable number tandem repeat (VNTR) and RFLP markers examined by Southern hybridization were used to detect LOH of HCC. Microsatellite markers amplified by PCR were detected for LOH by denatured PAGE. Using microsatellite primers, 3 rounds of PCR amplification were carried out to screen positive genomic clones. The contig was constructed by PCR detecting the reaction between microsatellite markers and individual genomic clone. RESULT: Fifty-four paired HCC samples were analysed with 16 polymorphic markers on chromosome 17p13.3. The data revealed that the region between D17S5 and D17S34 had a high rate of LOH (> 63%), but three markers (proximal to D17S5) toward centromere had low or no LOH. TP53 marker on chromosome 17p13.1 had a LOH rate of 31% which was lower than that on D17S5-D17S34 region. No LOH was found at D17S34, D17S1866 (proximal to telomere) and D17S5, D17S1574 (distal to telomere) in 2 cases of HCC. However, there was LOH between D17S849 and D17S1574 in some cases. In LOH region, genomic clones relative to 18 of markers were obtained. A contig covering 9 markers was constructed. CONCLUSION: Determination of the minimum LOH region on chromosome 17p13.3 in HCC and the construction of genomic clone contig provide basis for further identification of putative new tumor suppressor gene(s) in HCC.

Carcinoma, Hepatocellular↗

PubMed2000

[Correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE and eosinophilic cation protein].

OBJECTIVE: To explore the correlation of asymptomatic bronchial hyperresponsiveness with serum specific IgE(sIgE) and eosinophilic cation protein(ECP). METHODS: Histamine inhalation provoking test (quantitative method) was used in a survey for bronchial responsiveress in 1,123 students aged between 11 to 14 years old, 41 individuals with asymptomatic bronchial hyperresponsiveness received further test for sIgE and ECP. 31 students with normal bronchial responsiveness were randomly selected as the control. RESULTS: 4%(41/1,123) of the students showed bronchial hyperresponsiveness. The incidence of bronchial hyperresponsiveness with family history of asthma (11/14, 79%) was higher than that without a family history (30/1,109, 3%), with statistical significance (P < 0.005). The positive rates for sigE (90%, 37/41, P < 0.01) and ECP (17%, 7/41, P < 0.05), sIgE q value (14.3 +/- 12.1) micrograms/L, (P < 0.01) and ECP value (44.3 +/- 60.2) micrograms/L, (P < 0.01) in asymptomatic bronchial hyperresponsiveness group were higher than those of the control with statistical significance. His PD20-FEV1 was negatively related to aIgE q value (P < 0.05) and not related to ECP (P > 0.05). CONCLUSION: The asymptomatic bronchial hyperresponsiveness was closely related to allergy but not to ECP. Those with a family history of asthma, or with positive sIgE should be followed.

Adolescent↗

PubMed2000

[Expression of nm23 protein and estrogen receptor and prognosis of colorectal cancers].

OBJECTIVE: To explore the relationship between clinicobiological action and expression of nm23 protein and estrogen receptor (ER) for colorectal cancer. METHODS: The expression of nm23 protein and ER for 209 cases of colorectal cancer was detected by immunohistochemistry assay (LSAB). RESULTS: The expression of nm23 protein was correlated with that of ER for colorectal cancer (r = 0.5319, P < 0.01). The expression of nm23 protein and ER in colorectal cancers was not related with patient's age, sex, tumor position, pathological type, histological type, and Dukes stage (r < 0.4, P > 0.05). The expression was related with the prognosis of colorectal cancer (P < 0.01). The higher the expression of nm23 protein and/or ER the better the prognosis, whereas the less the expression of nm23 protein and/or ER the worse the prognosis. CONCLUSIONS: The abnormal expression of nm23 protein is correlated with the disturbance of estrogen metabolism in colorectal cancer. The detection of nm23 protein and ER is helpful for the diagnosis and prognostic evaluation of colorectal cancer.

Adult↗

PubMed1999

[Successful treatment of AML by HLA-compatible sibling umbilical cord blood stem cell transplantation--the first case report in China].

OBJECTIVE: To apply umbilical cord blood stem cell transplantation (UCBSCT) to the treatment of hematological malignancies, and to observe the persistent hematopoietic reconstitution, graft-versus-host disease (GVHD) and transplantation-related complications. METHODS: An 11-year-old patient with acute myeloid leukemia in complete remission (CR) received UCBSCT from a HLA-compatible sibling. The conditioning regimen was BU/CY (busulfan 4 mg.kg-1.d-1 x 4, cyclophosphamide 60 mg.kg-1.d-1 x 2). CsA was given for prophylaxis of acute GVHD. The patient received 0.35 x 10(8) nucleated cells/kg, including 1.82 x 10(4) CFU-GM/kg and 2.04 x 10(5) CD34+ cells/kg. RESULTS: The recipient showed hematopoietic reconstitution on day 14 post-transplantation; ANC > 1.0 x 10(9)/L on day 21; DNA fingerprinting showed engraftment on day 60, the blood type of the patient changed from O group to B group. In the follow-up of 330 days, the patient was in good condition without acute or chronic GVHD. CONCLUSION: It is the first case reported in China that have succeeded in the treatment of acute myeloid leukemia by allogeneic UCBSCT.

Blood Grouping and Crossmatching↗

PubMed1998

Prospective, randomized, controlled study of the effect of hormone replacement therapy on peripheral blood flow velocity in postmenopausal women.

OBJECTIVE: To investigate the effect of different types and methods of delivery of hormone replacement therapy (HRT) on peripheral vascular flow velocity in postmenopausal women. DESIGN: A prospective, randomized, operator-blinded, controlled study. SETTING: A hormone replacement clinic in a university teaching hospital. PATIENT(S): Sixty-eight women who had undergone surgical menopause. INTERVENTION(S): No treatment, oral estrogen, continuous combined estrogen and progestogen, or percutaneous estrogen. MAIN OUTCOME MEASURE(S): The pulsatility indices of the brachial, dorsalis pedis, popliteal, and radial arteries were measured under standardized conditions before the commencement of HRT and after 2 and 6 months of treatment. Serum E2 levels were measured at each visit. RESULT(S): There was an inverse correlation between the serum E2 levels and the pulsatility indices. There was a significant reduction in the pulsatility index in at least one of the four arteries after 2 months of HRT in all the treatment groups but not in the control group. The effect of HRT on the pulsatility index persisted until the completion of the study in all the treatment groups. CONCLUSION(S): These results confirm that the administration of HRT is associated with a reduction of the pulsatility index, and hence an increase in blood flow in the peripheral arteries; this change in the pulsatility index is related directly to serum E2 levels. The percutaneous route of administration of estrogen was at least as effective as oral treatment in improving peripheral vascular flow velocity. The beneficial effect of estrogen was not affected by the addition of a progestogen.

Adult↗

PubMed1998

[Telomerase activity in human gastric and colorectal cancer].

OBJECTIVE: To study telomerase activity in patients with gastric and colorectal cancer. METHODS: Telomerase activity in tumor samples, including 9 colonic, 20 rectal and 11 gastric carcinomas, was examined by telomeric repeat amplification protocol(TRAP) assay. Thirty-nine samples from tumor-adjacent tissues were also assayed. RESULTS: Ninety per cent(36 out of 40 tumor samples) exhibited telomerase activity regardless of tumor stage or differentiation. However, telomerase activity in the tumor-adjacent tissues could be detected only in 1 of 39 specimens. CONCLUSION: Telomerase may be a good diagnostic biomarker for tumor detection.

Adult↗

PubMed1998

[The relationship between nm23-H1 loss of heterozygosity and metastasis in hepatocellular carcinoma].

OBJECTIVE: To demonstrate the relationship between nm23-H1 loss of heterozygosity (LOH) and clinical pathological characteristics of hepatocellular carcinoma (HCC) from the DNA level. METHOD: Southern blot hybridization was used to analyze genomic DNA in liver cancer and its corresponding liver tissue. RESULT: nm23-H1 has diallelic bands at 7.6 Kb and 2.3 Kb. Allelic loss of heterozygosity in tumour tissues was detected in 31.25% patients (5 patients). LOHs were more common in the tumours with intrahepatic metastasis or portal vein tumour embolism and the tumours poorly differentiated (Edmondson's classification III, IV). CONCLUSION: nm23-H1 LOHs may induce the metastasis potential of HCC and help to predict recurrence and metastasis of HCC.

Carcinoma, Hepatocellular↗

PubMed1997

Predictors of successful external cephalic version at term: a prospective study.

OBJECTIVE: To investigate clinical and ultrasonographic predictors of outcome of external cephalic version at term. DESIGN: Prospective observational study. SETTING: University obstetric unit. POPULATION: All external cephalic versions performed over two years (n = 243). METHODS: Nineteen different clinical and ultrasonographic variables were recorded before each procedure. The ability of each of the 19 variables to predict the success or failure of external cephalic version was assessed by univariate analysis. The study population was then divided into two subgroups of 129 and 114 patients by random allocation using computer generated numbers. Logistic regression was performed in each subgroup to assess the relative importance and independence of the important variables. The derived regression models were then applied to the other subgroup of patients to assess accuracy and reproducibility. RESULTS: The overall success rate of the procedure was 69.5%. Both regression models identified the same three variables as independent predictors of failed versions: 1. presenting part engaged; 2. difficult to palpate the fetal head, and 3. a tense uterus on palpation. The two models correctly predicted 75.2% and 84.2% of outcomes in the other subgroup. If uterine tone, which was assessed after administration of tocolytic, was excluded from the analysis, the other two factors remained in the models, with the addition of nulliparity as a significant predictor of failed external cephalic version. The chance of success of external cephalic version in the original 243 women was found to be < 20% if two of these variables were present, 0% if all three were present, and 94% if none were present. CONCLUSIONS: The outcome of external cephalic version can be predicted by easily available clinical parameters.

Adolescent↗

PubMed1997

The implementation of external cephalic version at term for singleton breech presentation--how can we further increase its impact?

The overall incidence of breech presentation at delivery remained at 2 to 3% in a unit where external cephalic version (ECV) was the preferred treatment option for term singleton breech presentation. The objective of this study was to investigate which factors accounted for this high residual incidence, so that the impact of ECV could be further increased. All breech deliveries and ECVs over a 1-year period in a teaching hospital are reviewed. The incidence of term singleton breech delivery was 1.96% among 7,702 total deliveries. There were 115 patients counselled for ECV, of which 15.7% declined the offer and 4.1% went into labour before their scheduled ECV. Among the 93 ECVs performed, 74 were successful and 56 delivered vaginally in cephalic presentation. ECV was not performed in 131 cases. The major reasons were patients' refusal (13.7%), breech first diagnosed in labour or after rupture of membranes (44.3%), oligohydramnios or growth retardation (9.9%) and previous Caesarean section (8.4%). Only 5 patients were not counselled for ECV in the absence of contraindications. The practice of ECV reduced the overall Caesarean section rate by 0.65%, or 4.3% of the total number of Caesarean sections. In conclusion, ECV at term definitely reduces the Caesarean section rate. However, it is unlikely that the overall Caesarean section rate could be reduced by more than 1% even with 100% uptake of ECV unless the use of ECV is to be extended to those with prior Caesarean section, ruptured membranes, oligohydramnios, growth retardation or those who are in labour.

Breech Presentation↗

PubMed1997

[Identification of a novel gene overexpressed in hepatocellular carcinoma by differential hybridization].

OBJECTIVE: Searching for novel gene related to human hepatoma. METHODS: Twelve EST (expressed sequence tag) clones were examined with Northern blot analysis, looking for the gene(s) differentially expressed in hepatoma versus surrounding noncancerous hepatic tissue, and then compared with Gene Databases. RESULTS: Northern blot analysis showed that EST clone F9391 expressed at high level in all of the 6 hepatocellular carcinoma samples, but at low level in the surrounding noncancerous hepatic tissues and in 2 cases of normal liver tissues. Nucleotide sequencing indicated that this clone belonged to a novel gene that had not included in the Gene Databases (EMBL 96.6). CONCLUSION: F9391 gene is a novel gene overexpressed in hepatocellular carcinoma. Being related to cell proliferation, it might play an important role in liver oncogenesis. Forthermore, it may be used as a new marker for diagnosis and new target for treatment of hepatocellular carcinoma.

Base Sequence↗

PubMed1997

[Diagnosis and treatment of primary malignant tumors of the small bowel].

OBJECTIVE: To study the clinical characteristics, effective diagnostic methods and therapeutic measures of primary malignant tumors of the small bowel so as to improve therapeutic effect. METHODS: In this paper 75 cases of primary malignant tumors of the small bowel were analyzed. Survival rates were calculated with Life Table, and computer Cox multivariate analysis model was used for survival analysis. RESULTS: The most frequent clinical manifestations of primary malignant tumors of the small bowel were abdominal pain, abdominal mass, emaciation and intestinal obstruction. Gastrointestinal barium meal roentgenography was performed in 13 cases, with an accurate diagnostic rate of 84.6%. The 1-,3- and 5-year survival rate after radical resection was 87.5%, 68.7% and 48.1%, respectively, while that for palliative resection was 57.9%, 33.8% and 24.1%, respectively. The factors including age, histological type, tumor site and type of resection were selected into Cox model in survival analysis. CONCLUSION: For primary malignant tumors of the small bowel, gastrointestinal barium meal roentgenography is the most valuable method for diagnosis, and surgical radical resection is the most effective therapy. The significant prognostic factors are age, histological type, tumor site and type of resection. Chemotherapy had no effect on prognosis.

Adenocarcinoma↗

PubMed1997

[The partial cDNA cloning of a novel gene highly expressed in hepatocellular carcinoma].

OBJECTIVE: To search the novel gene related to human hepatoma. METHODS: Northern blot analysis was used to isolate from EST (expressed sequence tags) clones a cDNA fragment differentially expressed in hepatocellular carcinoma versus its surrounding noncancerous hepatic tissue. Human fetal liver cDNA library was screened with EST fragment probe. RESULTS: Northern blot analysis showed that EST clone F9391 expressed at high level in all the 6 hepatocellular carcinoma samples but low level in the surrounding noncancerous hepatic tissues and 2 normal liver tissues. In further screening of human fetal liver cDNA library, we obtained a positive clone named FL6. Nucleotide sequencing indicated that FL6 contained 1464 base pairs and the matched DNA sequence was not found in the gene data bases (EMBL 96.6). Northern blot analysis of various fetus tissues with FL6 probe showed a high level expression in lung, small intestine, skin and placenta, middle level expression in liver, stomach, colon and muscle but low level expression in brain, thyroid, thymus, heart, kidney, pancreas and bladder. CONCLUSION: The results suggested that FL6 gene related to cell proliferation and may play an important role in the process of oncogenesis.

Base Sequence↗

PubMed1996

[HP8: the partial cDNA clone of a novel member of C/EBP gene family].

OBJECTIVE: To explore the human C/EBP related genes. METHODS: Screening human placenta cDNA library with rat C/EBP cDNA probe. RESULTS: One positive clone, HP8 was obtained. This clone contained 1975 base pairs which include 604 coding base pairs. The matched DNA sequence was not found in the gene database (EMBL 95.6). The 201 amino acids encoded by this gene had the leucine zipper structure and demonstrated the highest homology (97%) with C/EBP throughout the DNA-binding domain and leucine repeat region (C-terminal 60 amino acids). Beyond this region, only low homology was detected in HP8 protein and C/EBP or C/EBP related proteins. Herewith, HP8 was defined as a novel member of C/EBP gene family. Genomic Southern blot analysis confirmed that HP8 was a single copy gene. Northern blot analysis in 14 different fetus tissues showed that high level of HP8 mRNA was expressed in small intestine and skin, middle level in adrenal gland, low level in liver, lung, kidney, thyroid gland and gallbladder. In 3 human adult liver tissues, only one low level HP8 mRNA, whereas of 5 hepatomas and one of their surrounding nontumorous hepatic tissues had, high level HP8 mRNA. CONCLUSION: These results suggested that HP8 gene might be a transactivator related to cell growth. As Northern blot analysis indicated, HP8 gene has about 2.7 Kb full length cDNA.

Adult↗