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Biomedical subjects

K J Chang

Publications and source records attributed to K J Chang.

At least 19 recordsLinked to original sources
PubMed1998

Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan (area of low incidence but early onset).

We have examined the role of the breast cancer susceptibility genes BRCA1 and BRCA2 and other loci in the vicinity of these 2 genes on the long arms of chromosomes 17 and 13 (17q and 13q) for the presence of genomic deletions in breast cancer among Taiwanese women. Breast cancer in Taiwan is particularly characterized by its low incidence rate and its early age of tumor onset. Twelve microsatellite markers spanning the region 17q12-21 and 8 microsatellite markers spanning the region 13q12-14 were analyzed for allelic loss or loss of heterozygosity (LOH) in 90 patients with primary infiltrating ductal carcinoma. Compared with the background LOH level (10-12%) estimated by LOH at 4 unrelated loci, 17 markers (11 at 17q and 6 at 13q) demonstrated a significantly increased frequency (21-42%) of allelic loss (p < 0.05). Subsequent construction of deletion maps based on LOH at these significant loci localized the 6 smallest regions of overlap, including those harboring BRCA1, BRCA2, the retinoblastoma gene and 3 novel regions (the 1st located approximately 0.5 to 1 cM telomeric to BRCA1, the 2nd centromeric to BRCA1 flanked by D17S857/D17S846 and the 3rd closely adjacent to BRCA2), suggesting sites of susceptibility genes. Allelic loss at BRCA1 and BRCA2 was specifically associated with poorly differentiated tumors.

Aged↗
PubMed1998

Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in invasive ductal carcinoma of the breast in Taiwan.

To evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) in breast cancer, an immunohistochemical assay was performed in 150 patients with invasive ductal carcinomas. The PCNA labeling index (PCNA-LI) was classified into two subgroups at a cut-off point of 45% that gave the best prognostic estimates for PCNA in survival analyses. Seventy-eight tumors had a low PCNA-LI of < or =45% and 72 tumors had a high PCNA-LI of >45%. A high PCNA-LI correlated significantly with p53 overexpression (P<0.03), positive axillary node (P<0.04), short disease-free survival (P<0.001) and overall survival (P<0.0002), but not with other factors. In multivariate analysis, the PCNA-LI predicted the disease-free (P<0.008) and overall survival (P = 0.0007) independently. Our study indicates that the PCNA-LI has independent prognostic value.

Adult↗
PubMed1998

Distribution of the cadherin-catenin complex in normal human thyroid epithelium and a thyroid carcinoma cell line.

E-cadherin is the major cell-cell adhesion molecule expressed by epithelial cells. Cadherins form a complex with three cytoplasmic proteins, alpha-, beta-, and gamma-catenin, and the interaction between them is crucial for anchoring the actin cytoskeleton to the intercellular adherens junctions. The invasive behavior of cancer cells has been attributed to a dysfunction of these molecules. In this study, we examined the distribution of the cadherin-catenin complex in a Chinese human thyroid cancer cell line, CGTH W-2, compared with that in normal human thyroid epithelial cells. In the normal cells, using immunofluorescence staining, E-cadherin and alpha-, beta-, and gammm-catenin were found to be localized at the intercellular junction and appeared as 135, 102, 90, and 80 kD proteins on Western blots. In CGTH W-2 cells, no E-cadherin and gamma-catenin immunoreactivity was detected by immunofluorescence or Western blotting; alpha- and beta-catenin were detected as 102 and 90 kD proteins on blots but gave a diffuse cytoplasmic immunofluorescence staining pattern in most cells, while beta-catenin was also distributed throughout the cytoplasm in most cells but was found at the cell junction in some, where it colocalized with alpha-actinin. The present data indicate that the loss of cell adhesiveness in these cancer cells may be due to incomplete assembly of the cadherin-catenin complex at the cell junction. However, this defect did not affect the linkage of actin bundles to vinculin-enriched intercellular junctions.

Actinin↗
PubMed1998

Oral contraceptives and breast cancer risk in Taiwan, a country of low incidence of breast cancer and low use of oral contraceptives.

One hundred and seventy four (81% of all) pathologically confirmed new incident cases of female breast cancer identified from a medical center in Taipei from February, 1993 to June, 1994 were selected as the case group. Four hundred and fifty three inpatient controls who were without obstetric-gynecological, breast, or malignant diseases were individually matched for each case by age and date of admission. Information was obtained through direct interview and review of medical records. Conditional logistic regression was used to estimate the effects of each risk factor. After adjusting for education level, body mass index, age at menarche and first full-term pregnancy, parity, menopausal status and age at menopause, lifetime lactation, use of lactation inhibition hormones, and family history of breast cancer, breast cancer risk significantly elevated in use of OC before 25 years old and before 1971. In stratified analysis, significantly higher risk were found in OC use before 25 years old and in duration of use less than one year among post-menopausal subjects. Our results support the notion that OC use in early life for younger women and in early calendar years increase breast cancer risk.

Age Factors↗
PubMed1998

In situ detection of Epstein-Barr virus in breast cancer.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and some lymphoepithelioma-like carcinomas from other anatomic sites. This study investigates the presence of EBV in breast cancer. Immunohistochemistry for EBV proteins (EBV nuclear antigen-2 and latent membrane protein-1) and in situ hybridization for EBV-encoded small nuclear RNAs (EBER-1 and -2) were performed in 60 invasive breast cancers. None of the 60 breast cancer samples showed detectable EBV. These results suggest that EBV may not play a significant role in the etiology of breast cancers in Taiwan.

Adult↗
PubMed1998

Taurine protects the liver against lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis.

The purpose of this study was to determine the effects of taurine supplementation on both hepatic morphological changes and the extent of hepatic lipid peroxidation and membrane disintegration during rat hepatocarcinogenesis. Sprague Dawley rats were fed high fat diets containing 15% corn oil and were maintained on drinking water with or without 1% taurine. Two weeks after the appropriate feeding regimen, hepatocarcinogenesis was induced by a modification of the Solt and Farber method. This involved a 8 week protocol, including diethylnitrosamine initiation, 3 weeks of 2-acetylaminofluorene feeding and finally a 70% partial hepatectomy. Morphological changes of the hepatocyte were observed by transmission electron microscopy (TEM). Hepatocytes of the carcinogen-treated rat not exposed to taurine contained normal nuclei, but the endoplasmic reticulum (ER) and the mitochondria (Mi) were almost destroyed. By contrast, although the hepatocytes from the taurine supplemented group contained some irregular contour nuclei, the ER and Mi were normal. In the carcinogen-treated groups, lipid peroxidation was decreased because of the activation of several detoxifying enzymes. Glutathione S-transferase (GST) activity increased in the carcinogen-treated groups but less so in the group supplemented with taurine before treatment with the carcinogen. In the group supplemented with taurine prior to treatment with the carcinogen, glutathione peroxidase (GPx) activity was higher than in the carcinogen-treated group lacking taurine exposure. Consistent with the severe destruction to the membrane in the carcinogen-treated rats, hepatic glucose-6-phosphatase (G6Pase) activity, an index of membrane stability, was also decreased. However, both the fall in G6Pase activity and the degree of membrane damage was reduced in the carcinogen-treated animals receiving oral taurine. These results suggest that taurine appears to inhibit lipid peroxidation, to alter the activity of the defense enzymes and to protect the liver against membrane disintegration during rat hepatocarcinogenesis.

Animals↗
PubMed1998

Effects of taurine supplementation on lipid peroxidation, blood glucose and blood lipid metabolism in streptozotocin-induced diabetic rats.

The purpose of this study was to determine the effect of taurine on several complications of diabetes, including oxidative stress, glucose intolerance and blood lipid profile. Sprague Dawley male rats were fed an experimental diet for 7 weeks, at which time they were maintained on drinking water with or without 1% taurine. The experimental period was 7 weeks and the rats were administered streptozotocin (STZ) to induce diabetes. Thiobarbituric acid reactive substances (TBARS) content was increased following the STZ injection, but was lowered by prior treatment with taurine. The primary diabetic symptoms, such as polydipsia and polyuria, were ameliorated in rats supplemented with taurine before the STZ injection. Plasma triglyceride (TG) levels of the diabetic group were decreased by taurine supplementation, although plasma total cholesterol (T-chol) and HDL cholesterol (HDL-chol) were not different among the groups. LDL cholesterol (LDL-chol) levels of the control group were significantly decreased by taurine supplementation, however, the time of taurine administration affected the response of the diabetic group; only diabetic rats treated with taurine after the administration of STZ showed a decrease in LDL cholesterol. Therefore, taurine inhibits lipid peroxidation and decreases blood TG and LDL-chol levels, however, the time and dose of taurine supplementation are variables that need to be considered in the treatment of diabetes.

Animals↗
PubMed1998

Abdominal sonography screening of clinically diagnosed or suspected appendicitis before surgery.

We conducted a prospective study to evaluate the value of abdominal sonography in the diagnosis of acute appendicitis and determine the need for abdominal sonography before operation. Altogether 191 patients with clinically diagnosed or suspected appendicitis underwent an abdominal sonography examination performed by a staff surgeon before operation. The sonographic findings are classified into three categories: appendicitis, other diseases, or normal screening. A total of 158 patients (82.7%) with positive findings of appendicitis proceeded to surgery; 18 patients (9.4%) were found to have other diseases, and they were treated for their conditions; and 15 patients (7.9%) with normal screening were discharged from the hospital and were reevaluated 2 weeks later. Only one patient had a false-negative finding. Of the 158 patients undergoing operation, 143 (90.5%) were proved to have appendicitis by the pathologic reports. A total of 32 negative appendectomies (16.8%) were prevented after sonographic examination. Abdominal sonography for detecting acute appendicitis had a sensitivity of 99.3%, a specificity of 68.1%, an accuracy of 91.6%, a positive predictive value of 90.5%, and a negative predictive value of 97.0%. The value of meticulous history-taking, physical examination, and laboratory tests cannot be overemphasized. Our experience suggests that patients with clinically diagnosed or suspected acute appendicitis should routinely undergo abdominal sonography examination, performed by an experienced surgeon, to further decrease the negative appendectomy rates.

Acute Disease↗
PubMed1998

High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers.

High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.

Adult↗
PubMed1998

Overexpression of p53 predicts shorter survival in diffuse type gastric cancer.

BACKGROUND: It has been suggested that p53 plays an important part in gastric carcinogenesis but the data remain inconclusive. METHODS: Alteration of the tumour suppressor gene p53 was prospectively investigated by immunohistochemistry in 168 primary gastric cancers. RESULTS: Positive staining, indicative of gene mutations, was detected in 34 tumours (20.2 per cent). No correlation was observed between expression of p53 and various clinicopathological factors, including age, sex, tumour site, gross type, tumour size, depth of invasion, lymph node metastases, distant metastases, and tumour node metastasis stage. However, p53 overexpression was different between intestinal and diffuse type gastric cancer. Survival analysis revealed a significant survival disadvantage of p53 expression in diffuse type gastric cancer (P=0.039) but not in the intestinal type. Multivariate analysis of all 168 patients revealed that independent predictors of recurrent disease included age, invasion depth and nodal involvement but not p53 expression. CONCLUSION: The presence of p53 overexpression may identify a subset of more aggressive tumours with a poor prognosis in diffuse type gastric cancer.

Adenocarcinoma↗
PubMed1998

Water-soluble contrast study predicts the need for early surgery in adhesive small bowel obstruction.

BACKGROUND: The optimal period of conservative treatment for adhesive small bowel obstruction remains controversial. This study sought to determine whether a 24-h abdominal radiograph after oral Urografin is a reliable indicator for operation in patients with adhesive small bowel obstruction. METHODS: One hundred and sixty-one patients who suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene underwent a Urografin study. Some 40 ml Urografin mixed with 40 ml distilled water was administered either orally or via a nasogastric tube to each patient. Serial plain abdominal radiographs were taken 4, 8, 16 and 24 h later. If an earlier plain radiograph showed that contrast medium had reached the ascending colon, subsequent radiographs were not taken. RESULTS: Contrast medium reached the colon within 24 h in 112 patients (70 per cent). These patients were all treated successfully with non-operative methods. Contrast medium was not observed in the colon within the first 24 h in 49 patients (30 per cent). Operation was performed in 47 of these patients and non-operative treatment was given in two. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of Urografin reaching the colon within 24 h as an indicator for non-operative treatment were 98, 100, 99, 100 and 96 per cent respectively. CONCLUSION: All patients with evidence of Urografin reaching the colon within 24 h were treated successfully with non-operative methods. The results of this prospective study suggest that patients with adhesive intestinal obstruction in whom contrast medium fails to reach the colon within 24 h should receive prompt surgical intervention.

Adult↗
PubMed1998

Accuracy of auscultation in the detection of haemopneumothorax.

OBJECTIVE: To assess the accuracy of auscultation in the detection of haemopneumothorax. DESIGN: Prospective study. SETTING: University hospital, Taiwan. PATIENTS: 148 patients with chest injuries admitted between July 1994 and August 1996. MAIN OUTCOME MEASURES: Correlation between the results of auscultation and radiographic findings in 148 patients with injuries to the chest. 83 (56%) had internal injuries, of whom 38 had pneumothoraces, 24 haemothoraces, and 21 haemopneumothoraces. RESULTS: Auscultation had a sensitivity of 84%, a specificity of 97%, an accuracy of 89% and a positive predictive value of 97% in the detection of these injuries. CONCLUSIONS: Auscultation is not as accurate as chest radiography. Chest tubes can be inserted before chest radiography in patients in whom auscultation has indicated an injury. A chest radiograph is essential in those patients with normal breath sounds to exclude a haemopneumothorax that had been missed by auscultation.

Adolescent↗
PubMed1998

Tissue plasminogen activator reduces intraperitoneal adhesion after intestinal resection in rats.

We investigated whether tissue plasminogen activator (tPA), a plasma serine protease that catalyzes the initial and rate-limiting step in fibrinolysis, inhibits postoperative intraperitoneal adhesion formation in rats. Male Wistar rats weighing 200 to 250 g underwent laparotomy with a 15-cm intestinal resection and reanastomosis; the intestinal serosa was scratched to induce adhesion formation. The rats were divided into three groups: the control group received no medication; the normal saline group received peritoneal irrigation with 6 mL normal saline intraoperatively; and the tPA group received peritoneal irrigation with 6 mL tPA solution (5 mg/L) intraoperatively. The rats were killed 7 or 14 days later. The scores (severity of adhesion, 0-3 point scale), strength, and extent of fibrous bands were recorded on the day the rats were killed. Wound strength was measured using an Instron tensionmeter immediately after the rats were killed. The concentrations of plasma tPA and plasminogen activator inhibitor (PAI)-1 and -2 were measured. The scores and strength of fibrous bands in the tPA group were lower than those in the control and saline groups whereas wound strength was similar in all groups. The plasma tPA concentration was significantly higher and the plasma PAI-1 and PAI-2 concentrations were significantly lower in the tPA group than in the control and saline groups on the 7th and 14th postoperative days. Our findings suggest that tPA can reduce the incidence of postoperative intraperitoneal adhesions without impairing wound healing.

Animals↗