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Biomedical subjects

K J Chang

Publications and source records attributed to K J Chang.

At least 37 records · Page 2Linked to original sources

Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells.

PURPOSE: To determine whether an increase in tumor angiogenesis facilitates intravasation of colorectal epithelial cells, we compared intratumoral microvessel counts with the presence of circulating colorectal epithelial cells in the portal venous blood from patients with colorectal carcinomas. EXPERIMENTAL DESIGN: Circulating colorectal epithelial cells were detected by a reverse transcription-PCR assay to amplify guanylyl cyclase C (GCC) transcripts. The extent of tumor vascularization was quantitatively assessed by immunohistochemical staining with anti-CD31 antibody. RESULTS: Colorectal epithelial cells (as measured by GCC mRNA expression) were detected in the portal venous blood in 30 of 58 patients (52%). The mean (+/- SD) microvessel count in the tumors from patients with expression of GCC mRNA in their portal venous blood was 82.74 +/- 24.97. The corresponding values in the tumors from patients without expression of GCC mRNA in portal venous blood was 65.96 +/- 19. For each 10-microvessel increase per x200 field, the risk of colorectal epithelial cell presence in the portal venous blood increased 1.52-fold (95% confidence interval, 1.19-2.12; P = 0.005). CONCLUSION: High intratumoral vessel count was noted to be a valuable factor for predicting the presence of colorectal epithelial cells in the portal venous blood.

Adenocarcinoma↗

Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients.

The purpose of this study was to investigate the clinical usefulness of the color Doppler vascularity index (CDVI) in patients with colon cancer before surgery. Forty-four patients with sonographically visible tumor mass of colon cancer were investigated. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). The correlation between the CDVI and clinicopathological factors, mode of recurrence, and patient survival was studied. For comparison, microvessel density (the mean number of microvessels in three areas of highest vascular density at x200 magnification) of the tumors of these 44 patients was also evaluated by using immunohistochemical staining of surgical specimens with anti-CD34. The microvessel density was not correlated with Dukes' classification, clinicopathological factors, and survival. The CDVI was significantly higher in the patients with lymph node metastases and vascular invasion than in those without such metastases and invasion (P = 0.006 and P = 0.0098, respectively). Moreover, in patients with a high CDVI (> 15%) and positive vascular invasion, survival was significantly poorer than in those with low CDVI (< or = 15%) and negative invasion (P = 0.0037 and 0.0039, respectively). Multivariate analysis indicated that liver metastasis, vascular invasion, and CDVI are independent prognostic factors in the patients with colon cancer. According to the mode of recurrence in 36 patients who underwent curative resection, the frequency of the distant organ recurrence was significantly higher in the high CDVI group (40%) than in the low CDVI group (0%). The CDVI is a good preoperative indicator of recurrence and patient survival in colon cancer. Thus, the CDVI may be helpful in stratifying patients for adjuvant therapy.

Adult↗

Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma.

BACKGROUND: To the authors' knowledge, there are no other published clinical studies that have employed either systemic or local biologic response modifiers in the treatment of patients with pancreatic carcinoma. The purpose of this study was to determine the feasibility and safety of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound (EUS)-guided fine-needle injection (FNI) in patients with advanced pancreatic carcinoma. METHODS: Eight patients with unresectable adenocarcinoma of the pancreas were enrolled: 4 patients in Stage II, 3 in Stage III, and 1 in Stage IV. Cytoimplants were delivered locally into the tumor using a novel EUS-guided FNI technique. Escalating doses of 3, 6, or 9 billion cells were implanted into the pancreatic tumor by a single EUS-guided FNI. Toxicity (modified National Cancer Institute criteria) was assessed at Day 1, Week 1, and Months 1 and 3. Clinical endpoints included Karnofsky performance status (KPS), CA 19-9, tumor response (computed tomography and/or EUS), and survival with follow-up examinations and imaging tests on months 3, 6, 9, 12, and 24. RESULTS: There were no bone marrow, hemorrhagic, infectious, renal, cardiac, or pulmonary toxicities. There were 3 transient Grade 3 gastrointestinal toxicities, and 3 patients had transient episodes of hyperbilirubinemia that were reversed by replacement of biliary stents. Seven of 8 patients (86%) experienced low grade fever that responded to acetaminophen, and all fever was resolved within the first 4 weeks. There were no procedure-related complications. There were 2 partial responses and 1 minor response, with a median survival of 13.2 months. CONCLUSIONS: A single injection of cytoimplant immunotherapy by EUS-guided FNI appears to be feasible and is not associated with substantial toxicity.

Adenocarcinoma↗

Effect of taurine and beta-alanine on morphological changes of pancreas in streptozotocin-induced rats.

In order to determine the effects of taurine supplementation or depletion on the morphological changes of pancreatic beta-cells in streptozotocin-induced diabetic rats, Sprague-Dawley male rats were fed the purified diets supplemented with 1, 2 or 3% taurine or 5% beta-alanine in their drinking water for 7 weeks. After 3 weeks, diabetes was induced by streptozotocin injection (50 mg/kg body-weight). Pancreatic morphology was observed by transmission electron microscopy. The pancreatic beta-cell of the non-diabetic (CO) group had the many secretory granules, rough endoplasmic reticulum and rod shaped mitochondria. However, the beta-cells of non taurine-supplemented diabetic (EO) group were severely damaged, showing depleted secretory granules. In the 1% taurine-supplemented diabetic group, the beta-cells were less damaged compared to the EO group and had some apparently normal secretory granules, but most of rough endoplasmic reticulum and mitochondria was destroyed. The beta-cell of 2% taurine-supplemented diabetic group had swollen rough endoplasmic reticulum, round-shaped mitochondria and some apparently normal secretory granules. The beta-cell of 3% taurine-supplemented diabetic group was little different from that of non-diabetic group. The pancreatic beta-cell of taurine-depleted diabetic group was not destroyed but had many small secretory granules which appeared immature. This was reflected in the blood glucose concentrations of this group. Therefore, taurine may prevent insulin-dependent diabetes by protection of the pancreatic beta-cell and may also preserve normal secretory granules. From these results, taurine supplementation may be recommended for prevention and treatment of diabetes.

Animals↗

Immunohistochemical localization of insulin in pancreatic beta-cells of taurine-supplemented or taurine-depleted diabetic rats.

The purpose of this study was to observe the effects of taurine supplementation or depletion on the immunohistochemical localization of insulin in pancreas of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were fed for 7 weeks with a purified diet that was supplemented with 0, 1, 2 or 3% taurine in their drinking water. To induce taurine depletion, rats were treated with 5% beta-alanine in their drinking water. After 3 weeks, diabetes was induced by streptozotocin injection (50 mg/kg body-weight). The pancreatic tissue was stained immunocytochemically, using an antibody to insulin, and examined by light microscopy. The insulin levels in pancreatic beta-cells of the diabetic group that received no taurine-supplement were significantly decreased, compared to the non-diabetic group. The levels of insulin in beta-cell of 1% and 2% taurine-supplemented diabetic groups were significantly higher than those of the diabetic group, whereas the levels in the group receiving 3% taurine were not significantly different from that of non-diabetic rats. Therefore, it may be suggested that taurine protect pancreatic beta-cells against destruction by ptozotocin injection in a dose-dependent way.

Animals↗

A multispecialty approach to the diagnosis and management of pancreatic cancer.

This article reviews recent developments in pancreatic cancer research and offers a multispecialty perspective on the diagnosis and management of this challenging disease. Current findings in the molecular biology of the disease and their implications for management are examined, as well as development in diagnostic techniques, including helical computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), and, particularly, endoscopic ultrasound-guided fine-needle aspiration. Surgical management, the role of adjuvant/neoadjuvant chemoradiation therapy, and the critical importance of accurate preoperative imaging are also addressed in this review. Palliative techniques, including endoscopic stenting for malignant obstructive jaundice and chemotherapy for locally advanced and metastatic disease, are discussed, and results of recent clinical trials in pancreatic cancer are summarized. Finally, future directions for research are identified.

Humans↗

Utility assessment for different clinical phases of breast cancer in Taiwan.

BACKGROUND AND PURPOSE: Utility is an important index of health-related quality of life (HRQoL). The purpose of this study was to assess utility in different clinical phases of breast cancer in patients in Taiwan. METHODS: Based on a review of HRQoL literature pertaining to breast cancer and medical records of 979 breast cancer patients admitted to National Taiwan University Hospital from 1991 to 1995, a semi-open checklist describing the diagnosis and treatment activities and impacts of different clinical phases of breast cancer was constructed. The checklist was then reviewed and revised in consultation with surgeons, medical oncologists, radiation oncologists, nurses, and breast cancer patients. Thirty-one clinical and public health experts were invited to assess the utility of each phase with the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) methods, according to the description of the average patient's life in the checklist. The Delphi technique was used to reach expert consensus. RESULTS: The VAS utility scores were highest during screening phases (100 or 90), lower in phases of incidental finding of a tumor (75) and diagnosis (70), and lower still in the initial treatment phases, especially during adjuvant chemotherapy (50). The scores improved during the follow-up phases. There was a higher score for breast-conserving surgery (65) than modified radical mastectomy (60) only in the early follow-up phase. The scores for recurrence or metastasis (30) and terminal stage were considerably lower and reached the lowest level (10 in a general ward and 12.5 at home or in a hospice) among all phases. The utility scores assessed by SG and TTO were higher than those assessed by VAS. CONCLUSIONS: In this study, we established a consensus among clinical and public health experts on the impact of different clinical phases of breast cancer on utility. The results of this study may be useful in cross-cultural comparisons and cost-utility analyses for breast cancer.

Adult↗

Endoscopic mucosal resection. Current concepts.

Recent advances in endoscopic mucosal resection of superficial early digestive tract cancers are truly remarkable. The extraordinary long-term outcomes of patients who have been treated with endoscopic mucosal resection have encouraged the widespread practice of endoscopic mucosal resection in Japan. These minimally invasive techniques allow safe and effective treatment of diseases that would otherwise require major surgery. This article provides an overview of endoscopic mucosal resection techniques, their associated outcomes, and other potential applications of endoscopic mucosal resection.

Colonic Neoplasms↗

Endoscopic and endosonography guided fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration is emerging as the preferred technique for the cytologic diagnosis of various gastrointestinal lesions. This technique may not be routinely available, but there is still a role for endoscopic or endoscopic ultrasound-assisted fine-needle aspiration. This article provides an overview of the evolution of these various techniques and discusses the advantages, disadvantages, indications, and contraindications of each.

Biopsy, Needle↗

Effects of hyperthermia on the cytoskeleton and focal adhesion proteins in a human thyroid carcinoma cell line.

Hyperthermia is reported to act as a sensitizer to chemotherapeutic drugs in the treatment of cancer. Thyroid follicular carcinoma were used to elucidate the effects of hyperthermic treatment (41-43 degrees C) on cell morphology, cytoskeleton, and the focal adhesion complex. The critical temperature that resulted in inhibition of cell proliferation as the cell number in the same area did not increase over a 23 h time course and irreversible changes in cell morphology was 42-43 degrees C. An immunofluorescence study on heat-treated cells (43 degrees C, 1-5 h) demonstrated that depolymerization of actin filaments, intermediate filaments, and microtubules accounted for the rounding-up of cells and detachment from the substratum. Characteristic staining patterns for integrin alphav, focal adhesion kinase, and vinculin were noted in untreated cells, but the immunoreactive intensities for these proteins became weaker with time of heat treatment. Anti-phosphotyrosine staining revealed less immunoreactivity in the focal adhesions in treated cells compared with control cells. The disappearance of integrin alphav from the cell surface may result in inhibition of integrin-mediated activation of focal adhesion kinase, which results in dephosphorylation of focal adhesion components and its disassembly. These results indicate that hyperthermia induces disruption of integrin-mediated actin cytoskeleton assembly and, possibly, of other integrin-mediated signaling pathways.

Actins↗

Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility.

Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we conducted a multigenic case-control study to determine whether polymorphisms of the genes responsible for CE formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) are associated with an elevated risk for breast cancer in Taiwanese women, and whether the association between genotype and risk may be modified by estrogen exposure. One hundred and fifty breast cancer patients and 150 healthy controls were recruited. PCR-based RFLP assays were used to determine the genotypes of estrogen-metabolizing genes. The breast cancer risk associated with individual susceptibility genotypes varied among the three genes and was highest for COMT, followed by CYP1A1 and CYP17. After simultaneous consideration of all three genes and other well-established risk factors of breast cancer, the COMT genotype remained the most significant determinant for breast cancer development and was associated with a 4-fold increase in risk (95% confidence interval, 1.12-19.08). Furthermore, a trend of increasing risk for developing breast cancer was found in women harboring higher numbers of high-risk genotypes (P = 0.006), including the high activity CYP17 (CYP17 A2/A2), high inducibility CYP1A1 (CYP1A1 MspI vt/vt), and low activity COMT (COMT L/L) genotypes. The association of risk with the number of susceptibility genotypes was stronger in women with prolonged estrogen exposure (indicated by a higher number of estrogen exposure years or a higher number of estrogen exposure years between menarche and first full-term pregnancy), women with higher estrogen levels (implied by early menarche), and women with a higher body mass index (> or = 22.5). On the basis of comprehensive profiles of estrogen metabolism, this study supports the possibility that breast cancer can be initiated by estrogen exposure.

Body Mass Index↗

Association between N-acetyltransferase 2 (NAT2) genetic polymorphism and development of breast cancer in post-menopausal Chinese women in Taiwan, an area of great increase in breast cancer incidence.

The incidence of breast cancer has increased greatly in Taiwan over the past 2 decades. Increased exposure to environmental carcinogens, including aryl aromatic amines, as a result of the economic boom, is suspected to be one factor contributing to this increase. The enzyme N-acetyltransferase 2 (NAT2) determines the rate of metabolism of aryl aromatic amines, and therefore the NAT2 slow acetylator genotype is associated with an increased risk of cancer. Our present case-control study of 150 breast cancer patients and 150 healthy controls in Taiwan was performed to explore the association between NAT2 genetic polymorphism and individual susceptibility to breast cancer. A structured questionnaire was used to collect relevant information regarding all known or suspected risk factors of breast cancer. The NAT2 genotype was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 139 cases and 133 controls, and 28.8% and 21.1%, respectively, were found to have slow acetylator genotypes. Multivariate analysis, simultaneously considering other risk factors, including age at menarche, nulliparity or age at first full-term pregnancy, body mass index (BMI), hormone replacement therapy (HRT) and smoking status, showed that the NAT2 slow acetylator genotype was associated with an increased risk with borderline significance (Odds Ratio, 1.81; 95% CI, 1.01-3.31). Interestingly, this association was not significant in premenopausal women, but was significant in post-menopausal women. Further stratification of our study subjects based on different risk factor status showed that the increased risk for an NAT2 slow acetylator was more marked in post-menopausal women who were not using HRT or who had a lower BMI. Our findings suggest that NAT2 polymorphism is a susceptibility factor for breast cancer in Taiwanese women, and that NAT2-metabolized carcinogens are probably present in the environment and may be associated with induction of breast cancer.

Acetylation↗

Mucin expression in mucinous carcinoma and other invasive carcinomas of the breast.

To investigate mucin expression in breast cancer, immunohistochemical staining was performed on 30 mucinous carcinomas and 95 non-mucinous invasive carcinomas. MUC2 expression was detected in all mucinous carcinomas, but only in 11.1% of invasive ductal carcinomas, and in none of the invasive lobular carcinomas and medullary carcinomas. MUC1 is often expressed in invasive breast carcinoma, but not in medullary carcinoma. Strong cytoplasmic staining was seen in invasive ductal carcinoma, in contrast to surface membrane staining in mucinous carcinoma and intracytoplasmic vacuole staining in invasive lobular carcinoma. CA19-9 and CA50 expression in more than 25% of tumor cells was seen in 17.2 and 16.0% of invasive ductal carcinomas, respectively, but not in mucinous carcinomas. CA125 and human gastric mucin were rarely expressed in breast cancer, irrespective of histologic type.

Adenocarcinoma, Mucinous↗

p27 expression as a prognostic factor of breast cancer in Taiwan.

p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. It binds to a variety of cyclin/CDK complexes, inhibits kinase activity, and blocks the cell cycle. Absent or reduced p27 expression has been shown to be a significant predictor of poor survival in breast, colorectal, prostate, non-small cell lung and esophagus carcinomas. An immunohistochemical assay was performed on 169 patients with primary breast cancers to evaluate the biologic significance of p27 expression. Decreased p27 expression was significantly associated with high grade (P = 0.00025), negative estrogen receptor (P = 0.00004), and negative progesterone receptor (P = 0.0038) breast cancers. Univariate analysis reveals that p27 expression inversely correlated significantly with overall survival (P = 0.0001). By multivariate analysis, p27 predicted the overall survival independently (P = 0.0096). Our study indicates that p27 expression is an independent prognostic marker of breast cancer in Taiwan.

Adult↗

Oral urografin in postoperative small bowel obstruction.

The aim of our study was to determine whether Urografin has the potential to offer surgeons a way of differentiating complete from partial small bowel obstruction and whether partial small bowel obstruction can be treated nonoperatively. Altogether 116 patients who had postoperative small bowel obstructions without any toxic signs underwent Urografin studies. Urografin (40 ml) mixed with 40 ml of distilled water was administrated either orally or via nasogastric tube to each patient. Serial plain abdominal radiographs were taken 2, 4, and 8 hours later. A total of 74 patients (63.8%) whose contrast medium reached the colon within the first 8 hours were considered to have partial obstruction and were successfully treated with intravenous hydration and nasogastric decompression. The remaining 42 patients (36.2%) in whom the contrast medium failed to reach the colon within the first 8 hours were regarded as having complete obstruction, and 34 of those patients (81.0%) underwent surgery; 8 (19.0%) received conservative treatment. Adhesion bands with complete bowel obstruction were observed in all 34 patients (100.0%) during laparotomy. Regardless of the presence of an air-fluid level on a plain abdominal radiograph or abdominal pain, a liquid diet followed by a soft diet could be given to those patients whose Urografin emptied into the colon. All the patients with partial bowel obstruction were treated successfully with nonoperative methods. The presence of Urografin in the colon within 8 hours of ingestion as an indicator for nonoperative treatment had a sensitivity of 90.2%, a specificity of 100%, and an accuracy of 93. 1%. Urografin, a safe and reliable water-soluble contrast medium, can be used to differentiate partial intestinal obstruction from complete intestinal obstruction. Early oral intake was found to be a major advantage of Urografin use in this study, and the potential of Urografin use to shorten the period of conservative treatment for postoperative small bowel obstruction needs further investigation.

Administration, Oral↗