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C T Shun

Publications and source records attributed to C T Shun.

At least 37 records · Page 2Linked to original sources

Cyst-like chylous coagulum in the urinary bladder of a patient with recurrent chyluria.

We report a rare case of recurrent chyluria in a 64-year-old man, who had undergone sclerosing therapy for chyluria with complete remission 40 years previously. The chyluria recurred 4 months before the present hospital admission. The patient presented with acute urine retention and weight loss of 6 kg during the past 6 months. Urine biochemistry studies showed elevated concentrations of albumin (0.7 g/dL), globulin (0.6 g/dL), cholesterol (0.59 mmol/L), and triglyceride (0.89 mmol/L), confirming the diagnosis of chyluria. Intravenous urography showed a substantial filling defect in the urinary bladder. Cystoscopy revealed milky urine flowing out of the right ureteral orifice, and a large chylous coagulum presenting as a cyst-like mass in the urinary bladder. The chyluria was successfully treated with sclerosing therapy with injection of 76% Urografin (Shering AG, Berlin, Germany) into the right upper urinary tract, and the chylous coagulum was evacuated endoscopically. No evidence of chyluria recurrence has been noted during a year of follow-up, and the patient has regained 6 kg of body weight. This particular presentation of chylous coagulum in a chyluria patient has not been previously reported in the literature.

Chyle↗

Induction of pulmonary fibrosis in organ-cultured rat lung by cadmium chloride and transforming growth factor-beta1.

Cadmium chloride (CdCl2) exposure has been reported to induce pulmonary fibrosis in rats. Accumulating evidence has shown that cytokines play a pivotal role in the excessive production of connective tissue components in pulmonary fibrosis. In this report, rat lung slice cultures were used to study the synergistic involvement of transforming growth factor-beta1 (TGF-beta1) in CdCl2-induced alveolar fibrosis. Rat lung slices were maintained at the interphase of air and medium on a polyester mesh stretched on a plastic scaffold. Treatment of lung slices with 2.5, 5 or 10 microM CdCl2 for 7 days resulted in 85, 40 and 6% respectively for relative survival. Under these culture conditions, CdCl2 alone did not induce alveolar fibrosis in rat lung slices. However, in the presence of 0.5 ng/ml TGF-beta1, CdCl2 at a dose ranging from 1 to 5 microM increased the thickness of alveolar septa. Furthermore, the thickness of alveolar septa in lung slices treated with CdCl2 was dose-dependently increased by the presence of TGF-beta1. The thickened alveolar septa were apparently due to the deposition of excessive extracellular matrix, as revealed by trichrome stain and ultrastructural examination. Our results also show that fibrogenic activity induced by the combined treatment with CdCl2 and TGF-beta1 can be reduced by co-treatment with 200 microg/ml lambda-carrageenan, a TGF-beta1 inhibitor. Therefore, the present results indicate that TGF-beta1 can synergistically stimulate the fibrogenic activity in lung tissue subsequent to CdCl2 injury.

Animals↗

High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy.

BACKGROUND: In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS: To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS: Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P < 0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P < 0.01, log rank test). CONCLUSIONS: The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

Adenocarcinoma↗

Clinicopathological significance of altered loci of replication error and microsatellite instability-associated mutations in gastric cancer.

Replication errors (RERs) judged by microsatellite instability and its associated mutations have been recognized as an important mechanism in tumorigenesis of gastric cancers (GCs). To gain a deeper insight into its significance, we examined the frequency of RERs using nine microsatellite markers and screened mutations in the polydeoxyadenine tract of the transforming growth factor beta type II receptor gene (TGF-betaRII) and polydeoxyguanine tracts of insulin-like growth factor II receptor and BAX genes. Twenty-four (30%) of 80 patients with GC had RERs, of which 3, 8, and 13 had one, two, and three or more loci, respectively. In 13 tumors with RERs in three or more loci, frameshift mutations of TGF-betaRII, insulin-like growth factor II receptor, and BAX were identified in 12, 3, and 2, respectively. Compared with GC with none, one or two RER-positive loci as a group, GC with RERs in three or more loci showed a significantly higher frequency of antral location (12 of 13 versus 35 of 67; P = 0.01), intestinal subtype (11 of 13 versus 30 of 67; P = 0.01), and previous Helicobacter pylori infection (12 of 13 versus 41 of 67; P = 0.05) and a lower incidence of lymph node metastasis (5 of 13 versus 49 of 67; P = 0.02) and tended to be in an advanced stage (12 of 13 versus 54 of 67; P = 0.28). These data indicate that GC with multiple RERs manifest distinct clinicopathological characteristics, and that a high frequency of frameshift mutations involving the TGF-betaRII gene may be causatively linked with tumorigenesis and progression.

Adult↗

Regional difference in epidermal thinning after skin denervation.

Denervation of skin has a profound influence on epidermis; epidermal thinning was a consistent finding in rats. However, it is not clear whether the degree of epidermal thinning was similar in the region receiving the same innervation. In mice, how early epidermal nerves were degenerated after nerve injury remained unknown. To address these issues, we transected the sciatic nerve in mice and compared the changes of epidermal thickness in different areas of the hind foot skin. Epidermal nerves degenerated within 48 h after nerve transection, similar to what was observed in rats. Seven days after nerve transection, there was differential thinning of epidermis. The interpad area, in the center of the sciatic nerve-innervated region, exhibited the most profound degree of epidermal thinning (34.6 +/- 3.1 vs 47.8 +/- 2.4 microns, P < 0.01). The heel area, in the periphery of the sciatic nerve-innervated zone, did not show significant thinning of epidermis after denervation (37.3 +/- 4.8 vs 41.5 +/- 5.1 microns, P > 0.05). The degree of epidermal thinning after denervation in the pad area was the intermediate one: with 98.8 +/- 4.8 vs 120.1 +/- 7.3 microns, P < 0.02, in the rete pegs, and 51.1 +/- 4.1 vs 62.1 +/- 6.0 microns, P < 0.02, in the dermal papilla. The differential thinning was obvious when the thickness of the denervated epidermis was normalized to that of the control epidermis with the ratios of 0.73 +/- 0.03 in the interpad area, 0.83 +/- 0.04 in the rete peg, 0.85 +/- 0.05 in the dermal papilla, and 0.92 +/- 0.05 in the heel. Epidermal thinning was reversed by reinnervation of the epidermis after sciatic nerve crush (41.5 +/- 1.5 vs 45.0 +/- 2.0 microns in the interpad area, P > 0.05). These findings suggest that sensory nerves exhibit trophic influences on the epidermis presumably through the effects of diffusible factors.

Animals↗

Soluble adhesion molecules and cytokines in perennial allergic rhinitis.

BACKGROUND: Increasing evidence suggests adhesion molecules and cytokines in patients with inflammatory airway diseases are involved in steps of entrapment and migration of inflammatory cells. Recently, soluble forms of adhesion molecules and cytokines have been detected in the sera and other body fluids of patients with various diseases. OBJECTIVE: Eosinophilia in nasal mucosa is characteristic of allergic rhinitis. Vascular adhesion molecules expressed on the endothelium are essential for eosinophils to move from the peripheral blood into the sites of inflammation. Herein, soluble forms of vascular adhesion molecules and eosinophil-activating cytokines are measured to investigate the significance of their appearance in the sera with eosinophil infiltration in the nasal mucosa of perennial allergic rhinitis. METHODS: With the quantitative sandwich enzyme immunoassay technique, the sera of 36 patients of perennial allergic rhinitis and 20 nonatopic subjects were used to measure the levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (endothelial leukocyte adhesion molecule-1, sELAM-1), interleukin-3 (IL-3), and interleukin-5 (IL-5). RESULTS: No significant differences in the levels of soluble vascular adhesion molecules were noted between the two groups. Eosinophil-activating cytokines, IL-3 and IL-5, were significantly increased in the group with perennial allergic rhinitis, and were correlated with eosinophil infiltration in nasal scrapings. CONCLUSION: Although the vascular adhesion molecules expressed on the endothelium are necessary for eosinophils to appear in allergic tissues, eosinophil-activating cytokines as IL-3 and IL-5 are likely to be essential for eosinophils to function in tissues. The elevated concentrations of IL-3 and IL-5 in allergic rhinitis may reflect the inflammatory response occurring in the T cell activation and in relation to manifestation of eosinophils.

Adolescent↗

Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia.

Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each associated with an increased risk of gastric cancer (GC). To explore further the influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95% confidence intervals of developing GC were calculated for each risk factor using multiple logistic regression analysis. ORs for H. pylori infection and IM were 2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II and 39.75 (14.34-110.2) for type III. Stratification analysis by histological subtype and stage of GC showed a particularly high OR for IM in intestinal type (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both H. pylori and IM are related to GC risk. Type III IM is a more specific marker of premalignancy, with relevance, in particular, to the early and intestinal type of GC.

Adult↗

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Humans↗

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↗

The effect of biological dyes and contrast media on the vas deferens in Long Evans rats.

The conventional diagnostic procedure of vasography utilizes a contrast medium to evaluate the patency of the vas deferens. With the development of microsurgical reconstruction for obstructive azoospermia in the past two decades, intraoperative vasography with saline or biological dye injection has replaced the use of radiographic contrast media. However, there are few reports on the effect of biological dyes on the healthy vas deferens. Therefore, we used experimental vasography to evaluate histological changes and functional patency of the vas deferens after infusion with a contrast medium and biological dye. Four groups of 10 Long Evans male rats were injected by vasopuncture with 1% methylene blue, 1% gentian violet and 38% Urografin or saline into the vas deferens. The animals were killed 30 days later, and the vasa deferentia were excised and examined for histological changes and for functional patency. Vasopuncture with saline injection induced minimal change both at the puncture site and in the distal vas deferens. In both the Urografin- and methylene blue-injected groups, inflammation at the puncture site was found in 20-22% of cases, and 10-11% of cases revealed functional obstruction of the vasal lumen. In the gentian violet-injected group, severe histological and obliterated changes were found in all cases. Leakage of the dye and contrast medium or the sperm reaction may be responsible for the inflammation; otherwise, methylene blue and urografin did not seem to be harmful to the vas deferens. Although gentian violet is a blue dye, as is methylene blue, it has marked destructive effects on the vas deferens. It is concluded that some biological dyes used for vasal injection can cause occlusion of the vasal lumen, while inflammatory responses can occur from placing a needle transmurally.

Animals↗

Relatively low expression of multidrug resistance-1 (MDR-1) and its possible clinical implication in gastric cancers.

The mechanism of drug resistance of gastric cancer cells has rarely been investigated. We specifically examine the magnitude and the biologic significance of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All patients had previously been treated in prospective clinical trials for advanced gastric cancer in our institution. Patients with adequate prechemotherapy gastric cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were selected for the determination of the expression rate of MDR-1. The results were designated as negative or positive by the independent interpretation of two pathologists. A subgroup of patients who had been treated with doxorubicin- or etoposide-containing regimens were selected for further correlation with drug sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women with a median age of 55 years, were studied. Eight (13.3%; 95% confidence interval, 6%-25%) of them had MDR-1 expression. None of the pertinent clinicopathologic features, including the histopathologic types of the tumors and the extent of the diseases, correlated with the expression of MDR-1. Among the 30 patients who had received doxorubicin- or etoposide-containing combination chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas 19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer is relatively low. Its expression, however, is clinically relevant and is useful in predicting the chemoresistance of patients with gastric cancer receiving doxorubicin- or etoposide-containing combination chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Loss of pS2 protein expression is an early event of intestinal-type gastric cancer.

To investigate the prevalence of pS2 expression in gastric cancer with respect to tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori) infection, pathologic specimens of 91 patients with gastric cancer were immunostained for pS2. Such immunoreactivity was correlated with the status of H. pylori infection, tumor staging, histology, subtyping, and associated intestinal metaplasia. Positive pS2 staining was seen throughout all non-neoplastic epithelia, and in all 9 patients with the complete type of intestinal metaplasia. In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2 staining (P < 0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2 expression in the cancer tissues proper. There was no correlation of pS2 expression with age, gender, depth of invasion, duodenal involvement, lymph node metastasis, venous invasion or H. pylori infection. Negative pS2 staining was significantly higher in the intestinal (74.5%) and Borrmann type I, II, III (64.2%) tumors than the diffuse (43.2%, P < 0.005) and Borrmann type IV (20%, P < 0.05) tumors. Our results indicate that loss of pS2 expression may occur as an early event in the malignant transformation process of intestinal-type tumors.

Adult↗

Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.

Aged↗

Quantitative analysis of mRNA encoding MUC1, MUC2, and MUC5AC genes: a correlation between specific mucin gene expression and sialomucin expression in non-small cell lung cancer.

The expression of mucins is important for tumor invasiveness and metastasis. In our previous report (Am. J. Respir. Crit. Care Med. 1997; 155:1419-1427), non-small cell lung cancers bearing sialomucin expression tended to relapse earlier than those without sialomucin. However, it remained unclear whether the expression of sialomucin in lung cancer is caused by an abnormal glycosylation process or by the expression of a specific mucin gene product. To address this problem, we established a modified quantitative competitive polymerase chain reaction (QC-PCR) analysis. RNA internal standards of MUC1, MUC2, and MUC5AC non-tandem repeat sequences were constructed, and known copy numbers of mucin RNA internal standards were introduced into reverse transcription-polymerase chain reactions (RT-PCR) for each mucin gene in order to compete with native mucin gene RNA during the reaction. The RNA of Gbeta-like gene (a housekeeping gene) was used as internal control for the RNA analysis. Twenty-five lung cancer tissues (13 adenocarcinomas and 12 squamous cell carcinomas) were used for analysis. Mann-Whitney rank sum test was applied to compare the expression amounts of different mucin genes in tissues. The results revealed that adenocarcinoma expressed higher amounts of MUC5AC gene than did squamous cell carcinoma (P = 0.03). The expression amount of MUC5AC correlated positively with the expression status of sialomucin (P = 0.012). Further studies are anticipated to elucidate the underlying mechanism contributing to this phenomenon.

Adenocarcinoma↗

Loss of imprinting and overexpression of IGF2 gene in gastric adenocarcinoma.

Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome 11p15.5 in close vicinity to each other, and are imprinted on different parental alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI) leading to the biallelic expression of IGF2 and H19 genes has recently been reported in a variety of tumors. To study the role of IGF2 and H19 genes in gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these two genes were determined in 70 patients with gastric cancer. Among them, 30 patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and 42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15, 53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no obvious alterations of expression of H19 were noted by Northern hybridization. These data suggest that LOI leading to overexpression of IGF2 plays an important role in carcinogenesis of diffuse type gastric cancer.

Adenocarcinoma↗

Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Adenocarcinoma↗