Recent investigations have revealed that autocrine growth factors and their receptors are closely related and play an important role in controlling cancer cell growth. We performed an immunohistochemical study on the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R), c-erbB-2, and PCNA labelling index in 60 cases of human gastric carcinomas. TGF-alpha was detected in 38 cases (63.3%), EGF in 26 cases (43.3%), EGF-R in 44 cases (73.3%), and c-erbB-2 in 18 cases (30%). These growth factors, EGF-R and c-erbB-2, were found more often in advanced gastric cancers. The PCNA labeling index was significantly higher in tumors with the expression of EGF-R or c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGF-R and c-erbB-2 was associated with a high PCNA labeling index. A correlation was observed between the synchronous expression of growth factors and its receptors and histological differentiation. The results suggest that the expression of EGF, TGF-alpha, EGF-R and c-erbB-2 are closely related and plays an important role in the growth and progression of human gastric carcinoma.
Epidermal Growth Factor* ; Humans ; Intercellular Signaling Peptides and Proteins ; Peptides* ; Proliferating Cell Nuclear Antigen ; Receptor, Epidermal Growth Factor ; Stomach Neoplasms ; Transforming Growth Factor alpha

No abstract available.
Fever*

Background : It has been suggested that thrombospondin (TSP) is a p53-dependent negative regulator of tumor angiogenesis. TSP expression and localization in hepatocellular carcinomas (HCCs) and its association with overexpression of p53 protein were investigated. Methods : TSP-1 and -2 expressions were examined in 40 HCC specimens by immunohistochemical staining and in 4 HCC cell lines by Western blotting. In addition, p53 protein expression and microvessel density (MVD) were correlated with the TSP expression. Results : Strong immu- nopositivity for TSP-1 was observed in fibroblasts, vascular endothelial cells, and some vas- cular smooth muscle cells of the stroma in 18 cases (45%), and in tumor cells in 3 cases (7.5%) of 40 cases of HCC. Immunoreactivity for TSP-2 was observed in only the sinusoidal lining cells of the tumor in 15 cases (46%), and in tumor cells in 2 cases (6%) of 32 cases of HCC. TSP-1 expression was inversely correlated with MVD (p=0.028), but TSP-2 expression did not show any correlation with MVD. Although p53 was overexpressed in 17 cases, there was no significant correlation between TSP and p53 expressions. None of the HCC cell lines expressed TSP-1 or -2. Conclusions : These findings indicate that TSP-1 is mainly derived from nonparenchymal cells, and may decrease tumor angiogenesis in HCC.
Angiogenesis Inhibitors ; Blotting, Western ; Carcinoma, Hepatocellular* ; Cell Line ; Endothelial Cells ; Fibroblasts ; Microvessels ; Myocytes, Smooth Muscle ; Thrombospondin 1 ; Thrombospondins

Recently, the incidence of Achilles tendon rupture has been increasing with an increase in the elderly and the sports population. Various kinds of surgical options have been introduced up to now. Among them, the traditional open repair is most commonly used despite the risk of re-rupture or post-operative infections, which in turn can impair the blood flow to the Achilles tendon. Therefore, minimally invasive methods to overcome these complications have been studied with excellent outcomes.

Recently, the incidence of Achilles tendon rupture has been increasing with an increase in the elderly and the sports population. Various kinds of surgical options have been introduced up to now. Among them, the traditional open repair is most commonly used despite the risk of re-rupture or post-operative infections, which in turn can impair the blood flow to the Achilles tendon. Therefore, minimally invasive methods to overcome these complications have been studied with excellent outcomes.

BACKGROUND: We previously demonstrated that a GRE/TRE composite sequence, which is located between 200 bp and 220 bp relative to the transcriptional start site of rat TRH gene, is responsible for the dexamethasone (DEX)- and TPA-induced transcriptional activation, and the transcriptional activation by DEX is mediated by interaction between glucocorticoid receptor (GR) and a TRE-binding transcriptional factor such as c-Jun. However, a non-specific binding with the transciption factors can not be excluded as the mutants used in the previous report could not inhibit the binding of GR and c-Jun completely, and it remains unclear which one of the two TRE-like sequences is critical for the interaction of the two transcription factors. METHODS: Luciferase expressing plasmids that contain a part of rat TRH promoter including the composite GRE sequence or its mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX or/and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX and TPA increased the transcriptional activity of the wild type composite sequence by 3 folds and 4 folds, respectively, and the combined stimulation increased the activity by 10 folds. The mutants of which all 6 nucleotides of the GRE half site were replaced and removed almost did not bind to GR and eould not enhance the transcriptional activity at all in response to DEX. The GRE-deleted mutant bound to c-Jun with a remarkably lower affinity and showed a lower response to TPA, whereas the GRE-replaced mutant bound to c-Jun with a similar affinity and showed a similar response to TPA compared to those of the wild type. In response to the combined simulation with DEX and TPA, the mutants showed 30-40% of the trancriptional activity of the wild type. Basal transcriptional activity of all the TRE mutants was significantly lower than that of the wild type. While they almost could not bind to c-Jun, their binding affinity to GR was comparable to that of the wild type. Whereas the DEX- and TPA-induced transcriptional activity of 5 TRE mutant was 10% and 15% of that of the wild type, it responded to those agents in a similar pattern as the wild type. The 3 TRE mutant and the mutant of both TRE sites did not respond to DEX and TPA. The GRE-deleted mutant hardly formed the DNA-protein complex as did the wild type, while the GRE -replaced mutant could form the complex in a less amount with nuclear extract of HeLa celL CONCLUSION: These results suggest that GRE/TRE composite sequence of rat TRH gene specifically binds to GR and c-Jun, providing a site for interaction between the two transcription factors, and that both TRE sites play an important role in basal transcription, and that the 3 TRE site is more critical in the interaction between GRE and TRE for DEX-induced transcriptional activation. (J Kor Endocrinol 14:278-292, 1999)
Animals ; Dexamethasone ; Electrophoretic Mobility Shift Assay ; HeLa Cells ; Humans ; Luciferases ; Mutagenesis, Site-Directed* ; Nucleotides ; Plasmids ; Rats* ; Receptors, Glucocorticoid ; Response Elements* ; Transcription Factors ; Transcriptional Activation

BACKGROUND: We previously demonstrated that the promoter of rat TRH gene has GRE half site (TGTTCT) between -210 bp and -205 bp flanking with similar sequences of TPA response element (TRE), TAGTCA, at a distance of several base pairs from the GRE half site. It promps us to hypothesize that this composite GRE/TRE sequence can provide a site for interaction between glucocorticoid receptor (GR) and c-Jun. Thus, we investigated whether the composite sequence mediates transcriptional regulation induced by dexamethasone (DEX) and 12-O-tetradecanoyl phobol-13-acetate (TPA), and whether it binds GR and c-Jun. METHODS: A luciferase expressing plasmids that contain a part of rat TRH promoter including the composite sequence or their mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX increased the transcriptional activity of the plasmid containing the wild type GRE by 2.5 folds, and TPA increased the transcriptional activity by 4 folds. The simultaneous stimulation with DEX and TPA synergistically increased the transcriptional activity by 10 folds. Two mutants whose GRE half sits were altered showed no responses to DEX, and suppressed the TPA-induced or both agents-induced transcriptional activity by 50%. Two mutants whose TRE-like sites were altered suppressed the DEX-induced transcriptional activity by 20%, TPA-induced trarptional activity by 25%, and both agents-induced transcriptional activity by 50%. Gel retardation assay showed that the composite sequence fonned a complex with GR and its mutants bound to GR with remarkably less affinity. c-Jun also bound to the composite sequence to form two cornplexes with less affinity compared to the AP-1 consensus sequence. The mutants of the TRE-like sequence bound to c-Jun with a significantly lower affinity compared to that of the wild type. Simulateous binding of the composite sequence with GR and c-Jun did not form any larger complex. The complex of GR and the composite sequence was much smaller than that formed by c-Jun, suggesting that GR binds to the composite sequence as a monomer. CONCLUSION: These results suggest that the composite sequence of GRE half site and TRE-like site on the promoter of rat TRH gene provides binding sites for GR and c-Jun, which mediate the interaction between two signal transduction pathways. (J Kor Soc Endocrinol 14:265-277, 1999)
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid ; Animals ; Base Pairing ; Binding Sites ; Consensus Sequence ; Dexamethasone ; Electrophoretic Mobility Shift Assay ; HeLa Cells ; Humans ; Luciferases ; Plasmids ; Rats ; Receptors, Glucocorticoid ; Response Elements ; Signal Transduction ; Transcription Factor AP-1

A 52-year-old women, suffering from generalized pruritus due to intrahepatic and common hepatic duct stones, was treated with astemizole, 30mg daily. Sixty one days later, convulsions and syncope developed suddenly during hospitalization. She had no history of arrhythmia, heart disease, electrolytes imbalance, or CNS disorders. As another case, a 44-year-old man suffering from pruritus due to liver cirrhosis, was treated with astemizole, 30mg daily. Thirty two days later, palpitations and syncope also developed suddenly during hospitalization. He was diagnosed liver cirrhosis, 3 years ago and there was no history of arrhythmia, heart disease, electrolytes imbalance, or CNS disorders. Administration of astemizole was stopped immediately. The laboratory investigations revealed the normal range of serum potassium, calcium and magnesium in both cases. The ECG finding showed the prolongation of QTc interval, frequent VPCs and intermittent polymorphic drugs. On 1st and 3rd day, after discontinue of astemisole, the ECG abnormalities disappeard. It is suggested that astemizole overdose can induce prolongation of QTc interval and torsade de pointes, especially in the patient with liver disease.
Adult ; Arrhythmias, Cardiac ; Astemizole* ; Calcium ; Electrocardiography ; Electrolytes ; Female ; Heart Diseases ; Hepatic Duct, Common ; Hospitalization ; Humans ; Liver Cirrhosis ; Liver Diseases ; Magnesium ; Middle Aged ; Potassium ; Pruritus ; Reference Values ; Seizures ; Syncope ; Torsades de Pointes*

For the estimation of the proliferative activity, related to the biologic behaviour, malignant potential, and prognosis, of human thyroid tumors, PCNA(proliferating cell nuclear antigen) immunohistochemical staining was performed on paraffin-embedded sections of 9 normal thyroid tissues, 9 adenomatous goiters, 9 follicular adenomas, 4 Hurthle cell tumors, 12 papillary carcinomas, 4 follicular carcinomas, and 3 anaplastic carcinomas. The results were as follows: 1) The PCNA labeling indices in adenomatous goiter, follicular adenoma, and Hurthle cell tumor were 1.1, 1.5, and 2.4, respectively. They were significantly higher than the labeling index in normal thyroid. 2) The PCNA labeling indices in papillary carcinoma and follicular carcinoma were 3.5 and 4.4, respectively. They were significantly higher than the labeling indices in adenomatous goiter and follicular adenoma, but there was no significant difference between papillary and follicular carcinoma. 3) The PCNA labeling index in anaplastic carcinoma, 14.1, was significantly higher than those in benign and other malignant tumors. According to the results, the PCNA labeling index was well correlated with the malignant potential of a tumor. So the PCNA immunohistochemical staining is thought to be a useful method for the evaluation of the malignant potential and prognosis of a tumor.
Humans

The syndrome of inappropriate ADH secretion is a disorder characterized by hyponatremia which results from water retention attributable to ADH release. The hallmark of SIADH is hyponatremia due to water retention, in the presence of urinary osmolality above plasma osmolality. The SIADH was initially described by Schwartz et al (1957). This syndrome, first recognized in patients with bronchogenic carcinoma, has now been observed in a variety of other illnesses. Recently, we encountered a 59 year-old female with small cell lung cancer, also she had SIADH. Thus, we present a case and review the literature on the subject.
Carcinoma, Bronchogenic ; Female ; Humans ; Hyponatremia ; Inappropriate ADH Syndrome* ; Osmolar Concentration ; Plasma ; Small Cell Lung Carcinoma* ; Water