1.The Relation between Cell Proliferation and Apoptosis According to the Histologic Types in Chemically Induced Rat Mammary Tumorigenesis.
Tae Jung JANG ; Woo Hee JUNG ; Kwang Gil LEE
Korean Journal of Pathology 1998;32(3):174-185
Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.
9,10-Dimethyl-1,2-benzanthracene
;
Adenoma
;
Animals
;
Apoptosis*
;
Breast Neoplasms
;
Bromodeoxyuridine
;
Carcinogenesis*
;
Carcinoma, Ductal
;
Carcinoma, Intraductal, Noninfiltrating
;
Cell Death
;
Cell Proliferation*
;
Classification
;
Female
;
Homeostasis
;
Humans
;
Kinetics
;
Rats*
;
Rats, Sprague-Dawley
;
Transforming Growth Factor beta
2.A Case of Squamous Cell Carcinoma of the Skin Resembling Atypical Fibroxanthoma.
So Young JIN ; Woo Hee JUNG ; Kwang Gil LEE ; Jung Bok LEE
Korean Journal of Pathology 1986;20(2):250-253
Both spindle cell variant of squamous cell carcinoma and atypical fibroxanthoma are most commonly presented as a solitary, often ulcerated nodule, occurring on sun-exposed skin of the elderly. These lesions also share the histologic features of diffuse or indistinct fascicular arrangement of polygonal or pulmp spindle cells. Therefore it is not easy to differentiate immunohistochemistry is done. A case of 73 year old woman with squamous cell carcinoma of the skin resembling atypical fibroxanthoma is presented.
Female
;
Humans
3.Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.
Yoon Jung CHOI ; Woo Hee JUNG ; Hy De LEE ; Kwang Gil LEE
Korean Journal of Pathology 2000;34(9):652-664
Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.
Basement Membrane
;
Breast Neoplasms*
;
Breast*
;
Carcinoma, Ductal
;
Estrogens
;
Humans
;
Immunohistochemistry
;
Lymph Nodes
;
Matrix Metalloproteinases
;
Microvessels
;
Multivariate Analysis
;
Neoplasm Metastasis
;
Peptide Hydrolases
;
Prognosis
;
Receptors, Progesterone
;
Recurrence
;
Survival Rate
;
Tissue Inhibitor of Metalloproteinase-1
;
Tissue Inhibitor of Metalloproteinase-2
;
Transforming Growth Factor beta1
4.Fine needle aspiration cytology of proliferative fasciitis.
Yoon Jung CHOI ; Sang Yeop YI ; Woo Ick YANG ; Soon Hee JUNG ; Kwang Gil LEE
Korean Journal of Cytopathology 1993;4(1):52-56
No abstract available.
Biopsy, Fine-Needle*
;
Fasciitis*
5.Cytologic findings of pancreatic islet cell tumor with lymph node metastasis.
Yee Jeong KIM ; Yoon Jung CHOI ; Kyu Rae KIM ; Woo Hee JUNG ; Kwang Gil LEE
Korean Journal of Cytopathology 1992;3(2):60-66
No abstract available.
Islets of Langerhans*
;
Lymph Nodes*
;
Neoplasm Metastasis*
6.A Case of Polyarteritis Nodosa Combined with Dilated Cardiomyopathy.
Hee Jung CHOI ; Seong Ae JUNG ; Eun Young LEE ; Hae Kyung JUNG ; Gil Ja SHIN ; Woo Hyung LEE
Korean Circulation Journal 1994;24(4):668-674
Polyarteritis nodosa is systemic necrotizing vasculitis of medium and small-sized arteries and results in variable manifestations due to ischemia of the involving organs. Diagnosis can either be made pathologically by demonstrating necrotizing vasculitis of arteries or angiographycally by demonstrating small arterial aneurysm. We experienced a case of PAN with dilated cardiomyopathy, confirmed by clinical feature, renal biopsy, angiography and echocardiography.
Aneurysm
;
Angiography
;
Arteries
;
Biopsy
;
Cardiomyopathy, Dilated*
;
Diagnosis
;
Echocardiography
;
Ischemia
;
Polyarteritis Nodosa*
;
Vasculitis
7.The Effects of Mixture of Mivacurium and Vecuronium on Neuromuscular Blockade during General Anesthesia.
Wha Joo CHAE ; Yung Gil CHOI ; Jung Ae LIM ; Nam Sik WOO
Korean Journal of Anesthesiology 1999;37(1):6-12
BACKGROUND: This study was designed to examine the interactions between mivacurium and vecuronium when administered during a standardized technique. METHODS: Eighty patients (ASA physical status I or II) were randomly assigned to one of four groups (n=20). Their neuromuscular function was measured in response to ulnar nerve supramaximal square-wave TOF stimulation at 10-sec intervals. After the attainment of a stable baseline neuromuscular response, the patients were randomly assigned to receive a rapid iv bolus of either: (1) 3M group (n=20): mivacurium 0.21 mg/kg. Alone, or (2) 2M1V group (n=20): mivacurium 0.14 mg/kg plus vecuronium 0.05 mg/kg, or (3) 1M2V group (n=20): mivacurium 0.07 mg/kg plus vecuronium 0.10 mg/kg, or (4) 3V group (n=20): vecuronium 0.15 mg/kg alone. The onset time of the neuromuscular block, time of recovery of T1 to 25% and reblock time (the time from the reinjection of vecuronium at the time of recovery of T1 to 25% to the time of recovery of T1 to 25%: T25-25) were measured. The intubating condition was evaluated clinically with a scoring system. RESULTS: The onset of block in the 3M group was 33% slower than in the 3V group. The time durations until 25% recovery in the 2M1V, 1M2V and 3V groups were longer than in the 3M group, and the durations in the 1M2V and 3V groups were longer than in the 2M1V group. The T25-25 reblock times of the 2M1V, 1M2V and 3V groups were prolonged in comparison to that of the 3M group. There was no difference in intubating conditions between any of the groups. CONCLUSIONS: A combination of mivacurium with vecuronium provides rates of onset and duration of block which are more effective than an equivalent dose of mivacuriun alone as an additive reaction.
Anesthesia, General*
;
Humans
;
Neuromuscular Blockade*
;
Ulnar Nerve
;
Vecuronium Bromide*
8.Patterns of Left Ventricular Hypertrophy and Geometric Remodeling in Essential Hypertension.
Seock Ah IM ; Hye Kyung JUNG ; Si Hoon PARK ; Gil Ja SHIN ; Woo Hyung LEE
Korean Circulation Journal 1995;25(2):423-433
BACKGROUND: Left ventricular hypertrophy is a major cardiovascular risk factor for sudden death, acute myocardial infarction and congestive heart failure. The left ventricle is generally thought to adapt to sustained arterial hypertension with increased total peripheral resistance by developing concentric hypertrophy. In recent years, the echocardiogrphy has been developed as a noninvasive method for evaluation of left ventricular geometry and left ventricular mass. However, left ventricular adaptation to hypertension has been shown to be more complex than expected. In fact, many patients with mild to moderate hypertension exhibit normal left ventricular mass and wall thickness, other hypertensive patients have eccentric ventricular hypertrophy that is not related to systolic dysfunction, but rather to increased cardiac output and preload and in some hypertensive patients absolute and relative wall thickness is increased with normal ventricular mass(concentric remodeling). There are differences in the hemodynamics, systolic function and diastolic function in each group. METHODS: From september 1992 to August 1994, in 144 patients with untreated essential hypertension and 50 age and gender matched normal adults studied by two-dimensional, M-mode and Doppler echocardiography. In the present study we used echocardiographically derived left ventricular mass and relative wall thickness to assess the patterns of ventricular geometric adaptation to systemic hypertension and their relations to systemic hemodynamics, left ventricular load and contractile performance. RESULTS: Hypertensive group was 144 cases(M:F=68:76), the mean age 56+/-13years. Normotensive group was 50 cases(M:F=22:28), the mean age 52+/-9years. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 42 cases(29%), 24 cases(17%) had increased relative wall thickness with normal ventricular mass(concentric remodelin),48 cases(33%) had both increased relative wall thickness and ventricular mass(concentric hypertrophy), 30 cases(21%) had increased left ventricular mass with normal relative wall thickness(eccentric hypertrophy). Concentric hypertrophy and normal left ventricle group are more common in untreated hypertensive patients in Korea. Systemic hemodynamics showed tendency to paralleled ventricular geomety. In groups with concentric remodeling and hypertrophy, perpheral resistance was increased. Cardiac index was midly increased in eccentric hypertrophy. Diastolic dysfunction was prominent tn concentric hypertrophy. CONCLUSION: Each patterns of left ventricular geometry had different systemic hemodynamics, ventricular pressure overload and ventricular volume overload. Therefore, appropriate selection of antihypertensive agent for the patients with each patterns of hypertrophy reduce the left ventricular hypertrophy and may improve the prognosis.
Adult
;
Cardiac Output
;
Death, Sudden
;
Echocardiography
;
Echocardiography, Doppler
;
Heart Failure
;
Heart Ventricles
;
Hemodynamics
;
Humans
;
Hypertension*
;
Hypertrophy
;
Hypertrophy, Left Ventricular*
;
Korea
;
Myocardial Infarction
;
Prognosis
;
Risk Factors
;
Vascular Resistance
;
Ventricular Pressure
9.Clinical Observation on Effect of Diltiazem(Herben(R)) in Angina Pectoris.
Hong Bum KIM ; Jung Gil LEE ; Sung Dong LEE ; Yung Woo SHIN ; Yung Kee SHIN
Korean Circulation Journal 1982;12(2):193-197
We evaluate the effects of diltiazem in 19 patients with ischemic heart disease (15 patients) of classical anginal pectoris & 4 patients of variant angina) by means of clinical status & electrocardiographic changes and obtain the results as follows: 1. The pulse rate & blood pressure were decreased by diltiazem slightly but these decreases were not significant in statistical meaning. 2. Diltiazem administration of 4 weeks duration normalized EKG completely in 4 patients & partially in 3 patients among the 13 patients who showed abnormal resting EKG initially. 3. All 19 patients who received diltiazem showed clinical improvement; 9 patients had excellent responses, 7 patients good responses & 3 patients fair responses. 4. Diltiazem had side effects in 3 patients, drowsiness, mild euphoria & possibly tolerance respectively in each patients.
Angina Pectoris*
;
Blood Pressure
;
Diltiazem
;
Electrocardiography
;
Euphoria
;
Heart Rate
;
Humans
;
Myocardial Ischemia
;
Sleep Stages
10.Correlation of Heregulin mRNA and Her-2/neu Protein Expression with Node Metastasis and DNA Ploidy Pattern in Human Invasive Breast Carcinoma.
Yee Jeong KIM ; Woo Hee JUNG ; Hyde LEE ; Sung Kong LEE ; In Gul MOON ; Kwang Gil LEE
Korean Journal of Pathology 1998;32(8):563-573
The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.
Animals
;
Breast Neoplasms*
;
Breast*
;
Cell Line
;
Diploidy
;
DNA*
;
Epidermal Growth Factor
;
Fibroblasts
;
Flow Cytometry
;
Formaldehyde
;
Glycoproteins
;
Humans*
;
Immunohistochemistry
;
Intercellular Adhesion Molecule-1
;
Lymph Nodes
;
Neoplasm Metastasis*
;
Neuregulin-1*
;
Phosphorylation
;
Ploidies*
;
Polymerase Chain Reaction
;
Prognosis
;
Protein-Tyrosine Kinases
;
Rats
;
Receptors, Steroid
;
Reverse Transcription
;
RNA, Messenger*
;
Tetraploidy
;
Tyrosine