Heregulin-β1, a ligand of ErbB-2 and ErbB-3/4 receptors, has been reported to potentiate oncogenicity and metastatic potential of breast cancer cells. In the present work, treatment of human mammary cancer (MCF-7) cells with heregulin-β1 resulted in enhanced cell migration and expression of manganese superoxide dismutase (MnSOD) and its mRNA transcript. Silencing of MnSOD abrogated clonogenicity and migrative ability of MCF-7 cells. Heregulin-β1 treatment also increased nuclear translocation, antioxidant response element binding and transcriptional activity of NF-E2-related factor 2 (Nrf2). A dominant-negative mutant of Nrf2 abrogated heregulin-β1-induced MnSOD expression. Treatment with heregulin-β1 caused activation of protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK). The pharmacological inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase 1/2, which are upstream of Akt and ERK, respectively, attenuated heregulin-β1-induced MnSOD expression and nuclear localization of Nrf2. In conclusion, heregulin-1 induces upregulation of MnSOD and activation of Nrf2 via the Akt and ERK signaling in MCF-7 cells, which may confer metastatic potential and invasiveness of these cells.

Heregulin-β1, a ligand of ErbB-2 and ErbB-3/4 receptors, has been reported to potentiate oncogenicity and metastatic potential of breast cancer cells. In the present work, treatment of human mammary cancer (MCF-7) cells with heregulin-β1 resulted in enhanced cell migration and expression of manganese superoxide dismutase (MnSOD) and its mRNA transcript. Silencing of MnSOD abrogated clonogenicity and migrative ability of MCF-7 cells. Heregulin-β1 treatment also increased nuclear translocation, antioxidant response element binding and transcriptional activity of NF-E2-related factor 2 (Nrf2). A dominant-negative mutant of Nrf2 abrogated heregulin-β1-induced MnSOD expression. Treatment with heregulin-β1 caused activation of protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK). The pharmacological inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase 1/2, which are upstream of Akt and ERK, respectively, attenuated heregulin-β1-induced MnSOD expression and nuclear localization of Nrf2. In conclusion, heregulin-1 induces upregulation of MnSOD and activation of Nrf2 via the Akt and ERK signaling in MCF-7 cells, which may confer metastatic potential and invasiveness of these cells.

BACKGROUND: A new technique resecting the hepatic parenchyma without inflow occlusion using a Cavitron Ultrasonic Surgical Aspirator (CUSA(R) ) reduces intraoperative blood loss and perioperative morbidity. This study was designed to identify the incidence and severity of venous air embolism (VAE) using transesophaseal echocardiography (TEE) in hepatic resection using CUSA(R) . METHODS: Forty patients undergoing hepatic resection using CUSA(R) of ASA class 1 and 2 were selected. After insertion of an epidural catheter for postoperative analgesia, all patients were anesthetized with sevoflurane in 50% air/O2. After the induction of anesthesia, A TEE probe was inserted into the esophagus. Blood pressure, heart rate, central venous pressure, end tidal CO2, and arterial carbon dioxide tension were recorded after induction, and during and after hepatic resection. During hepatic resection, an anesthesiologist evaluated the degree of VAE by transesophageal echocardiography in the 4-chamber view. RESULTS: The mean time of using CUSA(R) was 65.3 +/- 24.4 minutes. Of 40 patients, 9 had VAE grade I, 14 grade II, 14 grade III, and 3 grade IV. However, no significant difference was observed in hemodynamics or PaCO2 after induction, or during or after hepatic resection. The mean amount of blood loss was 887.0 ml +/- 598.8 ml and the mean transfused amount was 123.1 +/- 351.3 ml. CONCLUSIONS: All patients showed air embolism during hepatic resection with CUSA(R) . Serious complications associated with air embolism would occur in patients with an undiagnosed intracardiac right to left shunt. Therefore, meticulous monitoring by transesophageal echocardiography might be recommended in hepatic resection with CUSA(R) .
Analgesia ; Anesthesia ; Blood Pressure ; Carbon Dioxide ; Catheters ; Central Venous Pressure ; Echocardiography* ; Echocardiography, Transesophageal ; Embolism, Air* ; Esophagus ; Heart Rate ; Hemodynamics ; Humans ; Incidence* ; Ultrasonics*

BACKGROUND: Glomerular compensatory hypertrophy maintains decreased renal function after uninephrectomy (UNX). Proliferation and apoptosis of renal cells may be involved in hypertrophy. METHODS: In small and large male Sprague-Dawley rats, contralateral kidneys were harvested 1, 7, 14 and 30 days after UNX. Apoptosis was assessed by the Tdt-mediated dUTP-digoxigenin nick end labelling method. Proliferating cell nuclear antigen and Fas ligand (FasL) expression was determined by immunohistochemically. RESULTS: Morphometrically, glomerular hypertrophy was observed in both small and large rats after UNX, and it was more significant in the small rats. The glomerular proliferation index (PI) was gradually increased from day 7 but decreased on day 30 in the small rats. Glomerular PI was significantly increased from day 7 in large rats and peaked at day 14. Apoptotic cells in the glomeruli were slightly increased on day 1 and on day 7 in both groups of rats. The expression of FasL was gradually increased in the distal tubular epithelium in both groups. CONCLUSIONS: These results demonstrate different profiles regarding the compensatory growth of the kidney, cell proliferation, and apoptosis during the period of compensatory hypertrophy in uninephrectomized rats of different weight and age. Apoptosis may play a role in regressing a number of proliferated cells during renal compensatory hypertrophy.
Animals ; Apoptosis* ; Cell Proliferation ; Epithelium ; Fas Ligand Protein ; Humans ; Hypertrophy* ; Kidney ; Male ; Pathology ; Proliferating Cell Nuclear Antigen ; Rats* ; Rats, Sprague-Dawley

Hemangioendotheliomas are vascular neoplasms characterized by histologic appearance that are intermediate between hemangiomas and angiosarcomas first described by Weiss and Enzinger in 1982. They are classified into at least 3 subgroups, including epithelioid hemangioendothelioma, spindle cell hemangioendothelioma, and malignant endovascular angioendothelioma, and have been reported principally in soft tissues of the extremities, lung, liver, and bone. The cases involving the central nervous system reported are very rare. We report an intraspinal epithelioid hemangioendothelioma occurring in a 52-year-old man. To our knowledge, it is first case of spinal hemangioendothelioma in Korea.
Central Nervous System ; Extremities ; Hemangioendothelioma ; Hemangioendothelioma, Epithelioid* ; Hemangioma ; Hemangiosarcoma ; Humans ; Korea ; Liver ; Lung ; Middle Aged ; Spinal Cord* ; Vascular Neoplasms

Epithelioid hemangioendothelioma(EH) is a rare vascular tumor of low-grade malignancy. It was previously described as intravascular bronchioloalveolar tumor (IVBAT). But electron microscopic study and immunohistochemical staining results have proved endothelial origin. Patients are usually asymptomatic and the tumors are found incidentally on routine chest X-rays. Most patients show a slowly progressive clinical course, even though some patients occasionally die as results of respiratory failure or extrathoracic complications. Confirmative diagnosis is made through thoracoscopic or open-lung biopsy. There is still no effective therapeutic modality for pulmonary EH. We have experienced a 55-year-old woman whose simple chest x-ray film revealed bilateral multiple small nodules. The nodules were histopathologically and immunohistochemically diagnosed as primary epithelioid hemangioendothelioma of the lung. The possibility of metastatic disease was excluded thorough clinical, laboratory and radiological studies. Comparison of radiographic chest film taken 3 years ago showed no significant progression of the pulmonary nodular lesions. Conservative management was instituted and careful 4 months follow-up showed no significant changes.
Biopsy ; Diagnosis ; Female ; Follow-Up Studies ; Hemangioendothelioma, Epithelioid* ; Humans ; Lung ; Middle Aged ; Respiratory Insufficiency ; Thorax ; X-Ray Film

Transformation and progression of breast cancer are thought to be caused by an accumulation of complex genetic alterations, but little is known about specific changes. In this study, the author has undertaken a genome-wide screening to detect genetic changes in 20 cases of breast cancer among Koreans, including 16 infiltrating ductal carcinomas, 2 medullary carcinomas, 1 invasive lobular carcinoma, and 1 borderline phyllodes tumor. Comparative genomic hybridization (CGH) was used to screen for DNA sequence gains and losses across all human chromosomes. Simultaneous immunohistochemical staining for c-erbB-2 (Her-2/neu), c-myc, cyclin D1, and p53 protein was done to make comparisons with nuclear grade and that with CGH results. Biotin-labeled tumor DNA and digoxigenin-labeled normal DNA were hybridized to normal metaphase cells. The fluorescence signals were captured by fluorescence microscope after detection by avidin-FITC and anti-digoxigenin rhodamine. Then, the ratio of fluorescence was calculated by an image analyzer. The immunohistochemical staining was done in paraffin-embedded tissue with an LSAB kit and avidin-biotin complex (ABC) method. The CGH results showed gains on chromosomes 8q (40%), 1q (30%), 17q (15%), 20q (15%), 18q (15%), 5p (15%), and 13q (15%). Deletions were on chromosomes 17p (45%) and 22q (20%). High-level amplifications (green/red ratio >1.5) were noted on chromosomes 1p31, 1q, 3q25-qter, 5p, 7q31-qter, 8q, 9p22-qter, 10p, 11p, 11q22-qter, 12p, 12q24, 14q21-qter, 15q23-qter, 17q, 18p, 18q12-qter, 20p, and 20q. By comparison with infiltrating ductal carcinoma, the two medullary carcinomas showed high-level amplification on chromosomes 1p31, 1q, 8q, 10p, 11p and 12p. c-erbB-2, c-myc, cyclin D1, and p53 protein expression was immunohistochemically detected in 9 of 20 (45%), 8 of 20 (40%), 10 of 20 (50%), and 13 of 20 (65%), respectively. The results indicate that the amplification on chromosome 8q, 1q and the deletions on chromosomes 17p and 22q are the most frequent genetic alterations in breast cancers among Koreans. The results reveal a different pattern of genetic alteration from previous studies. The CGH results were not correlated with the immunohistochemical profiles. The amplification pattern of medullary carcinomas was quite different from the pattern of infiltrating ductal carcinomas. The CGH was thought to be very useful in the screening of genetic alterations of solid tumors.
Base Sequence ; Breast Neoplasms ; Breast* ; Carcinoma, Ductal ; Carcinoma, Lobular ; Carcinoma, Medullary ; Chromosomes, Human ; Comparative Genomic Hybridization* ; Cyclin D1 ; DNA ; Fluorescence ; Humans ; Mass Screening ; Metaphase ; Phyllodes Tumor ; Rhodamines

Infiltrating lipoma is one of the most deep-seated benign soft tissue tumor which occupies less than 1% in lipomas. There are two different types of infiltrating lipoma, one intramuscular lipoma, and the other intermuscular lipoma. Nevus lipomatosus cutaneous superficialis is a very rare skin disease which is characterized by the ectopic presence of mature adipose tissue in the dermis. In this disease two clinical types are distinguished: The first classic type is the multiple lesions of zonal distribution usually on the buttocks or on the lower back area. The second type is the solitary papule or nodule with less restricted tendency in its distrubution. We described a 31-year-old man who had a relatively well-defined localized, skin colored, 20x20cm sized, subcutaneous mass partially covered with brown colored papules and plaque on the left subscapular area. The skin lesion began about 11 years ago with brown colored papules and gradually increased in size to 20x20cm mass. Histopathological and clinical findings showed ectopic fat lobules consisted of almost mature cells in the dermis, between the each muscle fibers, and each muscle bundles.
Adipose Tissue ; Adult ; Buttocks ; Dermis ; Fluconazole ; Humans ; Lipoma* ; Nevus* ; Skin ; Skin Diseases

PURPOSE: The purpose of this study is to evaluate the diagnostic capability of MR imaging for distinguishingcholesteatoma from other causes of inflammation. MATERIALS AND METHODS: We prospectively evaluated the MR imagesof 17 patients with a fully opacified middle ear in whom CT of the temporal bone suggested cholesteatoma. Allpatients underwent middle ear surgery and cholesteatoma was verified in 15 cases, granulation tissue in 15,cholesterol granuloma in four and hemotympanium in one. For each lesion, MR and pathologic findings werecorrelated. RESULTS: All cases of cholesteatoma showed low to intermediate signal intensity on T1-weightedimages. On T2-weighted images, 11 cases showed high signal intensity, while seven were less than CSF and four werethe same. Four cases revealed central low signal intensity with peripheral rim of high signal intensity. On GdDTPA-enhanced images, peripheral or marginal enhancement due to surrounding granulation tissue was noted in 12cases. Two appeared to be totally enhanced. One case of congenital cholesteatoma showed no enhancement. OnT2-weighted images, all cases of granulation tissue showed high signal intensity, and on neither T1- norT2-weighted images could these be distinguished from cholesteatoma. On Gd DTPA-enhanced study, all cases ofgranulation tissue were enhanced, and on T1WI, all cases of cholesterol granuloma showed homogeneous bright signalintensity on T1WI. One case of cholesterol granuloma in the mastoid showed bright signal intensity mixed withirregular areas of dark signal intensity. A further comparison of MR imaging with CT is that two case oflabyrinthitis and one of meningitis were diagnosed on Gd- enhanced T1-weighted images. CONCLUSION: Todifferentiate cholesteatoma from granulation tissue and cholesterol granuloma by the evaluation of their signalintensities and enhancement patterns, MR imaging is superior to CT. When there are cholesteatoma-associatedcomplications such as labyrinthitis or meningitis, postcontrast MR imaging can provide better information.
Cholesteatoma* ; Cholesterol ; Ear, Inner ; Ear, Middle ; Granulation Tissue ; Granuloma ; Humans ; Inflammation ; Labyrinthitis ; Magnetic Resonance Imaging ; Mastoid ; Meningitis ; Prospective Studies ; Temporal Bone*

BACKGROUND: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11ql3) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore play a key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. PURPOSE: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. METHOD: Total Si cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell 11mg cancer from January 1., 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. RESULTS: The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was 22.76+/-3.50 months in cyclin D1 positive group and 45.38 +/- 5.64 months in cyclin D1 negative group. There was a nearly significant difference in overall survival Between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. CONCLUISON: Based on this study, cyclin D1 overexpressiom appears at important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.
Adenocarcinoma ; Antibodies, Monoclonal ; Carcinogenesis ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cell Cycle ; Classification ; Cyclin D1* ; Cyclins* ; Follow-Up Studies ; Genes, bcl-1 ; Head ; Humans ; Lung Neoplasms ; Lymph Nodes ; Neck ; Neoplasm Metastasis ; Recurrence ; S Phase