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*

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

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

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

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

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

Fine needle aspiration cytology(FNAC) has been used effectively as the initial modality in evaluating various thyroid lesions. We correlated cytologic and histopathologic features to investigate the diagnostic pitfalls of FNAC of the thyroid. A total of 1,593 FNACs of the thyroid were diagnosed at the Department of Pathology, Hanyang University Hospital, from January 1993 to December 1997. There were 963 cytologically benign cases(60.5%), 97 suspicious cases(6.1%), and 75 malignant cases(4.71%). The remaining 458 cases(28.8%) were unsatisfactory. Subsequent surgical resection was done in 192 cases. Seventy-two cases(37.5%) were cytologi cally diagnosed as benign, 45 cases(23.4%) suspicious, 56 cases(29.2%) malignant, and 19 cases(9.9%) unsatisfactory. Histopathologically, 101 cases were benign(11 thyroidites, 52 adenomatous hyperplasias, 34 follicular adenomas, and four Hurthle cell adenomas), and 91 cases malignant(72 papillary carcinomas, 16 follicular carcinomas, one medullary carcinoma, one anaplastic carcinoma, and one granular cell tumor). After excluding 19 unsatisfactory cases, 63 were misdiagnosed. They included 17 benign(three thyroidites and 14 adenomatous hyperplasias), 27 suspi cious(16 follicular adenomas, four Hurthle cell adenomas, and seven follicular carcinomas), and 19 malignant(16 papillary carcinoma, one medullary carcinoma, one anaplastic carcinoma, and one granular cell tumor) lesions. The accuracy rates in the benign, suspicious, and malignant categories were 54.9%, 49.8%, & 92.8%, respectively. The cytological pitfalls were as follows: (1) bloody background, (2) crowded follicular cell clusters indistinguishable between follicular neoplasia and adenomatous hyperplasia, (3) papillary structure, irregular nuclear membrane and pleomorphism mimicking those of papillary carcinoma, (4) indistinct eosinophilia in follicular epithelial cells, (5) unusual cellular components not commonly seen in FNACs of the thyroid.
Adenoma ; Biopsy, Fine-Needle* ; Carcinoma ; Carcinoma, Medullary ; Carcinoma, Papillary ; Diagnostic Errors* ; Eosinophilia ; Epithelial Cells ; Hyperplasia ; Nuclear Envelope ; Pathology ; Thyroid Gland*

Primary lymphoma of bone, first described by Parker and Jackson in 1939, is derived from bone marrow reticuloendothelial systems. It is uncommon neoplasm representing only 5% of all extranodal non-Hodgkin's lymphoma. Primary bone non-Hodgkin's lymphoma is characterized by initial symptoms of bone pain with associated single or multiple radiological bone lesions, with or without local soft tissue swelling, pathologic fractures,or regional/distant metastasis. Isolated bone marrow non-Hodgkin's lymphoma is rare, and determining the diagnosis difficult. The common features are fever, abnormal liver function, pancytopenia, polyserositis, neurologic symptoms, opportunistic infections, and a short, fatal course. Treatment includes surgery, radiotherapy, and chemotherapy depending on multiple factors, including histopathologic type of tumor, stage of disease, location of the lesion, and extent of osseous involvement. Five year survival rate is above 80%, when treated by combined radiation & chemotherapy. We experienced a patient who admitted to our department of Internal Medicine. She had mutiple bone pain, general weakness and diagnosed as primary lymphoma of the bone with severe pancytopenia. Her presentation, treatment, and clinical progress were discussed.
Bone Marrow ; Diagnosis ; Drug Therapy ; Fever ; Humans ; Internal Medicine ; Liver ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Mononuclear Phagocyte System ; Neoplasm Metastasis ; Neurologic Manifestations ; Opportunistic Infections ; Pancytopenia* ; Radiotherapy ; Survival Rate