Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition

The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane A2-, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities.

Therapeutic effects of orally administered CJLP55 for atopic dermatitis via the regulation of immune response

Atopic dermatitis (AD) is an inflammatory skin condition accompanied by symptoms such as edema and hemorrhage. Kimchi is a traditional fermented Korean dish consisting of various probiotics. In this study, the therapeutic effect of Lactobacillus plantarum CJLP55 isolated from Kimchi was studied in AD-induced mice. Orally administered Lactobacillus strain, CJLP55, suppressed AD symptoms and high serum IgE levels. CJLP55 administration reduced the thickness of the epidermis, infiltration of mast cells and eosinophils into the skin lesion, enlargement of axillary lymph nodes, and increase in cell population in axillary lymph nodes. CJLP55 treatment decreased the production of type 2 cytokines, such as interleukin (IL)-4, IL-5, IL-10, IL-12, interferon (IFN)-γ, and IL-6,which were stimulated by house dust mite extracts, in the axillary lymph node cells. Orally administered CJLP55 exhibited a therapeutic effect on house dust mite-induced AD in NC/Nga mice after onset of the disease by altering immune cell activation. The Lactobacillus strain, CJLP55, isolated from Kimchi, suppressed AD. Our results suggest its possible use as a potential candidate for management of AD.

Extremely Low Frequency Magnetic Field Modulates the Level of Neurotransmitters

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and gamma -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.

A Case of Epithelioid Blue Nevus

No abstract available.

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-alpha, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-alpha and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

Correlation of AR, EGFR, and HER2 Expression Levels in Prostate Cancer: Immunohistochemical Analysis and Chromogenic In Situ Hybridization / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues. MATERIALS AND METHODS: The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues. RESULTS: The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens. CONCLUSION: This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.

Solitary Extramedullary Plasmacytoma of the Apex of Arytenoid: Endoscopic, CT, and Pathologic Findings

Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm that occurs mainly in the soft tissues of head and neck region, with the paranasal sinuses, nasal cavity and nasopharynx being the most common sites. Solitary EMP of the larynx is very rare but increasingly reported recently. Common sites of involvement in larynx in the order of frequency are the epiglottis, ventricles, vocal folds and ventricular folds. We report an extremely rare case of solitary EMP involving in the apex of arytenoids that was successfully treated by only surgical excision. Because solitary EMP of the apex of artytenoids is extremely rare, it should be included in the differential diagnosis for laryngeal mass. Also, solitary, small, pedunculated and localized EMP of the larynx could be completely removed by laryngeal microsurgery.

Influence of Exposure to Extremely Low Frequency Magnetic Field on Neuroendocrine Cells and Hormones in Stomach of Rats

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatin-positive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in BaSO4 suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.

A Case of Undifferentiated Carcinoma with Osteoclast-Like Giant Cells in the Pancreas / 대한내과학회지

Undifferentiated carcinomas with osteoclast-like giant cells are rare pancreatic and periampullary neoplasms that mimic giant cell tumors of bone morphologically. Recently, we experienced an osteoclast-like giant cell tumor arising in the tail of the pancreas. A 76-year-old male was admitted with epigastric discomfort and indigestion. Abdominal computed tomography (CT) and abdominal magnetic resonance imaging (MRI) showed a 3x3-cm mass containing necrotic and hemorrhagic areas in the tail of the pancreas. A distal pancreatectomy and splenectomy were performed. Histological examination showed tumor cell components consisting of mononuclear pleomorphic cells admixed with osteoclastic giant cells. The final diagnosis was undifferentiated carcinoma with osteoclast-like giant cells with ductal adenocarcinoma in the pancreas.

A Metastatic Granulocyte Colony-Stimulating Factor Producing Sarcomatoid Carcinoma of the Lung Causing Jejunal Intussusception: Report of a Case

A 75-year-old man was referred to our hospital with intestinal obstruction caused by intussusception. Abdominal computed tomography (CT) revealed seven polypoid masses in the small intestine, while chest CT revealed a mass in the right lower lobe. Preoperative laboratory tests showed white blood cell (WBC) and neutrophil differential counts of 63,630/mm3 and 95%, respectively. The serum granulocyte colony-stimulating factor (G-CSF) was 114 pg/mL, which was elevated (normal range, <18.1 pg/mL). After resection of the small bowel, the WBC count decreased to 20,510/mm3. The pathology showed a poorly differentiated carcinoma with sarcomatous components confirmed by positive immunostaining of cytokeratin (AE1/AE3) and vimentin in the small intestine. Furthermore, immunohistochemistry with specific monoclonal antibodies against G-CSF was positive. A lung biopsy revealed the same histological findings as the small intestine lesion. Therefore, the patient was diagnosed as having a G-CSF producing sarcomatoid carcinoma of the lung with metastasis to the small intestine.

In vivo Tracking of Mesenchymal Stem Cells Labeled with a Novel Chitosan-coated Superparamagnetic Iron Oxide Nanoparticles using 3.0T MRI

This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl2 and FeCl3. The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microgram Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.

Effects of Three Different Types of Anti-adhesive Agents in a Rat Abdominal Wall Defect Model

PURPOSE: Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. Several adhesion barriers have been developed in the form of solution, membrane or film in an attempt to solve these problems. The purpose of the present study is to compare the efficacy of antiadhesive agents in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. METHODS: We examined forty Sprague-Dawley rats, which is a cecal abrasion with partial peritonectomy model. Three treatment groups (Group I: Film-type Surgiwrap(R), Group II: Solution-type Guardix-sol(R), Group III: Membrane-type Interceed(R)), each consists of 10 rats, and a control group of 10 rats were used by saline. Ten days after surgery, the rats were killed, and the levels of adhesion were graded. Immunohistochemical staining for microvessel density (CD34, MVD) and macrophage (ED1) were performed in adhesion tissue. RESULTS: The peritoneum adhesion mean scores are as follows: control group: 2.2+/-0.78, Group I: 1.0+/-1.06, Group II: 0.9+/-0.99, Group III: 0.6+/-0.84. All treatment groups showed significantly less peritoneum adhesion (P=0.006), while there was no significant difference in each group. The intraperitoneal organs adhesion mean scores are as follows: control group: 2.8+/-0.91, Group I: 2.6+/-1.06, Group II: 1.4+/-0.84, Group III: 1.0+/-0.81. Group I had no significant difference about intraperitoneal organs adhesion with control group, but Group II and Group III showed less intraperitoneal organs adhesion. The mean numbers of microvessel density are as follows: control group: 42.5+/-4.83, Group I: 40.8+/-6.53, Group II: 30.9+/-6.15, Group III: 15.60+/-4.37, from which there was a significant difference between Group II and Group III with control group (P<0.001). The mean numbers of macrophage are as follows: control group: 223.3+/-33.12, Group I: 211.25+/-10.96, Group II: 171.60+/-23.96, Group III: 147.0+/-12.22, from which there was a significant difference between Group II and Group III with control group (P<0.001). CONCLUSION: In our animal model, three different types of antiadhesive agents (Surgiwrap(R), Guardix-sol(R), Interceed(R)) were effective in adhesion prevention, but Surgiwrap(R) had less antiadhesive effect for intraperitoneal organs adhesion. Membrane-type Interceed(R) had a better effect for microvessel density (MVD) and macrophage than solution-type Guardix-sol(R).

Effects of Extremely Low Frequency Elecromagnetic Fields on Thyroid Carcinogenesis Induced by N-bis(2-hydroxypropyl)nitrosamine and Sulfadimethoxine

PURPOSE: Long-term exposure to extremely low-frequency (60 Hz) electromagnetic fields (ELF-EMF) raises the questions of the induction of biological effects including tumorigenesis. One mechanism through which ELF-MFS could influence neoplastic development is the imbalance of cellular proliferation and cell apoptosis. The present study investigated the effect of ELF-EMF on chemically-induced thyroid carcinogenesis in a rat. METHODS: We examined cellular proliferation index measured by anti-Ki-67 antigen, apoptosis, apoptosis related proteins such as caspase 3 and p53, and cell cycle-related proteins (cyclin D1 and p21(WAF1/Cip1)). Forty Male F344 rats received a subcutaneous N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2,800 mg/kg) injection, and 1 week later were allowed free access to drinking water containing sulfadimethoxine (0.1%) for 12 weeks. Twenty rats were exposed by ELF-EMF. During the carcinogenesis, sequential histological changes from hyperplasia, adenoma, and ultimately to overt carcinomas were noted. RESULTS: The exposure group of ELF-EMF, significantly increases the number size of carcinomas. Also, the proliferative and apoptotic indices were significantly increased in the ELF-EMF exposure group than in the control group. The caspase 3 protein expression did not show any significant changes between ELF-EMF group and control group. The p53 protein was not detected in both ELF-EMF exposure and control group. Among the cell cycle related proteins, cyclin D1, not p21(WAF1/Cip1), was significantly increased in adenomas and carcinomas in ELF-EMF exposure group compared with the control group. CONCLUSION: Exposure of ELF-EMF effects on chemically-induced rat thyroid carcinogenesis as results of altered increase of cellular proliferation, apoptosis, and cyclin D1 expression.

Atherosclerotic Progression Attenuates the Expression of Nogo-B in Autopsied Coronary Artery: Pathology and Virtual Histology Intravascular Ultrasound Analysis

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.

Intravascular Leiomyosarcoma of the Femoral Vein: A Case Report

Intravascular leiomyosarcomas of the femoral vein are extremely rare. Our patient was initially diagnosed with a deep vein thrombosis based on ultrasonography and venography. The thrombectomy specimen consisted of typical spindle cells with variable anaplasia arranged in a fasciculating and interlacing pattern. The final diagnosis was proved to be an intravascular leiomyosarcoma confirmed by immunohistochemical studies for smooth muscle actin, desmin, vimentin, CD34 and CD68.

Adrenal Ganglioneuroma Treated by Laparoscopic Surgery

Adrenal ganglioneuromas are rare benign tumors arising from the neural crest tissue of the sympathoadrenal nervous system. Because most of these tumors are hormonally silent and patients with them are often asymptomatic, they are often identified incidentally in patients undergoing abdominal imaging studies for unrelated reasons. Diagnosis of this entity is very difficult to make, with definitive diagnosis being based on histological examination. Surgical resection may be both diagnostic and therapeutic. A technique for laparoscopic adrenalectomy of benign adrenal tumors has recently been developed. If the tumor is excised with an adequate resection margin, the postoperative prognosis is very good. In this report, we describe two cases of adrenal ganglioneuroma that were treated using a laparoscopic resection procedure, and we also present a review of the pertinent literature.

Immunohistochemical Analysis of Nuclear Factor, p38, and Cyclin D1 Proteins in Premalignant Lesions and Carcinomas of the Colorectal Mucosa / 대한소화기학회지

BACKGROUND/AIMS: Nuclear factor-kappa B p65 (NF-kappa B p65), nuclear factor-kappa B1 p50 (NF-kappa B p50) have been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated protein kinase (MAPK)/ NF-kappa B/ cyclin D1 signaling pathway has been shown to play an important part in the pathogenesis of human cancers. This study was designed to investigate the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal adenocarcinoma. METHODS: Paraffin sections of 20 normal mucosa, 20 low-grade tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were analysed immunohistochemically for the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins. RESULTS: The expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins were significantly higher in adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappa B p50 was more frequent in poorly differentiated histologic grade, presence of nodal metastasis, and advanced stage. Expression of p38 MAPK alpha protein was higher in advanced tumor stage, presence of nodal metastasis and advanced stage. Synchronous expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins were significantly higher in adenocarcinoma tissue. CONCULSIONS: With the increased expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins, p38 MAPK/ NF-kappa B/ cyclin D1 signaling pathway may play a role in the pathogenesis of colorectal carcinoma.

Analysis of expression of survivin, caspase 3, and p53 protein in cervical neoplasia comparing with Ki-67 index / 부인종양

OBJECTIVE: The aim of this study was to determine the role of survivin, caspase 3, p53 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 94 patients with a diagnosis of Low grade CIN (31 cases), High grade CINL (32 cases) and squamous cell carcinoma (31 cases) were evaluated immunohistochemically for the expression of survivin, caspase 3, p53 and Ki-67 in paraffin sections. RESULTS: Survivin, p53 and Ki-67 expressions were progressively increased in accordance with the increasing degree of malignancy, but caspase 3 immunoreactivity was higher in high grade CIN than in low grade CIN and invasive cervical cancers. There was no significant difference between Ki-67 index and survivin, caspase 3 and p53 expression with the increasing degree of malignancy. The Ki-67 index was closely related to p53 overexpression in invasive cervical carcinoma group. CONCLUSION: A sequential increase of survivin, p53, and Ki-67 was observed in paralleling the progression of grade of CIN and cervical cancer. In addition, caspase 3 expression increased proportionally to the low-grade CIN to high grade CIN.

Expression of Proteins Related Cell Cycle and Apoptosis during Diethylnitrosamine (DEN)-induced Hepatocarcinogenesis in Rats

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.

Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis / 결핵및호흡기질환

PURPOSE: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. METHODS: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. RESULTS: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. CONCLUSIONS: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.