Biomedical subjects

Joungho Han

Publications and source records attributed to Joungho Han.

At least 55 records · Page 3Linked to original sources

PubMed2004

Aberrant methylation of the FHIT gene in chronic smokers with early stage squamous cell carcinoma of the lung.

Fragile histidine triad (FHIT) gene plays an important role in the pathogenesis of lung cancer. However, the clinicopathological significance of CpG island hypermethylation of FHIT gene in non-small cell lung cancer (NSCLC) remains to be elucidated. We studied FHIT methylation in 254 NSCLCs in order to further understand the clinicopathological and prognostic significance of FHIT methylation in NSCLC. Methylation status of the FHIT gene was examined using Methylation-Specific PCR. All statistical analyses were two-sided, with a 5% type I error rate. Hypermethylation of the FHIT gene occurred more frequently in squamous cell carcinoma than adenocarcinoma. For 93 adenocarcinomas there was no statistically significant association between FHIT methylation and age, gender, smoking history, pathologic stage and p16 methylation. However, FHIT methylation in 125 squamous cell carcinomas was associated with exposure to tobacco smoke and p16 methylation, but not with age, gender and pathologic stage. Hypermethylation of FHIT in squamous cell carcinomas occurred more frequently in current smokers (45%) than in never-smokers (13%). FHIT methylation was significantly associated with p16 methylation in current- and ex-smokers (P = 0.02 and P = 0.01, respectively) with squamous cell carcinoma and in patients with pathologic stage I squamous cell carcinoma (P = 0.001). Patients with p16 methylation were 3.74 times [95% confidence interval (CI) = 1.62 - 7.95; P = 0.001] more likely to have FHIT methylation in squamous cell carcinoma. FHIT methylation in squamous cell carcinoma occurred at a 4.62 times (95% CI = 1.26 - 34.97; P = 0.02) higher prevalence in current smokers than in never-smokers. No prognostic effect of FHIT methylation was observed in stage I and stage II NSCLCs. In conclusion, hypermethylation of the FHIT gene did not have a prognostic significance in early stage NSCLCs. The FHIT methylation is associated with the p16 methylation and smoking in squamous cell carcinoma, suggesting that FHIT may cooperate with p16 for the development of squamous cell carcinoma of lung in individuals exposed to tobacco smoke.

Acid Anhydride Hydrolases↗

PubMed2004

Tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer.

PURPOSE: The aim of this study was to identify tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer (NSCLC) by differentiating the age-related methylation from the tumor-specific methylation in NSCLC. PATIENTS AND METHODS: Eighty-five NSCLC patients and 127 cancer-free subjects participated in this study. Aberrant methylation at the promoters of the p16, Ras association domain family 1A (RASSF1A), fragile histidine triad (FHIT), H-cadherin, and retinoic acid receptor beta (RARbeta) genes were evaluated in the resected tumor tissues and bronchial lavage samples of NSCLC patients and in the bronchial lavage samples of cancer-free subjects by methylation-specific polymerase chain reaction. RESULTS: Of the 127 cancer-free samples, methylation was detected in 6% for p16, 13% for RARbeta, 3% for H-cadherin, 4% for RASSF1A, and 28% for FHIT. Hypermethylation of the p16, RARbeta, H-cadherin, and RASSF1A genes was not associated with patient age and smoking, whereas hypermethylation of the FHIT promoter occurred more frequently in older patients (P =.02) and was associated with exposure to tobacco smoke (P =.001). A strong correlation between age and smoking was found in patients with hypermethylation of the FHIT gene (r = 0.36; P =.03). A total of 68% of the bronchial lavage samples from the 85 NSCLC patients showed methylation of at least one of p16, RARbeta, H-cadherin, and RASSF1A genes. CONCLUSION: Our study suggests that tumor-specific methylation of the p16, RASSF1A, H-cadherin, and RARbeta genes may be a valuable biomarker for the early detection of NSCLC in bronchial lavage, and that the age-related methylation of FHIT gene in the normal bronchial epithelium is related to the exposure to tobacco smoke.

Acid Anhydride Hydrolases↗

PubMed2004

Nontuberculous mycobacterial pulmonary infection in immunocompetent patients: comparison of thin-section CT and histopathologic findings.

PURPOSE: To identify and describe the thin-section computed tomographic (CT) findings of nontuberculous mycobacterial (NTM) pulmonary infection in immunocompetent patients and to compare these findings with histopathologic findings. MATERIALS AND METHODS: Between April 2002 and March 2003, the thin-section chest CT findings in and histopathologic lung tissue specimens from 22 patients who fulfilled the American Thoracic Society diagnostic criteria for NTM pulmonary infection were retrospectively reviewed. The lung lesion patterns (ie, small nodules, branching centrilobular nodules [ie, tree-in-bud pattern], consolidation, cavities, bronchiectasis, and volume loss) seen at CT at the sites of transbronchial lung biopsy (n = 22) or lobectomy (n = 1) were compared with the histopathologic findings. RESULTS: Thirteen of the 22 patients were found to have Mycobacterium abscessus pulmonary infection; seven, to have Mycobacterium avium-intracellulare complex infection; and two, to have Mycobacterium fortuitum infection. Regardless of the specific infective mycobacterial species, bilateral small nodules (in 22 [100%] lung locations), cylindric bronchiectasis (in 20 [91%] locations), and branching centrilobular nodular lesions (in 17 [77%] locations) were the most common CT findings seen at the biopsy sites. All of the transbronchial lung biopsy specimens showed a thickened bronchiolar wall and bronchiolar and peribronchiolar inflammation at histopathologic analysis. Dilated bronchioles were identified in 19 (86%) patients, and epithelioid granulomas with or without caseation were seen in seven (32%). CONCLUSION: Regardless of the specific infective mycobacterial species, the most common thin-section CT findings of NTM pulmonary infection are bilateral small nodules, cylindric bronchiectasis, and branching centrilobular nodules. These findings correspond histopathologically to bronchiolectasis and bronchiolar and peribronchiolar inflammation with or without granuloma formation.

Adult↗

PubMed2004

Pulmonary nocardiosis with multiple cavitary nodules in a HIV-negative immunocompromised patient.

The radiological manifestations of pulmonary nocardiosis are very diverse, and include non-segmental consolidation and pulmonary nodule(s). Cavitary nodules most commonly appear in AIDS patients, and are uncommon in non-AIDS patients. We report a case of pulmonary nocardiosis with bilateral multiple cavitary nodules in a HIV-negative 60-year-old man with nephrotic syndrome who was receiving corticosteroid treatment. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of multiple cavitary nodules on chest radiographs, even in non-AIDS immunocompromised patients.

HIV Seronegativity↗

PubMed2004

Sixteen cases of sclerosing hemangioma of the lung including unusual presentations.

Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, the biologic behavior of this tumor has not yet been characterized adequately. The clinicopathologic features were reviewed and analyzed for 16 cases of SH. The age of the patients ranged from 37 to 73 yr (mean 50.6 yr). There were fifteen female and one male patient. The SH located at the intraparenchyme in 14 cases, the interlobar fissure in one case and the visceral pleura in one case. The size of SH ranged from 0.3 cm to 8 cm (mean 2.6 cm). There were five unusual presentations of SH including a case having two SH with multiple nodules of atypical adenomatous hyperplasia in the same lobe, a case showing adenocarcinoma-like area within the SH, a case showing one peribronchial lymph node metastasis (N1 nodal stage) with location of interlobar major fissure, a case showing alveolar adenoma-like area within the SH, and one case with a large visceral pleural-based pedunculated mass presenting as mediastinal mass. All patients were alive and well without recurrence at the last follow up. Here, we reviewed previously published literatures and discussed the histogenesis of SH.

Adolescent↗

PubMed2004

E-cadherin and cytokeratin subtype profiling in effusion cytology.

Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic antigen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.

Biomarkers, Tumor↗

PubMed2004

Pulmonary metastases of uterine endometrial stromal sarcoma: diffuse micronodular and ground glass opacities: a case report.

Pulmonary metastases of uterine endometrial stromal sarcoma (ESS) are uncommon. The patterns of uterine ESS metastasis to the lung are multiple pulmonary nodules, single nodule, or cystic lesions. Pulmonary intraalveolar micronodular metastases of uterine ESS are unusual and have not been reported. We experienced a case of metastatic uterine ESS presenting as pulmonary diffuse micronodules with ground glass opacities on chest computed tomography of a 37-yr-old woman who previously underwent hysterectomy due to low grade ESS of the uterus four years ago. The histologic findings of video assisted thoracotomy biopsy showed numerous intraalveolar polypoid micronodules protruding from the alveolar septums. All tumor nodules were composed of short spindle cells arranged in ill-defined whorls, and nuclear feature and sparse cytoplasm were seen in uterine ESS. Immunohistochemically, these cells showed strong nuclear staining for estrogen receptor and progesterone receptor, and diffuse cytoplasmic staining for CD10.

Adult↗

PubMed2003

Relationship of Ras association domain family 1 methylation and K-ras mutation in primary non-small cell lung cancer.

Recently, several groups have reported that Ras association domain family 1 (RASSF1A) interacts with Ras and mediates Ras-dependent apoptosis. However, the mechanism by which RASSF1A plays a role as a tumor suppressor in human cancer is unclear. In this study, we investigated the relationship between the RASSF1A methylation and K-ras mutation and their effects on patient's survival in 242 primary non-small cell lung cancers (NSCLCs) to understand the role of RASSF1A in Ras-mediated oncogenic transformation. RASSF1A methylation was not found to be associated with the K-ras mutation in NSCLCs (P = 0.37). For patients with stage I adenocarcinoma, those with RASSF1A methylation and K-ras mutation had a poorer prognosis than those with either RASSF1A methylation or K-ras mutation (P = 0.001). In stage II-III adenocarcinoma patients, the median survival of those with RASSF1A methylation and K-ras mutation was 9 months, and this was poorer than that of those with either RASSF1A methylation or K-ras mutation (P = 0.001). The hazard of failure for those with RASSF1A methylation and K-ras mutation was approximately 2.94 times higher compared with that of those with neither K-ras mutation nor RASSF1A methylation (95% confidence interval = 1.67-9.42; P = 0.01). Our results suggest that RASSF1A methylation and K-ras mutation are not mutually exclusive in NSCLC. In addition, RASSF1A methylation, in combination with K-ras mutation, may have an adverse synergistic effect on patient's survival in NSCLCs.

Aged↗

PubMed2003

Hypermethylation of RASSF1A promoter is associated with the age at starting smoking and a poor prognosis in primary non-small cell lung cancer.

Cigarette smoking is the most common cause of lung cancer. The greatest risk of lung cancer is among those who started smoking early in life and continued throughout their lives. However, the molecular mechanisms responsible for the susceptibility to lung cancer in the young smoker are not clear. Recently, several groups have reported that the hypermethylation of CpG islands is associated with exposure to tobacco smoke. We studied the association between the age at starting smoking and hypermethylation of p14, p16, and RASSF1A promoters in 204 primary non-small cell lung cancer patients. We also examined whether hypermethylation of the RASSF1A promoter is an independent prognostic factor. Methylation rates in the 204 samples were detected in 9% for p14, 27% for p16, and 32% for RASSF1A. There was no relationship between the hypermethylation of p14 and p16 and the age at starting smoking. However, hypermethylation of the RASSF1A promoter was found to be significantly associated with the age at starting smoking (P = 0.001). No relationship was found between the methylation status of the RASSF1A promoter and other smoking variables, such as pack-years, smoking status, and the duration of smoking. The age at starting smoking in patients with hypermethylation of RASSF1A was earlier than that of patients without hypermethylation of the RASSF1A promoter (19 +/- 8 versus 25 +/- 7; P = 0.001). Young smokers who started smoking before age 19 were 4.23 times [95% confidence interval (CI) = 1.03-9.67; P = 0.001] more likely to have hypermethylation of the RASSF1A promoter than smokers who started smoking after the age of 19. Furthermore, hypermethylation of the RASSF1A promoter was found to be associated with a poor prognosis in non-small cell lung cancer patients at stages 1 and 2 (P = 0.02 and 0.01, respectively; Log-rank test). The hazard of failure was approximately 3.27 times higher for patients with hypermethylation of the RASSF1A promoter than for those without hypermethylation of the RASSF1A promoter (95% CI = 1.42-8.71; P = 0.01). Young smokers who started the habit before the age of 19 also had a poorer prognosis than those who started after the age of 19 (hazard ratio = 2.14, 95% CI = 1.22-9.11; P = 0.02). Our results suggest that starting cigarette smoking at an early age is associated with hypermethylation of the RASSF1A promoter and that hypermethylation of the RASSF1A promoter may be an independent prognostic factor in primary non-small cell lung cancer.

Adult↗

PubMed2003

Prognostic significance of E-cadherin and beta-catenin in resected stage I non-small cell lung cancer.

OBJECTIVES: E-cadherin and its associated intracellular molecules, catenins, are important for cell-cell adhesion. Impaired expression of these molecules are frequently observed in several cancers. E-cadherin and beta-catenin are often expressed in non-small cell lung cancers. The aim of this study was to investigate the expressions of E-cadherin and beta-catenin and their significance as prognostic markers in pathological stage I non-small cell lung cancer. METHODS: Paraffin embedded tumor tissue blocks were obtained from 141 patients who underwent resection without preoperative radiotherapy or chemotherapy with pathological stage I non-small cell lung cancer. Tumor samples were prepared in tissue microarrays and they were stained by immunohistochemistry with antibodies against E-cadherin and beta-catenin. The expressions of E-cadherin and beta-catenin were analyzed with relation to the clinico-pathological data. The median follow-up period of the patients was 41 months (range, 2-88 months). RESULTS: Preserved expressions of E-cadherin and beta-catenin were observed in the membrane and the cytoplasm of normal epithelial cells and tumor cells. Absent or reduced expression for E-cadherin and beta-catenin were observed in 60% and 45% of all the patients, respectively. There was a significant positive correlation between E-cadherin and beta-catenin expression (P<0.01). Absent or reduced expression of E-cadherin was observed in 72.5%, 36.6%, and 60.0% of squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma, respectively. There was a significant decrease of E-cadherin expression in squamous cell carcinoma compared to adenocarcinoma (P<0.01). Patients with reduced expression of beta-catenin had poor recurrence free survival in adenocarcinoma, but not in squamous cell carcinoma. CONCLUSION: Decreased expressions of E-cadherin and beta-catenin were closely correlated in resected stage I non-small cell lung cancer. Reduced expression of E-cadherin and beta-catenin indicates tumor cell dedifferentiation and reduced expression of beta-catenin had poor recurrence free survival in adenocarcinoma of the resected stage I non-small cell lung cancer.

Adult↗

PubMed2003

Renal tissue reconstitution by the implantation of renal segments on biodegradable polymer scaffolds.

Renal units were created in vivo by transplanting isolated renal segments on three-dimensional, biodegradable polymer scaffolds. Renal segments, freshly isolated from rat kidneys, were seeded on polymer scaffolds and subcutaneously implanted in athymic mice for two and four weeks. Three-dimensional renal reconstructs were formed with glomeruli and tubules, showing a possibility of reconstituting renal structures by transplanting renal segments.

Absorbable Implants↗

PubMed2003

Pulmonary lymphangioleiomyomatosis and multiple hepatic angiomyolipomas in a man.

Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disease that to this point has been known to occur exclusively in reproductive women. To our knowledge, only one case of pulmonary LAM that was proven pathologically has been reported in a genotypical and phenotypical man. Multiple occurrence of hepatic angiomyolipomas is also rare, and only six cases have been found in the literature. Here, we report a biological and phenotypical man who had pulmonary LAM and multiple hepatic angiomyolipomas, leading to a presumptive diagnosis of tuberous sclerosis. This unusual presentation further broadens the wide spectrum of various clinicopathological aspects of pulmonary lymphangioleiomyomatosis and hepatic angiomyolipoma. Here, we emphasize that multiple hepatic angiomyolipomas should be distinguished from hepatic tumors, particularly in an endemic area for hepatocellular carcinoma. Further, pulmonary lymphangioleiomyomatosis can be a cause of cystic pulmonary disease even in a man.

Angiomyolipoma↗

PubMed2003

Tracheal stenosis depends on the extent of cartilaginous injury in experimental canine model.

To test the hypothesis that the development of tracheal stenosis would depend on the extent of tracheal cartilaginous injury, either 90 degrees (n=6) or 180 degrees (n=6) of anterior wall of 4 tracheal rings were cauterized in 12 mongrel dogs using Nd-YAG laser. Beginning at 3 weeks after cauterization, 180 degrees tracheal injury resulted in life-threatening tracheal stenosis whereas 90 degrees injury did not. Gross and microscopic examinations showed that after 180 degrees injury, tracheal stenosis was accompanied by the loss of tracheal cartilage and dense fibrosis. These results indicate that tracheal stenosis depends on the extent of tracheal injury in experimental canine model.

Animals↗

PubMed2003

Bizarre leiomyoma of the scrotum.

Scrotal leiomyomas with atypical bizarre nuclei are rare, which might be misdiagnosed as malignant tumor. We describe a case of scrotal bizarre leiomyoma in a 65-yr-old man. The tumor was a 1 cm-sized, well circumscribed, oval mass arising from the tunica dartos muscle. Histologically, it was formed by whorling bundles of fusiform cells with occasional atypical, pleomorphic nuclei and pseudo-inclusions. Mitosis was not found. Although morphologically atypical, scrotal bizarre leiomyomas take on a biologic behavior not different from that of conventional leiomyoma, they should be distinguished from leiomyosarcoma to avoid unnecessary treatment.

Aged↗

PubMed2003

Nasal rhinoscleroma in a nonendemic area: a case report.

Rhinoscleroma is a chronic, granulomatous infectious lesion most frequently affecting the respiratory tract mucosa. This disease is endemic to Africa, Central and South America, South Central and Eastern Europe, the Middle East, and China. We report an extremely rare disease of nasal rhinoscleroma in Korea. The patient was a 63-yr-old man, who suffered from chronic nasal obstruction and septal deviation. Characteristic histology from a nasal biopsy was proven and special stains for bacteria were employed: periodic acid-Schiff, Warthin-Starry silver, Giemsa, and Gram stains. Isolation of Klebsiella rhinoscleromatis from a culture of nasal discharge was failed, but ultrastructural examination of numerous phagocyzed bacilli in the Mikulicz cells confirmed the diagnosis. The histiocytic nature of the Mikulicz cells was confirmed, using CD 68 and alpha-1 antitrypsin, and by the ultrastructural features of Mikulicz cells. Here, we emphasize the recognition of this rare entity in nonendemic regions, frequently leading to delayed diagnosis.

Endemic Diseases↗

PubMed2002

Importance of open lung biopsy in the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies.

Invasive pulmonary aspergillosis is a serious infectious complication in immunocompromised patients. Recent reports indicate its favorable clinical outcomes by early diagnosis with chest computed tomography scan. We retrospectively analyzed our experiences with histopathological evaluation by open lung biopsy in 31 patients (32 cases) with hematologic malignancies, suspected of having invasive pulmonary aspergillosis clinically and radiologically. Although the initial computed tomography findings of all cases were highly indicative of invasive pulmonary aspergillosis by demonstrating nodules or masses with a halo sign (16 cases), segmental area of consolidation with ground-glass attenuation (7 cases), both nodules or masses with a halo sign and segmental area of consolidation with ground-glass attenuation (7 cases) and poorly defined centrilobular nodules (2 cases), we could histopathologically confirm invasive fungal infections only in 17 cases (53.1%) by open lung biopsy. There were 13 cases of invasive pulmonary aspergillosis, two cases of aspergilloma, and two cases of mucormycosis. No fungal hyphae were found in the other 15 cases: organizing pneumonia in seven cases, pulmonary hemorrhage in three cases, brochiolitis obliterans with organizing pneumonia in two cases, and CMV pneumonia, pulmonary tuberculosis, candida pneumonia in one case each, respectively. We could perform open lung biopsy without mortality and significant morbidity. In view of the low positive predictive value of chest computed tomography scan and the very low morbidity of open lung biopsy, this procedure is recommendable for the diagnosis of invasive pulmonary aspergillosis and determination of its treatment.

Adolescent↗

PubMed2002

Interstitial lung diseases associated with collagen vascular diseases: radiologic and histopathologic findings.

Collagen vascular diseases that demonstrate features of interstitial lung disease include systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, dermatomyositis and polymyositis, ankylosing spondylitis, Sjögren syndrome, and mixed connective tissue disease. At histopathologic analysis, interstitial lung diseases associated with collagen vascular diseases are diverse and include nonspecific interstitial pneumonia, usual interstitial pneumonia, bronchiolitis obliterans organizing pneumonia (BOOP), apical fibrosis, diffuse alveolar damage, and lymphocytic interstitial pneumonia. Although proportions of interstitial pneumonias vary, nonspecific interstitial pneumonia accounts for a large proportion, especially in progressive systemic sclerosis, dermatomyositis and polymyositis, and mixed connective tissue disease. The more favorable prognosis in interstitial pneumonia associated with collagen vascular diseases than in idiopathic interstitial pneumonias may be explained by the larger proportion of nonspecific interstitial pneumonia than of usual interstitial pneumonia. High-resolution computed tomography seems to help characterize and determine the extent of interstitial lung disease in collagen vascular diseases.

Arthritis, Rheumatoid↗

PubMed2002

Viral pneumonias in adults: radiologic and pathologic findings.

Numerous viruses, including influenza virus, measles virus, Hantavirus, adenovirus, herpesviruses, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, can cause lower respiratory tract infection in adults. Viral pneumonia in adults can be classified into two clinical groups: so-called atypical pneumonia in otherwise healthy hosts and viral pneumonia in immunocompromised hosts. Influenza virus types A and B cause most cases of viral pneumonia in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus, herpesviruses, measles virus, and adenovirus. The radiographic findings, which consist mainly of patchy or diffuse ground-glass opacity with or without consolidation and reticular areas of increased opacity, are variable and overlapping. Computed tomographic findings, which are also overlapping, consist of poorly defined centrilobular nodules, ground-glass attenuation with a lobular distribution, segmental consolidation, or diffuse ground-glass attenuation with thickened interlobular septa. The radiologic findings reflect the variable extents of the histopathologic features: diffuse alveolar damage (intraalveolar edema, fibrin, and variable cellular infiltrates with a hyaline membrane), intraalveolar hemorrhage, and interstitial (intrapulmonary or airway) inflammatory cell infiltration. Clinical information such as patient age, immune status, community outbreaks, symptom onset and duration, and presence of a rash remain important aids in diagnosis of viral causes.

Adenovirus Infections, Human↗