• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.748-756
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• 2000

Background : Bronchogenic carcinoma is generally considered as a disease that predominantly affects middleaged and elderly men. A small percentage of patients with lung cancer are diagnosed in the third or fourth decade of life or earlier. The current study was performed to review the clinical characteristics of bronchogenic carcinoma in patients younger than 40 years of age at Chungnam National University Hospital. Method : To determine the clinicopathologic characteristics including survival rates of lung cancer patients younger than 40 years of age and to compare them with those of patients 이der than 40 years of age at diagnosis, data of 905 patients diagnosed as lung cancer from January. 1990 to Marm 1997 were analyzed. Result : Twenty-three of 905 patients(2.5%) belonged to the young age group (less than 40 years). Male to female ratios of young age group and control group were 2.8 : 1 and 5.3 : 1, respectively. The mean duration of symptoms from onset to the definite diagnosis was 3.2 months in the young age group. The most common initial symptoms in the young age group were cough(52.2%) and dyspnea(43.5%). Adenocarcinoma (43.5%) was more frequent in the young age group than in the control group(20.1%). Stage III and IV(70%) tumors were more frequent in the young age group than in the control group(52.3%). Distant metastasis rate of the young age group(56.5%) was higher than that of the control group(22.3%). Conclusion : The predominance of adenocarcinoma, the lower male-female ratio, and the high incidence of advanced stage tumor at diagnosis are the characteristics of lung cancer in patients younger than 40 years of age.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.720-727
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• 1996

Objectives: $^{201}TI$ - chloride, $^{99m}Tc$ - MIBI, $^{99m}Tc$(V) - DMSA SPECT has been used in distinguishing lung cancer from benign lesion. To compare the diagnostic efficacy of SPECT with these tumor - seeking agents, we perfonned three consecutive SPECT using $^{201}TI$, $^{99m}Tc$ - MIBI, $^{99m}Tc$(V) - DMSA in same subjects with a solitary pulmonary lesion. Methods: SPECT was carried out at 10min and 3hr for $^{201}TI$ after injection of 20mCi, and 2hr for $^{99m}Tc$ - MIBI and $^{99m}Tc$(V) - DMSA after injection of 20mCi, respectively, in 37 patients with a solitary pulmonary lesion(27 lung cancer and 10 benign diseases). In patients showing visual uptake on lesion site, we obtained the lesion - to - background(target lesion/contralateral normal lung) uptake ratio from transverse slice for each radionuclide and also calculated the retention index for $^{201}TI$. Results: The diagnostic sensitivity of $^{201}TI$, $^{99m}Tc$ - MIBI and $^{99m}Tc$(V) - DMSA SPECT to lung cancer was 100%, 96% and 73%, and the specificity was 40%, 70% and 70%, respectively. The low specificities for these agents were mainly due to high positive uptake in patients with active pulmonary tuberculosis. There were no significant differences in uptake ratios and retention index between malignant and benign lesions, and among the histologic types of lung cancer. Conclusion : $^{201}TI$ and $^{99m}Tc$ - MIBI showed higher sensitivity than $^{99m}Tc$(V) - DMSA for detecting lung cancer, but was of limited usefulness in distinguishing lung cancer from benign lesion due to low specificity, especially in area with a high prevalence of active pulmonary tuberculosis.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.94-97
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• 2014

Purpose: Standardized uptake value (SUV) is a simple semi-quantitative method that can measure the ratio of the tissue radioactivity between the tumor and normal. SUV is commonly used in PET/CT, however, SUV is affected by various factor. The purpose of this study was to evaluate the impact of the residual activity on SUV depending on the location of catheter insertion device post injection. Materials and Methods: NEMA IEC Body Phantom was imaged using a Discovery 600 PET scanner. In 22 mm diameter sphere, the different activity of $^{18}F-FDG$ (7.4, 14.8, 22.2, 29.6, 37, 55.5 MBq) was filled and background was filled with $^{18}F-FDG$ (5.7 kBq/mL). We scaned the phantom on the assumption that the radioactivity in sphere was residual activity in insertion device. Simulation of PET was divided into three groups based on the location of sphere in Scan FOV (SFOV); inclusion, 1/2 inclusion and exclusion group. Results: Among three groups, the group of excluded sphere showed the highest SUV regardless of the amount of $^{18}F-FDG$ activity. In case of 7.4 MBq, average SUV of inclusion group, 1/2 inclusion and exclusion group was 0.780, 0.840 and 0.896 respectively. However, average SUV of 55.5 MBq showed 0.372, 0.460 and 0.508 with same order. Depend on residual radioactivity in the sphere and position of sphere, the SUV was different minimum of 10.4%, maximum of 62.8%. Conclusion: This study showed that SUV is underestimated as the residual radio-activity is increased. In addition, SUV was a changed according to the position of residual radio-activity. And among the position, exclusion group showed the difference of SUV was lowest. If we measure the residual radio-activity of inserting devices and radio-activity from extra-vasation in the patients, it seems to be more useful in clinical field.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.348-355
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• 2003

Background: The prognostic significance of lymph node micrometastasis in non-small cell lung cancer remains controversial. We therefore investigated the clinicopathologic factors related to lymph node micrometastsis and evaluated the clinical relevance of micrometastasis with regard to recurrence. Material and Method: Five hundred six lymph nodes were obtained from 41 patients with stage 1 non-small ceil lung cancer who underwent curative resection between 1994 and 1998. Immunohistochemical staining using anti-cytokeratin Ab was used to detect micrometastasis in these lymph nodes. Result: Micrometastatic tumor cells were identified in pN0 lymph nodes in 14 (34.1%) of 41 patients. The presence of lymph node micrometastasis was not related to any clinicopathoiogic factor (p) 0.05). The recurrence rate was higher in patients with micrometastasis (57.1%) than in those without (37.0%), but the difference was not significant (p=0.22). Patients with micrometastasis had a lower 5-year recurrence-free survival rate (48.2%) than those without micrometastasis (64.1%), with a borderline significance (p=0.11), The S-year recurrence-free survival rate (25.0%) in the patients with 2 or more micrometastatic lymph nodes was significantly lower than that in the patients with no or single micrometastasis (p=0.02). In multivariate analysis, multiple lymph node micromestasis us was a significant independent predictor of recurrence (p=0.028, Risk ratio=3.568). Conclusion: Immunehistochemical anti-cytokeratin staining was a rapid, sensitive, and easy way of detecting lymph node micrometastasis. The presence of lymph node micrometastasis was not significantly associated with the recurrence, but had a tendency toward a poor prognosis in stage 1 non-small cell lung cancer. Especially, the presence of multiple micrometastatic lymph nodes was a significant and independent predictor of recurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6273-6276
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• 2012

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.2
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• pp.74-80
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• 2015

Purpose Breast lymphoscintigraphy is an important technique to present for body surface precisely, which shows a lymph node metastasis of malignant tumors at an early stage and is performed before and after surgery in patients with breast cancer. In this study, we evaluated several methods of body outline imaging to present exact location of lesions, as well as compared respective exposure doses. Materials and Methods RANDO phantom and SYMBIA T-16 were used for obtaining imaging. A lesion and an injection site were created by inserting a point source of 0.11 MBq on the axillary sentinel lymph node and 37 MBq on the right breast, respectively. The first method for acquiring the image was used by drawing the body surface of phantom for 30 sec using $Na^{99m}TcO_4$ as a point source. The second, the image was acquired with $^{57}Co$ flood source for 30 seconds on the rear side and the left side of the phantom, the image as the third method was obtained using a syringe filled with 37 MBq of $Na^{99m}TcO_4$ in 10 ml of saline, and as the fourth, we used a photon energy and scatter energy of $^{99m}Tc$ emitting from phantom without any addition radiation exposure. Finally, the image was fused the scout image and the basal image of SPECT/CT using MATLAB$^{(R)}$ program. Anterior and lateral images were acquired for 3 min, and radiation exposure was measured by the personal exposure dosimeter. We conducted preference of 10 images from nuclear medicine doctors by the survey. Results TBR values of anterior and right image in the first to fifth method were 334.9 and 117.2 ($1^{st}$), 266.1 and 124.4 ($2^{nd}$), 117.4 and 99.6 ($3^{rd}$), 3.2 and 7.6 ($4^{th}$), and 565.6 and 141.8 ($5^{th}$). And also exposure doses of these method were 2, 2, 2, 0, and $30{\mu}Sv$, respectively. Among five methods, the fifth method showed the highest TBR value as well as exposure dose, where as the fourth method showed the lowest TBR value and exposure dose. As a result, the last method ($5^{th}$) is the best method and the fourth method is the worst method in this study. Conclusion Scout method of SPECT/CT can be useful that provides the best values of TBR and the best score of survey result. Even though personal exposure dose when patients take scout of SPECT/CT was higher than another scan, it was slight level comparison to 1 mSv as the dose limit to non-radiation workers. If the scout is possible to less than 80 kV, exposure dose can be reduced, and also useful lesion localization provided.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.157-163
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• 2005

Background: Clinical outcomes of esophageal cancer have not been satisfactory in spite of the development of surgical skills and protocols of adjuvant therapy. We analyzed the results of corrective surgical patients for esophageal cancer from January 1992 to July 2002. Material and Method: Among 129 patients with esophageal cancer, this study was performed in 68 patients who received corrective surgery. The ratio of sex was 59 : 9 (male : female) and mean age was $61.07\pm7.36$ years old. Chief complaints of this patients were dysphagia, epigastric pain and weight loss, etc. The locations of esophageal cancer were 4 in upper esophagus, 36 in middle, 20 in lower, 8 in esophagogastric junction. 60 patients had squamous cell cancer and 7 had adenocarcinoma, and 1 had malignant melanoma. Five patients had neoadjuvant chemotherapy. Result: The postoperative stage I, IIA, IIB, III, IV patients were 7, 25, 12, 17 and 7, respectively. The conduit for replacement of esophagus were stomach (62 patients) and colon (6 patients). The neck anastomosis was performed in 28 patients and intrathoracic anastomosis in 40 patients. The technique of anastomosis were hand sewing method (44 patients) and stapling method (24 patients). One of the early complications was anastomosis leakage (3 patients) which had only radiologic leakage that recovered spontaneously. The anastomosis technique had no correlation with postoperative leakage, which stapling method (2 patients) and hand sewing method (1 patient). There were 3 respiratory failures, 6 pneumonia, 1 fulminant hepatitis, 1 bleeding and 1 sepsis. The 2 early postoperative deaths were fulminant hepatitis and sepsis. Among 68 patients, 23 patients had postoperative adjuvant therapy and 55 paitents were followed up. The follow up period was $23.73\pm22.18$ months ($1\~76$ month). There were 5 patients in stage I, 21 in stage 2A, 9 in stage IIB, 15 in stage III and 5 in stage IV. The 1, 3, 5 year survival rates of the patients who could be followed up completely was $58.43\pm6.5\%,\;35.48\pm7.5\%\;and\;18.81\pm7.7\%$, respectively. Statistical analysis showed that long-term survival difference was associated with a stage, T stage, and N stage (p<0.05) but not associated with histology, sex, anastomosis location, tumor location, and pre and postoperative adjuvant therapy. Conclusion: The early diagnosis, aggressive operative resection, and adequate postoperative treatment may have contributed to the observed increase in survival for esophageal cancer patients.