• The Korean Journal of Nuclear Medicine Technology
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• v.15 no.2
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• pp.116-124
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• 2011

Purpose: To establish accurate external quality assurance (EQA) test, cross institutional and modality tests were performed using WHO certificated reference material (CRM) and same pooled patients serum. Materials and Methods: Accuracy and precision were evaluated using CRM and pooled patients' serum for AFP, CEA, PSA, CA 125, CA 19-9, T3, T4, Tg, TSH. To evaluate the accuracy and precision, recover test and coefficient variation were measured. RIA test were performed in major 5 RIA laboratory and EIA (CLIA) test were done in 5 major EIA laboratory. same sample of CRM and pooled serum were delivered to each laboratory. Results: In 2009, mean precision of total tumor marker of RIA was $14.8{\pm}4.2%$ and that of EIA(CLIA) was $19.2{\pm}6.9%$. In 2010, mean precision of 5 tumor marker and T3, T4, Tg, TSH was $13.8{\pm}6.1%$ in RIA and $15.5{\pm}7.7%$ in EIA (CLIA). There was no significant difference between RIA and EIA. In RIA, the coefficient variations (CV) of AFP, CEA, PSA, CA 125, T3, T4, TSH were within 20%. The CV of CA 19-9 was over 20% but there was no significant difference with EIA (CLIA) (p=0.345). In recovery test using CRM, AFP, PSA, T4, TSH showed 92~103% of recovery in RIA. In recovery test using commercial material, CEA, CA 125, CA 19-9 showed relatively lower recovery than CRM but there was no significant difference between RIA and EIA (CLIA). Conclusion: By evaluating the precision and accuracy of each test, EQA test could more accurately measured the quality of each test and performance of laboratory.

• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.251-260
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• 2007

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.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.159-168
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• 2004

Background : In recent years, numerous human tumor specific antigens such as melanoma antigen gene(MAGE) that is recognized by autologous cytotoxic T lymphocytes have been identified. MAGE is expressed in many human malignancies in various organs, such as lung, breast, stomach, esophagus and leukemia. Therefore MAGE has been studied widely for tumor diagnosis and immunotherapy. But, so far there were no clinical studies evaluating the role of MAGE in pleural effusion. We investigated the expression of MAGE in the patients with exudative pleural effusion for it's diagnostic utility and the results were compared with those of cytologic examinations. Methods : Diagnostic thoracentesis was performed in 44 consecutive patients with exudative pleural effusion during 6 months. We examined the expression of MAGE and cytology with the obtained pleural effusion. Expression of MAGE was interpreted by means of a commercial kit using RT-PCR method. Enrolled patients were divided into two groups such as malignant and benign and we analyzed its' sensitivity and specificity. Results : There were no significant differences between two groups in age, sex, white blood cell counts in pleural fluid, pleural fluid/serum protein ratio and pleural fluid/serum LDH ratio. The sensitivity and specificity of MAGE were 72.2% and 96.2% respectively and the positive predictive value and negative predictive value of MAGE were also 92.9% and 83.3% respectively. The sensitivity and negative predictive value of cytologic examinations were 66.7% and 81.3% respectively. There were no significant differences between sensitivities of MAGE and cytologic examinations but false positive result of MAGE was found in 1 case of tuberculous pleurisy. Conclusion : MAGE is a sensitive and specific marker for the differential diagnosis between benign and malignant effusion in patients with exudative pleural effusion. And MAGE would provide the equal sensitivity compared with that of cytologic examination in patients with malignant pleural effusion if 5mL of the pleural fluid is examined.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.90-101
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• 1997

The purpose of this study is to evaluate the diagnostic accuracy of various quantitative indices for the differentiation of benign from malignant primary soft tissue tumors by FDG-PET. A series of 32 patients with a variety of histologically or clinically confirmed benign (20) or malignant (12) soft tissue lesions were evaluated with emission whole body (5min/bed position) PET after injection of [$^{18}F$]FDG. Regional 20min transmission scan for the attenuation correction and calculation of SUV was performed in 16 patients (10 benign, 6malignant) followed by dynamic acquisition for 56min. Postinjection transmission scan for the attenuation correction and calculation of SUV was executed in the other 16 patients (10 benign, 6 malignant). The following indices were obtained. the peak and average SUV (pSUV, aSUV) of lesions, tumor-to-background ratio acquired at images of 51 min p.i. ($TBR_{51}$), tumor-to-background ratio of areas under time-activity curves ($TBR_{area}$) and the ratio between the activities of tumor ROI at 51 min p. i. and at the time which background ROI reaches maximum activity on the time-activity curves ($T_{51}/T_{max}$). The pSUV, aSUV, $TBR_{51}$, and $TBR_{area}$ in malignant lesions were significantly higher than those in benign lesions. We set the cut-off values of pSUV, aSUV, $TBR_{51},\;TBR_{area}$ and $T_{51}/T_{max}$ for the differentiation of benign and malignant lesions at 3.5, 2.8, 5.1, 4.3 and 1.55, respectively. The sensitivity, specificity and accuracy were 91.7%, 80.0%, 84.4% by pSUV and aSUV, 83.3%, 85.0%, 84.4% by $TBR_{51}$, 83.3%, 100%, 93.8% by $TBR_{area}$ and 66.7%, 70.0%, 68.8% by $T_{51}/T_{max}$. The time-activity curves did not give additional information compared to SUV or TBR. The one false negative was a case with low-grade fibrosarcoma and all four false positives were cases with inflammatory change on histology. The visual, analysis of FDG-PET also detected the metastatic lesions in malignant cases with comparable accuracy In conclusion, all pSUV, aSUV, $TBR_{51}$, and $TBR_{area}$ are useful metabolic semi-quantitative indices with good accuracy for the differentiation of benign from malignant soft-tissue lesions.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.91-98
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• 1998

Purpose : The relationship between environmental PH on the radiation induced-apoptosis in SCK mammary adenocarcinoma cells and cell cycle dependence was investigated. Material and Methods : Mammary adenocarcinoma cells of A/J mice(SCK cells) in exponential growth phase were irradiated with a $l37^Cs$ irradiator at room temperature. The cells were irradiated 1 hour after the media was replaced with fresh media at a different pHs. After incubation at $37^{\circ}C$ for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Bssults : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. When the cells were irradiated and maintained in pH 7.5 medium, the percentage of cells in $G_2/M$ phase rapidly increased to about $70\%$ at 12 h after an exposure to 120y and returned to control level by 36 h. The percentage of cells in G1 phase decreased as the percentage of cells in $G_2/M$ increased. On the other hand, in pH 6.6 medium the percentage of cells in G2/M phases gradually increased to about $45\%$ at 24 h after 12Gy irradiation and then slowly recessed and consequently, as much as $30-35\%$ of the cells were still in the Ga/M phase 48 h after irradiation. The percentage of cells in G1 phase then increased as the Ga/M arrest began to recede. The radiation-induced Ga/M arrest in PH 0.0 medium lasted markedly longer than that in pH 7.5 medium. Conclusion : Radiation-induced apoptosis in SCK tumor cells are reversely suppressed in an acidic environment. Radiation-induced Ga/M arrest is prolonged in an acidic environment indicating that the suppression of radiation-induced apoptosis and prolongation of radiation-induced Ga/M arrest in an acidic environment are related.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.172-180
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• 2007

Among the nuclear medicine imaging methods available today, $H_2^{15}O-PET$ is most widely used by cognitive neuroscientists to examine regional brain function via the measurement of regional cerebral blood flow (rCBF). The short half-life of the radioactively labeled probe, $^{15}O$, often allows repeated measures from the same subjects in many different task conditions. $H_2^{15}O-$ PET, however, has technical limitations relative to other methods of functional neuroimaging, e.g., fMRI, including relatively poor time and spatial resolutions, and, frequently, insufficient statistical power for analysis of individual subjects. However, recent technical developments, such as the 3-D acquisition method provide relatively good image quality with a smaller radioactive dosage, which in turn results in more PET scans from each individual, thus providing sufficient statistical power for the analysis of individual subject's data. Furthermore, the noise free scanner environment $H_2^{15}O$ PET, along with discrete acquisition of data for each task condition, are important advantages of PET over other functional imaging methods regarding studying state-dependent changes in brain activity. This review presents both the limitations and advantages of $^{15}O-PET$, and outlines the design of efficient PET protocols, using examples of recent PET studies both in the normal healthy population, and in the clinical population.

• The Journal of Korean Society for Radiation Therapy
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• v.29 no.1
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• pp.19-26
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• 2017

Purpose: The application of density override is very important to minimize dose calculation errors by fiducial markers of metal material in proton treatment plan. However, density override with actual material of the fiducial marker could make problem such as inaccurate target contouring and compensator fabrication. Therefore, we perform density override with surrounding material instead of actual material and we intend to evaluate the usefulness of density override with surrounding material of the fiducial marker by analyzing the dose distribution according to the position, material of the fiducial marker and number of beams. Materials and Method: We supposed that the fiducial marker of gold, steel, titanium is located in 1.5, 2.5, 4.0, 6.0 cm from the proton beam's end of range using water phantom. Treatment plans were created by applying density override with the surrounding material and actual material of the fiducial marker. Also, a liver cancer patient who received proton therapy was selected. We located the fiducial marker of gold, steel, titanium in 0, 1.5, 3.5 cm from the proton beam's end of range and the treatment plans were created by same method with water phantom. Homogeneity Index(HI), Conformity Index(CI) and maximum dose of Organ At Risk(OAR) in Planning Target Volume(PTV) as the evaluation index were compared according to the material, position of the fiducial marker and number of beam. Results: The HI value was more decreased when density override with surrounding material of the fiducial marker was performed comparing with density override with actual material. Especially the HI value was increased when the fiducial marker was located farther from the proton beam's end of the range for a single beam and the fiducial marker's position was closer to isocenter for two or more beams. The CI value was close to 1 and OAR maximum dose was greatly reduced when density override with surrounding material of the fiducial marker was performed comparing with density override with actual material. Conclusion: Density override with surrounding material can be expected to achieve more precise proton therapy than density override with actual material of the fiducial marker and could increase the dose uniformity and target coverage and reduce the dose to surrounding normal tissues for the small fiducial markers used in clinical practice. Most of all, it is desirable to plan the treatment by avoiding the fiducial marker of metal material as much as possible. However, if the fiducial marker have on the beam path, density override of the surrounding material can be expected to achieve more precise proton therapy.

• Progress in Medical Physics
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• v.25 no.2
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• pp.100-109
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• 2014

In stereotactic body radiotherapy (SBRT), the accurate location of treatment sites should be guaranteed from the respiratory motions of patients. Lots of studies on this topic have been conducted. In this letter, a new verification method simulating the real respiratory motion of heterogenous treatment regions was proposed to investigate the accuracy of lung SBRT for Volumetric Modulated Arc Therapy. Based on the CT images of lung cancer patients, lung phantoms were fabricated to equip in $QUASAR^{TM}$ respiratory moving phantom using 3D printer. The phantom was bisected in order to measure 2D dose distributions by the insertion of EBT3 film. To ensure the dose calculation accuracy in heterogeneous condition, The homogeneous plastic phantom were also utilized. Two dose algorithms; Analytical Anisotropic Algorithm (AAA) and AcurosXB (AXB) were applied in plan dose calculation processes. In order to evaluate the accuracy of treatments under respiratory motion, we analyzed the gamma index between the plan dose and film dose measured under various moving conditions; static and moving target with or without gating. The CT number of GTV region was 78 HU for real patient and 92 HU for the homemade lung phantom. The gamma pass rates with 3%/3 mm criteria between the plan dose calculated by AAA algorithm and the film doses measured in heterogeneous lung phantom under gated and no gated beam delivery with respiratory motion were 88% and 78%. In static case, 95% of gamma pass rate was presented. In the all cases of homogeneous phantom, the gamma pass rates were more than 99%. Applied AcurosXB algorithm, for heterogeneous phantom, more than 98% and for homogeneous phantom, more than 99% of gamma pass rates were achieved. Since the respiratory amplitude was relatively small and the breath pattern had the longer exhale phase than inhale, the gamma pass rates in 3%/3 mm criteria didn't make any significant difference for various motion conditions. In this study, the new phantom model of 4D dose distribution verification using patient-specific lung phantoms moving in real breathing patterns was successfully implemented. It was also evaluated that the model provides the capability to verify dose distributions delivered in the more realistic condition and also the accuracy of dose calculation.