• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.516-524
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• 1997

Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

• The Journal of Korean Society for Radiation Therapy
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• v.29 no.2
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• pp.101-108
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• 2017

Purpose: The proton used in proton therapy has a characteristic of giving a small dose to the normal tissue in front of the tumor site while forming a Bragg peak at the cancer tissue site and giving up the maximum dose and disappearing immediately. It is very important to verify the proton arrival position. In this study, we used the off-line PET CT method to measure the distribution of positron emitted from nucleons such as 11C (half-life = 20 min), 150 (half-life = 2 min) and 13N The range and distal falloff point of the proton were verified by measurement. Materials and Methods: In the IEC 2001 Body Phantom, 37 mm, 28 mm, and 22 mm spheres were inserted. The phantom was filled with water to obtain a CT image for each sphere size. To verify the proton range and distal falloff points, As a treatment planning system, SOBP were set at 46 mm on 37 mm sphere, 37 mm on 28 mm, and 33 mm on 22 mm sphere for each sphere size. The proton was scanned in the same center with a single beam of Gantry 0 degree by the scanning method. The phantom was scanned using PET-CT equipment. In the PET-CT image acquisition method, 50 images were acquired per minute, four ROIs including the spheres in the phantom were set, and 10 images were reconstructed. The activity profile according to the depth was compared to the dose profile according to the sphere size established in the treatment plan Results: The PET-CT activity profile decreased rapidly at the distal falloff position in the 37 mm, 28 mm, and 22 mm spheres as well as the dose profile. However, in the SOBP section, which is a range for evaluating the range, the results in the proximal part of the activity profile are different from those of the dose profile, and the distal falloff position is compared with the proton therapy plan and PET-CT As a result, the maximum difference of 1.4 mm at the 50 % point of the Max dose, 1.1 mm at the 45 % point at the 28 mm sphere, and the difference at the 22 mm sphere at the maximum point of 1.2 mm were all less than 1.5 mm in the 37 mm sphere. Conclusion: To maximize the advantages of proton therapy, it is very important to verify the range of the proton beam. In this study, the proton range was confirmed by the SOBP and the distal falloff position of the proton beam using PET-CT. As a result, the difference of the distally falloff position between the activity distribution measured by PET-CT and the proton therapy plan was 1.4 mm, respectively. This may be used as a reference for the dose margin applied in the proton therapy plan.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.3-8
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• 2016

Purpose SUV is one of the parameters that assist diagnosis in origin, metastasis and staging of cancer. Specially, it is important to compare SUV before and after chemo or radiation therapy to find out effectiveness of treatment. Storing PET data which has no quantitative change is needed for SUV comparison. However, there is a possibility to loss the data in external hard drive or MINIpacs that are managed by department of nuclear medicine. The aim of this study is to evaluate SUV and metabolic tumor volume (MTV) among reconstructed data (R-D) in workstation, R-D and re-sliced data (S-D) in PACS. Materials and Methods Data of 20 patients (aged $60.5{\pm}8.3y$) underwent $^{18}F-FDG$ PET (Biograph truepoint 40, mCT 40, mCT 64, mMR, Siemens) study were analysed. $SUV_{max}$, $SUV_{peak}$ and MTV were measured in liver, aorta and tumor after sending R-D in workstation, R-D and S-D in PACS to syngo.via software. Results R-D of workstation and PACS showed the same value as mean $SUV_{max}$ in liver, aorta and tumor were $2.95{\pm}0.59$, $2.35{\pm}0.61$, $10.36{\pm}6.15$ and $SUV_{peak}$ were $2.70{\pm}0.51$, $2.07{\pm}0.43$, $7.67{\pm}3.73$(p>0.05) respectively. Mean $SUV_{max}$ of S-D in PACS were decreased by 5.18%, 7.22%, 12.11% and $SUV_{peak}$ 2.61%, 3.63%, 10.07%(p<0.05). Correlation between R-D and S-D were $SUV_{max}$ 0.99, 0.96, 0.99 and $SUV_{peak}$ 0.99, 0.99, 0.99. And 2SD in balnd-altman analysis were $SUV_{max}$ 0.125, 0.290, 1.864 and $SUV_{peak}$ 0.053, 0.103, 0.826. MTV of R-D in workstation and PACS show the same value as $14.21{\pm}12.72cm^3$(p>0.05). MTV in PACS was decreased by 0.12% compared to R-D(p>0.05). Correlation and 2SD between R-D and S-D were 0.99 and 2.243. Conclusion $SUV_{max}$, $SUV_{peak}$, MTV showed the same value in both of R-D in workstation and PACS. However, there was statistically difference in $SUV_{max}$, $SUV_{peak}$ of S-D compare to R-D despite of high correlation. It is possible to analyse reliable pre and post SUV if storing R-D in main hospital PACS system.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.14-20
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• 2016

Purpose Tongue cancer is 1.8% of all cancer tumors occur in the tongue, it is known that the high incidence enough to account for 75% of oral cancer conducted a PET / CT examination for early diagnosis, metastasis, staging, etc. and. Tongue when PET / CT scan of a cancer patient and a Torso taken to close mouth lesions if the condition was caused due to the overlapping or corresponding artifacts are not clearly observed. The purpose of this study is to evaluate the changes that occur during PET / CT scan with open mouth and its usefulness under. Materials and Methods From June 2015 to March 2016 complained of herein by May 21 had received a diagnosis of tongue cancer underwent PET / CT scan patients were treated with a target (16 males, 5 female). The first was taken to close mouth Torso state, it was taken to add 1 bed open mouth condition. Tumor (T), measuring the Normal Tongue (NT), Lymph Node (LN) standard intake coefficient by setting a region of interest in the (standardized uptake value, SUV) SUVmean, the average value was measured SUVmax, drawn to each region of interest 3 times and Background (Carotid artery) was out of the SUV. In Chapter 3 of the slice to the tumor clearly visible by setting the region of interest to measure the change Tumor size was calculated average value. Gross Image resolution assessment were analyzed statistically through were divided into 1-5 points by the Radiation 7 people in 2, more than five years worked in specialized nuclear medicine compare to proceed with the blind test nonparametric test (wilcoxon signed rank test). (SPSS ver.18) Results $SUV_{mean}$ T's were in close mouth $5.01{\pm}2.70$ with open mouth $5.48{\pm}2.88$ (P<0.05), $SUV_{max}$ were respectively $8.78{\pm}5.55$ and $9.70{\pm}5.99$ (P<0.05). $SUV_{mean}$ in the NT were respectively $0.43{\pm}0.30$ and $0.34{\pm}0.24$ (P=0.20), $SUV_{max}$ was $0.56{\pm}0.34$ and $0.45{\pm}0.25$ (P=0.204). LN $SUV_{mean}$ were respectively $1.62{\pm}1.43$ and $1.69{\pm}1.49$ (P=0.161), $SUV_{mean}$ was $2.09{\pm}1.88$ and $1.99{\pm}1.74$ (P=0.131). Tumor size change is close mouth $4.96{\pm}4.66cm^2$ $5.33{\pm}4.64cm^2$ with 7.45% increase was (P<0.05), gross image resolution evaluation is $2.87{\pm}0.73$, $3.77{\pm}0.68$ with open mouth examinations 30.5% increase was (P<0.05). Conclusion Tumor SUV on the changes that had an increase in open mouth during inspection, the normal tongue and lymph node, but there was no significant difference in the change slightly. It is also one open mouth PET / CT scan will provide improved image to all patients with tongue cancer, but it could be confirmed that similar overall through the blind test, or tumor size changes and showing a high resolution image. It can be the perfect alternative method for problems that occur when the close mouth Open mouth PET / CT scan, but is believed to be through the open mouth to observe the boundary of overlapping or tumor of the oral cavity other structures a little more clearly. Tongue cancer patients how to recommend that the shooting further open mouth PET / CT.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.882-893
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• 1996

Background : Over one-third of solitary pulmonary nodules are malignant, but most malignant SPNs are in the early stages at diagnosis and can be cured by surgical removal. Therefore, early diagnosis of malignant SPN is essential for the lifesaving of the patient. The incidence of pulmonary tuberculosis in Korea is somewhat higher than those of other countries and a large number of SPNs are found to be tuberculoma. Most primary physicians tend to regard newly detected solitary pulmonary nodule as tuberculoma with only noninvasive imaging such as CT and they prefer clinical observation if the findings suggest benignancy without further invasive procedures. Many kinds of noninvasive procedures for confirmatory diagnosis have been introduced to differentiate malignant SPNs from benign ones, but none of them has been satisfactory. FOG-PET is a unique tool for imaging and quantifying the status of glucose metabolism. On the basis that glucose metabolism is increased in the malignant transfomled cells compared with normal cells, FDG-PET is considered to be the satisfactory noninvasive procedure which can differentiate malignant SPNs from benign SPNs. So we performed FOG-PET in patients with solitary pulmonary nodule and evaluated the diagnostic accuracy in the diagnosis of malignant SPNs. Method : 34 patients with a solitary pulmonary nodule less than 6 cm of irs diameter who visited Samsung Medical Center from Semptember, 1994 to Semptember, 1995 were evaluated prospectively. Simple chest roentgenography, chest computer tomography, FOG-PET scan were performed for all patients. The results of FOG-PET were evaluated comparing with the results of final diagnosis confirmed by sputum study, PCNA, fiberoptic bronchoscopy, or thoracotomy. Results : (I) There was no significant difference in nodule size between malignant (3.1 1.5cm) and benign nodule(2.81.0cm)(p>0.05). (2) Peal SUV(standardized uptake value) of malignant nodules (6.93.7) was significantly higher than peak SUV of benign nodules(2.71.7) and time-activity curves showed continuous increase in malignant nodules. (3) Three false negative cases were found among eighteen malignant nodule by the FDG-PET imaging study and all three cases were nonmucinous bronchioloalveolar carcinoma less than 2 em diameter. (4) FOG-PET imaging resulted in 83% sensitivity, 100% specificity, 100% positive predictive value and 84% negative predictive value. Conclusion: FOG-PET imaging is a new noninvasive diagnostic method of solitary pulmonary nodule thai has a high accuracy of differential diagnosis between malignant and benign nodule. FDG-PET imaging could be used for the differential diagnosis of SPN which is not properly diagnosed with conventional methods before thoracotomy. Considering the high accuracy of FDG-PET imaging, this procedure may play an important role in making the dicision to perform thoracotomy in diffcult cases.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.17-25
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• 1998

Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.