• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.465-472
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• 2005

Background : The survival benefit associated with first-line chemotherapy in lung cancer has led to the need for second-line chemotherapy, for which Docetaxel ($Taxotere^{(R)}$) has proven efficacy in both settings. This study evaluated the safety and efficacy of docetaxel in patients with non-small cell lung cancer who had failed first-line platinum-based chemotherapy. Methods : Thirty one patients with non-small-cell lung cancer, who had failed first-line platinum-based chemotherapy, between March 1999 and August 2003, were enrolled in this study. Patients received intravenous docetaxel, either $75mg/m^2$ or $100mg/m^2$, with routine premedication every three weeks. Results : Fourteen patients (45.2%) had a partial response. The median survival and progression-free survival times were 12.5 months (95% CI 7.3-17.6) and 3.0 months (95% CI 1.6-4.5), respectively. This study showed 2 factors gave different survival benefits; the age (< 60 years: 20.1 months vs. ${\geq}60years$: 6.6 months, p = 0.0105) and the histological type (adenocarcinoma: 25.6 months vs. others: 7.9 months, p=0.0055). The predominant toxicity was neutropenia, which occurred as WHO grade 3 or 4 in 38.7 % of patients. One treatment-related death was also reported. Non-hematological toxicity was minor and easily controlled. There were no significant statistical differences in the survival benefit and toxicity between the two doses. Conclusion : Docetaxel, as second-line monotherapy, was well tolerated and effective in patients with non-small-cell lung cancer who failed first-line platinum-based chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.304-313
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• 2006

Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Journal of Life Science
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• v.20 no.9
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• pp.1324-1331
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• 2010

Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

• The Korean Journal of Nuclear Medicine
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• v.34 no.3
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• pp.243-251
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• 2000

Purpose: This prospective study was performed to evaluate the usefulness of preoperative radioimmunoscintigraphy and intraoperative scintimetric examination (radioimmunoguided surgery: RIGS) using $^{99m}Tc-anti-CEA\;F(ab')_2$ fragment. Materials and Methods: Nineteen patients with rectal cancer underwent preoperative whole body planar scintigraphy at 4 hours after injection of $^{99m}Tc-anti-CEA\;F(ab')_2$ fragment and SPECT imaging at 18 hours. Surgical operation was performed at 24 hours after injection. During laparotomy, radioactivities from intraabdominal viscera were measured by gamma probe. The radioactivities from excised tumor and lymph nodes were also measured and compared with pathology. Results: All nineteen patients were confirmed to have adenocarcinomas in the rectum. Twenty-seven of 97 excised lymph node groups had metastasis and 2 patients had liver metastasis in pathology Preoperative radioimmunoscintigraphy detected primary tumors in 11 patients (sensitivity 55%) and it could not detect any lymph nodes or liver metastasis. All patients showed high radioactivity in the kidneys, liver, spleen, and major vessels in intraoperative measurement by gamma probe, and tumor activity was not discriminated from background activity However, radioactivity from excised tumor was higher than normal rectum (T/B ratio; $3.47{\pm}2.25$). When excised lymph node activity/background activity ratio >1.5 was considered as positive criteria of metastasis, sensitivity, specificity, positive and negative predictive values were 78.6%, 73.9%, 55.0% and 89.5%, respectively. Conclusion: Radioimmunoscintigraphy using $^{99m}Tc-anti-CEA\;F(ab')_2$ has no additional value for preoperative staging and use of early RIGS using $^{99m}Tc-anti-CEA\;F(ab')_2$ is inappropriate. For early RIGS using $^{99m}Tc$ labeled antibodies in rectal cancer patients, further development of more specific antibodies and methods to reduce background activity are needed.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.2
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• pp.129-136
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• 2009

Purpose: To determine optimal imaging time for diagnostic I-123 whole body scan in the follow-up of patients with differentiated thyroid cancer(DTC), we compared the image quality of 6- and 24-hour images of the same subjects. Materials and Methods: Four hundred ninety-eight patients(M:F = 55:443, Age $47.6{\pm}12.9$ years) with DTC who had undergone total thyroidectomy and I-131 ablation therapy underwent diagnostic whole body scanning 6 hour and 24 hour after oral ingestion of 185 MBq(5 mCi) of I-123. Serum thyroglobulin measurement and ultrasonography of the neck were performed at the time of imaging. In 40 patients underwent additional I-131 therapy, post-therapy I-131 images were obtained and compared with diagnostic I-123 images. Results: In 440 patients(88.4%), 6- and 24-hour diagnostic I-123 images were concordant, and 58 patients(11.6%) showed discordant findings. Among 58 discordant patients, 31 patients showed abnormal tracer uptake on only 6-hour image, which turned out false-positive findings in all cases. In 12 patients with positive findings on only 24-hour image, remnant thyroid tissue(4 patients) and cervical lymph node metastasis(3 patients) were presented. Among 40 patients underwent additional I-131 therapy, 6-hour and 24-hour images were discordant in 13 patients. All 5 patients with abnormal uptake on only 6-hour image revealed false-positive results, whereas most of 24-hour images were concordant with post-therapy I-131 images. Conclusion: I-123 imaging at 24-hour could reduce false-positive findings and improve diagnostic accuracy, compared with 6-hour image in the follow-up of patient with DTC.

• Parasites, Hosts and Diseases
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• v.24 no.2
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• pp.137-144
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• 1986

The author has studied the $\beta$-glucuronidase activity in several tissues such as liver, stomach and small intestine of the male and female rabbits infected with different doses of metacercariae of Clonorchis sinensis. The metacercariae of Clonorchis sinensis were isolated from Pseudorasbora parva caught in Kim Hae by digestion technic. The experimental animals were sacrificed in the period of 1, 7, 14, 21, 28 and 35th days following the infection. The results obtained were summarized as follows. 1. In the groups infected with 100 metacercariae, $\beta$-glucuronidase activity was slightly increased during the entire periods than control rabbits. It was the highest in the first day with 1.535 and $1.421m{\mu}/g$, 14th days with 2.521 and $2.200m{\mu}/g$, and then lowered by the time, gradually. 2. In the groups infected with 500 metacercariae, $\beta$-glucuronidase activity was highly increased on the first day with 1.535 and $1.856m{\mu}/g$ than that 100 metacercariae groups according to each organs. It was the highest on the 7th day and 14th day. 3. In the groups infected with 1,000 metacercariae, $\beta$-glucuronidase activity was remarkably increased in the first and 14th days according to each organs, and then lowered gradually day by day. 4. $\beta$-glucuronidase activity of all organs was more increased than that of normal organs and the highest activity in the liver with $2.521m{\mu}/g$, intestine(1.612) and stomach (1.581) respectively. 5. $\beta$-glucuronidase activity of rabbits was higher in the female than in the male. On the basis of these results, it was suggested that $\beta$-glucuronidase activity was affected by the duration of infection and by the number of Clonorchis sinensis, according to the organs and sex of the rabbits.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.615-623
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• 2009

Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.499-505
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• 2010

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.