• Journal of Chest Surgery
• /
• v.41 no.4
• /
• pp.447-456
• /
• 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
• /
• v.52 no.5
• /
• pp.441-452
• /
• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.66 no.3
• /
• pp.178-185
• /
• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.6
• /
• pp.523-530
• /
• 2007

Background: A ThinPrep$^{(R)}$ Processor was developed to overcome the limitations of conventional cytology and is widely used to diagnose various cancers. This study compared the diagnostic efficacy of conventional cytology for lung cancer with that of the ThinPrep$^{(R)}$ cytology using the bronchial washing fluid. Methods: The bronchial washing fluid of 790 patients from Jan. 2002 to Dec. 2006, who were suspected of gaving a lung malignancy, was evaluated. Both ThinPrep$^{(R)}$ and conventional cytology were performed for all specimens. Result: Four hundred forty-six men and 344 women were enrolled in this study, and 197 of them were diagnosed with cancer from either a bronchoscopic biopsy or a percutaneous needle aspiration biopsy. ThinPrep$^{(R)}$ cytology showed a sensitivity, specificity, positive predictive value, negative predictive value and false negative error rate of 71.1%, 98.0%, 92.1%, 91.1%, 8.9%, respectively. The conventional cytology showed sensitivity, specificity, positive predictive value, nagative predictive value and false negative error rate of 57.9%, 98.0%, 90.5%, 87.5%, 12.5%, respectively. For central lesions, the sensitivity of conventional cytology and ThinPrep$^{(R)}$ were 70.1% and 82.8%, respectively. Conclusion: ThinPrep$^{(R)}$ cytology showed a higher sensitivity and lower false negative error rate than conventional cytology. This result was unaffected by the histological classification of lung cancer. Therefore, ThinPrep$^{(R)}$ cytology appears to be a useful method for increasing the detection rate of lung cancer in bronchial washing cytology test.

• Progress in Medical Physics
• /
• v.24 no.3
• /
• pp.154-161
• /
• 2013

This study assessed compared photon and proton treatment techniques, such as intensity modulated radiation therapy (IMRT), uniform scanning proton therapy (USPT), and intensity modulated proton therapy (IMPT), for a total of 10 prostate cancers. All treatment plans delivered 70 Gy to 95% of the planned target volume in 28 fractions. IMRT plans had 7 fields for the step and shoot technique, while USPT and IMPT plans employed two equally weighted, parallel-opposed lateral fields to deliver the prescribed dose to the planned target. Inverse planning was then incorporated to optimize IMPT. The homogeneity index (HI) and conformity index (CI) for the target and the normal tissue complication probability (NTCP) for organ at risk (OAR) were calculated. Although the mean HI and CI for target were not significantly different for each treatment techniques, the NTCP of the rectum was 2.233, 3.326, and 1.707 for IMRT, USPT, and IMPT, respectively. The NTCP of the bladder was 0.008, 0.003, and 0.002 respectively. The NTCP values at the rectum and bladder were significantly lower using IMPT. Our study shows that using proton therapy, particularly IMPT, to treat prostate cancer could be beneficial compared to 7-field IMRT with similar target coverage. Given these results, radiotherapy using protons, particularly optimized IMPT, is a worthwhile treatment option for prostate cancer.

• The Korean Journal of Nuclear Medicine
• /
• v.36 no.2
• /
• pp.121-132
• /
• 2002

Purpose : Taxol(Paclitaxel), an antineoplastic agent, has been used in the treatment of ovarian and breast cancers. The determination of optimal Taxol concentrations in human serum was required for enhancing therapeutic effect and maintaining the appropriate Taxol level in blood. This study was aimed to synthesizeradiolabeled Taxol derivatives as radiotracer in competitive radioimmunoassay for monitoring Taxol concentrations in blood and to determine the usefulness of its derivatives. Materials and Methods : Hemisucdcinyltaxol(HT) was synthesized by esterification of Taxol with succinic anhydride. Tyraminehemisuccinyltaxol(THT) was synthesized by coupling of HT with tyramine using isobutylchlormate as coupling agent and purified by HPLC. By using chloramine-T($5.25mg/ml,\;10{\mu}{\ell}$) as oxidant agent, THT($4mg/ml,\;30{\mu}{\ell}$) was labeled wity $^{125}I\;(37MBq,\;1mCi)$. To estimate the stability of purified THT, $^{125}I-iodotyraminehemisuccinyltaxol(^125}ITHT)$ was dissolved in 80% acetonitrile aqueous solution, and the solution was incubated at $4^{\circ}C\;and\;37^{\circ}C$ for 7 days. At various time intervals, the stability of THT and $^{125}ITHT$ was monitored. The titer of Taxol monoclonal antibody, 3G5A7, was determined by competitive radioimmunoassay using $^{125}ITHT$ as a labeled antigen. A standard dose-response curve was demonstated by Taxol competitive radioimmunoassay. Resulls : HT and THT were synthesized with 79.9% and 19.5% yield, respectively. The labeling yield of $^{125}ITHT$ was 93%. After 7 days, the chemical purity of THT was 96.5% at $4^{\circ}C$, and 97.5% at $37^{\circ}C$. After 3 days, $^{125}ITHT$ was stable with 94.7% at $4^{\circ}C$ and 93.4% at $37^{\circ}C$. After 7 days, fadiochemical purity was diminished to 88.1% at $37^{\circ}C$. The titer of Taxol monoclonal antibody, 3G5A7, was determined to 1:256. A standard dose-response curve demonstated good collinearity ($R^2=0.971$) as Taxol concentration-dependent manner. Conclusion : Competitive radioimmunoassay using $^{125}I-iodotyraminehemisuccinytaxol$ as radiotracer could be used to monitor for concentration of Taxol in the human serum.

• Journal of Yeungnam Medical Science
• /
• v.17 no.1
• /
• pp.39-48
• /
• 2000

Background: There arc two theories in the development of colon cancer. One is the adenoma-carcinoma sequence theory and the other is the de novo cancer theory. Western countries believe in the adenoma-carcinoma sequence theory, however there are many recent reports from, Japan about cancers developing from small adenomas. Methods: The present study analyzed 408 polyps from 508 cases that were taken by colonoscopic polypectomy at the Department of internal Medicine, Yeungnam University Hospital. Results: The percentage of patients who had a polyp was 41.3% (210 cases out of 526 cases), and the peak incidence was noted in patients in their 50s and 60s, There was no difference between the sexes, but we noted significant increase in the incidence of polyps in patients over the age of thirty. We found 395 polyps below 1cm and 13 polyps above 1cm. Among 408 polyps, 5 cases were cancerous polyps and 3 cases showed polyp size of less than 1cm each. The first case was a polyp of 0.4cm in size with elevated mucosa at the ascending colon. The second was 0.5cm in size with round elevation and hyperemic mucosa in the rectum. The third was 0.6cm in size with tubular elevation at the hepatic flexure. Conclusions: Colon polyp is a common disease in Koreans, Even small polyps can have cancer tissue, which should be removed if discovered during colonoscopy. We believe that not all colon cancer originates in the manner described by the adenoma-carcinoma sequence theory. However further studies with a larger sample population arc needed to determine the exact role of colon polyps in the development of colon cancer.

• Journal of the Korean Applied Science and Technology
• /
• v.29 no.1
• /
• pp.71-80
• /
• 2012

Vinca alkaloids produced from Catharanthus roseus are one of the most important natural product drugs in treatments of human cancers. These anticancer drugs are derived from coupling of the two monomeric indole alkaloids, catharanthine and vindoline. In order to investigate vindoline biosynthesis, tabersonine-$CD_3$ 1a is synthesized to use as a deuterium labeled precursor, which is distinguished clearly from the natural counterpart. We show that these deuterium labeled tabersonine 1a are successfully incorporated into the vindoline biosynthetic pathway to yield three deuterated vindoline intermediates. 16-Hydroxytabersonine-$CD_3$ (m/z 356) 2a, 16-Methoxytabersonine-$CD_3$ (m/z 370) 3a, 16-Methoxy-2,3-dihydro-3-hydroxytabersonine-$CD_3$ (m/z 388) 4a are produced from the cell suspension culture measured by UPLC/MS at 5 and 13 days after feeding tabersonine. The conversion rates from 1a to 2a and 2a to 3a are fast, whereas that from 3a to 4a is much slower. This indicates that the rate determining step among the first three vindoline biosynthesis is the last step. As a result of the slow conversion rate from 3a to 4a, the accumulation level of 16-Methoxytabersonine-$CD_3$ 3a is significantly increased up to 13 days. The accumulation ratio among 2a, 3a and 4a is 1, 2 and 0.1 at 5 days. However, the peaks of desacetoxyvindoline-$CD_3$ 5a, deacetylvindoline-$CD_3$ 6a and vindoline-$CD_3$ 7a are not found from the cell extracts even after 13 days of incubation which may indicate no presence of their corresponding enzymes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.909-913
• /
• 2013

Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, ${\gamma}$-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

• Investigative Magnetic Resonance Imaging
• /
• v.18 no.1
• /
• pp.34-42
• /
• 2014

Purpose : To evaluate the correlation of lesion-to-normal ratio (LNR) of signal intensity from double inversion recovery MR imaging and total choline-containing compound (tCho) resonance from single voxel MR spectroscopy in breast cancers. Materials and Methods: Between August 2008 and December 2009, 28 patients who were diagnosed as breast cancer and had undergone both double inversion recovery (DIR) MR imaging and MR spectroscopy (MRS) were included in this study. The signal intensities of the lesion (L) and ipsilateral normal breast tissue (N) were measured in region of interest of each breast cancer in DIR and contrast enhance MR image (CE-T1WI) to calculate the LNR value for each technique. MRS was performed using single-voxel MR spectroscopy. The height, width and area of tCho resonance were compared with each LNR of DIR and CE-T1WI. We used Pearson's correlation coefficient(r) for correlation analysis and the significance level was p=0.05. Results: There was no statistically significant correlation between LNR of CE-T1WI and height (r=-0.322, p=0.094), width (r=-0.233, p=0.232) and area (r=-0.309, p=0.109) of MRS tCho. There was no statistically significant correlation between LNR of DIR and height (r=0.067, p=0.735), width (r=-0.287, p=0.139) and area (r=0.012, p=0.953) of MRS tCho, either. The Pearson's correlation coefficient was 0.186 between LNRs of CET1WI and DIR (p=0.344). Conclusion: There was no statistically significant correlation between LNR of DIR and relative amount of tCho resonance of MRS.