Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.
Background: There have been controversies whether mitral valvular surgery is necessary in the patients with moderate ischemic mitral regurgitation undergoing coronary artery bypass grafting. The purpose of this study is to evaluate the long term clinical results of patients with moderate ischemic mitral regurgitation. Material and Method: Between January 1992 and February 2005, 44 patients with moderate ischemic mitral regurgitation underwent coronary artery bypass grafting. Concomitant mitral valvular procedure was performed in 20 patients (group 1) and isolated coronary artery bypass grafting was performed in 24 patients (group 2). There were no significant difference between groups except cardiopulmonary bypass time (p<0.01). Postoperative follow up duration was $30.1{\pm}29.6$ months and last follow up echocardiographic examination was performed at $21.2{\pm}28.0$ months. Result: There was no difference in operative mortality between groups (group 1 vs group 2, 15.0% vs 8.3%, p=0.493). Grade of mitral regurgitation ${(0.81{\pm}0.91\;vs\;1.50{\pm}0.05,\;p=0.046)}$ and reduction in regurgitation grade ${(1.75{\pm}0.93\;vs\;0.70{\pm}1.26,\;p=0.009)}$ were different between two groups. But there were no significant differences in left ventricular ejection fraction ${(34.1{\pm}11.4%\;vs\;41.6{\pm}12.9%)}$, left ventricular end systolic volume ${(118.2{\pm}63.9\;ml%\;vs\;85.6{\pm}281\;ml)}$, New York Heart Association functional class ${(2.1{\pm}0.2\;vs\;2.4{\pm}1.2)}$ and 5 year survival rate ${(85{\pm}8%\;vs\;82{\pm}8%)}$. There was no risk factor for operative mortality and the only risk factor for late death was preoperative atrial fibrillation (p=0.042). There was no significant correlation between mitral valvular surgery and late death. Conclusion: Concomitant mitral valvular procedure in patients with moderate ischemic mitral regurgitation undergoing coronary artery bypass grafting had no significant positive effect on survival and ventricular function compared with isolated coronary artery bypass grafting. Prospective randomized study may be needed to evaluate the necessity of concomitant mitral procedure and to find more effective method for the improvement of ventricular function.
RNase E is an essential Escherichia coli endoribonuclease that plays a major role in the decay and processing of a large fraction of RNAs in the cell and expression of N-terminal domain consisted of 1-498 amino acids (N-Rne) is sufficient to support normal cellular growth. By utilizing these properties of RNase E, we developed a genetic system to screen for amino acid substitutions in the catalytic domain of the protein (N-Rne) that lead to various phenotypes. Using this system, we identified three kinds of mutants. A mutant N-Rne containing amino acid substitution in the S1 domain (I6T) of the protein was not able to support survival of E. coli cells, and another mutant N-Rne with amino acid substitution at the position 488 (R488C) in the small domain enabled N-Rne to have an elevated ribonucleolytic activity, while amino acid substitution in the DNase I domain (N305D) only enabled N-Rne to support survival of E. roli cells when the mutant N-Rne was over-expressed. Analysis of copy number of ColEl-type plasmid revealed that effects of amino acid substitution on the ability of N-Rne to support cellular growth stemmed from their differential effects on the ribonucleolytic activity of N-Rne in the cell. These results imply that the genetic system developed in this study can be used to isolate mutant RNase E with various phenotypes, which would help to unveil a functional role of each subdomain of the protein in the regulation of RNA stability in E. coli.
Kim, Sun-Young;Lee, Kyung-Joo;Hong, Suk-Chul;Han, Pyo-Sung;Lee, Jong-Jin;Cho, Hae-Jung;Kim, Ju-Ock
Tuberculosis and Respiratory Diseases
/
v.40
no.1
/
pp.23-28
/
1993
Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.
Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.
Purpose : To evaluate the role of postoperative radiation therapy after curative resection of sigmoid colon cancer Materials and Methods : From 1988 to 1993, a total of 93 Patients with curative resectable sigmoid colon cancer of modified Astler-Coiler (MAC) stage B2, B3, C2, C3 was divided into two groups on the basis of those who received radiation treatment and those who did not. Forty-three patients who treated by surgery alone were classified as postop RT (-) group The remaining 50 patients who underwent postoperative radiotherapy were classified as postop RT (+) group. In all patients in Postop RT (+) group. radiation therapy was delivered using 4 or 10 MV linear accelerators to treat the tumor bed with approximately 5cm margin to a total dose 50.4-61Gy(median 54Gy) in 1.8Gy per fraction. Thirty-two patients were treated. with 5-Fluorouracil based adjuvant chemotherapy at least 3 cycles. but these was no significant difference between two groups. Treatment failure Pattern, 5-year local failure-free survival rates (LFFS), and 5-year disease-free survival rates (DFS) were compared between two groups. Result : Five year LFFS and DFS were $85.1\%,\;68.5\%$, respectively, In Postop RT (-) group, LFFS was $76.2\%$ compared with $91.7\%$ in Postop RT (+) group. Improved LFFS and DFS were seen for patients with stage C3 sigmoid colon carcinoma with postoperative radiation therapy compared with postop RT (-) group (P=0.01, p=0.06 respectively), in stage B3, LFFS washigher in postop RT (+) group than that in Postop RT (-) group. although itwas not significant. Especially, local control was higher in stage 74 inpostop RT (+) group than that in postop RT (-) group, Conclusion : This studv showed significantly improved LFFS and DFS in MAC Stage C3 and improved tendency of LFFS and DFS in MAC Stage B3 disease. Large scale prospective study is required to verify the role of adjuvant radiation therapy in resectable sigmoid colon cancer.
Choi Byung Ock;Choi Ihl Bhong;Chung Su Mi;Kim In Ah;Choi Myoung Gyu;Chang Suk Kyun;Shinn Kyeong Sub
Radiation Oncology Journal
/
v.13
no.3
/
pp.243-252
/
1995
Purpose : Intraluminal high dose rate brachytherapy is an accepted treatment for the tumors of GI tract. However, there is only some limited clinical data for intraluminal high dose rate brachytherapy for the tumors of GI tract. Materials and Methods : Between February 1991 and July 1993, 18 Patients who have the tumors of GI tract (esophageal cancer-8 cases, rectal cancer-10 cases) were treated with high dose rate Iridium-192 afterloading system (Microselectron-HDR, Nucletron CO, Netherland) at the department of therapeutic radiology, St. Mary's hospital, Catholic university medical college. Age range was 47-87 years with a mean a9e 71 years. All patients were treated with intraluminal high dose rate brachytherapy within two weeks after conventional external radiation therapy and received 3-5 Gy/fraction 3-4 times per week to a total dose 12-20 Gy (mean 17 Gy). Standard fractionation and conventional dose were delivered for external radiation therapy. Total dose of external radiation therapy ranged 41.4-59.4 Gy (mean 49.6 Gy). Median follow up was 19 months Results : The analysis was based on 18 patients, The complete response and partial response in esophageal cancer was similar (38%). Two year rates for survival and median survival were 13% and 10 months, respectively. Among 10 patients of rectal cancers, partial response was obtained in 6 patients (60%). There was no complete response in the patients with rectal cancer, but good palliative results were achieved in all patients. Conclusion : Although the number of patients was not large and the follow-up period was relatively short, these findings suggested that intraluminal high dose rate brachytherapy could be useful in the treatment of the patients with advanced tumors of GI tract.
Background: The durability of the tissue valve is important in choice between a mechanical valve and a tissue valve in cardiac surgery. We studied the mid-term results of tissue valve in the aortic position. Material and Method: The subjects were 380 patients who had undergone aortic prosthesis replacement between May 1990 and March 2009. We retrospectively analyzed hospital and outpatient records: the mean age was $69{\pm}9$ years; the male to female ratio was 227 : 162; and the mean follow-up duration was $46.7{\pm}40.8$ months (range 0~196 months). Result: 389 surgical cases in total had been taken with 380 patients. Early death occurred in 15 patients (3.9%). Overall survival rate at 1, 5 and 10 years were 92.3%, 78.1% and 54.2% respectively. Freedom from reoperation at 1, 5 and 10 years were 98.4%, 97.1% and 91.7% respectively. Freedom from structural valvular deterioration at 1, 5 and 10 years were 96.1%, 92.3% and 88.0% respectively. In the multivariate analysis of preoperative risk factors, young age (p<0.001) was significant risk factor for reoperation. High peak velocity in the postoperative period (p=0.034) and young age (p=0.029) were significant risk factors for structural valvular deterioration. Old age (p=0.001), long bypass time (p=0.035), concomitant coronary artery bypass graft surgery (p=0.003) and preoperative low left ventricular ejection fraction (p=0.003) were significant factors for early mortality. Preoperative estimated glomerular filtration rate (< 60 mL/min) (p=0.025) and persistent left ventricular hypertrophy (p=0.032) were the risk factors for late mortality. Conclusion: This study showed that the freedom from reoperation and the freedom from structural valvular deterioration in aortic tissue valve replacement were acceptable. It will be necessary to conduct further studies with long-term follow-up and more patients.
$\underline{Purpose}$: To evaluate biological characteristics of neutron beam generated by MC50 cyclotron located in the Korea Institute of Radiological and Medical Sciences (KIRAMS). $\underline{Materials\;and\;Methods}$: The neutron beams generated with 15 mm Beryllium target hit by 35 MeV proton beam was used and dosimetry data was measured before in-vitro study. We irradiated 0, 1, 2, 3, 4 and 5 Gy of neutron beam to EMT-6 cell line and surviving fraction (SF) was measured. The SF curve was also examined at the same dose when applying lead shielding to avoid gamma ray component. In the X-ray experiment, SF curve was obtained after irradiation of 0, 2, 5, 10, and 15 Gy. $\underline{Results}$: The neutron beams have 84% of neutron and 16% of gamma component at the depth of 2 cm with the field size of $26{\times}26\;cm^2$, beam current $20\;{\mu}A$, and dose rate of 9.25 cGy/min. The SF curve from X-ray, when fitted to linear-quadratic (LQ) model, had 0.611 as ${\alpha}/{\beta}$ ratio (${\alpha}=0.0204,\;{\beta}=0.0334,\;R^2=0.999$, respectively). The SF curve from neutron beam had shoulders at low dose area and fitted well to LQ model with the value of $R^2$ exceeding 0.99 in all experiments. The mean value of alpha and beta were -0.315 (range, $-0.254{\sim}-0.360$) and 0.247 ($0.220{\sim}0.262$), respectively. The addition of lead shielding resulted in no straightening of SF curve and shoulders in low dose area still existed. The RBE of neutron beam was in range of $2.07{\sim}2.19$ with SF=0.1 and $2.21{\sim}2.35$ with SF=0.01, respectively. $\underline{Conclusion}$: The neutron beam from MC50 cyclotron has significant amount of gamma component and this may have contributed to form the shoulder of survival curve. The RBE of neutron beam generated by MC50 was about 2.2.
Safflower(Carthamus tinctorius $Linn\acute{e}$ has been traditionally used for the treatment of blood stasis, and Dipsasi Radix has been used as a drug for fracture in Chinese medicine. The purpose of present study was to examine the biologic effects of safflower extract and Disasi radix extracts on the periodontal. ligament cells and osteoblastic cells and on the wound healing of rat calvarial defect. The ethanolic extract of safflower blossom, safflower seed and Dipsasi Radix(125, 250, and 500 ${\mu}g/ml$) were prepared as test group, and PDGF-BB(lOng/ml) and unsafonifiable fraction of Zea Mays L.(125, 250, and 500 ${\mu}g/ml$) were employed as positive control. The effects of each agents on the growth and survival, ALPase activity, expression of PDGF-BB receptor, chemotactic response of PDL cell and ATCC human osteosarcoma MG63 cells in vitro were examined. The tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8mm defect in rat calvaria after oral administration of 3 different dosages groups : 0.02, 0.1 and 0.35g/kg, per day. It was also employed the same dosages of unsaponifiable fraction of Zea Mays L. as positive controls. Safflower blossom extract, safflower seed extract, and Dipsasi Radix extract stimulate the cellular activity of MG63 cells in concentration range of $125-500{\mu}g/ml$, and safflower bolssom extract and safflower seed extract stimulate also the cellular activity of periodontal ligament cells in concentration range of $250-500{\mu}g/ml$. In activity of ALPase, $250-500{\mu}g/ml$ of safflower blossom extracts showed significant stimulating effects on MG63 cells, and the same concentration range of safflower seed extracts showed significant effect on periodontal ligament cells. In the recovery on PDGF-BB receptor expression which was depressed by $IL-1{\beta}$, $125-250{\mu}g/ml$ of safflower blossom extracts and $250-500{\mu}g/ml$ of safflower seed extracts showed significant increasing effect on MG63 cells, and $500{\mu}g/ml$ of safflower blossom extract and $250-500{\mu}g/ml$ of safflower seed extracts showed significant effect on periodontal ligament cells. In chemotactic response, among all tested group, safflower seed extracts only were chemotactic to MG63 cells and periodontal ligament cells in concentration range of $125-500{\mu}g/ml$. Also in the view of bone regeneration in rat calvarial defect model, the only group that was orally administrated 0.35g/kg, day of safflower seed extract showed significant new bone formation. These results suggested that safflower extracts might have a potential possibilities as an useful drug for adjunct to treatment for regeneration of periodontal defect.
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