• Tuberculosis and Respiratory Diseases
• /
• v.52 no.2
• /
• pp.107-116
• /
• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

• Journal of Life Science
• /
• v.22 no.12
• /
• pp.1621-1627
• /
• 2012

Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

• Journal of Gastric Cancer
• /
• v.7 no.3
• /
• pp.132-138
• /
• 2007

Purpose: In Korea, the number of laparoscopy-assisted distal gastrectomies for early gastric cancer patients has been on the increase. Although minimally invasive surgery is more beneficial, no reported case of a total laparoscopic gastrectomy has been reported because of difficulty with intracorporeal anastomosis. This study attempts, through our experience, to determine the safety and feasibility of a total laparoscopic gastrectomy with various types of intracorporeal anastomosis using laparoscopic linears stapler in treating early gastric carcinomas. Materials and Methods: We investigated the surgical results and clinicopatholgical characteristics of 81 patients that underwent a totally laparoscopic distal gastrectomy at our department between June 2004 and May 2007. The intracorporeal anastomoses were performed by using laparoscopic linear staplers. Results: The mean operative time was 287 minutes, the mean anastomotic time was 40 minutes, and the mean number of laparoscopic linear staplers used for an operation was 7.5. The mean time to the first flatus, the first food intake, and discharge from hospital was 2.9, 3.6, and 10.3 days respectively. There were 11 cases of postoperative complications, but no case of postoperative mortality or conversion to an open procedure. In 75 patients with an adenocarcinoma, the mean number of lymph nodes harvested was 38.1 and the stage distribution was as follows: stage I, 72 patients; stage II, 2 patients; stage IV, 1 patient. During the mean follow-up period of 14 months, 5 patients died of other causes and there were no cases of cancer recurrence. Conclusion: A total laparoscopic gastrectomy with intracorporeal anastomosis by using a laparoscopic linear stapler was found to be safe and feasible. We were able to obtain acceptable surgical outcomes in terms of minimal invasiveness.

• The Korean Journal of Nuclear Medicine
• /
• v.34 no.2
• /
• pp.119-128
• /
• 2000

Purpose: The aim of this study was to investigate the diagnostic role of $^{99m}Tc$-Tetrofosmin in detection of breast cancer and compared with that of $^{99m}Tc$-MIBI. Material and Methods: Forty-eight patients with a clinically palpable mass or abnormal mammographic or ultrasonographic findings had $^{99m}Tc-MIBI\;and\;^{99m}Tc$-Tetrofosmin scintimammographies after intravenous injection of 925 MBq of radiopharmaceuticals. The scintimammographs were correlated with histopathologic findings. Results: Thirty-three patients were diagnosed with breast cancer and 15 patients with benign breast diseases. The numbers of true positive, true negative, false positive, and false negative cases of $^{99m}Tc$-MIBI scintimammography were 29, 10, 5, and 4 respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of $^{99m}Tc$-MIBI scintimammographies were 87.8%, 66.7%, 85.3%, and 71.4% respectively. The numbers of true positive, true negative, false positive, and false negative cases of $^{99m}Tc$-Tetrofosmin were 31,10, 5, and 2 respectively. The sensitivity, specificity, positive predictive value, negative predictive value of $^{99m}Tc$-Tetrofosmin were 93.9%, 66.7%, 86.1%, and 73.3% respectively. One patient was false negative in both $^{99m}Tc-MIBI\;and\;^{99m}Tc$-Tetrofosmin acintimammographies and its size was 0.5 cm. Conclusion: $^{99m}Tc-Tetrofosmin\;and\;^{99m}Tc-MIBI$ were non-invasive and useful in detection of breast cancer and $^{99m}Tc$-Tetrofosmin was comparable to the $^{99m}Tc$-MIBI in detection of primary breast cancer.

• Journal of Chest Surgery
• /
• v.29 no.12
• /
• pp.1329-1336
• /
• 1996

From January, 1994 to January. 1996, mitral valve replacement was performed in 27 patients. Among these, 17 patients underwent mitral valve replacement(MVR) with preservation of the annulo-papillary continuity(PAPCMVR) (-Group I), and 10 patients underwent conventional methods of excision of all the chordae(Group II). The operative technique for PAPCM VR consists of the division of the anterior leaflet into anterior and posterior segments, shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas. This retrospective study has been designed to evalute the postoperative left ventricular function in the two groups. In the group 1, LVEF(Left Vnetricular Ejection Fraction : %) was 52 $\pm$ 3 preoperatively And 50$\pm$3 postoperatively, LVESI Vent icular End Systolic Volume Index/mL/m2) wIns 59 :6 and 51 $\pm$ 7, LVEDI Ventricular End Diastolic Volume Index/mL/m2) was 124$\pm$ 11 and 91 :8. In the group II, LVEF was 56$\pm$1 and 47:), LVESVI 62$\pm$12 and 61$\pm$15, LVEDVI 133$\pm$27 and 104$\pm$17. : the variation of the LVEF in these two group was statistically different(p(0.05). A comparison of left ventricular function data between Group I(n: 17) and Group II(n: 10) revealed better results in echocardiographic LVEF(p<0.05), LVEDVI(p<0.01) in the former group. The mean functional class(UYHA) was 2.6 preoperative and improved to 1.0 postoperatively In group 1, and 2.8 and to 1.0 in group II. We conclude that maintenance of continuity between the mitral annulus and papillary muscles is expected to have a beneficial effect on postoperative left ventricular performance.

• Radiation Oncology Journal
• /
• v.9 no.2
• /
• pp.249-252
• /
• 1991

A Retrospective study to analyze the failure pattern in locally advanced stomach cancer, treated with radical surgery and post-op chemotherapy was perfomed. Among 107 patients who underwent radical gastrectomy in Asan Medical Center between June 1989 and August 1990. there were 20 stage II(T2NO, T2N1) and 87 stage III(T3N1, T3N2) and 91 patients were eligible for study. 57 patients treated with 6 cycles of postop adjuvant chemotherapy. Among 57 patients treated with postop adjuvant chemotherapy, local failure occurred in $21\%$ and distant failure in $12\%$. Among 34 patients who were not treated with postop chemotherapy, local failure occurred in $24\%$ and distant failure in $26\%$. Among 29 failures including 13 locoregional, 9 distant metastasis and 7 locoregional and distant metastasis, 11 cases recurred in the anastomotic site, 3 in the gastric bed,7 in the regional lymph nodes and peritoneal seeding occurred in 6 cases. The true incidences of gastric bed, nodal and peritoneal failures may be higher in the longer follow-up or reoperative or autopsy series. Our data sugest that postop chemocherapy is beneficial by reducing distant failure rate. Our data suggest that postop chemocherapy is beneficial by reducing distant failure rate. Postop adjuvant locoregional radiotherapy in addition to the systemic adjuvant therapy may reduce the local failure rate and potentially benefit in at least $20\%$ of patients who developed the local failure only.

• Radiation Oncology Journal
• /
• v.24 no.1
• /
• pp.58-66
• /
• 2006

Purpose: Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Materials and Methods: Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Results: Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-1 mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Conclusion: Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.

• Radiation Oncology Journal
• /
• v.24 no.1
• /
• pp.11-20
• /
• 2006

Puroose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ${\leq}3$ and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range $3{\sim}20$ months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

• Radiation Oncology Journal
• /
• v.20 no.3
• /
• pp.206-214
• /
• 2002

Purpose : The aim of this study was to assess the effectiveness, survival rate and complications of radiation therapy and chemoradiation treatment in hypopharyngeal cancer. Methods and Materials : From January 1984 to December 1999, 56 patients who had hypopharyngeal carcinoma treated with curative radiation therapy were retrospectively studied. Twenty four patients $(42.9\%)$ were treated with radiation therapy alone (Group I) and $32\;(57.1\%)$ treated with a combination of chemotherapy and radiation (Group II). Total radiation dose ranged from 40.5 to 83. 5 Gy (median 67.9 Gy). Radiotherapy was given with conventional technique in 9 patients $(16.4\%)$, with hyperfractionation I ($1.15\~1.2$ Gy/fr., BID) in 26 $(47.2\%)$, hyperfractionation II (1.35 Gy/fr., BID) in 18 $(32.7\%)$, and accelerated fractionation (1.6 Gy/fr., BID) in 2 $(3.6\%)$. In chemotherapy, 5-FU ($1,000\;mg/m^2$ daily for 5 consecutive days) and cisplatin ($100\;mg/m^2$ on day 1) were administered in a cycle of 3 weeks interval, and a total of 1 to 3 cycles (average 2..3 cycles) were given prior to radiation therapy. Follow up duration was $1\~195$ months (median 28 months). Results : Overall 2 and 5 year survival rates were $40.6\%\;and\;27.6\%;\;50.0\%\;and\;30.0\%$ in Group I, and $36.4\%\;and\;26.3\%$ in Group II, respectively. Complete local control rates in Group I and II were $70.0\%\;and\;67.7\%$, respectively. The response to radiotherapy and nodal stage were statistically significant prognostic factors. The complication rate was increased in Group II and was decreased in hyperfractionation. Conclusion : The response to radiotherapy and nodal stage were valid factors to indicate the degree of control over the hypopharyngeal cancer. The induction cisplatin, 5-Fu chemotherapy was not valid in terms of local control rate and survival rate, but did contribute to an increased complication rate. The use of hyperfractionation was valid to reduce the late radiation complications.

• Radiation Oncology Journal
• /
• v.29 no.1
• /
• pp.44-52
• /
• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.