• Journal of Korean Neurosurgical Society
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• v.30 no.sup2
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• pp.273-280
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• 2001

Objectives : The purpose of this study is to assess the long-term outcome and delayed complications of Gamma Knife radiosurgery for low grade glioma(LGG). Methods : Among 31 patients of LGG who had been treated by using Leksell Gamma Knife between March 1992 and December 1996, we could follow up more than 5 years(range 5-9 years) in 17 patients and evaluated their clinical feature, changes of tumor volume and post-radiosurgical complications. Results : During the mean follow-up period of 7.6 years, the tumor was decreased in 5 patients(29.4%), unchanged in 4(23.5%), increased in 4(23.5%) and recurred in 4(23.5%). The tumor control rate was 52.9%(9/17). We have experienced eighteen postradiosurgical complications in 10 patients(58.8%). Early complication was none and delayed complications included radiation necrosis with cyst in ten cases, bleeding in five, radiation-induced edema in one and malignant transformation in one. Two patients ultimately died as a result of tumor progression during the follow-up period. The mortality rate was 11.7%. Conclusion : Gamma Knife radiosurgery may be useful as an adjunctive therapy for small volume, deep-seated LGG. Although radiosurgery can effectively prevent growth of solid tumor, several delayed complications such as radiation necrosis, cyst formation, bleeding or malignant transformation can develop during the long-term followup period. Because of the possible slow growth rate of LGG and development of the delayed complications, the long-term efficacy of radiosurgery requires further analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2781-2785
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• 2016

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.147-152
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• 2021

C-11 Radiolabeled amino acid-based radiopharmaceuticals such as [¹¹C]MET for brain tumor PET imaging have limitations due to their short half-life (20 min). F-18 radiolabeled amino acid derivatives have been developed to overcome for the short half-life, one of which is [¹⁸F]FET. Brain tumor imaging using [¹⁸F]FET showed high uptake in tumor region and no non-specific uptake in inflammatory tissue, which was useful in discriminating the difference between inflammation and tumor especially. In this study, [¹⁸F]FET was synthesized using an automatic synthesis module and quality tests were carried out including enantiomeric purity analysis with reference compounds. Radiochemical yield was 50.3 ± 4.9% (n=7, decay-corrected) with molar activity of 76 ± 17 GBq/mmol. The radiochemical purity of >99%. Enantiomeric purity of [¹⁸F]FET using chiral HPLC analysis showed >99%, which was confirmed by co-injection with the L-FET and D-FET authentic standards. [¹⁸F]FET was prepared with high radiochemical yield and molar activity including no racemate mixture.

• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.465-475
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• 2023

Objective : Our objective is to analyze the occurrence, clinical course and risk factors for glioma patients with leptomeningeal metastasis (LM) according to different metastasis patterns and clinical variables. Methods : We retrospectively reviewed data from 376 World Health Organization (WHO) grade II-IV adult glioma patients who were treated in the National Cancer Center from 2001 to 2020. Patients who underwent surgery at other institutions, those without initial images or those with pathologically unconfirmed cases were excluded. LM was diagnosed based on magnetic resonance imaging (MRI) findings or cerebrospinal fluid (CSF) cytology. The metastasis pattern was categorized as nodular or linear according to the enhancement pattern. Tumor proximity to the CSF space was classified as involved or separated, whereas location of the tumor was dichotomized as midline, for tumors residing in the thalamus, basal ganglia and brainstem, or lateral, for tumors residing in the cerebral and cerebellar hemispheres. Results : A total of 138 patients were enrolled in the study. A total of 44 patients (38%) were diagnosed with LM during a median follow-up of 9 months (range, 0-60). Among the clinical variables, tumor proximity to CSF space, the location of the tumor and the WHO grade were significant factors for LM development in univariate analysis. In multivariate analysis, the midline location of the tumor and WHO grade IV gliomas were the most significant factor for LM development. The hazard ratio was 2.624 for midline located gliomas (95% confidence interval [CI], 1.384-4.974; p=0.003) and 3.008 for WHO grade IV gliomas (95% CI, 1.379-6.561; p=0.006). Conclusion : Midline location and histological grading are an important factor for LM in glioma patients. The proximity to the CSF circulation pathway is also an important factor for WHO grade IV glioma LM. Patients carrying high risks should be followed up more thoroughly.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.167-176
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• 1997

The present investigation was focussed mainly on the development of the tumors and proliferating cells on the intestinal tracts of 1, 2-dimethyl-hydrazine(DMH)-treated young or adult rats. 26 rats(Wistar, 14 young rats weighting approximately 130~180gm and 12 adult rats weighting approximately 500~550gm) were given subcutaneously once weekly with 20mg of DMH/kg body weight(BW)/week for 8~22 weeks. Individual body weight were recorded weekly at the same day and time. The rats were killed at 8, 13, 15. 17, 19, 21 and 22 weeks. The intestinal tracts were opened longitudinally and carefully examined for tumors. The localization, number, and size of tumors were noted. Tumor-bearing areas were dissected out and fixed on neutral buffered 10% formalin and normal-looking mucosa from 8~22 weeks rats were also taken for fixation. Paraffin sections were stained by H-E for histopathological examination or with immunohistochemical stain for bromodeoxyuridine(Brdur) positive cells. 1. The growth proportion of body weight appeared to be decreased in the DMH-treated young rats than in control young rats and body weight of DMH-treated adult rats appeared to be 13.4% or less lower than weighted on 0 week. 2. Macroscopically, the developed tumors in the intestinal tracts were not observed as early as the 13 weeks after DMH treatment. The number of developed tumors per rat was found to be 14.3, 18.8, 22.3 in 15, 17 and 22 weeks. The numbers of tumors in intestinal regions per rat were 2.1, 4.3, 5.4, 2.5 in duodenum, jejunum, ilium and colon on 15 weeks, 2.3, 6.4, 7.8, 2.3, on 17 weeks, and 2.7, 9.3, 9.0, 1.3 on 22 weeks, respectively and the ileum and jejunum were higher in appearance rate of tumors and tumor types are dome shapes and diameter of largest tumor were 6.3mm. 3. Histopathologically, intestinal mucosa were thickened by the irregular distorted and distended crypts following hyperplasia. The tumors developed on the mucosa and submucosa and were recognized to be adenocarcinoma. 4. Immunohistochemically, the labeling index(LI) was calculated as the ratio of the number of Brdur-labeled cells to the total number of column cells of the crypts with longitudinal axis. LI of Brdur positive cells per crypt were 5.6%, 8.0% on small intestine of control and 22 week group, respectively and 3.7%, 12.7% on large intestine of control and 22 week group, respectively and were appeared to be increase in 22 week group than in control group and to be more number of proliferating cells in 22 week group than in control group. 5. LI of Brdur positive cells in 1, 2, 3, 4, 5 segments of crypt column were 11.7%, 10.7%, 3.8%, 0.6%, 0% in small intestine of control group and 23.5%, 11.8%, 2.3%, 2.4%, 0.8% in small intestine of 22 week group, and 5.4%, 7.4%, 3.8%, 1.0%, 0.4% in large intestine of control group and 29.5%, 20.3%, 5.9%, 6.3%, 1.3% in large intestine of 22 week group respectively. So results indicate that the number of proliferating cells by DMH treatment increase and were concentrated on the 1, 2 segments of crypt columns.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4589-4594
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• 2014

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.299-303
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• 2011

Objective : Brainstem metastases are rarely operable and generally unresponsive to conventional radiation therapy or chemotherapy. Recently, Gamma Knife Radiosurgery (GKRS) was used as feasible treatment option for brainstem metastasis. The present study evaluated our experience of brainstem metastasis which was treated with GKRS. Methods : Between November 1992 and June 2010, 32 patients (23 men and 9 women, mean age 56.1 years, range 39-73) were treated with GKRS for brainstem metastases. There were metastatic lesions in pons in 23, the midbrain in 6, and the medulla oblongata in 3 patients, respectively. The primary tumor site was lung in 21, breast in 3, kidney in 2 and other locations in 6 patients. The mean tumor volume was $1,517mm^3$ (range, 9-6,000), and the mean marginal dose was 15.9 Gy (range, 6-23). Magnetic Resonance Imaging (MRI) was obtained every 2-3 months following GKRS. Follow-up MRI was possible in 24 patients at a mean follow-up duration of 12.0 months (range, 1-45). Kaplan-Meier survival analysis was used to evaluate the prognostic factors. Results : Follow-up MRI showed tumor disappearance in 6, tumor shrinkage in 14, no change in tumor size in 1, and tumor growth in 3 patients, which translated into a local tumor control rate of 87.5% (21 of 24 tumors). The mean progression free survival was 12.2 months (range, 2-45) after GKRS. Nine patients were alive at the completion of the study, and the overall mean survival time after GKRS was 7.7 months (range, 1-22). One patient with metastatic melanoma experienced intratumoral hemorrhage during the follow-up period. Survival was found to be associated with score of more than 70 on Karnofsky performance status and low recursive partitioning analysis class (class 1 or 2), in terms of favorable prognostic factors. Conclusion : GKRS was found to be safe and effective for management of brainstem metastasis. The integral clinical status of patient seems to be important in determining the overall survival time.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.223-229
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• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.149-155
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• 1987

The success of radioation therapy depends on exact treatment of the tumor with significant high dose for maximizing local control and excluding the normal tissues for minimizing unwanted complications. To achieve these goals, correct estimation of target volume in three dimension, exact dose distribution in tumor and normal critical structures and correction of tissue inhomogeneity are required. The effect of therapy oriented CT (plannng CT) were compared with conventional simulation method in necessity of planning change, set dose, and proper distribution of tumor dose. Of 365 new patients examined, planning CT was performed in 104 patients $(28\%)$. Treatment planning was changed in $47\%$ of head and neck tumor, $79\%$ of intrathoracic tumor and $63\%$ of abdmonial tumor. in breast cancer and musculoskeletal tumors, planning CT was recommended for selection of adequate energy and calculation of exact dose to critical structures such as kidney or spinal cord. The average difference of tumor doses between CT planning and conventional simulation was $10\%$ in intrathoracic and intra-abdominal tumors but $20\%$ in head and neck tumors which suggested that tumor dose may be overestimated in conventional simulation Although some limitations and disadvantages including the cost and irradiation during CT are still criticizing, our study showed that CT Planning is very helpful in radiotherapy Planning.