• Radiation Oncology Journal
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• v.16 no.4
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• pp.389-398
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• 1998

Purpose : To evaluate the role of conventional postoperative adjuvant radiotherapy in the management of supratentorial malignant glioma and to determine favorable prognostic factors affecting survival. Materials and Methods : From Sep. 1985 to Mar. 1997, the number of eligible patients who received postoperative radiotherapy completely was 69. They ranged in age from 7 to 66 years (median, 47). Forty-two (61$\%$) patients were glioblastoma multiforme and the other 27 (39$\%$) were anaplastic astrocytoma. Twenty patients (29$\%$) had Karnofsky score equal or more than 80 preoperatively. Forty-three patients (62$\%$) had symptom duration equal or less than 3 months. Twenty-four patients (35$\%$) had gross total resection and forty patients(58$\%$) had partial resection, the remaining five patients (7$\%$) had biopsy only. Radiotherapy dose ranged from 50.4 Gy to 61.2 Gy (median, 55.8; mode, 59.4) with fraction size of 1 8 Gy-2.0 Gy for 33-83 days(median, 48) except three patients delivered 33, 36, 39 Gr, respectively with fraction size of 3.0 Gy due to poor postoperative performance status. Follow-up rate was 93$\%$ and median follow-up period was 14 months. Results : Overall survival rate at 2 and 3 years and median survival were 38$\%$, 20$\%$, and 16 months for entire patients; 67$\%$, 44$\%$, and 34 months for anaplastic astrocytoma; 18$\%$, 4$\%$, and 14 months for glioblastoma multiforme, respectively (p=0.0001). According to the extent of surgery, 3-year overall survival for gross total resection, partial resection, and biopsy only was 38$\%$, 11$\%$, and 0$\%$, respectively (p=0.02) The 3-year overall survival rates for patients age 40>, 40-59, and 60< were 52$\%$, 8$\%$, and 0$\%$, respectively (p=0.0007). For the variate of performance score 80< vs 80>, the 3-year survival rates were 53$\%$ and 9$\%$, respectively (p=0.008). On multivariate analysis including covariates of three surgical and age subgroups as above, pathology, extent of surgery and age were significant prognostic factors affecting overall survival. On another multivariate analysis with covariates of two surgical (total resection vs others) and two a9e (50> vs 50<) subgroups, then, pathology, extent of surgery and performance status were significant factors instead of age and 3-year cumulative survival rate for the five patients with these three favorable factors was 100$\%$ without serious sequela. Conclusion : We confirmed the role of postoperative conventional radiotherapy in the management of supratentorial malignant glioma by improving survival as compared with historical data of surgery only. Patients with anaplastic astrocytoma, good performance score, gross total resection and/or young age survived longest. Maximum surgical resection with acceptable preservation of neurologic function should be attempted in glioblastoma patients, especially in younger patients. But the survival of most globlastoma patients without favorable factors is still poor, so other active adjuvant treatment modalities should be tried or added rather than conventional radiation treatment alone in this subgroup.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.263-271
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• 2001

Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup2
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• pp.189-196
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• 2001

Objective : We tested the hypothesis that photodynamic therapy(PDT) with Photofrin inhibits tumor invasion of U87 human glioma cells using several in vitro assay to measure tumor invasiveness. The effects of PDT on cell growth, directional migration and cell invasion were investigated. Material and Method : Tumor cells were treated with Photofrin at various doses and at a fixed optical(632nm) dose of $100mJ/cm^2$. Cytotoxicity was tested using the MTT method. Invasion assays including the matrigelartificial basement membrane barrier migration and spheroid confrontation with confocal microscopic analysis were used to study the relationship between PDT and invasiveness. Result : U87 cells showed a dose dependent cytotoxic response to increasing Photofrin dose. Data from the matrigel artificial basement membrane assay indicate that PDT inhibits the U87 cell migration dose dependently. Low doses of subcytotoxic PDT treatment, such as 2.5ug/ml Photofrin dose, also appeared to significantly inhibit migration of U87 cells(p<0.05). In co-cultures between U87 cell spheroids and brain aggregates, progressive invasion with destruction of the brain aggregate occurs. The extent of tumor cell infiltration and proportion or intact brain aggregate remaining after 24h differs in Photofrin PDT treated versus Photofrin only control, with changes suggestive of a dose-response effect. Conclusion : our data indicate that PDT with Photofrin significantly inhibits the invasiveness of U87 cells, and this inhibition is dose dependent.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.5-12
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• 2001

This study was designed to investigate the mechanism of cell death after cisplatin treatment in human glioblastoma A172 cells. Cis-diamminedichloroplatinum(Cisplatin) demonstrated cytostatic or cytotoxic effects on A172 cells in a dosedependent manner. Cisplatin-mediated cytotoxity in A172 cells was revealed as an apoptosis characterized by high molecular weight DNA fragmentation by agarose electrophoresis as well as nuclear fragmentation by Hoechst staining. Cisplatin also resulted in the activation of caspase 3-like protease as well as poly(ADP-ribose) polymerase(PARP) cleavage. Interestingly, the anti-apoptotic Bcl2 protein was degraded and furthermore, expression of p53 protein was increased by cisplatin in a time-dependent manner. Taken together, these results suggest that anticancer drug, cisplatin induces the apoptotic death of human glioblastoma A172 cells via the activations of caspase 3-like protease, degradation of anti-apoptotic Bcl2 protein and increase in the expression of p53.

• Journal of Biomedical Engineering Research
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• v.42 no.4
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• pp.159-166
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• 2021

In order to analyze cell images, accurate segmentation of each cell is indispensable. However, the reality is that accurate cell image segmentation is not easy due to various noises, dense cells, and inconsistent shape of cells. Therefore, in this paper, we propose an algorithm that combines marker-based watershed segmentation and ellipse fitting method for glioblastoma cell segmentation. In the proposed algorithm, in order to solve the over-segmentation problem of the existing watershed method, the marker-based watershed technique is primarily performed through "seeding using local minima". In addition, as a second process, the concave point search using ellipse fitting for final segmentation based on the connection line between the concave points has been performed. To evaluate the performance of the proposed algorithm, we compared three algorithms with other algorithms along with the calculation of segmentation accuracy, and we applied the algorithm to other cell image data to check the generalization and propose a solution.

• The Journal of Internal Korean Medicine
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• v.43 no.2
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• pp.320-325
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• 2022

Objective: The purpose of this report is to present the effects of integrative cancer treatment (ICT) on a patient diagnosed with glioblastoma multiforme (GBM). Methods: A 71-year-old male GBM patient received ICT from May 14 to October 12, 2021 and concurrently received temozolomide and radiotherapy. The effect on symptoms was evaluated using a visual analog scale (VAS), and changes in tumor size were assessed using magnetic resonance imaging. Results: After treatment, the VAS score for nausea decreased from 5 to 1, and the tumor size also reduced. Conclusion: ICT could be effective in treating GBM patients by reducing the size of the tumor as well as alleviating the side effects.

• Journal of Korean Neurosurgical Society
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• v.29 no.6
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• pp.731-737
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• 2000

Objective : Growth factor receptors on the tumor cells are known to be expressed highly allowing the tumor cells to bind growth factors to stimulate cellular division. Immunotoxin therapy is one of the novel approaches to the primary malignant brain tumor, and expression of cell-surface receptor is essential for the immunotoxin to have specific anti-tumor activity. Despite promising cytotoxic activity of immunotoxin, tumor responses are not curative on clinical trials, and additional studies are needed regarding various factors influencing the efficacy of the immunotoxin. The purpose of this study is to detect the expression of various growth factor receptors on brain tumor cell lines which are going to be used in these studies. Materials and Methods : The authors detected transferrin receptor(TR), insulin-like growth factor-1 receptor(IGF-1R), and interleukin-4 receptor(IL-4R) on medulloblastoma cell line(Daoy) and glioblastoma cell lines(U373 MG and T98 G) by flow cytometric analysis. Results : TR was expressed on Daoy, U373 MG, and T98 G. IGF-1R was expressed on Daoy and U373 MG, but not on T98 G. IL-4R was expressed on all cell lines tested. Conclusion : The transferrin and interleukin-4 receptors might be good targets for immunotoxin therapy. The results should be considered in additional in vitro and in vivo studies regarding immunotoxin and in establishing the proper treatment model of the immunotoxin therapy including selection of the adequate immunotoxin.

• Journal of Korean Neurosurgical Society
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• v.29 no.11
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• pp.1445-1450
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• 2000

Objectives : The Objective of this study was to analyze the prognostic factors affecting survival in the patients with glioblastomas. Methods : We retrospectively studied 55 consecutive patients with glioblastomas who were admitted to neurosurgery department from January 1988 to March 1998. Fifteen pateients were excluded from the analysis because of follow-up loss and surgical motality. There were 24 male and 16 female patients, with a mean age of 51 years. Surgery consisted of biopsy in 4(10.0%) patients, subtotal resection in 9(22.5%) patients and gross total resection in 27(67.5%) patients. Nine(22.5%) patients received second operation. Twenty-eight(70%) received postoperative radiation therapy. Various levels of radiation dose were used, 6,000 rad over 7 weeks in most cases. The variable factors were examined for their relationship with survival ; age at the time of diagnosis, gender, duration of neurological symptoms, preoperative neurological state(Karnofsky performance score), extent of surgical resection, location of tumor, reoperation, and postoperative radiotherapy and chemotherapy. Result : The mean survival time was 55 weeks, three(7.5%) of the 40 patients survived more than two years. Survival time with biopsy only cases was 24 weeks, for those with subtotal resection 43 weeks, and for those with gross total resection 67 weeks. A mean survival time from the time of reoperation was 42 weeks. Statistically significant survival factors in glioblastoma were extent of surgical resection, postoperative radiotherapy and reoperation. Summary : Results of our series support the views that the extent of surgery, reoperation and postoperative radiation are important prognostic factors. We also recommend radical tumor removal, postoperative radiotherapy and reoperation, if possible.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup2
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• pp.266-272
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• 2001

Objectives : Chemotherapy remains part of the treatment triad that includes surgery and radiotherapy for the management of glioblastomas, but disappointing results of chemotherapy have raised the suggestion that chemotherapy should perhaps be abandoned. In order to determine the chemotherapy effect given in addition to radiotherapy, we performed a randomized clinical study of irradiation alone and combination of irradiation with chemotherapy in the treatment of glioblastomas. Methods : From 1991 to 1999, 204 consecutive patients suffering from supratentorial glioblastomas were treated in our hospital. We compared the survival rates/times of these patients according to the treatment modalities[group I-67 patients treated by surgery with radiotherapy and adjuvant chemotherapy(ACNU, paclitaxel, tamoxifen, and others) ; group II-106 by surgery with radiotherapy ; and group III-31 by surgery only]. Results : The overall median survival time was 12 months, with overall survival rates at 1 and 2 year of 46.7% and 16.6%, respectively. On univariate analysis, median survival and 1- and 2-year survival rates were statistically improved by the use of chemotherapy ; group I-15 months, 75.7%, and 25.9%, group II-11 months, 39.3%, and 15.4%, and group III-3 months, 9.7%, and 6.5%, respectively(p=0.0001). But, on multivariate analysis considering compounding variables, survival was independently associated only with radiotherapy(p=0.0112). Conclusion : These results suggest that the addition of chemotherapy to radiotherapy does not affect the overall survival in glioblastomas. Mainly long-survivor glioblastoma patients might benefit by adjuvant chemotherapy, which probably means patients with initial favorable prognostic factors(young age, minimal residual tumors, good performance status). It is necessary to continue to search for an effective chemotherapy regimen to prolong survival of patients with glioblastomas.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.119-124
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• 1997

Purpose: To assess the utility of magnetic resonance(MR) cerebral blood volume (CBV) map in the evaluation of brain tumors. Materials and Methods: We performed perfusion MR imaing preoperatively in the consecutive IS patients with intracranial masses(3 meningiomas, 2 glioblastoma multiformes, 3 low grade gliomas, 1 lymphoma, 1 germinoma, 1 neurocytoma, 1 metastasis, 2 abscesses, 1 radionecrosis). The average age of the patients was 42 years (22yr -68yr), composed of 10 males and S females. All MR images were obtained at l.ST imager(Signa, CE Medical Systems, Milwaukee, Wisconsin). The regional CBV map was obtained on the theoretical basis of susceptibility difference induced by first pass circulation of contrast media. (contrast media: IScc of gadopentate dimeglumine, about 2ml/sec by hand, starting at 10 second after first baseline scan). For each patient, a total of 480 images (6 slices, 80 images/slice in 160 sec) were obtained by using gradient echo(CE) single shot echo-planar image(EPI) sequence (TR 2000ms, TE SOms, flip angle $90^{\circ}$, FOV $240{\times}240mm,{\;}matrix{\;}128{\times}128$, slice-thick/gap S/2.S). After data collection, the raw data were transferred to CE workstation and rCBV maps were generated from the numerical integration of ${\Delta}R2^{*} on a voxel by voxel basis, with home made software (${\Delta}R2^{*}=-ln (S/SO)/TE). For easy visual interpretation, relative RCB color coding with reference to the normal white matter was applied and color rCBV maps were obtained. The findings of perfusion MR image were retrospectively correlated with Cd-enhanced images with focus on the degree and extent of perfusion and contrast enhancement. Results: Two cases of glioblastoma multiforme with rim enhancement on Cd-enhanced Tl weighted image showed increased perfusion in the peripheral rim and decreased perfusion in the central necrosis portion. The low grade gliomas appeared as a low perfusion area with poorly defined margin. In 2 cases of brain abscess, the degree of perfusion was similar to that of the normal white matter in the peripheral enhancing rim and was low in the central portion. All meningiomas showed diffuse homogeneous increased perfusion of moderate or high degree. One each of lymphoma and germinoma showed homogenously decreased perfusion with well defined margin. The central neurocytoma showed multifocal increased perfusion areas of moderate or high degree. A few nodules of the multiple metastasis showed increased perfusion of moderate degree. One radionecrosis revealed multiple foci of increased perfusion within the area of decreased perfusion. Conclusion: The rCBV map appears to correlate well with the perfusion state of brain tumor, and may be helpful in discrimination between low grade and high grade gliomas. The further study is needed to clarify the role of perfusion MR image in the evaluation of brain tumor.