PURPOSE: To characterize strain-specific differences in radiation response in murine tissues with different radiosensitivity. MATERIALS AND METHODS: Six-week old male mice of 2 strains, C57Bl/6J and C3H/HeJ, were given whole body gamma-radiation with a single dose of 10 or 25 Gy. At different times after irradiation, mice were killed and tissues with different radiosensitivity, thymus and liver, were collected. Each tissue sample was stained with hematoxylin and eosin and apoptotic cells were scored. Expression of p53, Bcl-2, Bcl-x, and Bax was analysed by western blotting and densitometry. RESULTS: Radiation induced massive apoptosis in thymus with a peak level at 8 h after radiation. With 10 Gy irradiation, apoptotic indices in C57Bl/6J and C3H/HeJ were 81.0 2.5% and 59.4 4.0%, respectively (p<0.05). Radiation upregulated the expression of p53, Bcl-x, and Bax, but not Bcl-2; p53 with a peak level of 2.5 fold (C57Bl/6J) and 1.4 fold (C3H/HeJ) at 4 h, Bax with a peak level of 2.6 fold (C57Bl/6J) and 1.3 fold (C3H/HeJ) at 8 h, and Bcl-x with a peak level of 11.1 fold (C57Bl/6J) and 8.2 fold (C3H/HeJ) at 8 h after radiation. In liver, however, radiation-induced apoptosis was minimal (peak apoptotic index of 2.1% in C57Bl/6J and 1.7% in C3H/HeJ). None of p53, Bcl-2, Bcl-x, and Bax was significantly increased. CONCLUSIONS: Induction of apoptosis and regulation of related genes by radiation were tissue specific. Strain difference of radiation-induced apoptosis was well coupled with theinduction of related genes in thymus, a radiosensitive tissue. This study shows that quantitative difference of radiation induced apoptosis by strain is regulated at the gene level with the involvement of multiple genes.
Animals ; Apoptosis* ; Blotting, Western ; Densitometry ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Liver ; Male ; Mice ; Radiation Tolerance ; Thymus Gland

Transient hyperkalemia has been reported to occur in eletric burn patients following intravenous administration of succinylcholine. We have studied the origin of the elevated serum K+ concentration after injection of succinylcholine from both the non-burned area and from the burned area in electirc burn patients. Blood samples for serum K+ measurement were drawn 1,2,3,4,5 and 10 minutes after administration of succinylcholine from both the burned are and the non-burned area in 6 electric burn patients. The following results were obtained: 1) Serum K+ levels increased in the burned group in 3 minutes after injection of succinylcholine. 2) The serum K+ concentration of venous samples from the electric burn area were more increased than from the non-burned area injection of succinylcholine.
Administration, Intravenous ; Burns ; Burns, Electric ; Humans ; Hyperkalemia ; Succinylcholine*

BACKGROUNDS: The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. METHODS: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21WAF1/CIP1. RESULTS: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gemcitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21WAF1/CIP1. CONCLUSION: Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.
Animals ; Apoptosis ; Blotting, Western ; Cisplatin ; Doxorubicin ; Drug Therapy* ; Fluorouracil ; Mice ; Paclitaxel ; Radiation Dosage

PURPOSE: To determine whether TNF-alpha increases the antitumor effect of radiotherapy in murine syngeneic tumor system. MATERIALS AND METHODS: Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I (hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter, mice were treated with TNF-alpha, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-alpha mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 microgram per mouse for 7 days. In combination of radiation and TNF-alpha, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. RESULTS: Among 4 tested tumors, TNF-alpha alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-alpha showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-alpha alone and radiation, i.e., 6.5 days and 26.9 days, respectively (p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-alpha did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-alpha alone and radiation. CONCLUSIONS: TNF-alpha alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-alpha acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-alpha and radiation has different therapeutic potential depending on tumor model and further study is advocated.
Animals ; Korea ; Leg ; Mice ; Radiotherapy* ; Tumor Necrosis Factor-alpha*

No absract available.
Follow-Up Studies* ; Urinary Bladder Neoplasms* ; Urinary Bladder*

No abstract available.

PURPOSE: We tried to evaluate the clinical characteristics, the treatment methods, the results of treatments, and the patterns of failure in ovarian dysgerminoma retrospectively. According to the results we would like to suggest the proper management guideline of stage la ovarian dysgerminoma patients who want to maintain fertility. METHODS AND MATERIALS : Between 1975 and 1990, 34 patients with ovarian dysgerminoma were treated at the Yonsei University Hospital. The case records of these patients have been reviewed for presenting symptoms, treatment methods, local control, and survival following treatment. Excluded from analysis were five patients with mixed ovarian germ cell tumors and gonadoblastomas (46,XY). Treatment results of the twenty nine patients were analysed by each treatment modality. Twenty one patients were treated with surgery and postoperative adjuvant radiotherapy(group 1). The other eight patients were treated with operation alone (group 2). The median age of twenty-nine patients was 23 years with a range of 8 to 39 years. Presenting symptoms were abdominal mass(20), pelvic discomfort or pain(5) et al. Radiotherapy was performed by 10MV LINAC or Co-60 teletherapy unit. The total radiation dose of the whole abdomen was 20-25 Gy/3weeks, 1-1.5 Gy/fraction with a boost to the whole pelvis 10-15 Gy / 1-2 weeks1.8-2.0 Gy/fraction. Advanced stage disease (stage II or stage III) patients received prophylactic mediastinal and supraclavicular irradiation to a dose of 16-26 Gy. Median duration of follow-up of living patients was 80 months (range : 13-201 months) RESULTS: All of the twenty one patients of group 1 were alive without disease (100%). Among the eight patients who were not treated with radiotherapy (group 2), six patients developed local recurrence. Four patients referred with recurrent disease were treated with salvage radiotherapy. Three of four patients were salvaged and one patient who had recurrent intra-abdominal disease died of progressed carcinomatosis at 11 months after salvage radiotherapy. The other two patients with recurrence were salvaged with chemotherapy (1 patient) or re-operation (1 patient). Twenty eight patients remained alive without disease at last follow up, so the 5 year local control rate and 5 year overall survival rate for all groups were 96.6% (28/29), respectively. Among thirteen patients with stage la unilateral tumors seven patients were treated with postoperative radiotherapy and the other six patients were treated with unilateral salpingo-oophorectomy alone. Five patients who did not received radiotherapy developed local failure but all of the recurrent ovarian dysgerminomas were salvaged with radiotherapy, chemotherapy or re-operation, So all the 13 patients with stage la ovarian dysgerminoma were free of disease from 20-201 months (median 80 months). CONCLUSION: The authors consider external irradiation to be an effective treatment as a complement to surgery in ovarian dysgerminoma. For those patients with disease presenting in stage la tumors who wish to maintain fertility, unilateral salpingo-oophorectomy alone may be curative and spare ovarian function considering excellent salvage rate of recurrent ovarian dysgerminoma in present study.
Abdomen ; Carcinoma ; Complement System Proteins ; Drug Therapy ; Dysgerminoma ; Fertility ; Follow-Up Studies ; Gonadoblastoma ; Humans ; Neoplasms, Germ Cell and Embryonal ; Pelvis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: To develop a patients' setup verification tool (PSVT) to verify the alignment of the machine and the target isocenters, and the reproducibility of patients' setup for three dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT). The utilization of this system is evaluated through phantom and patient case studies. MATERIALS AND METHODS: We developed and clinically tested a new method for patients' setup verification, using digitally reconstructed radiography (DRR), simulation, portal and digital images. The PSVT system was networked to a Pentium PC for the transmission of the acquired images to the PC for analysis. To verify the alignment of the machine and target isocenters, orthogonal pairs of simulation images were used as verification images. Errors in the isocenter alignment were measured by comparing the verification images with DRR of CT images. Orthogonal films were taken of all the patients once a week. These verification films were compared with the DRR were used for the treatment setup. By performing this procedure every treatment, using humanoid phantom and patient cases, the errors of localization can be analyzed, with adjustments made from the translation. The reproducibility of the patients' setup was verified using portal and digital images. RESULTS: The PSVT system was developed to verify the alignment of the machine and the target isocenters, and the reproducibility of the patients' setup for 3DCRT and IMRT. The results show that the localization errors are 0.8+/-0.2 mm (AP) and 1.0+/-0.3 mm (Lateral) in the cases relating to the brain and 1.1+/-0.5 mm (AP) and 1.0+/-0.6 mm (Lateral) in the cases relating to the pelvis. The reproducibility of the patients' setup was verified by visualization, using real-time image acquisition, leading to the practical utilization of our software. CONCLUSION: A PSVT system was developed for the verification of the alignment between machine and the target isocenters, and the reproducibility of the patients' setup in 3DCRT and IMRT. With adjustment of the completed GUI-based algorithm, and a good quality DRR image, our software may be used for clinical applications.
Brain ; Humans ; Pelvis ; Radiography ; Radiotherapy ; Radiotherapy, Conformal

PURPOSE: To evaluate influences associated with radiation treatment planning obtained with the patient breathing freely. MATERIAL AND METHODS: We compared reduction or elimination of planning target volume (PTV) margins with 2-D conventional plan with inclusion of PTV margins associated with breathing with 3-D conformal therapy. The respiratory non gated 3-D conformal treatment plans were compared with respiratory gated conventional 2-D plans in 4 patients with hepatocellular carcinomas. Isodose distribution, dose statistics, and dose volume histogram (DVH) of PTVs were used to evaluate differences between respiratory gated conventional 2-D plans and respiratory non gated 3-D conformal treatment plans. In addition, the risk of radiation exposure of surrounding normal liver and organs are evaluated by means of DVH and normal tissue complication probabilities (NTCPs). RESULTS: The vertical movement of liver ranged 2-3 cm in all patients. We found no difference between respiratory gated 2-D plans and 3-D conformal treatment plans with the patients breathing freely. Treatment planning using DVH analysis of PTV and the normal liver was used for all patients. DVH and calculated NTCP showed no difference in respiratory gated 2-D plans and respiratory non gated 3-D conformal treatment plans. CONCLUSION: Respiratory gated radiation therapy was very important in hepatic tumors because radiation induced hepatitis was dependent on remaining normal liver volume. Further investigational studies for respiratory gated radiation treatment combined with 3-D conformal treatment are required.
Carcinoma, Hepatocellular ; Hepatitis* ; Humans ; Liver ; Respiration

PURPOSE: The goal of this study was to improve the accuracy of three-dimensional conformal radio therapy (3-D CRT) by measuring the treatment setup error and physiological movement of liver based on the analysis of images which were obtained by electronic portal imaging device (EPID). MATERIALS AND METHODS: For 10 patients with hepatocellular carcinoma, 4-7 portal images were obtained by using EPID during the radiotherapy from each patient daily. We analyzed the setup error and physiological movement of liver based on the verification data. We also determined the safety margin of the tumor in 3-D CRT through the analysis of physiological movement. RESULTS: The setup errors were measured as 3 mm with standard deviation 1.70 mm in x direction and 3.7 mm with standard deviation 1.88 mm in y direction respectively. Hence, deviation were smaller than 5 mm from the center of each axis. The measured range of liver movement due to the physiological motion was 8.63 mm on the average. Considering the motion of liver and setup error, the safety margin of tumor was at least 15 mm. CONCLUSION: EPID is a very useful device for the determination of the optimal margin of the tumor, and thus enhance the accuracy and stability of the 3-D CRT in patients with hepatocellular carcinoma.
Axis, Cervical Vertebra ; Carcinoma, Hepatocellular* ; Humans ; Liver* ; Radiotherapy