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Objective: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy., Methods: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated., Results: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different., Conclusions: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.

Background: Patients with brain metastases of non-small cell lung cancer (NSCLC) have a poor prognosis, so chemotherapy and best-supportive care are typically pursued as initial treatments., Case Report: A 52-year-old man presented with symptoms of disorientation and disturbed consciousness as a result of multiple brain metastases. A histopathological examination revealed that the primary tumor was a large cell carcinoma located in the left upper lung. Whole brain irradiation (WBI) with a total dose of 50 Gy was immediately started. Since the brain tumors were successfully controlled, irradiation of the primary lung lesion with a total dose of 60 Gy was initiated 6 months after the WBI. Afterward, the patient was clinically free from lung cancer, but other cancers developed in the cecum and appendix and were surgically removed. He survived for more than 8 years after the WBI but eventually died of respiratory insufficiency caused by multiple lung metastases. The autopsy findings indicated that the lung lesions were metastatic adenocarcinomas from the appendiceal cancer, and the patient had remained disease-free from lung cancer., Conclusion: In view of the possibility of long-term survival in patients with stage IV NSCLC and brain metastasis, especially those with only intracranial metastases, careful consideration is be needed in the selection of treatment options.

Background: The previous trials of radiotherapy conducted for primary central nervous system lymphoma (PCNSL) have not been successful. Therefore, we have investigated the clinical outcomes and the role of radiation therapy in the treatment of PCNSL., Methods: Thirty-three consecutive patients with PCNSL treated with cranial radiotherapy (30-40 Gy whole brain plus 10-20 Gy boost) without administration of high-dose methotrexate were retrospectively analyzed. Nine patients received whole spinal irradiation (WSI) as an additional therapy. The median age of patients was 58 years (range: 28-78 years), and 70% showed a poor performance status (PS)., Results: The median survival time (MST) was 13 months, and the 5-year overall survival rate was 35%. The initial response and the number of tumors were significant prognostic factors, and WSI tended toward significance in a multivariate analysis. Four of five patients, who received prophylactic WSI, were 4-year survivors without a tumor relapse and none of them had tumor involvement in the vertebral canal. One patient developed radiation-induced brain necrosis, however, WSI did not seem to affect the late complications., Conclusions: We consider it important to reduce severe acute and late complications in patients qualified for receiving an aggressive therapy, and to explore the possible tolerable and curative treatment methods that can be used in order to improve the prognosis for PCNSL. Further modifications, including the application of WSI seem to be necessary in the management of PCNSL.

We report a case of small cell lung cancer whose initial presentation was a solitary brain metastasis. On chest radiography the primary tumor was unclear and only detected by bronchofiberscopy. A small single pulmonary metastasis was noted in the right lower lobe. Subtotal resection and external irradiation were applied to the brain tumor and external irradiation was applied to the lung. Concurrently one course of systemic chemotherapy was administered. The tumors in the brain and lung had disappeared by the end of the treatment. The patient has been alive and well for 5 years without recurrence.

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37 degrees C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1 - 7 Gy and time response with hyperthermia in the range of 40 - 46 degrees C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46 degrees C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.

The purpose of this paper is to determine the relationship between the response to radiation and the appearance of apoptosis and micronuclei with Trp53 protein in murine tumors after irradiation. Two murine tumors, EL4, which was derived from a mouse lymphoma, and FM3A, which was derived from a mouse mammary carcinoma, were locally irradiated with 15 Gy and sections were stained with H&E and an anti-Trp53 antibody. The response to radiation was greater in EL4 tumors than in FM3A tumors. The frequency of apoptotic cells in EL4 tumors was 6.1 +/- 1.2% at time zero, reached a peak of 36.3 +/- 3. 8% at 6 h, and then decreased with time through 72 h to 2.5 +/- 1.5% after 15 Gy irradiation. In FM3A tumors, no apoptotic cells were detected at 0, 1, 3, 6 or 24 h after exposure. At 48 and 72 h, the frequency was only 3.0 +/- 0.6% and 1.3 +/- 0.3%. Apoptotic cells increased significantly at 3, 6 and 24 h after irradiation in EL4 tumors (P < 0.008) and at 48 and 72 h in FM3A tumors (P < 0.006). The frequency of Trp53-positive cells was 17.9 +/- 2.2 and 15.2 +/- 2.3% at time zero in EL4 and FM3A tumors, respectively, increased to 74.5 +/- 4.5% in EL4 cells (P = 0.001), and increased to 33.9 +/- 1. 1% in FM3A cells (P = 0.005) 1 h after irradiation. Trp53-positive micronuclei appeared in cells in both tumors from 24 to 72 h after irradiation. The frequency of Trp53-positive micronuclei was 3.8 +/- 0.5 and 13.5 +/- 1.3% at 24 h in EL4 and FM3A tumors, respectively, and gradually decreased by 72 h. After exposure to 15 Gy, Trp53-positive micronuclei increased significantly in FM3A tumors compared to EL4 tumors at both 24 and 48 h (P < 0.02). The frequency of these micronuclei increased with increasing dose in FM3A tumors, and the difference between these percentages after 3 Gy and after 5, 10 and 15 Gy was significant (P < 0.02). Many apoptotic cells were observed in the radiosensitive EL4 tumor after irradiation. Death by apoptosis may be related to an early response to radiation in these tumors. The appearance of micronuclei may be an important mechanism of cell death in FM3A tumors in which no apoptosis was induced.

A case of giant cell tumor of the thoracic spine simulating mediastinal neoplasm was identified on plain films, CT scans, MR images, and with scintigraphy. CT showed a hypervascular soft-tissue mass with shell-like calcification in the right upper mediastinum. MR imaging showed a collapse of the T1 vertebral body and a mass extending to the mediastinum. The mass had a low signal on T1-weighted MR images and a predominantly high signal on T2-weighted images with heterogeneity. Technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in both the T1 and marginal parts of the mediastinal mass. There was no accumulation of gallium-67 citrate, but 18-fluorine fluorodeoxyglucose positron emission tomography showed marked uptake. The variation in these imaging findings played an important role in the differential diagnosis of this uncommon mediastinal mass.

The effect of the p53 gene on the survival of mouse testicular cells was evaluated by analysis of degenerating and terminal transferase-mediated end labeling (TUNEL)-positive cells and the subsequent production of further differentiated progeny. In p53 null mice, in contrast to wild-type mice, radiation induced negligible levels of degenerating or TUNEL-positive differentiating spermatogonia within 24 h. This was correlated with higher production of differentiated progeny of the differentiating spermatogonia in p53 null mice. Contrary to the differentiating spermatogonia, the stem spermatogonia of p53 null mice produced fewer differentiated progeny after irradiation than did the stem cells of wild-type mice. We conclude that, because the degeneration and TUNEL positivity of the differentiating spermatogonia in mice of different genotypes were correlated with each other and were dependent on p53, this process is indeed apoptosis. In the differentiating spermatogonia, p53-dependent apoptosis accounted for the bulk of the loss of their progeny after irradiation. Furthermore, whereas the differentiating spermatogonia died by apoptosis that was dependent on p53, the stem spermatogonia, which are more radioresistant, did not.

A case of intraorbital ectopic lacrimal gland was evaluated with various radionuclides. CT and MRI with contrast enhancement showed a soft-tissue mass in the orbit. The lesion was gallium-avid, but 18F-FDG PET demonstrated very faint uptake. On early and delayed 201Tl-Cl images, mildly increased uptake and mild retention were observed. Technetium-99m-(V)-DMSA SPECT showed intense accumulation on both the early and delayed images. Technetium-99m-pertechnetate SPECT, demonstrating marked uptake in the lesion, was useful for the differential diagnosis between intraorbital malignancy and this benign lesion. These scintigraphic variations played an important role in the tissue characterization of this uncommon lesion.

Xenografts of a human malignant glioma subcutaneously transplanted into nude mice were irradiated with graded single doses (2, 5, 10 or 20 Gy) or five types of fractionation schedules in two weeks: conventional [20 Gy in 10 fractions (fr)], hyperfractionated [24 Gy in 20 fr (two fractions per day)], and hypofractionated-1, 2, 3 [20 Gy, 18 Gy, 16 Gy in 4 fr]. All of the fractionated irradiation groups showed tumor regression. The hypofractionation-1 group (20 Gy in 4 fr) demonstrated the most prominent tumor regression, while the hyperfractionation group (24 Gy in 20 fr) showed the least effect. The hypofractionation-2 group (18 Gy in 4 fr) showed similar regression to the conventional fractionation group (20 Gy in 10 fr). Histologically, tumors in the control groups consisted of a homogenous population of small anaplastic cells, and only a small number of tumor cells were glial fibrillary acidic protein (GFAP)-positive. Following irradiation, the population of small anaplastic cells decreased and the percentage of GFAP-positive cells increased. Cellular pleomorphism became much more prominent after irradiation in all of the fractionated irradiation groups as compared with the graded single dose irradiation groups. In this study, hyperfractionation was not effective against human glioma xenografts compared with conventional fractionation and hypofractionation. This indicates that care is needed in applying hyperfractionation regimens to human malignant gliomas.

A new cell line producing alpha-fetoprotein, designated NMT-1, was established from rat yolk sac tumor with the potential for lymphatic metastasis in inbred Wistar rats. In this paper, we investigated the characteristics of NMT-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of NMT-1 cells during exponential growth was approximately 16 h in RPMI-1640 with 10% fetal calf serum. The D0 value for radiation sensitivity was 97 +/- 3 cGy. The extrapolation number, n, for NMT-1 was 1.08 +/- 0.15. In the log phase, the G0/G1, S and G2/M fractions were 23.2%, 62.1% and 14.3%, respectively. Tumor take was observed in all of the rats inoculated with NMT-1 cells. In the case of flank tumor, the mean survival time was 104 days after inoculation with 10(6) tumor cells. Inguinal, axillary, paraaortic, mesenteric and mediastinal lymphnode metastases were observed in all rats inoculated with NMT-1 cells. Rats which survived for a long time developed metastases in a lymphatic vessels of the liver, lung and/or kidney microscopically. The biological behavior and the histopathological features of the tumor induced by inoculation with NMT-1 cells were the same as those of the original tumor induced by fetectomy.