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Synergistic effect of perfluorochemicals on BCNU chemotherapy

Experimental study in a 9L rat brain-tumor model

Keiichi Kuwamura, Takashi Kokunai, Norihiko Tamaki, and Satoshi Matsumoto

examine the possible efficacy of adding Fluosol-43 to BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) chemotherapy. Materials and Methods The tumor cell (9L cell) used in this study was introduced in Fischer 344 rats with administration of 1-methyl-1-nitrosourea. 3 The 9L cells were maintained in modified Eagle's medium with Earl's salt, suspended with 10% fetal bovine serum, L-glutamine (398 µg/ml), and antibiotics (penicillin G 100 IU/ml, streptomycin 100 µg/ml). The cells were grown by the monolayer culture method at 37°C in a humidified chamber with 5% CO 2 and

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Esref Tel, Takao Hoshino, Marvin Barker, and Charles B. Wilson

T he rat intracerebral 9L tumor model has been used extensively to study brain tumor cell kinetics, immunology, and aspects of experimental chemotherapy and radiation therapy. The response of this animal model to treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been investigated in depth. We have shown that administration of BCNU 16 days after tumor implantation resulted in a greater increase in life span than treatment with BCNU 10 days after implantation. 1, 10 Using an in vitro colony formation assay to determine the efficacy of in vivo

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Alexander M. Spence and Joseph P. Geraci

T he standard therapy of supratentorial malignant astrocytic gliomas presently consists of surgical excision, which is usually subtotal, followed by a course of high-dose (5500 to 6000 rads), fractionated, whole-brain photon irradiation. This method of treatment yields a median survival time of 35 weeks. 24 Brain-tumor therapists are now evaluating a considerable number of chemotherapy protocols aimed at improving the results of this therapy. 6, 21, 22, 24, 25, 28 From this work, 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) has emerged as the leading single

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Rifaat Bashir, Fred H. Hochberg, Rita M. Linggood, and Kathleen Hottleman

T he prognosis of patients with glioblastoma multiforme remains very poor despite extensive use of surgery, radiation therapy, and chemotherapy. 12, 15 Recently, regional chemotherapy has gained increasing popularity in the oncology literature because it allows the delivery of high concentrations of drug with reduced systemic toxicity. 14 An appealing drug for regional therapy of malignant gliomas is 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) because of its short half-life, 2 high lipid solubility, 3 steep dose-response curve, 8 and attainment of higher

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Fred H. Hochberg, Amy A. Pruitt, Deborah O. Beck, Gerard DeBrun, and Kenneth Davis

I ntra-arterial administration represents a safe and easily performed means of achieving greater brain tumor levels of 1,3-bis(2-chloroethyl)-1-nitro-sourea (BCNU) compared to parenteral administration. Despite 22 years of use, clinical administration of BCNU has been shown to be no more than marginally effective in the treatment of glioblastoma. Intravenous delivery 15 of BCNU at doses of 240 mg/sq m provides only 20% improvement in survival time for glioblastoma patients after operative resection and irradiation. No clear evidence of improvement in quality

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Synergism between BCNU and irradiation in the treatment of anaplastic gliomas

An in vivo study using the avian sarcoma virus-induced glioma model

Paul Steinbok, M. Stephen Mahaley Jr., Raymond U, Douglas C. Zinn, Stan Lipper, Jane L. Mahaley, and Darell D. Bigner

rat chow ad libitum . At the time of weaning the rats were randomized into experimental groups of approximately 20 animals, with equal numbers of males and females. The groups were as follows: 1. Controls (no treatment) 2. Radiation therapy 3. BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) chemotherapy 4. Radiation therapy plus BCNU chemotherapy. Another group of animals was killed on Day 30 for histological verification of tumor induction. Two series of experiments were performed, with the same four experimental groups in each series, in order to

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John Calogero, David C. Crafts, Charles B. Wilson, Edwin B. Boldrey, Alan Rosenberg, and K. Jean Enot

U ntil recently malignant gliomas have been treated by surgical removal, as complete as possible, usually followed by adjuvant radiation therapy. Chemotherapeutic agents have been added to this regimen on a systematic trial basis in some centers. 1,3 bis (2-chloroethyl)-1-nitrosourea (BCNU) was found to be particularly effective against gliomas in preliminary studies, 8, 9 and has been the subject of a randomized study of its effects against malignant gliomas with and without radiation therapy. 7 We are reporting three patients treated with BCNU for their

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John Mealey Jr., Tsu T. Chen, and Robert Shupe

, controlled, randomized study of over 300 patients with glioblastomas or malignant cerebral gliomas has indicated that postoperative radiation (6000 rads, whole brain) does significantly increase the median survival after operation (p < .001). 45, 47 When patients who were entered in this collaborative study were randomized for additional treatment with 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) intravenously at 80 mg/M 2 per day for 3 days repeated bimonthly, the combination of postoperative radiation and BCNU chemotherapy resulted in an even greater increase in the

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Paul L. Kornblith and Paula E. Szypko

treated with these drugs respond clinically, 5, 18, 20, 23 it would be advantageous to determine which patients would benefit most from nitrosourea therapy, especially in view of the toxic side effects of these drugs, 18 and to identify those patients who should be offered alternative or additional drugs. In the present study, an in vitro microtiter assay has been used to measure the in vitro response of patient's cultured glial cells to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The series of cell lines tested were found to exhibit a range of responses to the

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Alan R. Cohen, Dennis D. Pietronigro, Humberto Cravioto, and Eugene S. Flamm

T he single most effective drug currently available for glioma chemotherapy is 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU), a small lipophilic alkylating agent. 55, 57 Recent clinical trials have suggested advantages of intra-arterial administration of this drug over the conventional intravenous route 16, 56 (WR Shapiro, et al. , unpublished data, 1984). These studies, however, have been limited by two elements: the absence of an animal model to assess efficacy of intra-arterial therapy, and the presence of a hazardous toxicity appearing as delayed brain