Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Gliosarcoma”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1990

Specific uptake of the auger electron-emitting thymidine analogue 5-[123I/125I]iodo-2'-deoxyuridine in rat brain tumors: diagnostic and therapeutic implications in humans.

Glial neoplasms of the human central nervous system are malignancies that have defied treatment. Part of the problem lies in the limitations of current diagnostic techniques which are unable to identify small collections of neoplastic glia within normal parenchyma and in the difficulty of sterilizing these tumors because of limited selectivity of the cytotoxic agents available. The thymidine analogue 5-iodo-2'-deoxyuridine (IdUrd) radiolabeled with 123I and 125I was injected directly into an intracerebral rat 9L gliosarcoma and found to be a sensitive and specific agent for the detection of this neoplasm in rats. External gamma camera imaging (123I) visualized tumors as small as 0.5 mm in diameter. Autoradiography (125I) indicated that IdUrd was incorporated into the DNA of neoplastic glia only. Since 123I emits gamma-photons suitable for scintigraphy, [123I]IdUrd holds promise for the diagnosis of brain tumors in humans as well. Furthermore, since 123I and 125I are Auger electron emitters that have demonstrated antineoplastic effects, direct administration of [123I]IdUrd or [125I]IdUrd into tumors may also have potential for the treatment of central nervous system malignancies.

Animals↗
PubMed1989

[Intrathecal perfusion of ACNU neurotoxicity and intrathecal pharmacokinetics in dogs].

We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high-performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies.

Animals↗
PubMed1989

[Expression of cell surface transformation-associated antigens TAAs on activated oncogene-transfected rat fibroblast and antitumor immunity by hosts].

The key point in this study was that the cell surface antigens in the events of transformation were analyzed using the same clonal-derived nontransformed cell and various oncogenes. WKA rat fetus-derived fibroblast line, WFB, showed the strict non-transformant phenotypes. Transfection of EJras and polyoma middle T oncogenes into WFB resulted in the acquisition of tumorigenicity in vitro and in vivo. The newly expressed cell-surface antigens on some transformants were analyzed using four monoclonal antibodies (Moabs) (#109, #061, #081 and #067) that were produced after immunization of BALB/c mice with EJ-ras-transformed WFB clone, W31 and W14. #109 recognized a glycoprotein composed of a single polypeptide chain with 86 KD. This antigen was also expressed in the FJ ras transformants of Fisher rat fetus-derived 3Y1 fibroblast, FTL43 rat T lymphoma, SP56 rat gliosarcoma, and ca. 16th-day embryo. #061 could react with WFB transformants, but not with fetus. Furthermore, these two antigens are expressed on TGF-beta-stimulated WFB. However, #109 but not #061 is expressed on PDGF-stimulated WFB, indicating that #109 expression does not require the transforming process. It is also indicated that these two antigens act as target structures in the Natural killer (NK) cytotoxicity assay. #081 could react with WFB transformants but not with FTL43, SP56 and 3Y1 ras transformants, suggesting a limited expression of #081 defined antigen on WFB transformants. #067 reacted with W31 but not with W14. This antigen is expressed on 5 clones out of approximately 40 highly tumorigenic WFB ras transformed clones. We also analyzed the expression dynamics of these TAAs during the morphological reversion of W31 to parental WFB using cAMP analogues such as dibutylic cAMP. The data indicated that, although W31 cells were reversed morphologically to WFB, the level of #109 antigen expression was not changed. #061 and #081 defined antigens were reduced by cAMP treatment for 4-5 days. However, it is of interest that #067-defined antigen expression was greatly enhanced during the morphological reversion of W31 to WFB by cAMP. This was also true when W31 was treated with 1% FCS for 5 days and heat shock, suggesting that this antigen is a heat shock-related protein.

Animals↗
PubMed1989

Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients.

Astroblastomas are rare, usually circumscribed, supratentorial tumors of young subjects and are characterized by a perivascular arrangement of the tumor cells. Their clinical behavior is unpredictable and their prognosis has been regarded as intermediate between that of astrocytomas and glioblastomas. A personal series of 23 astroblastomas was reviewed, adequate postoperative follow-up being available in 13 patients. Two distinct histological types were encountered: low-grade and high-grade. The low-grade type comprised tumors with better differentiated and more benign-appearing microscopical features. Five of the 8 patients with tumors of this type who were available for follow-up have survived from 3 to 20 years after treatment; in 1 patient the tumor converted into a fatal glioblastoma after 4 1/2 years. The high-grade type consisted of tumors with more anaplastic features. Three of the 4 patients with tumors of this type available for follow-up died after 1 1/2 to 2 1/2 years, the astroblastomas in 2 of them having converted into a glioblastoma and a gliosarcoma, respectively. One patient, however, has had an unexpected length of postoperative survival of 11 1/2 years. The best clinical results were obtained after total or subtotal resection of the tumor, followed by radiotherapy. The role of chemotherapy is still uncertain. This form of glioma illustrates the discrepancies that may sometimes be apparent between histopathological features and length of postoperative survival. The prognosis is also further complicated by the potential of the astroblastoma to convert into a more malignant type of glioma.

Adolescent↗
PubMed1988

Identification of the transformation-associated cell surface antigen expressed on the rat fetus-derived fibroblast.

A WKA rat fetus-derived fibroblast cell line WFB showed strict nontransformant phenotypes in vitro such as anchorage dependency of cell growth in soft agar, contact inhibition, and serum dependency on the monolayer cell culture. Transfection of 6.6-kilobase EJras oncogene into WFB resulted in the acquisition of tumorigenicity in vitro and in vivo. The cell surface antigen that is moderately or highly expressed on these WFB transformants, designated as W14 and W31, was analyzed using monoclonal antibody 109 that was produced after the immunization of BALB/c mice with W31. Moab 109 recognized a glycoprotein with a molecular weight of 36,000 composed of a single polypeptide chain with 5.4 isoelectric point value. This antigen was highly expressed on WFB EJras and polyoma middle T-DNA transformants, but was undetectable or at the best only faintly recognized on WFB parental cells, transfectants of WFB with c-myc, and normal thymus, liver and kidney of WKA adult rats. It was also clearly expressed on the EJras transformants of Fisher rat fetus-derived 3Y1 fibroblast, but very faintly on parental 3Y1. Furthermore, this antigen was detected on some rat T-lymphoma and gliosarcoma lines. However, it was undetectable on EJras transformants on NRK-49F rat kidney cells and NIH3T3 and BALB3T3 mouse cells. In addition, this antigen appeared on the cell surface of concanavalin A-activated WKA rat lymphocytes and WKA rat on the 16th day of embryo but not on the 8th. These results suggested that the cell surface antigen detected by Moab 109 was clearly unrelated to the ras oncogene product p21 that was highly expressed on EJras-transformants of WFB or 3Y1 cells. Furthermore, it was shown that W14 and W31 cells but not parental WFB cells were susceptible to rat splenic NK cells that were induced by poly(I-C) treatment. Pretreatment of these W14 or W31 cells with Moab 109 could block the NK cell activity against W14 and W31. These data suggest that this antigen may act as one of the NK target structures, and plays an important role as a tumor antigen on the host tumor surveillance, since the antigen was expressed (a) on the cell surface after the cell transformation or enhanced DNA synthesis of some particular cells, and (b) in the W31 tumor developing progressively in the syngeneic rats.

Animals↗
PubMed1988

In vivo and in vitro effect of adoptive immunotherapy of experimental murine brain tumors using lymphokine-activated killer cells.

Adoptive immunotherapy for the experimental murine brain tumor was investigated by using lymphokine-activated killer (LAK) cells both in vitro and in vivo. Supernatants of 48-h culture medium of spleen cells from Wistar rats in the presence of concanavalin A were used as interleukin 2 (IL-2). LAK cells were generated by cocultivation of spleen cells from Fischer rats with IL-2 with the peak reactivity on Day 2 or 3 of culture. Lytic activity was observed against not only syngenic tumor cells but also allogenic and xenogenic tumor cells, while no lytic activity was observed against normal brain cells. The cell depletion test, dye exclusion test, and immunofluorescence method using monoclonal antibodies revealed that LAK cells partially belonged to the population of the activated T-cell group, but the precursor cells did not react with any monoclonal antibodies used. On the basis of these results in vivo study was performed. LAK cells and immune spleen cells were adoptively transferred to the rats i.v. or intratumorally (i.t.) on the seventh day after the inoculation of T9, a gliosarcoma induced by methylcholanthrene from Fischer rats, into the right basal ganglia. Then the survival rate and necrotic foci were compared between the groups treated with those cells and the control. The survival rate of the groups treated with LAK cells was significantly higher than that of the control (administered i.v.; P less than 0.01, administered i.t.; P less than 0.05). But the treatment with immune spleen cells was not effective. The incidence and area of necrotic foci in the tumors treated with LAK cells were greater than those of the others. Microautoradiography was also performed using [3H]thymidine-labeled LAK cells, which were administered i.v. to the models on the 14th day after the inoculation of T9. It was revealed that LAK cells accumulated in the lung shortly after the administration and then in the liver and spleen, especially in the white pulp. IL-2 inhibitor activity of the sera from the tumor-bearing rats was greater than that of normal rats (P less than 0.001), but it was depressed markedly by cyclophosphamide (P less than 0.01). The adoptive transfer of LAK cells may be one of the effective treatments of malignant brain tumor. The nature of IL-2 inhibitors is necessary to be clarified for more effective immunotherapy.

Animals↗
PubMed1988

[Study on adoptive immunotherapy for experimental brain tumor].

Adoptive immunotherapy for the experimental murine brain tumor has been investigated using LAK cells generated in vitro from normal spleen cells with IL-2 and immune spleen cells from Fischer rats immunized against syngenic gliosarcoma, T9. IL-2 inhibitor(s) activity in serum was also studied. LAK cells and immune spleen cells were adoptively transferred to the rats intravenously or intratumorally on the 7th day after the inoculation of T9 into the right basal ganglia. Then the survival rate and necrotic foci were compared between the groups treated with those cells and the control. The survival rate of the groups treated with LAK cells was significantly higher than that of the control (administrated intravenously; P less than 0.01, administrated intratumorally; P less than 0.05). But the treatment with immune spleen cells was not effective. The incidence and area of necrotic foci in the tumors treated with LAK cells were greater than those of the others. Microautoradiography was also performed using 3H-TdR labeled LAK cells, which were administrated intravenously to the model. It was revealed that LAK cells accumulated in lung shortly after the administration, then in liver and spleen, especially in the white pulp. IL-2 inhibitor activity of the sera from the tumor-bearers was greater than that of normal rats, while it was depressed markedly by cyclophosphamide (60 mg/kg i.p.). In conclusion, the adoptive transfer of LAK cells can be one of the effective and attractive treatments of the brain tumor. In order to make immunotherapy more effective it should be necessary to clarify the nature of IL-2 inhibitor(s).

Animals↗
PubMed1988

Specific chromosomal abnormalities in malignant human gliomas.

Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one sex chromosome. The 42 tumors with abnormal karyotypes included 38 tumors which could be completely analyzed. Six of these 38 cases had near-triploid or near-tetraploid stemlines and 32 had near-diploid stemlines. Statistically significant numerical deviations in the near-diploid group were gains of chromosome 7 (26 of 32; P less than 0.001), and losses of chromosome 10 (19 of 32; P less than 0.001). Double minutes occurred in 18 of 32 near diploid tumors. The distribution of structural abnormalities was analyzed statistically by comparing the incidence of breakpoint in each chromosomal arm to the expected value based on chromosomal arm length. This analysis demonstrated that structural abnormalities of 9p and 19q were significant statistically (P less than 0.005 and P = 0.02, respectively). Although chromosome 1, 6p, the centromeric region of chromosome 11, 13q, and 15q were also frequently involved in structural abnormalities, the incidence of these breaks did not reach statistical significance. This demonstration of specific chromosomal abnormalities in near-diploid gliomas provides the basis for the investigation of genes which may be quantitatively or qualitatively altered in these neoplasms.

Adult↗
PubMed1987

[Possibility of overcoming ACNU resistance in ACNU-resistant sublines of rat brain tumors in vitro by a calmodulin inhibitor].

A calmodulin inhibitor, trifluoperazine, was found to enhance the cytotoxicity of ACNU in vitro in rat C6 glioma, 9L gliosarcoma and their ACNU-resistant sublines (C6/ACNU and 9L/ACNU). Uptake and retention of ACNU in these cells were studied with [14C]ACNU in the absence or presence of trifluoperazine. The results indicated that intracellular uptake and retention of ACNU in C6 and 9L cells were larger than those in C6/ACNU and 9L/ACNU cells, and that trifluoperazine increased the cellular uptake and retention of ACNU in C6 and 9L, especially in C6/ACNU and 9L/ACNU cells. The amounts of ACNU in C6/ACNU and 9L/ACNU cells reached almost the same level as those detected in C6 and 9L cells. When trifluoperazine were added along with ACNU to the culture in vitro at a concentration of 10 and 20 microM, ACNU resistance was completely overcome. Furthermore, treatment of C6 and C6/ACNU cells with 20 microM trifluoperazine did not change the cellular uptake rate of [14C]AIB (alpha-aminoisobutyric acid), which might indicate that the membrane permeability of the cells was kept intact during the drug treatment. The same phenomenon was observed in 9L and 9L/ACNU cells. It might be concluded that the enhanced effect of cytotoxicity of ACNU in ACNU-resistant rat brain tumor cells presented in this study is presumably due to the increase of intracellular concentration of ACNU resulting from the inhibition of the efflux of ACNU by trifluoperazine from the resistant cells. It was also suggested that ACNU resistance in malignant brain tumors could be overcome by combination chemotherapy with ACNU and calmodulin inhibitors.

Animals↗
PubMed1987

Products of cells cultured from gliomas. VI. Immunofluorescent, morphometric, and ultrastructural characterization of two different cell types growing from explants of human gliomas.

Explants derived from human gliomas have been characterized with respect to their cellular outgrowth pattern after 1-22 weeks in culture. A mat of cells which were fibronectin (FN)-positive and glial fibrillary acidic protein (GFAP)-negative (hereafter designated FN+ cells) with a polygonal, flat morphology covered the growth substrate in a swirling pattern for a mean diameter of 9.2 mm around FN+ explants. FN+ cells showed ruffled plasmalemma, dilated rough endoplasmic reticulin (RDR), and extracellular filamentous strands. Rare desmosomes were compatible with at most minor leptomeningeal components or differentiation. FN+ cells predominated in six of seven cultures at passage 2, and their features were the same from various high-grade gliomas and gliosarcoma. Around other explants, elongated or stellate cells which were GFAP+ and FN- grew in a netlike pattern with little cell-to-cell contact. These GFAP+ cells surrounded explants at a mean diameter of 2 mm, substantially less than FN+ cells (P less than 0.005), and they grew more slowly than FN+ cells around explants. GFAP+ cells had an area/perimeter ratio which was less than that of FN+ cells. GFAP+ cells contained abundant intracellular filaments, rare desmosomes, and narrow RER cisternae. In mixed explants, GFAP+ cells often grew on top of FN+ cells. Individual cells which stained for both GFAP and FN were evident only from one glioma (8% doubly positive). Cells negative for both proteins resembled FN+ cells morphologically. Frozen sections of original glioma tissue showed FN+ vessel walls and GFAP+ parenchyma. Results are evidence for very early overgrowth of a preexistent FN+ cell type distinct from the GFAP+ parenchymal cell. The features of this distinct cell type are mesenchymal and resemble the proliferating vascular elements of gliomas in situ. The tendency for GFAP+ cells to grow on top of these FN+ cells suggests a feeder layer interaction. More knowledge of the origins and interactions of these two cell types may increase our understanding of the mechanism of antigenic changes in gliomas and may provide clues to improved therapeutic approaches.

Antigens, Neoplasm↗
PubMed1987

Radiation-induced division delay in 9L spheroid versus monolayer cells.

The technique of percentage labeled mitoses was used to compare radiation-induced division delay in 9L rat gliosarcoma cells growing as spheroids or as exponential monolayers. The length of delay induced by each of five X-ray doses was determined as the difference between control and irradiated cultures in the time required to reach the half-height of the first peak of labeled mitoses. Spheroid cells were delayed significantly longer than monolayer cells; the slopes of the dose responses were 32 and 13 min/Gy, respectively. Cells in small spheroids (150 micron diameter) were delayed to the same extent as cells in large spheroids (800 micron diameter). Like the contact effect previously observed as enhanced radiation survival of cells grown as spheroids, the increased radiation-induced delay may be a consequence of the growth of cells in three-dimensional contact.

Animals↗
PubMed1985

Functional analysis of mononuclear cells infiltrating into tumors: differential cytotoxicity of mononuclear cells from tumors of immune and nonimmune rats.

A million syngeneic gliosarcoma (T-9) cells injected subcutaneously are sufficient to kill Fisher rats within 2 mo. Fisher rats became resistant to T-9 cells by surgical removal of the implanted tumor and repeated immunization with MMC-treated T-9 cells. Histopathologic studies revealed massive accumulation of mononuclear cells in tumor tissues of immune rats that were rejecting syngeneic T-9 tumors, whereas very few mononuclear cells were found in tumor tissues of nonimmune rats. Cell populations infiltrating into tumor tissues were identified by immunohistochemical techniques. Mononuclear cells found within the regressing tumors of immune rats were identified mostly to be T cells, and two-thirds of these T cells were OX-8 positive. In contrast, mononuclear cells found within the growing tumors of nonimmune rats were identified to be mixtures of macrophages and T cells, and very few OX-8 positive cells were found. Mononuclear cells were isolated from implanted T-9 tumors to determine whether mononuclear cells lysed T-9 cells specifically. Significant tumoricidal activity was seen when mononuclear cells from tumors of immune rats were used, whereas no detectable tumoricidal activity was observed with mononuclear cells from tumors of nonimmune rats. Winn assays confirmed in vitro 51Cr release assays by showing that tumors were rejected only when T-9 cells were implanted into normal Fisher rats along with mononuclear cells from tumors of immune rats.

Animals↗
PubMed1985

[Xanthoastrocytoma inf young subjects. Review of the literature apropos of 2 cases with discordant courses].

Two cases of pleomorphic xanthoastrocytoma (P X A) of young subjects (Kepes et al., 1979) are reported. Case 1 arose in 15-year-old boy admitted to the hospital with the complaint of severe headaches associated with nausea and vomiting of 1 month's duration. Computed tomographic scans showed a large well-defined low density area in the left temporo-parietal region of which an anterior portion was enhanced by contrast medium. Craniotomy revealed a large superficial and cystic tumor with a mural nodule. Histological and immunohistochemical features were those of a P X A confirmed by an electron microscopic study. No radiotherapy was given. The patient made a complete recovery, and 32 months later was asymptomatic. Case 2, a 17-year-old boy was admitted to the hospital in 1977. He presented with seizures that started 18 months prior to surgery. Carotid and humeral angiograms and air studies indicated the presence of a right, internal temporal mass with herniation. The craniotomy revealed a firm superficial tumor with an infratentorial, extraparenchymal extension. The histological diagnosis was giant cell glioblastoma or gliosarcoma. The patient received post-operative radiation of 5.500 rads and chemotherapy (CCNU and VM 26). He died on the 7th post-operative month. In this 2nd case, the diagnosis of P X A was made retrospectively based upon histological and immunohistochemical observations similar to case 1. We are aware of 24 P X A in the literature. In their clinical and histological features these neoplasms resemble closely each other. P X A are superficial, supratentorial astrocytomas occurring in youngs subjects (ages 3 to 32). Their typical microscopic structure include a marked cellular pleomorphism with bizarre giant cells, some mitotic figures and no necrosis. Many cells contain lipid and hyalin droplets in their cytoplasm. Characteristically, the tumoral stroma contain a very rich reticulin fiber network. Immunoperoxidase technique reveal glial fibrillary acidic protein in the tumor cells. Electron microscopic studies demonstrate abundant intracytoplasmic glial filaments. Individual cells or group of cells are surrounded by a prominent basal lamina. Some hemidesmosomes or primitive attachments are seen at the margins of the tumor cells. The biological behaviour of PXA with or without radiotherapy is relatively favorable. Long survival times (up to 25 years) are reported but in 5 cases, P X A follow a less favorable course with malignant transformation and death. Morphologic and immunohistochemical studies support the subpial astrocytic origin of P X A.

Adolescent↗
PubMed1982

[Schmidt Ruppin-D-ASV-induced primary rat brain tumor model for therapeutic screening].

It is important to evaluate the therapeutic and side effects of new therapy for malignant brain tumors in an adequate animal model prior to its initial clinical investigation. For decades, neurooncologists have argued for the use of primary, autochthonous tumors rather than transplanted tumors such as C 6 glioma cells and 9 L gliosarcoma cells. But unfortunately, no spontaneous animal astrocytomas are currently available as usable models. So we tried to establish the model of primary, autochthonous avian sarcoma virus-induced rat gliomas for experimental chemotherapy and immunotherapy. The present study was undertaken to determine the incidence and histologic pattern of tumors and the mean survival time of the animal model used. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of infectious cell free homogeneous subgroup D Schmidt-Ruppin avian sarcoma virus (SR-D-ASV) into 3-day-old inbred Fischer 344 rats induced small sized tumors in all rats 20 days later. The mean survival time of inoculated rats were 58.7 +/- 12 days. As to the classification of SR-D-ASV induced brain tumors in Fischer rats, astrocytoma was 70.6% (protoplasmic astrocytoma 23.5%, fibrillary astrocytoma 47.1%), sarcoma 17.6%, and mixed astrocytoma and sarcoma 11.8%. In conclusion, this SR-D-ASV induced tumor in the rat fulfilled the following criteria for the desirable animal model: (1) Spontaneously arising. (2) Glial origin. (3) Intraparenchymal growth. (4) Uniformly fatal within reasonable time period. Statistic evaluation of the effects of chemotherapy and immunotherapy was considered to be possible.

Animals↗
PubMed1984

Combination therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea and low dose rate radiation in the 9L rat brain tumor and spheroid models: implications for brain tumor brachytherapy.

We studied the effects of combination treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and low dose rate radiation in the 9L rat brain tumor in vivo model and the 9L multicellular tumor spheroid model. F-344 rats bearing intracerebral 9L gliosarcomas were implanted with removable 125I sources. Minimal (peripheral) tumor doses of 6387 rad produced an increased life-span (ILS) of 28% over that of control rats implanted with dummy sources, BCNU alone (13.3 mg/kg) produced in an ILS of 67%, and combination treatment with BCNU and implanted 125I sources produced an ILS of 167%. As measured by a colony-forming efficiency assay, the greatest cell kill in 9L spheroids occurred when BCNU was administered 24 hours before irradiation from a 137Cs source at a low dose rate of 5 rad/minute. At a higher dose rate of 210 rad/minute, the time dependence of the effects of combination treatment was identical and therefore independent of dose rate.

Animals↗
PubMed1978

[Early stages of experimental brain tumours in rats. Investigation of serial sections (author's transl)].

The results of transplacental induction of brain tumours by a single intravenous injection of ethylnitrosourea in a dosage of 20 or 30 mg/kg body weight to pregnant BD IX and Albino rats on the 17th day of gestation are presented. From 46 animals of the offspring 43 rats developed 185 intracranial neoplams. 157 of them were early stages. Most of the animals had multiple tumours. One rat showed 13 separate tumour nodules. The average number of brain tumours was 4.3 per rat. 101 tumours had a diameter of less than 1 mm. The neoplasms were classified as 179 glial tumours (mainly polymorphous gliomas, oligodendroastrocytomas and oligodendrogliomas), 4 sarcomas and 2 gliosarcomas. All the oligodendrogliomas and about two thirds of the polymorphous gliomas were early stages. The following preferential localizations in the rat brain were established: White matter of cerebrum, hippocampus, basal ganglia, cortex of cerebrum and brain stem. 25.4% of the tumours were localized in the subependymal area. Bulbus and tractus olfactorius, leptomeninx, and cerebellum were very rare sites of tumour growth.

Animals↗
PubMed1981

Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor.

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, was used alone and in combination with various single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to treat animals bearing murine glioma 26 and rat 9L gliosarcoma intracerebral tumors. Used as a single agent, DFMO has little or no effect against these tumors. However, in both intracerebral tumor models, pretreatment with DFMO p.o. before i.p. administration of BCNU potentiates the effect of BCNU without increasing toxicity. The effects of DFMO administered p.o. after BCNU or before and after various doses of BCNU indicate that DFMO may also effectively slow the repopulation of these tumors after BCNU therapy.

Animals↗
PubMed1982

Decreased cytotoxicity of cis-diamminedichloroplatinum(II) by alpha-difluoromethylornithine depletion of polyamines in 9L rat brain tumor cells in vitro.

Before treatment with the cytotoxic drug cis-dichlorodiammineplatinum(II) (cis-platinum), 9L rat brain gliosarcoma cells grown in vitro were depleted of intracellular polyamines by alpha-difluoromethylornithine (DFMO; 10 mM, 48 hr), an enzyme-activated, irreversible inhibitor of the polyamine-synthetic enzyme ornithine decarboxylase. In contrast to studies that showed that the cytotoxicity of 1,3-bis (2-chloroethyl)-1-nitrosourea as measured by colony-forming efficiency is enhanced by DFMO depletion of intracellular polyamines, the cytotoxicity of cis-platinum was significantly decreased in polyamine-depleted 9L cells. At 10, 1, and 0.1% survival levels, the dose modification factors were 2.0 to 2.1. Addition of exogenous putrescine to polyamine-depleted 9L cells 24 hr before treatment with cis-platinum partially reversed this phenomenon. When 9L cells were treated either with DFMO and cis-platinum or with DFMO, putrescine, and cis-platinum for 1 hr, a time period that is too short for DFMO to affect intracellular polyamine levels, the cytotoxicity of cis-platinum was decreased, but to a significantly lesser extent than by the 48-hr DFMO pretreatment. Putrescine alone did not alter the cytotoxic effect of cis-platinum when administered either 24 or 1 hr before treatment. DFMO appears to affect cis-platinum cytotoxicity by two different mechanisms, the first mediated through polyamine depletion and the second through a direct interaction with cis-platinum.

Animals↗