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 415 records · Page 23Linked to original sources
PubMed1999

Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens.

OBJECTIVE: Amplification of the epidermal growth factor receptor (EGFR) is a common event in the molecular pathogenesis of high-grade astrocytic tumors, occurring in 50% of glioblastoma multiforme (GBM) cases. A subset of GBMs also express a constitutively phosphorylated truncated receptor (EGFRvIII). Expression of transfected EGFRvIII in cells has been reported to activate the Ras-mitogen-activated protein kinase pathway and to provide a growth advantage. Novel therapeutic agents targeting signal transduction pathways are entering early clinical trials; determination of which GBMs express EGFRvIII might help identify patients who might benefit from these biological agents. METHODS: A cohort of 15 flash-frozen surgical specimens (12 GBMs, 2 gliosarcomas, and 1 adult low-grade glioma) were evaluated for EGFR and EGFRvIII expression and for EGFR activation status using immunohistochemical (IHC) analysis, Western blotting, and reverse transcription-polymerase chain reaction assays. Levels of activated Ras-guanosine triphosphate were measured using a nonradioactive luciferase-based technique. Mitogen-activated protein kinase activation was determined using a myelin basic protein assay. IHC analysis was performed on paraffin-embedded, formalin-fixed, pathological specimens. Normal control samples included white matter specimens distal to tumors (n = 5), a sample obtained during a lobectomy for treatment of epilepsy (n = 1), and cultured fetal human astrocytes (n = 1). RESULTS: We demonstrated higher levels of activated Ras and mitogen-activated protein kinase in GBM specimens, compared with normal brain tissue or the low-grade glioma. There was a very good correlation between results obtained using specialized molecular techniques and those obtained using routine IHC techniques. Screening for EGFRvIII expression may be of prognostic importance, because patients with EGFRvIII-positive tumors exhibited shorter life expectancies (mean survival time for patients with EGFRvIII-positive tumors, 4.5 +/- 0.6 mo; mean survival time for patients with EGFRvIII-negative tumors, 11.2 +/- 0.9 mo). CONCLUSION: We demonstrated that routine IHC techniques using commercially available antibodies are capable of identifying which GBM specimens express EGFRvIII and whether the EGFRs are activated. Such a molecular classification of GBMs might allow us to determine which patients might benefit from biologically targeted therapies. In addition, characterization of specimens with respect to their EGFRvIII status seems to be of prognostic value.

Adult↗
PubMed2001

Immunomodulation of glioma cells after gene therapy: induction of major histocompatibility complex class I but not class II antigen in vitro.

OBJECTIVE: Acquired immunity has been demonstrated in Fischer rats bearing syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene transfection and ganciclovir treatment. The nature of this immunity in rats and its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be determined. In this study, levels of major histocompatibility complex (MHC) Class I and II antigen expression were measured before and after HSV TK transfection, in an effort to document immunomodulatory changes caused by gene therapy. METHODS: Tumor cells from the 9L gliosarcoma cell line, three primary human glioma cultures, and the human glioma cell line U87 MG were transduced with HSV TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x 10(6) colony-forming units/ml) and selected in G418 medium for neomycin resistance. Clones were pooled or individually selected for cell-killing assays with ganciclovir, to confirm TK expression (10(3) cells/well in a 96-well dish). Northern analyses using MHC Class I and Class II complementary deoxyribonucleic acid probes were performed on blots containing total ribonucleic acid from wild-type tumor cells and HSV TK transfectants. A beta-actin complementary deoxyribonucleic acid probe served as an internal control. Cell surface expression was confirmed with flow cytometry. The induction of MHC Class I was tested for cycloheximide and genistein sensitivity. RESULTS: All cell cultures exhibited increases in MHC Class I but not MHC Class II expression, as determined by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did not diminish the up-regulation of MHC Class I after retroviral transfection, implicating a signal transduction pathway that does not require ongoing protein synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation of MHC Class I, implicating a tyrosine kinase in the signaling cascade. CONCLUSION: Induction of MHC Class I in rat and human glioma cells after HSV TK retroviral gene therapy is a primary effect that is dependent on tyrosine kinase activity. Specific immune responses generated after transfection may represent an important general side effect of gene therapy protocols. Elucidation of the mechanism of immunomodulation after gene therapy will likely yield safer and more effective clinical protocols.

Animals↗
PubMed1999

Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas.

Malignant gliomas frequently show genetic aberrations of genes coding for cell cycle regulatory proteins involved in the control of G1/S phase transition. These include mutation and/or deletion of the retinoblastoma (RB1) gene, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplification and overexpression of the CDK4 and CDK6 genes. The D-type cyclins (cyclin D1, D2, and D3) promote cell cycle progression from G1 to S phase by binding to and activating the cyclin dependent kinases Cdk4 and Cdk6. Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D-type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). We found the CCND1 gene amplified and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplification, but lacked significant overexpression of CCND2 transcripts. Amplification and overexpression of the CCND3 gene was detected in the glioblastoma cell line CCF-STTG1, as well as in one primary glioblastoma and in the sarcomatous component of one gliosarcoma. Our data thus suggest that amplification and increased expression of CCND1 and CCND3 contribute to the loss of cell cycle control in a small fraction of human malignant gliomas.

Blotting, Southern↗
PubMed2000

Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model.

PURPOSE: To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. MATERIALS AND METHODS: A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. RESULTS: Tumoral accumulation of LCDIO was 0.11% +/- 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% +/- 4.6) but was also taken up by macrophages in tumors (21.0% +/- 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% +/- 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines. CONCLUSION: Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates.

Animals↗
PubMed2004

Highly successful therapeutic vaccinations combining dendritic cells and tumor cells secreting granulocyte macrophage colony-stimulating factor.

In an attempt to induce potent immune antitumor activities, we investigated, within the rat 9L gliosarcoma model, distal therapeutic vaccinations associating three therapies: dendritic cell vaccination, intratumoral granulocyte macrophage colony-stimulating factor (GM-CSF) gene transfer, and tumor apoptosis induction. Vaccines of dendritic cells coinjected with processed GM-CSF secreting 9L cells induced systemic responses, resulting in the complete regression of distant preimplanted 9L tumor masses in, with the best strategy, 94% of male rats. All of the cured rats developed a long-term resistance to a rechallenge with parental cells. The curative responses were correlated with the detection of elevated specific cytotoxic activities and a CD4+, CD8+ T cell-, and natural killer (NK) cell-mediated IFN-gamma production. The survival rate of the rat seemed more directly linked to the amount of GM-CSF secreted by the transduced tumor cells, which in turn depended on the toxicity of the apoptosis-inducing treatment, than to the level of apoptosis induced. Unexpectedly, alive GM-CSF secreting 9L cells became apoptotic when injected in vivo. Thus we documented the positive role of apoptosis in the induction of therapeutic antitumor responses by comparing, at equal GM-CSF exogenous supply, the effects of dendritic cells coinjected with apoptotic or necrotic 9L cells. The data showed the superior therapeutic efficiency of combined vaccines containing apoptotic tumor cells. In conclusion, vaccinations with dendritic cells associated with apoptotic tumor cells secreting GM-CSF show a very high therapeutic potency that should show promise for the treatment of human cancer.

Animals↗
PubMed2005

Decreased replication ability of E1-deleted adenoviruses correlates with increased brain tumor malignancy.

E1 region replacement adenoviruses are replication defective and are propagated in cells providing adenovirus E1A and E1B proteins. Although they are being developed for antitumor therapies, the proliferative behaviors of these viruses in normal brain tissues or in brain tumors are unknown. To address this, freshly cultured cells from normal human brain and common brain tumors (astrocytomas and meningiomas) were infected using wild-type species C adenoviruses and adenoviruses missing E1A (H5dl312) or E1A plus E1B (H5dl434). Viral DNA replication, late viral protein expression, and production of infectious progeny were characterized. Wild-type adenoviruses grew efficiently in normal brain and brain tumor cells. In comparison, E1-deleted adenovirus DNA replication was delayed and lower in cells derived from normal brain tissues, meningiomas, and low-grade astrocytomas. However, in contrast, E1-deleted adenovirus DNA replication did not occur or was extremely low in cells derived from malignancy grade III and IV astrocytic tumors. Because wild-type adenoviruses infected and replicated in all cells, the malignancy grade-based differential E1-deleted adenovirus DNA replication was not explained by differential virus uptake. Infectious H5dl312 and H5dl434 production correlated with viral DNA replication. Compared with a 5-day average for wild-type infections, advanced cytopathology was noted approximately 4 weeks after H5dl312 or H5dl434 infection of meningioma, astrocytoma, and normal brain cells. Cytopathology was not observed after H5dl312 or H5dl434 infection of glioblastoma, anaplastic astrocytoma, and gliosarcoma cells. Because of this tumor grade-based differential growth, the E1-deleted adenoviruses may represent novel tools for studies of brain tumor malignancy.

Adenoviridae↗
PubMed2006

Inhibition of vascular endothelial growth factor (VEGF)-A causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D.

PURPOSE: Vascular endothelial growth factor (VEGF)-A is an important mediator of angiogenesis in almost all solid tumors. The aim of this study was to evaluate the effect of VEGF-A expression on tumor growth, perfusion, and chemotherapeutic efficacy in orthotopic 9L gliosarcomas. EXPERIMENTAL DESIGN: Stable 9L cell lines underexpressing and overexpressing VEGF-A were generated. Anatomic, susceptibility contrast, and continuous arterial spin-labeling magnetic resonance imaging were used to quantify the volume, blood volume, and blood flow of tumors orthotopically grown from these and wild-type 9L cells. Histologic, immunohistochemical, and quantitative reverse transcription-PCR analyses were also done on excised tumors. Finally, the effects of carmustine chemotherapy were also evaluated. RESULTS: Orthotopic tumors underexpressing VEGF-A had slower growth rates (increased median survival), greater blood flow, vessel density, and VEGF-D expression, but no statistical difference in blood volume and chemotherapeutic sensitivity, compared with tumors with wild-type levels of VEGF-A. Tumors overexpressing VEGF-A had faster growth rates, greater blood volume, vessel density, and blood flow but no statistical difference in VEGF-D expression and chemotherapeutic sensitivity compared with wild-type VEGF-A-expressing tumors. CONCLUSION: Blood volume and blood flow are independent and different biomarkers of tumor perfusion. Therefore, both should be measured when characterizing the efficacy of antiangiogenic therapies. Underexpression of VEGF-A does not result in complete inhibition of angiogenesis. Moreover, these tumors have a different perfusion phenotype, suggesting that angiogenesis is mediated by an alternative pathway. The results indicate that VEGF-D is a plausible alternative mediator of this angiogenesis.

Animals↗
PubMed2005

Dexamethasone normalizes brain tumor hemodynamics as indicated by dynamic susceptibility contrast MRI perfusion parameters.

The purpose of this study is to demonstrate the utility of dynamic susceptibility contrast (DSC) MRI-derived perfusion parameters to characterize the hemodynamic effects of dexamethasone in a 9L gliosarcoma tumor model. Twenty-four rats underwent intracerebral inoculation with 9L tumor cells. Fifteen were treated with a total of 3mg/kg of dexamethasone on days 10-14 post-inoculation, while the remaining 9 rats served as controls. Fourteen days post-inoculation, MRI images, sensitive to total and micro-vascular cerebral blood flow (CBF), mean transit time (MTT), and intravoxel transit time distributions (TTD)s were obtained using a simultaneous gradient-echo(GE)/spin-echo(SE) DSC-MRI method. Dexamethasone-treated animals had a microvascular (SE) tumor CBF that was 45.9% higher (p = 0.0008) and a MTT that was 47.8% lower (p = 0.0005) than untreated animals. With treatment, there was a non-significant 91.3% increase in total (GE) vascular CBF (p = 0.35), and a significant decrease in MTT (49.1%, p = 0.02). The total vascular and microvascular TTDs from the treated tumors were similar to normal brain, unlike the TTDs in the untreated tumors. These findings demonstrate that DSC-MRI perfusion methods can be used to non-invasively detect the morphological and functional changes in tumor vasculature that occur in response to dexamethasone treatment.

Animals↗
PubMed2003

Assessment of in vivo chemotherapy-induced DNA damage in a p53-mutated rat tumor by micronuclei assay.

Production of DNA damage is the basis of cancer treatments such as chemo- and radiotherapy. Such treatments induce mitotic catastrophe, a form of cell death resulting from abnormal mitosis and leading to the formation of interphase cells with multiple micronuclei. In this study, we compared apoptosis induction and micronuclei formation to assess the DNA damage provoked in vivo by cytotoxic agents in established 9L rat gliosarcoma tumors expressing a mutated p53 gene. Results from TUNEL assays revealed the efficiency of local gamma-irradiation at the tumor site to induce apoptosis within 9L tumor mass. However, little or no apoptosis was detected after systemic (ip) injection of cisplatin (1 mg/kg). Interestingly, the micronuclei assays showed that not only gamma-irradiation but also cisplatin treatment led to an increase in the emergence of binucleated cells with micronuclei. Apoptosis induction and micronuclei emergence are thus not absolutely correlated. However, micronuclei assays, rarely performed on solid tumors, appear more sensitive than apoptosis assays in evaluating DNA damage linked to chemotherapy.

Animals↗
PubMed1994

Desmoplastic infantile gangliogliomas: an approach to therapy.

Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Local immunotherapy with interleukin-2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE: Local delivery of carmustine (BCNU) from biodegradable polymers prolongs survival against experimental brain tumors. Moreover, paracrine administration of interleukin-2 (IL-2) has been shown to elicit a potent antitumor immune response and to improve survival in animal brain tumor models. We report the use of a novel polymeric microsphere delivery vehicle to release IL-2. We demonstrate both in vitro release of cytokine from the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from the microspheres in the rat brain. These microspheres are used to deliver IL-2, and biodegradable polymer wafers are used to deliver BCNU, directly at the site of an intracranially implanted glioma in the rat. The two agents administered locally show a synergistic effect. METHODS: Fischer 344 rats challenged intracranially with 9L gliosarcoma received an intracranial implant of either empty microspheres or microspheres containing IL-2 (IL-2 MS). Five days later, animals in each group were randomized to receive polymer implants loaded with 0, 3.8, or 10% BCNU at the tumor site. RESULTS: Animals that received the combination of IL-2 MS and 3.8% BCNU polymer (median survival, 28.5 d) or IL-2 MS and 10% BCNU polymer (median survival, 45.5 d) showed significantly improved survival compared with animals that received monotherapy with IL-2 microspheres (median survival, 24 d), 3.8% BCNU polymer (median survival, 24 d), or 10% BCNU polymer (median survival, 32.5 d). Control animals had a median survival of 18 days. The combination of either 3.8 or 10% BCNU polymer with IL-2 MS resulted in 7 and 25% long-term survivors, respectively. CONCLUSION: By showing synergy of IL-2 and BCNU in an animal glioma model and using a reproducible synthetic delivery system for each agent (i.e., one that did not rely on genetically engineered cells or viruses), we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical application in patients with malignant brain tumors.

Animals↗
PubMed2005

A quantitative model of tumor-induced angiogenesis in the nude mouse.

OBJECTIVE: Novel animal models allowing for the quantification of tumor-induced angiogenesis and cell migration may offer significant insight into the characterization and multidisciplinary treatment of brain tumors. In this study, we seek to establish such a model in tumor-bearing brain, allowing for a clear demarcation of primary and satellite tumor tissue in conjunction with precise quantification of cerebral microvasculature. METHODS: We used green fluorescent protein-transfected 9L-gliosarcoma cells stereotactically injected into the brain parenchyma of nude mice perfused with tetramethylrhodamine-dextran immediately before they were killed. New three-dimensional analytical software developed in our laboratory provided a quantitative analysis of laser-scanning confocal microscopy images of dextran-labeled cerebral microvessels. RESULTS: Our data confirm significant angiogenesis in tumor and brain adjacent to tumor. CONCLUSION: Because these highly infiltrative malignant brain tumors interdigitate with normal brain parenchyma through finger-like projections at the periphery of the solid tumor boundary, therapeutic options targeting tumor blood flow--combined with novel three-dimensional imaging to localize and track such interventions--may offer new hope for glioma management. To our knowledge, this system represents the first animal brain tumor model allowing for the precise colocalization and quantification of angiogenesis and tumor cell invasion, which may play an important role in the development of future therapy for brain tumors.

Animals↗
PubMed2000

An alternative method to stereotactic inoculation of transplantable brain tumours in large numbers of rats.

The rat 9L gliosarcoma brain tumour model has been widely used in brain cancer studies. Intracerebral implantation of the cells in the parietal lobe of the brain has been performed using the stereotactic or freehand inoculation methods. For large numbers of rats, we wished to develop a method more accurate and precise than the freehand method, but less labour intensive than the stereotactic method. A template implantation technique was developed and compared quantitatively with the stereotactic method. Rats were inoculated with either the template or stereotactic method at doses of 1000, 5000, 10000, 20000 or 40000 cells. Results of this comparison showed that the template method is precise and accurate for tumour placement within the brain cortex, and decreases labour requirements. Mean survival rates between groups were not significantly different at doses of 5000, 20000 or 40000 cells inoculated. Significance was seen at the low dose of 1000 cells (P < 0.001). This was attributable to an absence of tumour growth in five of six stereotactic rats in this group. Significance was also seen at the 10000 dose level (P < 0.05) with the stereotactic rats again surviving longer than the template rats. However, in this case all the stereotactic rats had tumour growth. Brain weights did not differ significantly between groups, except at the 1000 dose level where no growth of tumour occurred in five of the six stereotactic animals. Body weight gain within one week following surgery did not differ significantly between any of the groups at alpha = 0.05. Studies on rat cadavers showed no statistical difference in placement measurements between the stereotactic and template methods. These results indicate that the template method for intracerebrally implanting tumour cells in rats provides a precise, accurate and rapid procedure that maximizes reproducibility with a significant reduction in labour requirements, when compared with the conventional stereotactic methodology.

Animals↗
PubMed2006

Fluorescent nanoparticle uptake for brain tumor visualization.

Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP) tumors, mean overestimations of 2 and 24 microm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages) and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon) and primary (Gli36 glioma) brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

Animals↗
PubMed1995

Angiogenesis in microvascular endothelial cells induced by glioma cells and inhibited by tumor necrosis factor in vitro.

Neovascularization is a prerequisite for glioma growth, so inhibition of angiogenesis may achieve control of glioma growth. We examined whether glioma cells induce angiogenesis and proliferation in microvascular endothelial cells from Fisher 344 rat brains by co-culture in a physical separation system with rat C6 glioma cells or rat T9 gliosarcoma cells. Endothelial cells cultured on type 1 collagen formed capillary-like structures. C6 glioma cells co-cultured with endothelial cells promoted the formation of these capillary-like structures. However, conditioned medium from C6 cells inhibited the proliferation of endothelial cells. T9 cells had little effect on the formation of capillary-like structures and no effect on the proliferation of endothelial cells. We also examined the effects of human tumor necrosis factor (TNF)-alpha on the formation of the capillary-like structures and on the proliferation of endothelial cells. Human TNF-alpha inhibited the formation of capillary-like structures induced by C6 glioma cells at a concentration of 100 U/ml, as well as the proliferation of endothelial cells at a concentration of 1000 U/ml. These results indicate that induction of angiogenesis varies with glioma cell lines and angiogenesis does not correspond with proliferation of endothelial cells. TNF-alpha can inhibit angiogenesis in gliomas in vitro.

Animals↗
PubMed1997

Mn-metalloporphyrin conjugated with Gd-DTPA (Gd-ATN10): tumor enhancement agent for magnetic resonance imaging.

A conjugate of manganese-metalloporphyrin and gadolinium (Gd)-diethylenetriaminepenta-acetic acid (Gd-ATN10) was developed as a tumor-specific enhancement agent for magnetic resonance (MR) imaging. Gd-ATN10 was evaluated in an experimental 9L gliosarcoma rat tumor model. T1-weighted MR imaging showed enhancement of the tumor which persisted for up to 24 hours. Gd concentration measurement by inductively coupled plasma atomic emission spectroscopy revealed the peak Gd concentration was reached after 30 minutes and Gd was retained in the blood and tumor up to 24 hours. There was no uptake of Gd in the normal brain and little in the skin. Gd-porphyrin derivatives are potentially useful agents for tumor diagnosis on MR imaging and for neutron capture therapy.

Animals↗
PubMed1996

5-[125]iodo-2'-deoxyuridine in the radiotherapy of solid CNS tumors in rats.

We have been investigating the therapeutic efficacy of the thymidine analog 5-iodo-2'-deoxyuridine (IUdR) when radiolabeled with the Auger electron emitter 125I in rats bearing intrathecal (i.t.) or intracerebral (i.c.) 9L gliosarcoma solid tumors. [125I]IUdR was infused i.t. (via subarachnoid catheters) or intracerebrally over a 5- or 2-day period; equimolar concentrations of [127I]IUdR were infused into control animals. Hind-leg paralysis and/or survival were followed over time. The results indicate that compared with [127I]IUdR, rats bearing intrathecal tumors and infused i.t. with [125I]IUdR showed significant prolongation of the onset of median paralysis (15.2 versus 9 days). Similarly, the median survival of rats bearing intracerebral tumors and infused i.c. with [125I]IUdR was significantly increased (24 versus 17 days). The data substantiate the antineoplastic potential of [125I]IUdR and indicate a promising role for this radiopharmaceutical in the treatment of CNS cancers.

Animals↗
PubMed2003

Thymoma and multiple malignancies: a case of five synchronous neoplasms and literature review.

The presence of five discrete synchronous or metachronous primary neoplasms in a single patient is an extremely rare event. This is a report of a patient with a malignant (invasive) thymoma and four other independent primary neoplasms including: gliosarcoma, papillary thyroid cancer, meningioma and metastatic adenocarcinoma of the colon, found synchronously at autopsy. Thymoma patients appear to have an inherent predisposition towards developing additional neoplasms. Other than the thymoma, the presented patient had no obvious risk factors for neoplasia. This case provides evidence for an unusual syndrome of thymoma and multiple primary neoplasms. Further research is required to elucidate the mechanism of this association. Meanwhile, heightened awareness of this association may allow earlier detection and treatment of additional cancers in patients with a history of thymoma.

Adenocarcinoma↗