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 685 records · Page 38Linked to original sources
PubMed1995

Assessment of ganciclovir toxicity to experimental intracranial gliomas following recombinant adenoviral-mediated transfer of the herpes simplex virus thymidine kinase gene by magnetic resonance imaging and proton magnetic resonance spectroscopy.

Magnetic resonance imaging and in vivo localized H magnetic resonance spectroscopy were used to evaluate a gene therapy approach for treating experimental brain tumors. This approach involved the use of an adenoviral vector to transfer the herpes simplex virus thymidine kinase (HSVtk) gene into intracerebral 9L gliosarcomas in rats followed by systemic administration of the antiherpetic agent ganciclovir. Magnetic resonance imaging quantitation of changes in intracranial 9L tumor doubling times revealed a significant variation in therapeutic response. Localized H magnetic resonance spectra of 9L tumors treated with Ad.RSVtk/ganciclovir revealed a dramatic increase in the resonance intensity at 0.9-1.3 ppm, corresponding to mobile lipids and/or lactate. Changes in intracranial tumor doubling times correlated with changes in H tumor magnetic resonance spectra, suggesting that specific changes in tumor metabolite levels may be predictive of the effectiveness of this gene therapy approach.

Animals↗
PubMedDate not supplied

Selective radiosensitization of 9L glioma in the brain transduced with double suicide fusion gene.

PURPOSE: Suicide gene therapy has proved to be successful in enhancing the therapeutic index by sensitizing genetically modified tumor cells to prodrugs. Two of the most widely studied suicide genes, herpes simplex virus type 1 thymidine kinase and Escherichia coli cytosine deaminase, have proved effective at selectively eliminating malignant tumor cells. We previously demonstrated that transduced 9L glioma cells expressing E. coli cytosine deaminase and herpes simplex virus type 1 thymidine kinase concomitantly as a fusion protein exhibited greater levels of targeted cytotoxicity and radiosensitization than could be achieved by single suicide gene therapy. The present in vivo studies were carried out to determine whether double suicide gene therapy would enhance the tumor control rate of orthotopically implanted malignant glioma growing in the brain when coupled with radiotherapy. MATERIALS AND METHODS: Rat 9L gliosarcoma cells were transfected with retroviral vectors containing an E. coli cytosine deaminase and herpes simplex virus type 1 thymidine kinase fusion gene and maintained in Dulbecco's modified Eagle's medium. The antitumor response of 9L E. coli cytosine deaminase and herpes simplex virus type 1 thymidine kinase tumors growing in the brain of Fischer rats was evaluated with small tumors (6-day-old tumors) versus large tumors (14-day-old tumors) against single versus double prodrug treatments. In the large brain tumors, the therapeutic efficacy of the combined single and double prodrugs coupled with radiotherapy was evaluated. RESULTS: Double suicide gene therapy using two prodrugs, 5-fluorocytosine (500 mg/kg) and ganciclovir (30 mg/kg), was effective in achieving long-term tumor control (50% survival) against early-stage brain tumors (6 days after implantation) but was only marginally effective against advanced stage tumors (14 days old). However, when these prodrugs were combined with radiotherapy and double suicide gene therapy against advanced-stage tumors, more than 70% of the animals were cured, whereas radiotherapy alone (20 Gy) failed to achieve any cure at all. Combined radiotherapy and single prodrug therapy showed a moderate increase in the animal survival rate (17% and 40% for 5-fluorocytosine and ganciclovir, respectively) but was inferior to the combination therapy of radiation and double prodrugs. CONCLUSION: The present in vivo results indicate that double suicide gene therapy combined with radiotherapy may represent a new, effective approach to achieve a high tumor cure rate without producing any excessive normal tissue damage.

Animals↗
PubMed1998

Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy.

BACKGROUND: Cell adhesion molecules are among the key factors in the development of the malignant potential of brain tumors. The aim of this study was to investigate the expression of the neural cell adhesion molecule (NCAM) in human astrocytic tumors and assess any relationship between NCAM expression and the degree of malignancy. METHODS: The expression of NCAM was examined in 52 astrocytic tumors by Western blot analysis. From them the authors selected 23 adult supratentorial ordinary astrocytic tumors and performed quantitative Western blot analysis for each isoform (NCAM 172-180, NCAM 145, NCAM 125-130) to investigate any correlation between the expression of each NCAM isoform and the histologic and biologic malignancy (histology, proliferating cell indices [PCIs] determined by MIB-1 immunohistochemistry, and manifestation on magnetic resonance images [MRIs]). Immunohistochemistry with antihuman NCAM monoclonal antibody was also performed on the tumors from which cryostat sections were available. RESULTS: Most of the astrocytomas and anaplastic astrocytomas revealed 3 bands at 180, 145, and 125-130kD, whereas in glioblastomas the bands tended to diminish. The expression of each NCAM isoform in astrocytic tumors decreased in proportion to the progression of the histologic malignancy, and the results were also corroborated by immunohistochemical evaluation. An inverse correlation was also observed between the amount of NCAM expression and MIB-1 PCIs. NCAM expression was hardly detectable in those tumors with highly invasive manifestation on MRIs. CONCLUSIONS: To the authors' knowledge, this study provides the first direct evidence that NCAM is down-regulated in the development of the malignancy of astrocytic tumors; and it is suggested that reduced NCAM expression might be involved in the development of biologic malignancy.

Adult↗
PubMed2000

Lactate editing and lipid suppression by continuous wavelet transform analysis: application to simulated and (1)H MRS brain tumor time-domain data.

Determination of lactate concentrations in vivo is required in the noninvasive diagnosis, staging, and therapeutic monitoring of diseases such as cancer, heart disease, and stroke. An iterative filtering process based on the continuous wavelet transform (CWT) method in the time domain is proposed to isolate the lactate doublet signal from overlapping lipid resonances and estimate the magnetic resonance spectroscopy (MRS) parameters of the lactate methyl signal (signal amplitude, chemical shift, J-coupling and apparent transverse relaxation time (T*(2))). This method offers a number of advantages over the multiple quantum (MQ) and difference spectroscopy approaches, including: 1) full recovery of the lactate methyl signal, whereas the MQ methods usually detect 50% of the signal intensity; 2) in contrast to MQ methods, the lipid signal is retained together with J-coupling data on the lactate peak; 3) the CWT method is much less sensitive to motion artifacts than difference spectroscopy. Application of the method to simulated and real (1)H MRS data collected from human blood plasma and brain tumors demonstrated that this filter provides accurate estimates of the MRS parameters of the lactate doublet and efficiently removes lipid contributions.

Adult↗
PubMed2000

Thapsigargin-induced grp78 expression is mediated by the increase of cytosolic free calcium in 9L rat brain tumor cells.

Exposure of 9L rat brain tumor cells to 300 nM thapsigargin (TG), a sarcoendoplasmic Ca(2+)-ATPases inhibitor, leads to an immediate suppression of general protein synthesis followed by an enhanced synthesis of the 78-kDa glucose-regulated protein, GRP78. Synthesis of GRP78 increases significantly and continues to rise after 4 h of treatment, and this process coincides with the accumulation of grp78 mRNA. TG-induced grp78 expression can be suppressed by the cytosolic free calcium ([Ca(2+)](c)) chelator dibromo-1, 2-bis(aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA) in a concentration-dependent manner. Induction of grp78 is completely abolished in the presence of 20 microM BAPTA under which the TG-induced increase of [Ca(2+)](c) is also completely prevented. By adding ethyleneglycol bis(beta-aminoethyl)ether-N,N,N',N' tetraacetic acid in the foregoing experiments, in a condition such that endoplasmic reticulum calcium ([Ca(2+)](ER)) is depleted and calcium influx from outside is prevented, TG-induced grp78 expression is also abolished. These data lead us to conclude that increase in [Ca(2+)](c), together with the depletion of [Ca(2+)](ER), are the major causes of TG-induced grp78 expression in 9L rat brain tumor cells. By using electrophoretic mobility shift assays (EMSA), we found that the nuclear extracts prepared from TG-treated cells exhibit an increase in binding activity toward the extended grp78 promoter as well as the individual cis-acting regulatory elements, CRE and CORE. Moreover, this increase in binding activity is also reduced by BAPTA. By competitory assays using the cis-acting regulatory elements as the competitors as well as the EMSA probes, we further show that all of the tested cis elements-CRE, CORE, and C1-are involved in the basal as well as in the TG-induced expression of grp78 and that the protein factor(s) that binds to the C1 region plays an important role in the formation and maintenance of the transcription complex.

Animals↗
PubMed1994

In vivo versus in vitro degradation of controlled release polymers for intracranial surgical therapy.

Intracranial studies to analyze the degradation kinetics of the bioerodible polymer poly[bis(p-carboxyphenoxy)propane-sebacic acid] [p(CPP-SA) 20:80] copolymer wafers were conducted in a rat model. Rats were separated into four groups: those receiving 1) polymer, 2) polymer loaded with the chemotherapeutic agent BCNU, 3) drug-loaded polymer with previous tumor implantation, and 4) polymer and an absorbable hemostatic material. A polymer wafer was surgically implanted into the brain of each animal. Residual polymer was harvested at varying times for chromatographic analysis. In vitro effects of pH, mixing, and water availability on degradation were also studied. The results of in vitro and in vivo studies were compared to understand the behavior of polymers in a clinical setting. We found that degradation of p(CPP-SA) initially occurred more slowly in vivo than in vitro. The presence of BCNU, tumor, and absorbable hemostatic material did not affect the ultimate time of polymer degradation in vivo, and the intrinsic polymer degradation time of 1 mm thick p(CPP-SA) 20:80 disks in vivo was 6-8 weeks.

Animals↗
PubMed2005

Sodium magnetic resonance imaging of chemotherapeutic response in a rat glioma.

This study investigates the comparative changes in the sodium MRI signal and proton diffusion following treatment using a 9L rat glioma model to develop markers of earliest response to cancer therapy. Sodium MRI and proton diffusion mapping were performed on untreated (n = 5) and chemotherapy 1,3-bis(2-chloroethyl)-1-nitrosourea-treated rats (n = 5). Animals were scanned serially at 2- to 3-day intervals for up to 30 days following therapy. The time course of Na concentration in a tumor showed a dramatic increase in the treated brain tumor compared to the untreated tumor, which correlates in time with an increase in tumor water diffusion. The largest posttreatment increase in sodium signal occurred 7-9 days following treatment and correlated to the period of the greatest chemotherapy-induced cellular necrosis based on diffusion and histopathology. Both Na MRI and proton ADC mapping revealed early changes in tumor sodium content and cellularity. This study demonstrates the possibility of Na MRI to function as a biomarker for monitoring early tumor treatment and validates the use of monitoring changes in diffusion MRI values for assessing tumor cellularity.

Animals↗
PubMed1998

A chimeric fusion protein of cytochrome CYP4B1 and green fluorescent protein for detection of pro-drug activating gene delivery and for gene therapy in malignant glioma.

Quantity and distribution of transgene-expressing tumor cells are central issues in cancer gene therapy. These are critical for the efficiency of tumor killing and for the bystander effect. In an attempt to combine the advantages of a potent bioactivating "suicide" gene with a marker gene for living cells, cDNA encoding cytochrome CYP4B1 was fused to the green fluorescent protein (GFP) cDNA. The resulting chimeric fusion protein, 4B1EGFP, was expressed in rodent and human glioma cell lines in culture. The ability of this recombinant enzyme to destroy tumor cells by converting the prodrug 4-ipomeanol (4-IM) into alkylating metabolites was evaluated in comparison with the cytotoxicity of the native CYP4B1 enzyme. The most sensitive 4B1EGFP-expressing glioma cell clone had a LD50 of 0.75 microgram/ml for 4-IM, as compared to a 4-IM LD50 of 0.5 microgram/ml in glioma cells expressing the native CYP4B1. A strong bystander effect mediated by cell-to-cell contact was present in the 4B1EGFP clones, allowing for more than 50% bystander kill at a ratio of expressing to non-expressing cells of 1:100. A herpes-simplex amplicon (pHSVPrPUC delta Hind) was constructed with the 4B1EGFP fusion protein, and recombinant helper-free HSV particles were packaged in Vero cells. Fisher 344 rats were inoculated with 4 x 10(5) 9L tumor cells to produce epidural tumor. Recombinant HSV particles were injected into the tumor at a dose of 1 x 10(7) pfu. Tumor was resected in living anesthetized animals 24, 48, and 72 hours after virus injection, and cryostat sections were evaluated by fluorescent microscopy. HSV-mediated delivery of the fusion protein to tumor cells was successfully demonstrated. In conclusion, the chimeric fusion protein 4B1EGFP retains essentially all features of the native CYP4B1 enzyme, and, moreover, offers advantages in terms of gene transfer visualization, which may lead to improvement of gene transfer strategies.

Animals↗
PubMed1996

Proliferation and motility responses of primary and recurrent gliomas related to changes in epidermal growth factor receptor expression.

Astrocytic neoplasms show a high incidence of elevated or mutated epidermal growth factor receptor (EGFR) expression. Although proliferative effects from EGFR activation are well described, the role that changes in this receptor play in glioma growth and migration remain poorly addressed. This report characterizes changes in the levels of EGFR expression in three glial tumors at initial presentation (resection) and at the time of recurrence. By quantitative flow cytometry the mean level of EGFR expression increased, decreased, or remained the same in different recurrent astrocytomas relative to their primary tumor cells. Immunocytochemistry for EGFR on monolayer cells corroborated the level of expression in the recurrent tumors relative to their matched primary specimen. Immunoprecipitation indicated that 170 kd EGFR was expressed in each of the tumors, and showed normal down regulation following treatment with EGF. Proliferation response to EGF was seen in only 1/6 instances, but was concentration-dependent when observed. Stimulated migration of the cells was frequently seen and was also concentration-dependent on EGF; the magnitude of response was related to the relative level of 170 kd EGFR expression in the cells. EGFR immunostaining of tissue sections from the tumors confirmed the levels of EGFR expressed in primary and recurrent astrocytomas as was seen in the cultured cells. These results indicate that the relative levels of EGFR in early passage cell cultures from glioma specimens concurs with the measured tissue levels of expression. Human glioma cells are more responsive to migration induction than proliferation induction by EGF.

Cell Division↗
PubMed1994

CD34 immunoreactivity in nervous system tumors.

CD34 is a sialylated transmembrane glycoprotein of unknown function that is present in myeloid progenitor cells, endothelial cells, and some fibroblast-related mesenchymal cells. However, its tissue distribution is still incompletely characterized. In this study we evaluated the distribution of CD34 antigen in tumors of the central and peripheral nervous system. For comparison the tumors were also stained for CD31, also known as platelet-endothelium cell adhesion molecule (PECAM-1), a transmembrane glycoprotein so far considered to be endothelium specific beyond its reactivity with certain hematopoietic cells. Neurofibromas showed consistently high numbers of CD34-positive spindle cells, whereas peripheral and acoustic schwannomas were negative. A subset of meningiomas (15%) showed CD34-positive tumor cells, and some were also weakly positive for CD31. Gliomas were negative. Meningeal hemangiopericytomas were consistently CD34 positive, but CD31 negative. These results indicate a moderately widespread distribution of the CD34 antigen in nervous system tumors, and necessitate caution in making conclusions regarding endothelial cell differentiation of nervous system tumors on the basis of CD34 immunoreactivity.

Antigens, CD↗
PubMed1994

Karyotype analyses of 20 human glioma cell lines.

Human malignant gliomas are frequently associated with loss of gonosomes and chromosomes 13, 17, and 22. Their progression from anaplastic glioma to glioblastoma is marked by additional loss of chromosome 10. In addition, structural and numerical aberrations of chromosome 7 are frequently found. We report on the karyotypes of a series of 20 human gliomas of which 11 were analysed as established cell lines; 9 cases were investigated in early culture, 5 of which later also became established lines. In addition to the frequently reported overrepresentation of chromosome 7, four cell lines with polysomy for chromosome 22 were seen. A high incidence of structural chromosomal aberrations was present in early cultures as well as in cell lines after various in vitro passages. We found that the general characteristics of karyotypic aberrations found in early cultures or direct preparations of dispersed tumour material were reflected in the pattern of aberrations present in cell lines at much later time points. Thus it appears as if no systematic changes can be attributed to long-term cultures. Suspicious losses of chromosomes 14, 18, and 19 or gain of chromosome 22 indicate that individual cases may have originated due to other mechanisms than the ones already hypothesized, i.e., different suppressor genes or amplification of genes other than the EGF-R-gene. None of the established cell lines had a genomic rearrangement of c-erbB 1, c-erbB 2 or of the p 53 gene.

Adult↗
PubMed1997

Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors.

Two approaches for improving the interstitial administration of carmustine (BCNU) using 3.8% loaded poly(carboxyphenoxypropane-sebacic acid), an implantable biodegradable anhydride which significantly prolongs survival in patients with recurrent malignant gliomas, were evaluated. First, increasing the ratio of carboxyphenoxypropane (CPP) to sebacic acid (SA) in the polymer increases its hydrolytic stability, thus prolonging its half-life in vivo, and extending the period of drug release. A second approach is to increase the dose of drug loaded into the polymer. This study evaluated the relative merits of these two approaches by comparing release kinetics, safety, and efficacy of escalating BCNU does in polymers with 20:80 and 50:50 ratios of CPP to SA. At the highest dose tested, the 50:50 polymer released BCNU 2.5 times as long in vitro as the 20:80 polymer. Both formulations were nontoxic in rat brains for all BCNU doses tested except 32%. The 20:80 and 50:50 polymers were equally effective in the rat intracranial 9L-glioma model. A dose-response relationship for BCNU was observed (hazard ratio 0.8354 for each mg/kg increase, P < 0.001). The two highest loading doses of BCNU improved survival 40-fold (P < 0.001). The 20% BCNU-loaded 20:80 polymer achieved the best balance of toxicity and antitumor efficacy, yielding a 75% long-term survival rate. Further evaluation of this polymer in monkeys suggests that it might be used with acceptable toxicity. This study establishes that a dose-escalation strategy for improving BCNU controlled-release polymers is more effective than adjusting the ratio of CPP to SA to prolong drug release.

Animals↗
PubMed1998

Damage to tumour and brain by interstitial photodynamic therapy in the 9L rat tumour model comparing intravenous and intratumoral administration of the photosensitiser.

In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm3 haematoporphyrin derivative (HpD, 5 mg ml-1), followed by interstitial irradiation with 20 Joule (J) (630 nm) 5 h later. For comparison, seven rats were treated with 20 Joule 24 h after an intravenous injection of 10 mg kg-1 HpD (intravenous PDT). With the chosen PDT parameters there was no important difference between the damaged areas produced by intratumoural PDT or intravenous PDT. No selective tumour kill was observed. Even though normal brain tissue was heavily damaged, vital tumour parts were still present. Intravenous PDT caused extensive diffuse damage to small blood vessels in tumour and surrounding normal brain. Intratumoural PDT was characterised by an infiltration of polymorphonuclear cells into damaged tissue, dilatation of larger blood vessels and gross haemorrhage. These results suggest an immediate vascular shutdown in the intravenous approach, while in the intratumoural approach the vasculature remained patent initially. Because of the severe side effects observed, the use of HpD seems not advisable for intratumoural PDT of brain tumours.

Animals↗
PubMed1998

5-Aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain.

A new approach in photodynamic therapy is the use of endogenous porphyrins for sensitisation of tumours to light. The induction of endogenous porphyrins after intravenous injection of 5-aminolevulinic acid (ALA, 200 mg kg-1) was studied in 23 rats, bearing intracranial 9L or C6 tumours. After 0, 2, 4, 6, 8, and 22 hours the rats were sacrificed and the fluorescence distribution of endogenous porphyrins was studied in brain tissue sections with a standard fluorescence microscope and a confocal laser scanning microscope. The role of blood-brain barrier disruption on porphyrin production was studied in 2 rats with a cryo-lesion of the cortex. Additionally, 9L and C6 tumour cell cultures were incubated with ALA for 8 hours in vitro. Fluorescence was measured with a fluorescence spectrophotometer in cell cultures and in the brain sections. Porphyrins were detected in vitro in the tumour cells from 2 hours onwards and ex vivo in the tumour sections mainly from 2 to 8 hours, by 22 hours porphyrin fluorescence had almost disappeared. The contralateral brain showed low fluorescence levels between 2 and 6 hours after ALA administration. At the site of the cryo-lesions low fluorescence was measured 6 hours after ALA administration. The 9L tumours fluoresced homogeneously, with a sharp demarcation towards normal brain tissue. Fluorescence in the C6 tumours was patchy, with a poorly fluorescing edge. In both tumour models fluorescence was also detected in brain surrounding the tumour and sometimes in contralateral white matter and ventricle ependyma and pia mater. The slight increase of porphyrin fluorescence in the normal brain of tumour bearing rats, compared to the absence of this in rats without a tumour, was attributed to transport by bulk flow of porphyrins made in the tumours, and possibly also of circulating porphyrins or ALA leaking from the tumour vessels.

Aminolevulinic Acid↗
PubMed2005

Tenascin-C protein is induced by transforming growth factor-beta1 but does not correlate with time to tumor progression in high-grade gliomas.

BACKGROUND: Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-beta1 (TGF-beta1) plays an important role in the biology of high-grade gliomas, partly by regulating invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-beta1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma. METHODS: A series of 20 high-grade gliomas was stained immunohistochemically with Tenascin-C- and TGF-beta1- specific antibodies. Expression levels of both proteins were evaluated and correlated with each other, time to progression and molecular and morphological markers of invasion. A quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA by treatment with TGF-beta1 in vitro. RESULTS: Tenascin-C was expressed in 18 of 19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta1 in a significant percentage of cells. Treatment with TGF-beta1 did induce the expression of Tenascin-C at the mRNA and protein level in vitro. The expression of Tenascin-C and TGF-beta1 did neighter statistically correlate with each other nor with time to progression. CONCLUSION: In our series, Tenascin-C and TGF-beta1 were expressed in the vast majority of high-grade gliomas. We could not detect a correlation of one of the proteins with time to progression. Nevertheless, we describe induction of Tenascin-C by TGF-beta1, possibly providing a mechanism for the invasion of high-grade gliomas into healthy parenchyma.

Adult↗
PubMed2006

TGF-beta2 inhibition augments the effect of tumor vaccine and improves the survival of animals with pre-established brain tumors.

TGF-beta2 secretion by high grade gliomas has been implicated as one of the major factors contributing to tumor growth, alterations in the host immune response to tumor, and failure of gliomas to respond to current immunotherapy strategies. We hypothesized that targeted delivery and inhibition of TGF-beta2 by TGF-beta2 antisense oligonucleotides (AS-ODNs) would overcome tumor-induced immunosuppression and enhance the capacity of tumor vaccines to eradicate established brain tumors. Utilizing the mRNA sequences of TGF-beta2, specific AS-ODNs were constructed and tested for their ability to inhibit TGF-beta2 production in 9L glioma cells. The effect of combining local intracranial administration of antisense ODNs with systemic tumor vaccine was examined. Fisher 344 rats were vaccinated subcutaneously with irradiated 9L tumor cells 3 days after intracranial tumor implantation. Four days after vaccination, ODNs were administered into the tumor mass and survival was followed. ODNs delivered locally distributed widely within the brain tumor mass and inhibited TGF-beta2 expression. Survival of tumor-bearing rats treated with the combination of local antisense and systemic tumor vaccine was significantly enhanced (mean survival time (MST): 48.0 days). In contrast, MST for animals treated with nonsense plus vaccine, vaccine alone, antisense alone or PBS showed no survival advantage and no statistical differences between groups (33.5 days, 29.0 days, 37.5 days, and 31.5 days, respectively). Our data supports the hypothesis that local administration of antisense TGF-beta2 ODNs combined with systemic vaccination can increase efficacy of immunotherapy and is a novel, potentially clinically applicable, strategy for high-grade glioma treatment.

Animals↗
PubMed2006

Safety and efficacy of convection-enhanced delivery of ACNU, a hydrophilic nitrosourea, in intracranial brain tumor models.

Convection-enhanced delivery (CED) is a local infusion technique, which delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED distribution is significantly increased if the infusate is hydrophilic. This study evaluated the safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a hydrophilic nitrosourea, in rat 9 L: brain tumor models. The local neurotoxicity of ACNU delivered via CED was examined in normal rat brains, and the maximum tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD produced significantly longer survival time than systemic administration (P < 0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor occurred only in the CED-treated rats. The tissue concentration of ACNU was measured by high-performance liquid chromatography, which revealed that CED of ACNU at the dose of 100-fold less total drug than intravenous injection carried almost equivalent concentrations of ACNU into rat brain tissue. CED of hydrophilic ACNU is a promising strategy for treating brain tumors.

Animals↗
PubMed2005

Proton magnetic resonance spectroscopy of brain tumors correlated with pathology.

RATIONALE AND OBJECTIVES: Evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for assessing and grading brain tumors. MATERIALS AND METHODS: The research was done at Detroit Medical Center in a 1.5-T Siemens MR magnet using single-voxel or multivoxel MRS. This study consisted of 27 patients: 10 females and 17 males ages 22-83 years (average age 43.8). The data were recorded for three peaks-N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)-which were used to calculate the ratios Cho/NAA and Cho/Cr. RESULTS: Abnormal spectra were seen in 25 patients and normal spectra in 2. In 16 patients with brain astrocytoma of various grades, the pathology grading was correlated with Cho/NAA and Cho/Cr. These values were 6.53 and 3.35 for nine patients with Grade 4 astrocytoma; 1.85 and 1.62 for three patients with Grade 3 astrocytoma; 2.21 and 1.50 for three patients with Grade 2 astrocytoma; and 1.45 and 1.49 for one patient with Grade 1 astrocytoma. The remaining nine patients with abnormal spectra were also correlated with pathology. CONCLUSION: MRS ratios can be used to differentiate malignant and nonmalignant lesions from normal brain tissue. In general, high-grade astrocytoma have higher Cho/NAA and Cho/Cr ratios compared with low-grade astrocytoma.

Adult↗