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Tumor Metabolism (tumor + metabolism)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Hyaluronidase reduces human breast cancer xenografts in SCID mice

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2002
Svetlana Shuster
Abstract A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan-associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti-cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti-cancer therapeutics and one without toxic side effects. © 2002 Wiley-Liss, Inc. [source]

Unaliasing lipid contamination for MR spectroscopic imaging of gliomas at 3T using sensitivity encoding (SENSE),

MAGNETIC RESONANCE IN MEDICINE, Issue 5 2006
Esin Ozturk-Isik
Abstract 3D magnetic resonance spectroscopic imaging (MRSI) has been successfully employed to extract information about brain tumor metabolism, such as cell membrane breakdown, cellular energetics, and neuronal integrity, through its ability to differentiate signals coming from choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA) molecules. The additional presence of lipids within subregions of the tumor may indicate cellular membrane breakdown due to cell death. Another potential source of lipids is subcutaneous fat, which may be excited with point-resolved spectroscopy (PRESS) volume selection and aliased into the spectral field of view (FOV) due to the chemical shift artifact and the low bandwidth of the selection pulses. The purpose of our study was to employ a postprocessing method for unaliasing lipid resonances originating from in-slice subcutaneous lipids from the 3D MRSI of gliomas at 3T, using an eight-channel phased-array coil and sensitivity encoding (SENSE). Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source]

Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation

NMR IN BIOMEDICINE, Issue 6 2005
Fritz-Georg Lehnhardt
Abstract High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p,=,0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p,=,0.0001) and glutamate (Glu)/glutamine (Gln) (p,=,0.004). Meningiomas showed increased Ala (p,=,0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p,=,0.001) relative to astrocytomas, and N -acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p,=,0.029; tCho, p,=,0.034; Glu, p,=,0.015; tCho/tCr, p,=,0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p,=,0.037) and Glu (p,=,0.003) and metabolite ratio tCho/tCr (p,=,0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n,=,11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism. Copyright © 2005 John Wiley & Sons, Ltd. [source]

1H- and 31P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components

NMR IN BIOMEDICINE, Issue 5 2001
Fritz-Georg Lehnhardt
Abstract In vitro NMR spectrocopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. 31P- and 1H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. 31P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the 1H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the 31P- and the 1H-spectra. Based on the total detectable 31P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p,=,0.0003), whereas the level of sphingomyelin was about 45% lower in primary gioblastomas than in primary astrocytomas (p,=,0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p,=,0.0103) and ,23% (p,=,0.0314) change, respectively]. 1H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the 31P-spectra, the 1H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. 1H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution 1H- and 31P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies

THE PROSTATE, Issue 13 2010
Mark Stein
Abstract BACKGROUND A profound difference between cancer and normal tissues is the preferential utilization of glycolysis by cancer cells. To translate this paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and assessed 2DG uptake with fluorodeoxyglucose (FDG) positron emission tomography (PET) and the autophagy substrate p62 as a marker of 2DG resistance. METHODS Patients received 2DG orally on days 1,14 of a 21-day cycle in cohorts of three in a dose-escalating manner. Correlative assessments included PET scans at baseline and day 2 and p62 protein in peripheral blood mononuclear cells as a potential marker of 2DG resistance. RESULTS The dose of 45,mg/kg was defined as the recommended phase II dose, secondary to dose-limiting toxicity of grade 3 asymptomatic QTc prolongation at a dose of 60,mg/kg. PK evaluation of 2DG revealed linear pharmacokinetics with Cmax 45,µg/ml (277,µM), 73.7,µg/ml (449,µM), and 122,µg/ml (744,µM) in dose levels 30, 45, and 60,mg/kg, respectively. Five of eight patients assessed with FDG-PET scanning demonstrated decreased FDG uptake by day 2 of therapy, suggesting competition of 2DG with FDG. Five of six patients assessed for p62 had a decrease in p62 at 24,hr. CONCLUSIONS These data support the safety of 2DG, defined 2DG PK, demonstrated the effect of 2DG on FDG-PET imaging, and demonstrated the feasibility of assessment of p62 as an autophagic resistance marker. These data support future studies of 2DG alone or in combination with approaches to abrogate autophagy. Prostate 70: 1388,1394, 2010. © 2010 Wiley-Liss, Inc. [source]

Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma

ANNALS OF NEUROLOGY, Issue 4 2003
Juergen Voges MD
In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection-enhanced delivery of an HSV-1- tk gene,bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector-distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies. [source]