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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Size-dependent changes in therapeutically relevant and interrelated metabolic parameters of a murine fibrosarcoma (FSaII) were investigated in vivo using conscious (unanesthetized) animals and tumor sizes less than or equal to 2% of body weight. Tumor pH and bioenergetics were evaluated by 31P nuclear magnetic resonance spectroscopy (31P-MRS), and tumor tissue oxygen tension (pO2) distribution was examined using O2-sensitive needle electrodes. During growth FSaII tumors showed a progressive loss of phosphocreatine (PCr) and nucleoside triphosphate (NTP) with increasing inorganic phosphate (Pi) and phosphomonoester (PME) signals. Ratios for PCr/Pi, PME/Pi, NTP/Pi, and phosphodiester/inorganic phosphate (PDE/Pi) as well as pH determined by 31P-NMR (pHNMR) and the mean tissue pO2 progressively declined as the tumors increased in size. The only relevant ratio increasing with tumor growth was PME/NTP. When the mean tissue pO2 value was plotted against pHNMR, NTP/Pi, PCr/Pi, PME/Pi, and PDE/Pi for tumor groups of similar mean volumes, a highly significant positive correlation was observed. There was a negative correlation between mean tumor tissue pO2 values and PME/NTP. From these results we concluded that 31P-MRS can detect changes in tumor bioenergetics brought about by changes in tumor oxygenation. Furthermore, the close correlation between oxygenation and energy status suggests that the microcirculation in FSaII tumors yields an O2-limited energy metabolism. Finally, a correlation between the proportion of pO2 readings between 0 and 2.5 mmHg and the radiobiologically hypoxic cell fraction in FSaII tumors was observed. The latter finding might be of particular importance for radiation therapy.
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PMID:Correlations between 31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma. 259 69

31P MRS longitudinal relaxation times (T1) were determined for C3H murine fibrosarcomas (FSaII), and mammary carcinomas (MCaIV). Tumors were implanted in the foot dorsum, and were 100-300 mm3 in volume. T1s were repeated after the animal was allowed to breathe 100% oxygen for 30 min and then again 36-48 hr following 30 Gy. The spectrum were obtained using an 8.5 T spectrometer with a 8 cm bore and a 1.4 cm single turn antenna coil. The 31P relaxation times for untreated tumors in air breathing animals were: 3.78 sec for phosphomonoesters, 4.37 sec for inorganic phosphate (Pi), 2.73 sec for phosphocreatine, 1.37 sec for gamma ATP, 1.14 sec for alpha ATP, and 1.18 sec for beta ATP. The Pi T1s were 4.37 and 4.70 sec in control and irradiated tumors in air breathing animals. Respiration of oxygen for 30 min reduced the T1s to 3.02 and 2.62 sec in control and irradiated tumors respectively. The Pi T1 of an anoxic tumor, determined on an in situ tumor 60 min after death was 5.93 sec. The oxygen breathing induced decrease in the T1 of Pi is unlikely to have been caused by the paramagnetic properties of oxygen alone, and suggests a component of increased magnetization transfer secondary to the ATPase reaction. Oxygen breathing following 30 Gy, resulted in a decreased growth time (800 mm3 endpoint) and an increased proportion of cells in S-phase. These results support the hypothesis that the decrease in Pi T1 measured with oxygen breathing is a measure of tumor oxygen tension and metabolic rate, and suggests that T1 measurement may indirectly predict tumor growth rate and DNA synthesis.
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PMID:Estimation of tumor oxygenation and metabolic rate using 31P MRS: correlation of longitudinal relaxation with tumor growth rate and DNA synthesis. 296 30

MRS made especially versatile with current technology of multinuclear coils and time interlacing of signals is appropriately suited to multifaceted tumor biochemistry, where growth is a key metabolic feature. The established results that bioenergetics and lipid metabolite concentrations show a variety of responses in tumor growth and remission in response to anticancer procedures add a further novel dimension to tumor studies by MRS. Finally, the versatility of the multinuclear MRS approach seems most appropriate to the varied nature of cancer.
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PMID:Magnetic resonance spectroscopy of neoplasms. 307 39

Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal ATP were studied in vitro, and in both C3H and nu/nu mice. Daily ATP treatment prolonged tumor volume doubling time in vivo and in vitro. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH or the PCr/Pi, or beta ATP/Pi ratios (measured by MRS). In contrast to the reduced tumor growth rate, there was no change in bone marrow recovery after whole body irradiation. ATP is minimally toxic to animals at active dose levels. It slows tumor growth rate without adversely affecting bone marrow radiation tolerance. ATP might therefore be useful as a biological modifier of chemotherapy or radiation therapy.
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PMID:Effect of intraperitoneal ATP on tumor growth and bone marrow radiation tolerance. 777 34

The usefulness of 31P-MRS (phosphate magnetic resonance spectroscopy) for evaluation of the anti tumor effect of hyperthermic treatment was examined. FM3A, an experimental tumor transplantable to C3H mice, was used. FM3A, transplanted subcutaneously to the femoral region, was subjected to hyperthermic treatment and 31P-MRS were measured at various times. Because the ATP/Pi ratio indicates the energy status of tumor cells, we conducted measurement of its sequential changes after hyperthermic treatment. With a water bath, hyperthermic treatment was performed at 44 degrees C. Twenty four hours after treatment, the ATP/Pi ratio dropped as the heating time was prolonged, showing an obvious converse correlation to the tumor growth curve on heating. Immediately after hyperthermic treatment, the ATP/Pi ratio fell drastically, began to recover after 18 hrs and remained unchanged up to the 24 hrs. The finding that the ATP/Pi ratio obtained in tumor tissue 24 hrs after hyperthermic treatment was correlated with tumor inhibition suggested that the ratio can be a possible parameter for evaluation of the anti tumor effect by heating. The ATP/Pi ratio obtained by 31P-MRS could be used for non-invasive prediction of tumor tissue damage by heating.
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PMID:Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth delay. 796 91

We analyzed tumor growth delay in experimental tumors after hyperthermia alone, hydralazine (HDZ) injection alone and the combination of these modalities. We also analyzed the energy parameter (ATP/Pi ratio) obtained by 31P-MRS (magnetic resonance spectroscopy). The purpose of this study was to evaluate the usefulness of 31P-MRS as an index of anti-tumor effect. FM3A tumor cells were transplanted subcutaneously in the hind legs of C3H/He mice. We dipped the tumors into a heated circulating water bath. 31P-MRS was performed with a CSI spectrometer. The anti-tumor effect obtained with HDZ alone was insignificant, but combined treatment with hyperthermia and HDZ had a significant synergistic effect. The ATP/Pi ratios for all groups treated separately with HDZ or hyperthermia were not different from the control, but the ATP/Pi ratio decreased after combined use of these agents. There was a significant correlation between the decrease in ATP/Pi ratio and tumor growth delay. We observed a direct relation between the delay in tumor growth and the decline in ATP/Pi ratio after combined treatment with HDZ and hyperthermia. The ATP/Pi ratio 24 hr after treatment may be useful in predicting the efficacy of the combined use of HDZ and hyperthermia.
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PMID:[Study of anti-tumor effects of hyperthermia combined with hydralazine on experimental tumor]. 857 Mar 96

This study was performed to clarify whether changes in the metabolites observed by phosphorous-31 magnetic resonance spectroscopy (31P-MRS) could indicate an optimum interval between two doses of radiation in a murine tumor model. Murine mammary carcinoma cells, FM3A, were irradiated 7 days after transplantation with a single 5 Gy dose without anesthesia. 31P spectra were measured with a spectrometer up to 30 days. The beta-ATP/Pi and PCr/Pi values were calculated from the peak area of each spectrum. In a fractionation experiment, two fractions of irradiation at a 5 Gy per fraction were given at 0, 1, 2, 3 and 6 day intervals. Tumor growth delay was also scored to determine the fractionated radiation effect. In the control group, beta-ATP/Pi and PCr/Pi decreased with tumor growth. In the single irradiation group, the tumor did not grow up to day 6, and an initial rise and subsequent decrease in beta-ATP/Pi and PCr/Pi were observed. Maximum beta-ATP/Pi and PCr/Pi were observed on day 2 after irradiation. In a fractionation experiment, the greatest growth delay was observed in the two day interval group, in which maximum beta-ATP/Pi and PCr/Pi were demonstrated in 31P-MRS. Our results suggested that changes in the metabolites observed by 31P-MRS could be useful indicators for determining the fractionation schedule in radiation therapy.
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PMID:31P NMR spectroscopy can predict the optimum interval between fractionated irradiation doses. 989 81

(E)-2'-deoxy-2'-(fluoromethylene)cytidine (FMdC), was evaluated as a potential treatment for malignant gliomas using the rat 9L brain tumor model. FMdC was shown to be an effective inhibitor of cell proliferation in cultured 9L cells with an EC(50) of 40 ng/ml. In vitro studies also revealed that this compound significantly inhibited incorporation of [(3)H]thymidine in 9L cells. In vivo therapeutic efficacy of FMdC was evaluated in rats harboring intracerebral 9L tumors which were treated daily with 15 mg/kg, i.p. Treatment response was quantified from changes in tumor growth rates as assessed from sequential magnetic resonance imaging (MRI) tumor volume measurements. In vivo tumor cell kill in individual animals was calculated by fitting tumor volume data with an iterative computer routine. It was estimated that therapeutically responsive rats treated with FMdC daily produced a >/= 0.1 log kill per therapeutic dose which resulted in a significant reduction in tumor growth rate. In addition, localized (1)H-MRS of intracerebral 9L tumors revealed changes in metabolite levels which correlated with therapeutic response. These results provide evidence supporting the use of FMdC in clinical trials for the treatment of malignant gliomas and reveals that MR can play an important role in the pre-clinical evaluation of novel compounds using orthotopic tumor models.
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PMID:Evaluation of (E)-2'-deoxy-2'-(fluoromethylene)cytidine on the 9L rat brain tumor model using MRI. 1273 Sep 47

Activation of the Gi protein-coupled A3 adenosine receptor (A3AR) has been implicated in the inhibition of melanoma cell growth by deregulating protein kinase A and key components of the Wnt signaling pathway. Receptor activation results in internalization/recycling events that play an important role in turning on/off receptor-mediated signal transduction pathways. Thus, we hereby examined the association between receptor fate, receptor functionality, and tumor growth inhibition upon activation with the agonist 1-deoxy-1-[6-[[(3-iodophenyl)-methyl]amino]-9H-purine-9-yl]-N-methyl-beta-D-ribofuranuronamide (IB-MECA). Results showed that melanoma cells highly expressed A3AR on the cell surface, which was rapidly internalized to the cytosol and "sorted" to the endosomes for recycling and to the lysosomes for degradation. Receptor distribution in the lysosomes was consistent with the down-regulation of receptor protein expression and was followed by mRNA and protein resynthesis. At each stage, receptor functionality was evidenced by the modulation in cAMP level and the downstream effectors protein kinase A, glycogen synthase kinase-3beta, c-Myc, and cyclin D1. The A3AR antagonist MRS 1523 counteracted the internalization process as well as the modulation in the expression of the signaling proteins, demonstrating that the responses are A3AR-mediated. Supporting this notion are the in vivo studies showing tumor growth inhibition upon IB-MECA treatment and reverse of this response when IB-MECA was given in combination with MRS 1523. In addition, in melanoma tumor lesions derived from IB-MECA-treated mice, the expression level A3AR and the downstream key signaling proteins were modulated in the same pattern as was seen in vitro. Altogether, our observations tie the fate of A3AR to modulation of downstream molecular mechanisms leading to tumor growth inhibition both in vitro and in vivo.
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PMID:A3 adenosine receptor activation in melanoma cells: association between receptor fate and tumor growth inhibition. 1286 31

The aim of this study was to investigate the possible correlation between the 1H MRS mobile lipid signal, necrosis and lipid droplets in C6 rat glioma. First, the occurrence of necrosis and lipid droplets was determined during tumor development, by a histological analysis performed on 34 rats. Neither necrosis nor lipid droplets were observed before 18 days post-implantation. At later stages of development, both necrosis and lipid droplets were apparent, the lipid droplets being mainly located within the necrotic areas. Using a second group of eight rats, a temporal correlation was evidenced between mobile lipid signal detected by in vivo single-voxel one- (136 ms echo time) and two-dimensional J-resolved 1H MR spectroscopy, and the presence of necrosis and lipid droplets on the histological sections obtained from the brains of the same rats. Finally, spatial distribution of the mobile lipid signal was analyzed by chemical-shift imaging performed on a third group of eight animals, at the end of the tumor growth. The spectroscopic image corresponding to the resonance of mobile lipids had its maximum intensity in the center of the tumor where necrotic regions were observed on the histological sections. These necrotic areas contained large amounts of lipid droplets. All these results suggest that mobile lipids detected in vivo by 1H MRS (136 ms echo time) in C6 rat brain glioma arise mainly from lipid droplets located in necrosis.
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PMID:Correlation between the occurrence of 1H-MRS lipid signal, necrosis and lipid droplets during C6 rat glioma development. 1455 18


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