Biomedical subjects

Hadassa Degani

Publications and source records attributed to Hadassa Degani.

22 records · Page 2Linked to original sources

PubMed2002

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo (13)C MRS.

Enhanced glycolysis represents a striking feature of cancers and can therefore serve to indicate a malignant transformation. We have developed a noninvasive, quantitative method to characterize tumor glycolysis by monitoring (13)C-labeled glucose and lactate with magnetic resonance spectroscopy. This method was applied in MCF7 human breast cancer implanted in the mammary gland of female CD1-NU mice and was further employed to assess tumor response to hormonal manipulation with the antiestrogen tamoxifen. Analysis of the kinetic data based on a unique physiological-metabolic model yielded the rate parameters of glycolysis, glucose perfusion, and lactate clearance in the tumor, as well as glucose pharmacokinetics in the plasma. Treatment with tamoxifen induced a twofold reduction in the rate of glycolysis and of lactate clearance but did not affect the other parameters. This metabolic monitoring can thus serve to evaluate the efficacy of new selective estrogen receptor modulators and may be further extended to improve diagnosis and prognosis of breast cancer.

Animals↗

PubMed2002

Clinical testing of high-spatial-resolution parametric contrast-enhanced MR imaging of the breast.

OBJECTIVE: We performed a prospective clinical test of a high-spatial-resolution model-based parametric method for diagnosis of breast lesions detected on contrast-enhanced MR imaging. SUBJECTS AND METHODS: Fifty-seven women with 68 pathologically confirmed breast lesions were imaged (45 masses, 23 microcalcifications). Seven consecutive 2-min three-dimensional gradient-recalled echo acquisitions were performed after suitably timed gadopentetate dimeglumine injections. We derived a composite parametric image from three judiciously selected time points (three-time-point method), using a model-based kinetic algorithm. In this composite image, color brightness and hue signify contrast uptake and washout characteristics related to the product of microvessel surface area and permeability, as well as to the extracellular volume fraction. The reviewer was provided with the slice location of lesions, but with no other radiographic or clinical information. The reviewer then classified the lesions as benign or malignant using a 5-step receiver operating characteristic scale. RESULTS: Observers using the three-time-point method correctly diagnosed 27 of 31 malignant and 31 of 37 benign lesions (sensitivity, 87%; specificity, 84%). The area under the receiver operating characteristic curve was 0.911. False-negative results were found for three patients with low- to intermediate-grade ductal carcinoma in situ and one patient with 5-mm invasive ductal cancer. For the 45 solid lesions, sensitivity and specificity were 96% and 82%, respectively. CONCLUSION: Application of the three-time-point method permitted, in most cases, differentiation of malignant and benign lesions, even in the presence of complex breast enhancement patterns. Sensitivity for solid tumors was higher than for ductal carcinoma in situ.

Adult↗

PubMed2002

Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro.

The present investigation was performed to elucidate the role of purine nucleotides as potential indicators of chemosensitivity of malignant tumors. Drug-sensitive (s) and -resistant (r) tumor cell lines grown as monolayers (s: T47D, MCF-7 wild-type; r: NCI/ADR-RES, MCF-7/MDR) or as multicellular spheroids (T47D; NCI/ADR-RES) were exposed to 0.1, 1.0, and 10.0 microM Doxorubicin for up to 24 h. Purine nucleotides were assayed using HPLC and with some selected spheroids using imaging bioluminescence. The data show that in the time frame of the experiments reproducible and statistically significant changes in the nucleotides only occur at the highest drug concentration investigated. Under these conditions and using monolayer cultures, Doxorubicin caused a significant increase in ATP and GTP in sensitive but not in resistant cancer cells. Consequently, this differential change may be exploited for drug sensitivity testing in vitro. Doxorubicin exposure to spheroids was associated with significant increases in ATP and GTP in both sensitive and resistant variants. However, the kinetic of the changes in GTP was largely different between T47D and NCI/ADR-RES spheroids with a long-lasting, almost 3-fold elevation and a smaller, relatively short transient increase in GTP, respectively. Supplementing experiments with Doxorubicin treatment under inhibition of oxidative phosphorylation with Oligomycin abolished the drug-induced ATP and GTP peaks at persistent increases in ADP and AMP. Assuming that the spheroids may represent the in vivo situation to a better degree than monolayer cultures, experimental in vivo studies should clarify whether kinetic changes in GTP could be used as differential markers for the chemosensitivity of solid tumors. The experiments using Oligomycin support the hypothesis that purine nucleotides may be recycled from DNA fragments that result from the interaction of the drug with the DNA strands.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Parametric analysis of breast MRI.

Parametric analysis of breast MRI provides unique mapping of pathophysiological characteristics that cannot be obtained by standard conventional MRI. We describe in this review methods based on intrinsic contrast and tissue elasticity as well as methods that use external paramagnetic contrast agents and follow the time evolution of contrast. Processing of the raw data, frequently with new mathematical models and algorithms, yielded calculated parametric images that may help improve the noninvasive detection and diagnosis of breast cancer.

Breast↗