Effect of radiotherapy and chemotherapy on composition of tumor membrane phospholipids

Street, James C.; Koutcher, Jason A.

doi:10.1007/s11745-997-0007-2

Cited by 9 publications

(8 citation statements)

References 21 publications

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“…In spite of this limitation, the ability to observe the phospholipid resonance in vivo, provides a label that can be used to measure the kinetics of phospholipid turnover. Since the composition of the phospholipid membrane is tightly regulated, even in the presence of significant changes in PMEs and PDEs (11,12), our results indicate that these changes are probably due to a change in phospholipid turnover. Given this fact, a measurement of the rate of PC, breakdown is a measure of phospholipid turnover.…”

Section: Discussionmentioning

confidence: 66%

Study of the metabolism of choline and phosphatidylcholine in tumors in vivo using phosphonium‐choline

Street¹,

Szwergold²,

Matei³

et al. 1997

Magnetic Resonance in Med

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The results of an initial study on the feasibility of using the phosphonium analog of choline to follow the metabolism of phosphatidylcholine in tumors in vivo using 31P NMR are reported. C3H/He mice bearing a mammary carcinoma tumor on the foot pad were fed a choline-free diet supplemented with the phosphonium analog of choline. Metabolites of this compound, including the phosphonium analogs of phosphatidylcholine, phosphocholine, glycerophosphocholine, and betaine were observed noninvasively in vivo in tumors by 31P NMR after 2-3 weeks of feeding. Clearance of these phosphonium-labeled metabolites from tumors was measured after a change to a choline-containing diet. Significant decreases were seen in the levels of the analogs of betaine (P < 0.003) and phosphatidylcholine (P < 0.004) by Day 4. A significant increase in the level of authentic phosphocholine (P < 0.003) occurred over the same time period.

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Section: Discussionmentioning

confidence: 66%

Study of the metabolism of choline and phosphatidylcholine in tumors in vivo using phosphonium‐choline

Street¹,

Szwergold²,

Matei³

et al. 1997

Magnetic Resonance in Med

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“…Nevertheless, the possibility of its detection with 1 H MRS seems important, as indicated by similar studies in the literature at high doses with 31 P MRS, a less sensitive technique [13,14,33,34].…”

Section: Discussionmentioning

confidence: 99%

“…As far as the lipid precursors are concerned, we want to explore their sensitivity in predicting the response to radiotherapy in cells, as this seems a subject of great concern in the field of radiation. Studies in the literature relate to the use of 31 P MRS [13,14,33,34]. In the present study, we aimed to exploit the higher sensitivity of 1 H MRS and the possibility, with this latter technique, of observing the choline signal.…”

Section: Manymentioning

confidence: 99%

Radiation effects on soluble metabolites in cultured HeLa cells examined by 1H MRS: Changes in concentration of glutathione and of lipid catabolites induced by gamma rays and proton beams

et al. 2001

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SUMMARY Cultured HeLa cells were irradiated with a single acute dose of either gamma rays (40 Gy) or low-energy proton beams (20 Gy). 1H magnetic resonance spectra of intact cells harvested at different times after irradiation and of the correspondent perchloric acid (PCA) extracts prepared at different times after irradiation were run. Selected signals from glutathione and lactate were examined with the aim of investigating effects of irradiation on antioxidative stores and on mitochondrial activity. An increase of signal intensity of glutathione (GSH) takes place at 15 and 24 hr after irradiation, while a decrease of its signal intensity, accompanied by an increase of that of free glutamate, starts appearing 48 hr after irradiation. Lactate signal increases 48 hr after irradiation. Signals from lipid catabolites were also examined to explore their sensitivity in predicting the response to radiotherapy. Intensity ratios of signals of glycerophosphorylcholine and choline to that of phosphorylcholine increase with time after irradiation. Irradiating cells with gamma rays or proton beams at half a dose produces effects comparable to the metabolic variations presented here. The present experiments allow more insight into the complex pattern of the changes of GSH by irradiation and indicate that magnetic resonance spectroscopy signals from GSH, glutamate, lactate, and lipid catabolites are affected by irradiation. Finally, these data represent a first indication that the relative biological efficiency for some metabolic damage of low-energy proton beams with respect to gamma rays can reach a value of 2.

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“…This is the case of those within the overall lipophilicity range of cyclophosphamide/ifosfamide (Log OWPC-to-vdWD ratio, 0.14 nm -1 ; vdWD, 0.73 nm) (34,42,43) which are of larger size, and carmustine (Log OWPC-to-vdWD ratio, 1.41 nm -1 ; vdWD, 0.67 nm) (44), which is more lipophilic (44), for which there is a greater tendency to associate with and perturb CM phospholipids and the potential for a 1ary indirect pressuromodulation-mediated secondary increase in very high molecular weight (MW) protein transcription (17), while such small molecule xenobiotics of lipophilic character may only achieve intra-cellular levels at significant extracellular concentrations (45), which makes the more lipophilic xenobiotics of this category marginal chemoxenobiotics for effective transvascular delivery into solid tumor tissue (3)(4)(5)(6)(7) .…”

Section: Resultsmentioning

confidence: 99%

Conserved molecular mechanisms underlying the effects of small molecule xenobiotic chemotherapeutics on cells

Sarin¹

2015

Molecular and Clinical Oncology

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Abstract. For proper determination of the apoptotic potential of chemoxenobiotics in synergism, it is important to understand the modes, levels and character of interactions of chemoxenobiotics with cells in the context of predicted conserved biophysical properties. Chemoxenobiotic structures are studied with respect to atom distribution over molecular space, the predicted overall octanol-to-water partition coefficient (Log OWPC; unitless) and molecular size viz a viz van der Waals diameter (vdWD). The Log OWPC-to-vdWD (nm -1 ) parameter is determined, and where applicable, hydrophilic interacting moiety/core-to-vdWD (nm -1 ) and lipophilic incorporating hydrophobic moiety/core-to-vdWD (nm -1 ) parameters of their part-structures are determined. The cellular and sub-cellular level interactions of the spectrum of xenobiotic chemotherapies have been characterized, for which a classification system has been developed based on predicted conserved biophysical properties with respect to the mode of chemotherapeutic effect. The findings of this study are applicable towards improving the effectiveness of existing combination chemotherapy regimens and the predictive accuracy of personalized cancer treatment algorithms as well as towards the selection of appropriate novel xenobiotics with the potential to be potent chemotherapeutics for dendrimer nanoparticle-based effective transvascular delivery. IntroductionSmall molecules non-endogenous to the biological system, often referred to as xenobiotics, include a diverse variety of molecules, simple organic toxicants with uncomplicated structures and natural eukaryotic antibiotics and synthetic molecules of more complicated structures and cytotoxic properties (1), the latter of which have chemotherapeutic properties. Although small molecule chemoxenobiotics, of various traditional classes, form the basis of present synergistic cancer treatment strategies, their clinical efficacy remains questionable for the treatment of solid and hematopoietic malignancies alike, upon surgical resection in the former, and during bone marrow irradiation-transplantation and after in the latter. For this reason, a better understanding of the modes and character underlying molecular cellular interactions is necessary, particularly for the purposes of improving the tumor tissue selectiveness of enhanced permeation and retention (EPR)-based chemotherapy (2), which has a prolonged blood half-life but is non-selective for solid tumor foci. Along these lines, there has been relatively recent translational advancement towards the development of optimally sized dendrimer nanoparticle-based small molecule chemotherapy at ~9 nm (H D ) (3-7), which selectively delivers small molecule chemoxenobiotics into solid malignancies at effective concentrations without systemic toxicity (4,8). As such, with optimally sized dendrimer nanoparticle-based small molecule chemotherapy, there is the potential for complete tumor regression (3,9) in lieu of the possibility for the development of drug resistance phenotypes (1...

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Effect of radiotherapy and chemotherapy on composition of tumor membrane phospholipids

Cited by 9 publications

References 21 publications

Study of the metabolism of choline and phosphatidylcholine in tumors in vivo using phosphonium‐choline

Study of the metabolism of choline and phosphatidylcholine in tumors in vivo using phosphonium‐choline

Radiation effects on soluble metabolites in cultured HeLa cells examined by 1H MRS: Changes in concentration of glutathione and of lipid catabolites induced by gamma rays and proton beams

Conserved molecular mechanisms underlying the effects of small molecule xenobiotic chemotherapeutics on cells

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