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J D de Certaines

Publications and source records attributed to J D de Certaines.

At least 55 records · Page 3Linked to original sources

Limits of tumour treatment follow up by surface coil 31P magnetic resonance spectroscopy. The case of sarcosinamide-CNU treated ependymoblastoma.

Ependymoblastoma tumour bearing mice were treated with sarcosinamide-CNU and compared with untreated mice with regard to tumour growth, pathological examinations and levels of phosphorylated metabolites measured by in vivo nuclear magnetic resonance spectroscopy. The response to the drug was demonstrated by its effect on tumour growth and with pathological examinations. Spectra evolution was different from controls for only four treated tumours out of eight.

Animals↗

Proton NMR relaxation times of experimental Lewis lung carcinoma after irradiation.

NMR proton spin-lattice (T1) and spin-spin (T2) relaxation times were measured ex vivo on Lewis lung carcinoma after in vivo single irradiation with an absorbed dose of 4 Gy. The results were compared to tumoural volume evolution, pathological examinations, and cell kinetic measurements. Tumour growth decreased between the third and the sixth day after irradiation while relaxation times, especially T1, is increased 2 days before the clinical recurrence of the tumour is observed. Pathological morphometric measurements tempted to show that necrosis is less extended after irradiation. Cell cycle analysis demonstrated the G2/M phase blockade by radiation after one day, and its release 4 days later. These phenomena could be important for in vivo radiotherapy follow-up using determination of relaxation times by magnetic resonance imaging (MRI).

Animals↗

In vivo 31P MRS in new antineoplastic agents evaluation on experimental tumor models.

Two new antineoplastic agents, a nitrosourea and a DNA-bis-intercalator have been studied in vivo by 31P magnetic resonance spectroscopy on a rat glioma and Walker carcinoma. On rat glioma, spectra are modified when the tumor is treated by the nitrosourea, showing the depletion of high-energy phosphates. On Walker carcinoma both drugs delay the tumor evolution to necrosis, showing important levels of high-energy phosphates on NMR spectra. There appears to be a great dependence upon energy metabolism during chemotherapy, depending on the nature and physiology of the observed tumor.

Animals↗

Proton nuclear magnetic resonance of regenerating rat liver after partial hepatectomy.

Spin-lattice (T1) and spin-spin (T2) proton nuclear magnetic resonance relaxation times were measured over a 48-hours period of experimental liver regeneration in Wistar rats. T2 showed an early significant increase reaching a plateau 30% above baseline from the 10th hrs onwards. Laparotomized control animals showed no change in T2 values. The increase in T1 occurred at a later stage but was no different from that in laparotomized controls. T1 reached a peak, 20% above baseline, around the 30th hr. The changes observed were far less marked than those previously described for cancer tissue, which showed about a 60% increase in T1. Liver T1 fluctuations followed a circadian pattern, with a minimum at night's end and a maximum around mid-day. No circadian rhythm was seen for T2. The observed T1 and T2 changes were discussed with respect o mitotic and metabolic events known to occur during regeneration of the liver.

Animals↗

Tetra-p-aminophenylporphyrin conjugated with Gd-DTPA: tumor-specific contrast agent for MR imaging.

Tetra-p-aminophenylporphyrin (TPP) was conjugated with gadolinium diethylenetriaminepentaacetic acid (DTPA) and used as a contrast agent in magnetic resonance (MR) imaging to achieve tumor selectivity in nude mice. A substantial decrease in T1 was measured in excised tissues (kidneys, tumor, and liver) from mice that received the porphyrin derivative Gd2(DTPA)4 TPP. Toxicity and phototoxicity were less than those obtained with hematoporphyrin derivative in both L1210 lymphoblastic leukemia cells and HT 29 human colonic cancer cells, as determined with in vitro assays. MR images showed an enhancement of contrast between the tumor and adjacent tissue after injection of this agent. The results indicate that Gd2(DTPA)4TPP could be a useful prototype paramagnetic porphyrin MR imaging contrast agent with an affinity for tumors.

Adenocarcinoma↗

MR imaging of viscoelastic properties.

Mechanical waves in magnetic resonance imaging, which have been suggested for possible clinical applications, were analyzed with regard to imaging of the viscoelastic properties of large objects. The method is based on the Larmor frequency modulation caused by the application of mechanical waves. Possible clinical applications include all diseases that result in a change in the mechanical properties of biologic tissues (eg, atherosclerosis).

Elasticity↗

Cancellation of metal-induced MRI artifacts with dual-component paramagnetic and diamagnetic material: mathematical modelization and experimental verification.

A mathematical model of dual-component paramagnetic and diamagnetic material to cancel metal-induced MRI artifacts was developed and verified experimentally. The magnetization produced by metallic material and then the gradient linearity distortion can be cancelled by using such materials with opposing paramagnetic and diamagnetic properties. This concept of dual-component materials provides a novel solution to the problem of MRI artifacts.

Artifacts↗

In vivo 31P MRS of experimental tumours.

More than 50% of cancers fail to respond to any individual treatment and tumour follow-up after treatment plays a major role in routine therapy planning and pharmacological research. Today, MRS is the only technological approach providing non-invasive access to tumour biochemistry. Ten years ago, expectations were raised concerning 31P MRS as an exciting and promising technical approach to the study of tumours. However the expectations have not always come to fruition. How close are we now to seeing routine 31P NMR in clinical oncology? This review of the 127 published papers shows spectroscopy results in more than 150 experimental animal tumour models. These tumour/host/treatment systems provide us with a useful basis to evaluate the current state of the art, summarize the basic knowledge presently available, determine the key points underlying the present disappointment of some clinical oncologists and stimulate new basic research. The information collected concerns the discussion of the reliability of experimental models in oncology, the technical improvement of magnetic resonance technology and the monitoring of bioenergetic status, pH regulation and phospholipid metabolism in treated and untreated tumours. Recent advances (two-thirds of the papers have been published in the last 5 years) seem to provide more optimistic perspectives than those generally accepted a few years ago, in the depressing period following early pioneering work.

Animals↗

Multi-center trial with protocols and prototype test objects for the assessment of MRI equipment. EEC Concerted Research Project.

A trial was carried out in which the protocols and prototype test objects developed under a European Economic Community concerted research project for the assessment of MR imaging equipment were tested in a series of commercial imaging systems situated throughout Europe. In general, many imperfections were discovered in the imaging performance of the scanners and, in particular, the accuracy and precision with which the relaxation times T1 and T2 could be measured from the images were found to be rather disappointing.

European Union↗

In vivo 31P NMR assessed effects of dantrolene on mechanics and energy metabolism in tetanic stimulated rat gastrocnemius.

Dantrolene does not affect fatigue from submaximal effort and MVC while it decreases twitch tension. We hypothesize that dantrolene could modify the relation between energy metabolism and fatigue by inhibiting calcium release from the sarcoplasmic reticulum. The effects of dantrolene (10 mg) on mechanical and metabolic parameters of gastrocnemius muscle were examined by 31P NMR during an in vivo fatigue test. The fatigue test constituted of three successive 20 min periods of increased stimulation rhythms and followed by a 20 min recovery period. 31P NMR was used to determine phosphocreatine (PCr), ATP and intracellular pH changes, while tension was recorded. We showed that dantrolene increased mechanical fatigue while PCr levels were similar to those from control animals. Acidosis was most prominent in dantrolene treated rats. These results suggest that dantrolene firstly affects calcium cycling with additive effects to fatigue and, secondly, modifies the activation of oxidative metabolism and the energy cost of the generated tension.

Adenosine Triphosphate↗

Rat gastrocnemius high and low frequency fatigue without metabolic impairment by 31P NMR.

Metabolic status and intracellular pH were investigated using 31-P nuclear magnetic resonance spectroscopy during mechanical fatigue induced in rat gastrocnemius muscle in vivo by continuous stimulation either at low or high frequency. During high frequency stimulations, force decreased to low level (10% of initial in 3-6 min) while phosphocreatine declined abruptly to 28-30% of its initial level and pH fell to 6.36 in 45 seconds. Force then continued to fall but PCr and pH rose again to reach 80-85% of the initial phosphocreatine value and 6.96 (pH) at the end of the stimulation period. The major feature of these results at high frequency was that the muscle could not generate force despite high energy stores and normal pH. During low frequency stimulation, force decreased in 9 min, to 10% of initial level. Phosphocreatine decreased abruptly to become undetectable while pH declined to 6.08 in 90 seconds. But later, phosphocreatine rose again to 35% and pH recovered to 6.84 while force continued to fall. Our results showed that intracellular pH and energy stores are not involved in the development and maintenance of mechanical fatigue.

Animals↗

Is magnetic resonance imaging texture analysis a useful tool for cell therapy in vivo monitoring?

Assessment of anti-tumor treatment efficiency is usually done by measuring tumor size. Treatment may however induce changes in the tumor other than tumor size. Magnetic Resonance Imaging Texture Analysis (MRI-TA) is presently used to follow activated lymphocyte cell therapy. We used a 7T microimager to acquire high-resolution MR images of an experimental liver metastasis from colon carcinoma in rats treated (n = 4) or not (n = 3) with a cell therapy product. MRI-TA was then performed with Linear Discriminant Analysis and showed: i) a significant variation of tumor texture with tumor growth and ii) a significant modification in the texture of tumors treated with activated lymphocytes compared with untreated tumors. T2-weighted images or volume calculation did not evidence any difference. MRI-TA appears as a promising method for early detection and follow-up of response to cell therapy.

Adenocarcinoma↗

Differentiation of the P-gp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization.

We have previously demonstrated that proton NMR spectra of fatty acid chains in erythroleukemia K562 wild-type cells and their MDR1 counterparts show variations related to the phenotype over-expressing the P-glycoprotein (P-gp). Human lung cancer cells whose multidrug resistance (MDR) counterparts over-express the multidrug resistance-associated protein MRP1 have not yet been studied by NMR. Both P-gp and MRP1 belong to the same ATP-binding cassette transporter superfamily. A comparison of NMR spectra from both these multidrug-resistance phenotypes showed that the results previously obtained on the MDR1 family are not valid for MRP1. Furthermore, flow cytofluorimetry studies with external phosphatidylserine labelling showed that P-gp and MRP1 overexpressions have strong but differentiated effects on cell lipid pools.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma.

Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins.

Animals↗

Proton NMR spectroscopy of plasma lipoproteins: a marker of the immune function in cancer disease?

1H-NMR spectroscopy of cancer plasma statistically detects significant narrowing of the methyl and methylene line widths. This change is due to relative increase in light density lipoproteins (VLDL and LDL) compared to heavy density lipoproteins (HDL). This observation had raised great hopes for a simple and universal screening test of cancer patients. Furthermore, the same signal can be observed in the plasma of pregnant women and heart transplanted patients undergoing an immunosuppressive treatment. This signal disappears after child's birth and during graft rejection processes. These observations suggest that the test initially proposed by Fossel in 1986 reveals a specific immunological status developed by the organism in "symbiosis" with "foreign" cells, rather than a cancerous disease.

Adjuvants, Immunologic↗

Magnetic resonance spectroscopy in cancer: phospholipid, neutral lipid and lipoprotein metabolism and function.

A Special Symposium on "Lipid Metabolism and Function in Cancer. Significance of Magnetic Resonance Spectroscopy (MRS) Measurements in Relation to Biochemical Processes and Cellular Control" was held by the EU BIOMED 1 Concerted Action for "Cancer and Brain Disease Characterization and Therapy Assessment by Quantitative MRS", within the 5th International Conference of Anticancer Research (Corfu, 18-20 October 1995). The aims of the Symposium were to discuss present knowledge and problems in the field of phospholipid, neutral lipid and lipoprotein metabolism in cancer, together with the new potential of these inter-linked areas of research arising from advanced in vitro and in vivo MRS methodologies. This guest editorial is intended to introduce the reader of the Proceedings published in this issue, into the stimulating atmosphere of the Symposium, by summarizing some of the exciting proposals, views, ideas and open questions which emerged from presentations and multi-disciplinary, plenary discussions.

Humans↗