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Biomedical subjects

M Boisdron-Celle

Publications and source records attributed to M Boisdron-Celle.

25 records · Page 2Linked to original sources
PubMed1997

Plasma sialic acid as a marker of the effect of the treatment on metastatic colorectal cancer.

The concentration of total sialic acid (TSA) is increased in the plasma of patients with many types of cancer. The purpose of this study was to assess the usefulness of the TSA marker in predicting the efficacy of the treatment, and to compare TSA with two common markers, carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9). The study was performed on 44 patients treated for advanced colorectal carcinoma by a weekly 8 h continuous infusion of 5-fluorouracil (1300 mg/m2) plus bolus injection of L-folinic acid (100 mg/m2). TSA, CEA and CA 19-9 levels were measured before and after 3 months of treatment and their variations analysed as a function of the response to the treatment. TSA levels of patients with metastatic colorectal carcinoma before treatment (959 +/- 265 mg/l) were significantly higher than those of 32 healthy people (584 +/- 99 mg/l). The percentage of patients with TSA concentration above the cut-off level (782 mg/l) was 73% before treatment and 23% after. All patients who experienced an objective response to the treatment (complete, partial or minor response) (n = 29) had a significant decrease of TSA levels (t = 5.96; P < 0.001). When the disease was considered as stabilised (n = 10), TSA changed slightly, but it increased with progressive disease (4 out of 5 patients). Changes in CEA and CA 19-9 did not correlate as well as TSA to the treatment efficacy. Initial levels of TSA did not permit prediction of the efficacy of the treatment since they were not significantly different between the five response groups. TSA seems to be more likely involved in tumour changes than in tumour volume. Its determination could provide useful information about the spreading and metastatic properties of the tumour. TSA normalisation is an indicator of probable tumour growth arrest and its elevation could be a marker of relapse.

Adenocarcinoma↗
PubMed1997

Cumulative pharmacokinetic study of oxaliplatin, administered every three weeks, combined with 5-fluorouracil in colorectal cancer patients.

The cumulative pharmacokinetic pattern of oxaliplatin, a new diamminecyclohexane platinum derivative, was studied in patients with metastatic colorectal cancer. Oxaliplatin was administered by i. v. infusion (130 mg/m2) over 2 h every 3 weeks, and 5-fluorouracil and leucovorin were administered weekly. A very sensitive method, inductively coupled plasma-mass spectrometry, allowed for the determination of total plasma and ultracentrifugable (UC) and RBC platinum levels on day 1, at 0, 2, and 5 h, and on days 8, 15, and 22. Sixteen patients underwent three or more courses, and six of them underwent six or more courses. The platinum concentration curves were quite similar from one course to another, with a high peak value 2 h after administration (day 1, Cmax = 3201 +/- 609 microgram/liter) and a rapid decrease (day 8, 443 +/- 99 microgram/liter). Cmax of both total and UC platinum levels in plasma remained unchanged throughout the treatment. The mean total platinum half-life in plasma was 9 days. We found residual levels of total platinum on day 22 (161 +/- 45 microgram/liter), but we observed no significant accumulation for the four first cycles (P = 0.57). In contrast, platinum accumulated significantly in RBCs after three courses (+91% at day 22 of the third cycle versus day 22 of the first cycle, P = 0.000018), and its half-life there was equivalent to that of RBCs. The patterns of UC and total platinum concentration curves were very similar and correlated significantly (P < 10(-6)) at all sampling times. The mean UC:total platinum ratio was 15% at day 1 and 5% at days 8, 15, and 22 in the 3-week treatment course. Unlike cisplatin, which rapidly accumulates in plasma as both free and bound platinum, oxaliplatin does not accumulate in plasma, but it does accumulate in RBCs, after repeated cycles at the currently recommended dose (130 mg/m2) and schedule of administration (every 3 weeks).

Adult↗
PubMed1996

Effect of stereotactic implantation of biodegradable 5-fluorouracil-loaded microspheres in healthy and C6 glioma-bearing rats.

OBJECTIVE: Poly(lactic acid-co-glycolic acid) (PLAGA) microspheres are promising systems for interstitial chemotherapy of brain tumors. They can be readily implanted by stereotaxy and are biocompatible with the brain, in which they are totally biodegraded within 2 months. 5-Fluorouracil (5-FU) was selected for encapsulation, because this hydrophilic and antimetabolic drug is not directly neurotoxic and does not readily cross the blood-brain barrier. Also, its anticancer activity may be improved by sustained administration. Furthermore, it is a potent radiosensitizer. METHODS: To study their fate and toxicity, two types of 5-FU-loaded PLAGA microspheres were implanted in healthy rats by stereotaxy. One type presented a fast in vitro release profile (FR), and the second exhibited a slow in vitro release pattern (SR) (100% of the encapsulated 5-FU is released within 72 hours and 18 days, respectively). Periodically, rats were killed for microscopic examination. The efficacy of these microspheres on rat glioma was then evaluated. Seven days after stereotactic implantation of C6 malignant glioma cells in the brain, the rats were treated by intratumoral injection of 5-FU solution, blank microspheres, or 5-FU-loaded microspheres (FR and SR types). The mortality of these treated groups was compared by the log-rank test with that of an untreated group. RESULTS: After implantation of two types of 5-FU-loaded PLAGA microspheres, no sign of clinical or histological toxicity was observed. Entrapped 5-FU crystals were observed until Days 12 and 20 postimplantation within FR and SR microspheres, respectively, which suggests a longer releasing period in vivo than in vitro. In the therapeutic evaluation, only intratumoral implantation of SR-type 5-FU-loaded microspheres significantly decreased the mortality (P = 0.017). CONCLUSION: 5-FU-loaded PLAGA microspheres were implanted in rat brains without evident toxicity. Histological examination suggested a longer sustained delivery period in vivo than in vitro. Intratumoral implantation of SR-type 5-FU-loaded microspheres decreased the mortality of C6 tumor-bearing rats. This effect can be related to the local and the sustained delivery of the drug, because 5-FU administered systemically is ineffective against brain tumors.

Animals↗
PubMed1995

Preparation and characterization of 5-fluorouracil-loaded microparticles as biodegradable anticancer drug carriers.

To provide a device releasing 5-fluorouracil in a controlled manner and injectable into the brain by stereotaxy, biodegradable poly ((+/-)-lactide-co-glycolide) (PLAGA) microparticles were prepared by an emulsion-extraction process. Although the solubility profile of the drug was not suitable for its encapsulation by the aforementioned method, careful choice of process variables allowed significant drug loading, reaching 30%. Thus, the size of the 5-fluorouracil crystals, the organic phase/aqueous phase ratio, the theoretical drug loading and the microparticle size played a predominant role. The microsphere size was adjusted to 20-40 microns by selecting the appropriate PLAGA and polyvinylalcohol concentrations, and the stirring rate of the initial emulsion. It was shown that the microparticle structure depended directly on the experimental conditions governing the precipitation rate of the coating material: two types of microparticles, I and II, were characterized. The morphology of the particles influenced the 5-fluorouracil-release patterns, as did other process parameters, such as the 5-fluorouracil crystal size and the PLAGA concentration. It was possible to sustain the 5-fluorouracil release over 18 days.

Biocompatible Materials↗
PubMed1994

Drug targeting into the central nervous system by stereotactic implantation of biodegradable microspheres.

Controlled drug release in the central nervous system through an implantable polymeric vector has been developed in recent years. For this purpose, different polymeric devices composed primarily of synthetic biocompatible and biodegradable polymers have been investigated. The first polymeric devices developed were macroscopic implants (monolithic devices), which required open surgery for implantation. Microencapsulation methods, however, allow the production of microparticles or nanoparticles loaded with neuroactive drugs. Because of their size, these micro- or nanoparticles may be easily implanted by stereotaxy in discrete, precise, and functional areas of the brain without causing damage to the surrounding tissue. Presently, this method is most frequently applied in the fields of neuro-oncology and neurodegenerative diseases, but neurologically, the potential applications of drug targeting by stereotactic implantation of drug-loaded particles are legion.

Biodegradation, Environmental↗
PubMedDate not supplied

Formulation of BCNU-loaded microspheres: influence of drug stability and solubility on the design of the microencapsulation procedure.

The design of a microencapsulation procedure for the preparation of biodegradable BCNU-loaded microspheres used as intracerebral implants is the aim of this work. This approach will give sustained high local concentrations of the anti-tumour drug in the brain without the associated significant systemic toxicity. The microencapsulation technique used is a solvent-evaporation process based on the formation of an oil-in-water emulsion. The stability of BCNU in methylene chloride saturated with water and its high value of partition coefficient between methylene chloride and water justifies the selection of this organic solvent as the dispersed phase in the methodology. A spectrophotometric method for the quantification of BCNU in mixtures containing PLAGA is developed which allows the evaluation of drug photodecomposition. The volume of methylene chloride and the concentration of PVA in the external aqueous phase are the two variables that induce the largest variations of the microsphere size. The two main process parameters leading to the highest microencapsulation yield are the polymer concentration in the organic phase and the volume of the external aqueous phase; whereas the pH of the external aqueous phase and the use of co-solvents in the organic phase lead only to a small improvement in microsphere payload.

Antineoplastic Agents, Alkylating↗