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E Teissier

Publications and source records attributed to E Teissier.

At least 37 records · Page 2Linked to original sources
PubMed1998

Concomitant b.i.d. radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in unresectable squamous-cell carcinoma of the pharynx: clinical and pharmacological data of a French multicenter phase II study.

PURPOSE: The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed. METHODS AND MATERIALS: Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. RESULTS: Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. CONCLUSION: This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

Adult↗
PubMed1998

A high concentration of melatonin inhibits in vitro LDL peroxidation but not oxidized LDL toxicity toward cultured endothelial cells.

The pineal hormone, melatonin, was recently found to be a potent free scavenger for hydroxyl and peroxyl radicals. Melatonin also inhibits neuronal and thymocyte damage due to oxidative stress. Atherosclerosis development is mediated by low-density lipoprotein (LDL) oxidation and the endocytosis of oxidized LDL by resident macrophages in the subendothelial vascular wall. Furthermore, the cytotoxic effect of oxidized LDL increases atherogenicity. The goal of this study was to compare the antioxidant activities of melatonin and vitamin E against in vitro LDL oxidation and their cytoprotective actions against oxidized LDL-induced endothelial cell toxicity. An attempt at loading LDL with melatonin by incubating human plasma with an ethanolic melatonin solution gave only low protection against Cu2+-induced LDL oxidation in comparison with vitamin E and gave no detectable incorporation of melatonin into LDL, measured by high-performance liquid chromatography (HPLC) coupled to UV detection. High concentrations of melatonin (10-100 microM) added to the oxidative medium induced a clear inhibition of Cu2+-induced LDL oxidation, characterized as an increase in the lag-phase duration of conjugated diene formation and decreases in the maximal rate of the propagation phase and in the maximal amount of conjugated diene formation. Determination of the median efficacious dose (ED50) of melatonin and vitamin E by their ability to increase lag-phase duration showed that melatonin was less active than vitamin E (ED50, 79 vs. 10 microM, respectively). Melatonin was also less active than vitamin E in limiting the formation of thiobarbituric acid-reactive substances (TBARS) and LDL fluorescence intensity increase in the medium during Cu2+-induced LDL oxidation. Cu2+-induced LDL oxidation in the presence of 100 microM melatonin produced oxidized LDLs that were less recognizable for the scavenger receptors of J774 macrophages than were untreated LDLs. Vitamin E, 10 microM, was more active than 100 microM melatonin in inhibiting LDL oxidation and the resulting lipoprotein alterations leading to binding internalization and degradation by the J774 macrophages. Vitamin E, 100 microM, inhibited the pursuit of the oxidation of oxidized LDL mediated by bovine aortic endothelial cells (BAECs) in a culture medium containing Cu2+, whereas 100 microM melatonin had no antioxidant effect. Melatonin, 100 microM, as well as 100 microM vitamin E inhibited intracellular TBARS formation during the incubation of BAECs with highly oxidized LDL but had no influence on the increase in glutathione (GSH) concentration during this lengthy exposure (16 h) of BAECs to highly oxidized LDL. During this period, the same dose of vitamin E but not of melatonin tended to limit the decrease in adenosine triphosphate (ATP) concentration. Vitamin E, 100 microM, did not significantly reduce cellular lactate dehydrogenase (LDH) release in the culture medium during the incubation of oxidized LDL with BAECs, whereas 100 microM melatonin dramatically increased this release. These data show that melatonin is less active than vitamin E in inhibiting in vitro LDL oxidation and does not inhibit the cytotoxicity of oxidized LDL toward cultured endothelial cells. The concentrations necessary to inhibit LDL oxidation are far beyond those found in human plasma (100 microM vs. 100 pM). Therefore our results indicate that the pineal hormone melatonin per se appears to have little antiatherogenic property in the in vitro oxidation of LDL and the cytoprotective action against the toxicity of oxidized LDL. Nevertheless, in vivo LDL oxidation takes place in the subendothelium of the artery wall, and nothing is known about the concentration of melatonin or its catabolites in this environment.

Antioxidants↗
PubMed1998

Drug metabolism in in vitro organotypic and cellular models of mammalian central nervous system: activities of membrane-bound epoxide hydrolase and NADPH-cytochrome P-450 (c) reductase.

The membrane-bound form of epoxide hydrolase and NADPH-cytochrome P-450 (c) reductase are two important enzymes involved in the bioactivation/bioinactivation balance of cerebral tissue. In vivo, the developmental profiles and regional localizations of these two enzymes were investigated in the rat. The regional distribution study showed that they are ubiquitously present among the major brain structures. Both enzyme activities were present in the brain prior to birth, and hence tissue from early developmental stages is suitable to develop in vitro cellular or organotypic models for toxicity studies involving these metabolic pathways. Because various neurotoxicological effects can be dependent on spatio-temporally regulated cell-cell interactions, we aimed to employ organotypic tissue cultures in which the cytoarchitecture was well preserved. In such cultures, the temporal expression profiles of epoxide hydrolase and NADPH cytochrome(c) P-450 reductase reflected the in vivo situation. The technically less demanding pure neuronal and glial cell cultures were also investigated. Detoxification of benzopyrene-4,5-epoxide and superoxide production arising from the reductive metabolism of various drugs were determined in all three systems. The results indicate that though organotypic culture is a good model for the metabolic pathways studied, less complicated single cell cultures can also represent appropriate model systems, providing that the expression of the enzymes involved has been first established in these systems. NADPH-cytochrome P-450 reductase-dependent metabolism is active in both neuronal and glial cells, whereas the detoxification of reactive epoxides occurs mainly in glia.

Animals↗
PubMed1997

Ductal carcinoma in situ of the male breast. Analysis of 31 cases.

From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

Adult↗
PubMed1997

Hypoxia dramatically increases the nonspecific transport of blood-borne proteins to the brain.

Increased cerebrovascular permeability is an important factor for the development of cerebral edema. To investigate the effect of hypoxia on the transport of blood-borne proteins to the brain, we used a cell culture model of the blood-brain barrier (BBB) consisting of a coculture of brain capillary endothelial cells and astrocytes that closely mimics the in vivo situation. The permeability of albumin, a marker of the nonspecific transcellular route, is extremely low in this in vitro model of the BBB. After hypoxia, a huge increase in the permeability of albumin is detected. Despite the opening of the tight junctions already demonstrated after hypoxia, the increase in the permeability of albumin is mainly attributed to an increase of the non-specific vesicular transport in the cell, attested by the temperature dependence of the phenomenon and the visualization of labeled apotransferrin in the cytoplasm. The increase of this pathway could participate in the development of brain edema during hypoxia.

Astrocytes↗
PubMed1997

[A comparative study of 4 sequential first-line chemotherapy protocols in locally advanced breast cancer].

Between 1977 and 1994, our center administered successively 4 different chemotherapy regimens to 242 evaluable patients with locally advanced breast cancer. Patients with inflammatory signs were excluded. Sixty-eight patients were treated by AVCF (A (adriamycine) + V (vincristine) + C (cytoxan) + F (5FU)), 47 by AECF (A + E (vindesine) + C + F), 81 by CAFP (C + A + F + P (prednisone)) and 46 by AN (A + N (vinorelbine)). The mean number of cycle was 3. One hundred and twenty-five patients (52.5%) responded to chemotherapy and we recorded 35 complete response (14.7%). The response rates at the different combinations were respectively: AVCF: 29.4%, AECF: 53.2%, CAFP: 64.9%, AN: 65.2%, and were independent of tumor size, grade and receptor status. The response rate at the AVCF regimen was significantly worse than the others (p = 0.0005). Breast conserving surgery was performed in 31 patients (14%) and 17 patients (8%) had a complete response. Among the 35 patients with complete response, 21 were treated by radiotherapy alone. Local recurrence occurred in 19 patients (7.9%) and 96 (40%) had advanced disease. The mean follow-up of AVCF regimen was 150 months, 115 months for AECF, 111 for CAFP and 42 months for AN. The disease-free survival and the overall survival were significantly better with AECF, CAFP and AN regimens (DFS p < 0.04, OS p < 0.02). Survival was better in those patients with an objective response (p = 0.002) or with non-affected axillary node at the time of surgery. Our study showed already that AVCF combination was significantly lower than AECF, CAFP, AN in terms of response rate, disease-free survival and overall survival. Waiting the results of randomized studies about the impact of neoadjuvant chemotherapy on survival, we look for chemotherapy regimen improving the rate of conservative surgery.

Adult↗
PubMed1997

[Prognostic value of early normalization of CA 125 during chemotherapy in stages III and IV ovarian tumors].

The value of early CA 125 assays and analysis of its diminution kinetics during chemotherapy have been the subject of numerous studies. In contrast, routine utilization of CA 125 assays in clinical practice remains controversial or at best difficult to apply because the definitions and prognostic values associated with CA 125 assays vary greatly from one study to the next. This study was designed to determine whether serial CA 125 assays during induction chemotherapy for ovarian carcinoma, using simple evaluation criteria directly applicable in routine clinical practice such as early normalization (level < 35 UI/ml) are predictive of response to treatment or improved survival. This retrospective longitudinal analysis concerned a historical population of 140 patients with ovarian carcinoma stages III and IV treated at the Antoine-Lacassagne Cancer Center between 1978 and 1993. All the patients were treated by chemotherapy based on platinum salts every 21 days. Serum CA 125 assays were performed both before and after surgery and during each chemotherapy cycle. Eighty-four patients had a pre-operative CA 125 assay. No difference is observed in survival as a function of their preoperative CA 125 concentration (p = 0.4). Sixty-seven patients had a CA 125 assay the 6th week after initiation of chemotherapy, 62 the 9th week and 47 the 18th week. Normalization of CA 125 the 6th week (p = 0.0001), the 9th week (p = 0.0008) and the 18th week (p = 0.03) after the initiation of the chemotherapy cycle are correlated with survival. The median survival in our study is 42 months if the CA 125 is below 35 UI/ml the 6th week versus 13 months if the level of CA 125 remains more than 35 UI/ml. In all, 66 of the 105 FIGO stage III patients underwent second-look surgery. Normalization of CA 125 levels is correlated with the absence of any gross residual tumor at the second-look procedure, the 6th week of chemotherapy (p = 0.0019), the 9th week of chemotherapy (p = 0.0003) and the 18th week of chemotherapy (p = 0.0015). This correlation is not confirmed when the presence of histologic residual tumor in biopsy specimens obtained during second-look surgery is taken into consideration. Overall, 88% of patients whose CA 125 levels failed to normalize during evaluation at the second cycle of chemotherapy have residual tumor at second-look surgery. Outside of clinical trials, repeated early CA 125 assays to determine the chemosensitivity and the prognosis of patients with ovarian carcinoma are of little interest compared to a single CA 125 assay at the 6th week after initiation of chemotherapy. This approach seems to be a good compromise between the information sought and its practical use. However the interest of early modification of chemotherapy regimen after 2 cycles, if the level of CA 125 remains more than 35 UI/ml, will have to be showed.

Adenocarcinoma↗
PubMed1996

1,25-Dihydroxyvitamin D3 regulates gamma 1 transpeptidase activity in rat brain.

gamma-Glutamyl transpeptidase (gamma-GT), primarily described as a kidney enzyme, is also expressed in several cell types of the central nervous system (CNS). It is involved in the glutathione cycle and in cysteine transport. Here we report that the specific activity of this enzyme is transiently increased in the rat brain, following a treatment with 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D. In vitro experiments showed that this positive regulatory effect does not affect endothelial cells of the brain microvessels, but does affect pericytes and parenchymal astrocytes. Changes in the specific activity of gamma-GT were not correlated with any important modification of brain amino acid concentrations. Since gamma-GT is though to participate in the scavenging of reactive oxygen species, these data suggest that 1,25-D3 could be an effector controlling detoxification processes in the brain.

Amino Acids↗
PubMed1996

Proton therapy in ophthalmology: status report and problems encountered.

The proton therapy facility of the Centre Antoine-Lacassagne in Nice began treatment of ocular tumors in June 1991. Up to October 1995, a total number of 600 patients were treated. An overview of the cases treated during the first 4 years of activity is given and the main problems encountered in the field, possibly interacting with the accuracy and reliability of the dose distribution, are listed.

Cyclotrons↗
PubMed1996

Rapid quantification of alpha-tocopherol in plasma and low- and high-density lipoproteins.

We have developed two methods for measuring the alpha-tocopherol content in plasma and lipoproteins (LDL and HDL). In procedure 1, plasma or lipoproteins are deproteinized with ethanol containing delta-tocopherol as internal standard and then extracted with hexane or ethyl acetate. The organic layer is removed and evaporated, and the residue is redissolved in methanol and injected into a reversed-phase HPLC. In procedure 2, plasma or lipoproteins are diluted in a methanol and ethanol mixture containing the same internal standard. The solution is vortex-mixed, centrifuged, and directly injected into the column. The tocopherols are eluted with an isocratic methanol mobile phase at a flow rate of 1 mL/min and detected by fluorescence (lambda(exc)= 295 nm, lambda(em)= 330nm). Recoveries are approximately 100% in both cases. Between-run CVs were 8.39% for procedure 1 and 6.55% for procedure 2. Small sample requirement, simplicity of sample preparation, short assay time, and good reproducibility make procedure 2 ideal for clinical or research use. This method was applied to determination of alpha-tocopherol in plasma of patients whose diet was supplemented with alpha-tocopherol and in LDL and HDL.

Chromatography, High Pressure Liquid↗
PubMed1995

Hypoxia increases the susceptibility to oxidant stress and the permeability of the blood-brain barrier endothelial cell monolayer.

Using a cell culture model of the blood-brain barrier (BBB), we investigated the brain capillary endothelial cell (EC) response to hypoxia. The activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase and the GSH level of brain capillary ECs alone or in coculture with astrocytes, as well as those of pericytes, were compared with those obtained with freshly isolated microvessels. These results demonstrated that brain capillary ECs cocultured with astrocytes and used in the presence of a coculture-conditioned medium provided a relevant in vitro model for studying the effect of hypoxia-reoxygenation at the BBB level. The effect of hypoxia on antioxidant enzymes, GSH, and ATP levels was studied, as well as the modification of the permeability to small weight molecules. A decrease in all enzymes and the GSH level could explain an increase in the susceptibility of the brain capillary ECs to further oxidant injury. Second, profound rearrangements of F-actin filaments of the ECs and a decrease in the ATP level could be associated with an increase in the permeability of the monolayer. Furthermore, an apoptotic process was detected by in situ end labeling of DNA. These results indicate that hypoxia distorts the function of ECs and that these cells in culture provide a valuable tool for exploring mechanisms after hypoxia-reoxygenation.

Adenosine Triphosphate↗
PubMed1995

[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma].

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.

Adult↗
PubMed1995

[MRI of uterine leiomyosarcoma. Apropos of 2 cases].

Prognosis is poor for uterine leiomyosarcomas. Diagnosis is often an unexpected pathology discovery after hysterectomy for fibroma. Prognosis depends on the degree of locoregional extension and thus on early diagnosis. Echography and computed tomography scan are note very specific. There is little literature on imagining studies, and particularly on MRI in this pathology. Yet MRI, especially the T2 weighted sequences, is quite interesting for evaluating tumour extension in the uterus. It can be used whenever an abnormal increase in size is observed during the per- or postmenopausal period in a women with a fibroma. We report two cases of uterine leiomyosarcoma explored by MRI and review the literature.

Aged↗
PubMed1994

Reduction of a trisulfide derivative of glutathione by glutathione reductase.

Glutathione trisulfide was synthesized from glutathione disulfide and its reduction by glutathione reductase was studied. A two-step reaction was observed. In a first step, the rate of reduction was similar to that observed with glutathione disulfide. In addition to glutathione, a persulfide intermediate was detected by an electrochemical method and was carboxymethylated by iodoacetate to be identified by Plasma Desorption Mass Spectrometry. During the second step the reduction of this intermediate led to the formation of hydrogen sulfide and a second equivalent of glutathione.

Animals↗
PubMed1994

Effect of alpha Ni3S2 on arachidonic acid metabolites in cultured human lung cells (L132 cell line).

Our previous investigations have shown evidence of an interaction between alpha Ni3S2 and membranous and cellular lipids of lung cells with a significant increase in the linoleic, linolenic and arachidonic acid pool. The present work is designed to follow the metabolic fate of arachidonic acid in alpha Ni3S2-exposed human embryonic pulmonary epithelial cells (L132) in culture (50 microM alpha Ni3S2 for 3 days). The metabolites of arachidonic acid were assessed by HPLC determination coupled with UV or electrochemical detection. We determined malondialdehyde (MDA), hydroxyeicosatetraenoic acid (HETE), leukotrienes (LT) and reduced glutathione (GSH). In exposed cells we observed a significant increase of MDA, which is a breakdown product of lipid peroxidation. In addition, we noted significant increases of 5-HETE and 15-HETE in L132 cells resulting from the enzymatic reduction of 5-HPETE and 15-HPETE respectively. There was also a simultaneous decrease of GSH--confirmed by a strong decrease of GSH in exposed cells with respect to controls. 5-HPETE is furthermore converted to epoxides such as leukotriene A4 and we also quantified in exposed cells a significant increase of its subsequent catabolites LTB4, LTC4 and LTE4. These investigations show clearly that exposure of L132 cells to alpha Ni3S2 enhances lipid peroxidation based upon direct measurements of MDA and other metabolites of arachidonic acid. This lipid peroxidation is an autocatalytic free-radical process and could be responsible for DNA damage.

Arachidonic Acid↗
PubMed1993

[Demonstration and characterization of EGF receptors in cancer of the uterine cervix].

Epidermal Growth Factor in a polypeptide growth factor of which receptor EGFR has a prognosis value for some malignant tumours. Data are limited concerning the EGFR value in cervix tumours. EGFR was measured in biopsies obtained in cervix cancer patients before any treatment. Twenty-two patients (18 squamous carcinomas, 4 adenocarcinomas) were studied. EGF binding was characterized in seven tumour samples. Scatchard representation identified a single family of binding sites. Kd value revealed high affinity for EGF binding: 0.645 +/- 0.769 nmol/l. EGFR values were determined by a simplified competition method using a radiolabeled ligand. EGFR was found to be more elevated in tumours (n = 20) than in normal tissue (n = 4): (59.5 vs 10.5 fmol/mg proteins). There was a tendency for higher EGFR values in squamous tumours (m = 83.5 fmol/mg proteins) as compared to adenocarcinomas (m = 35.5 fmol/mg proteins), P = 0.09. There was no difference in the distribution of EGFR values according to tumour differentiation and staging. This work confirms the presence of EGFR in cervix tumours. Interestingly, we found that tumours with high EGFR values were more radiosensitive than tumours with low values.

Adenocarcinoma↗
PubMed1992

Radical surgery and conservative treatment of ductal carcinoma in situ of the breast.

70 cases of strictly intraductal breast carcinoma were treated from January 1975 to December 1987. 34 patients underwent radical modified mastectomy, and 36 patients had local excision (2), lumpectomy (26) or quadrantectomy (8), with a complementary irradiation in 34/36 cases (with boost in 32). The main histological subtype is comedocarcinoma (25/70). One local relapse (3%) is noted in radical surgery group at 55 months. 3 local relapses (9%) are noted in conservative treatment group, respectively at 27, 48 and 52 months. The obvious factor influencing the local recurrence is the inefficient surgical excision. Since breast screening programs may lead to early duct carcinoma in situ identification, our results suggest that appropriate conservative surgery associated to radiation therapy could be an adequate alternative to mastectomy in the treatment of this in situ lesion.

Adult↗