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Biomedical subjects

P Bey

Publications and source records attributed to P Bey.

At least 91 records · Page 5Linked to original sources
PubMed1992

Velotonsillar squamous cell carcinoma: 277 cases treated by combined external irradiation and brachytherapy--results according to extension, localization, and dose rate.

From 1977 to 1987, 277 patients with velotonsillar cancer (oropharyngeal cancer excluding base of tongue and valleculae) were treated by brachytherapy either alone (14 patients) or combined with external beam irradiation (263 patients) using a new afterloading Iridium-192 technique. The distribution of patients according to the localisation was as follows: 106 tonsillar region, 98 soft palate, 45 anterior pillar, 8 posterior pillar and 20 pharyngoglossal sulcus. According to the UICC TNM classification of 1979, the patients were staged as follows: 65 T1, 103 T2, 101 T3, 8 TX. 172 patients were NO, 74 N1, 3 N2, 20 N3 et 8 NX. According to the tumor extension, the 5 year actuarial local control, locoregional control, specific survival and overall survival by T stage (T1 [65 pts], T2 [103 pts.], T3 [101 pts]) were respectively: local control: 89%, 86%, 69%; locoregional control: 84%, 80%, 67%; specific survival (excluding patients dead with intercurrent disease or second cancer): 78%, 62%, 46%; overall survival: 62%, 53%, 43%. No local recurrence was detected after 3 years. According to the localization, the tumors arising from the tonsillar region, the soft palate and the posterior pillars (A Group) had a better prognosis than the tumors arising from the anterior pillars and glossotonsillar sulcus (B Group). The complications were classified into four grades according to their extension and duration: Grade 1 (minor) with very small tissue ulcer which healed within 2 months with medical treatment (20%). Grade 2 (moderate) (5%), grade 3 (severe) (1.4%), grade 4 (fatal) (0.4%). The dose rate seemed to be relatively higher in patients with grade 2 and 3 complications (70 cGy per hour on average) versus the dose rate of patients without complications (50 cGy per hour) but the difference was not significant. In conclusion, the brachytherapy boost after external irradiation can be performed under favourable conditions with an acceptable rate of complications. It was set out in order to attempt to improve the local control of the tumor while preserving the salivary function and lessening the muscular fibrosis. It shows how experienced the team is, however only a randomized study would allow to state whether this technique brings about a real improvement especially as for tumors T2 or T3.

Adult↗
PubMed1992

Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques.

Our purpose is to analyse local control, complications relative to the proportion of total dose delivered by external beam irradiation versus interstitial implant in 147 patients with previously untreated T2N0 squamous cell carcinoma of the oral tongue, managed between 1973 and 1986 (UICC staging system). These T2N0 patients are part of a larger group of 430 patients with oral tongue carcinoma (T1, T2, T3) treated with irradiation alone. Of these 147 T2N0 patients, 70 were treated with interstitial implant alone and 77 with both external beam irradiation and implant. In the group treated with interstitial implant alone, the 5-year local control was 89.8% against 50.6% in those treated with external beam irradiation and interstitial implant (log-rank test, p = 0.00002); 67.6% versus 46.5% for locoregional control (p = 0.029); and 62.2% versus 34.7% for specific survival (p = 0.0015). Since 1980, all the patients treated by iridium implantation were protected with a leaded spacing device between the tongue and the mandible. Soft tissue necrosis and bone exposure following treatment were scored according to the following criteria: minor, moderate or severe. Seven moderate and one severe complications were recorded in the brachytherapy group. None of the patients required surgery. In the combined treatment group, six moderate and two severe complications were observed. Patients treated with interstitial implant alone, and showing moderate or severe complications had received an average brachytherapy dose of 7600 cGy. In the same group, the patients without complications had received an average dose of 6800 cGy.(ABSTRACT TRUNCATED AT 250 WORDS)

Brachytherapy↗
PubMed1992

Late cardiopulmonary toxicity after treatment for Hodgkin's disease.

Cardiac and pulmonary functions were evaluated in 75 patients aged 50 years or under, treated for Hodgkin's disease by mantle radiotherapy at least 3 years earlier; all received the same mantle field radiotherapy: radiotherapy alone, MOPP chemotherapy plus radiotherapy, MOPP and ABVD chemotherapy plus radiotherapy. No patient had any symptom of heart disease. Only borderline abnormalities of ECG or echocardiogram were observed in 12 patients. One of them showed a moderate aortic stenosis which was known before the treatment; apical or septum hypokinesia were present in four patients and one patient had a slightly right ventricular dilatation. Twelve (16%) chest radiographs showed moderate or severe abnormalities, but there was no significant correlation between the results of pulmonary function tests and Xenon ventilation/perfusion scintigraphy, the clinical examination and the intensity of the radiological sequelae. Twenty-nine (64%) Xenon scintigraphies showed a reduction of lung perfusion in the irradiated areas without any symptom. The resting mean pulmonary function test was significantly lower for the patients than for the control group with regard to Total Capacity and Vital Capacity. The exercise tolerance, as indicated by analysis of blood gases, was below the one expected for only two patients who were dyspneic during the low level of exercise. We did not find any significant difference between the three treatment groups. We conclude that the treatment with mantle field under good technical conditions (high energy photons, moderate doses...) can result in minimal cardiopulmonary dysfunction.

Adolescent↗
PubMed1992

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.

Actuarial Analysis↗
PubMed1991

Antimalarial polyamine analogues.

A series of novel tetraamines of the general formula RNH(CH2)xNH(CH2)yNH(CH2)xNHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10(-6) M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.

Animals↗
PubMed1991

4',5'-unsaturated 5'-halogenated nucleosides. Mechanism-based and competitive inhibitors of S-adenosyl-L-homocysteine hydrolase.

The design and synthesis of (E)- and (Z)-5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (6 and 13, respectively), a new class of mechanism-based inhibitors of S-adenosyl-L-homocysteine (SAH) hydrolase, is described. A number of analogues of 6 and 13 were synthesized in order to determine the structure-activity relationship necessary for inhibition of the enzyme. Substitution of chlorine for fluorine in 6 (i.e. 44), addition of an extra chlorine to the 5'-vinyl position (i.e. 51 and 52), modification of the 2'-hydroxyl group to the deoxy (34 and 35) and arabino (36 and 37) nucleosides provided competitive inhibitors of SAH hydrolase. Nucleosides 6 and 13, as well as 5'-deoxy-5',5'-difluoroadenosine (14) proved to be time-dependent inhibitors of SAH hydrolase. All three compounds are postulated to inhibit through the potent electrophile derived from oxidation of the 3'-hydroxyl of 6 or 13 to the ketone (i.e. 3 and/or the E-isomer). Consistent with the proposed mechanism of inactivation of SAH hydrolase by 6, 13, and 14 was the observation that incubation of purified rat liver SAH hydrolase with 6 resulted in release of 1 equiv of fluoride ion (by 19F NMR) and incubation with 14 resulted in release of 2 equiv of fluoride ion. The general synthetic route developed for the synthesis of the title nucleosides utilized the fluoro Pummerer reaction for the introduction of fluorine into the requisite precursors. Preliminary antiretroviral data from Moloney leukemia virus (MoLV) is presented and correlates with SAH hydrolase inhibition. Antiviral activity (IC50 against MoLV) ranged from 0.05 to 10 micrograms/mL.

Adenosylhomocysteinase↗
PubMed1991

In vitro combination of high dose busulfan with radiotherapy on medulloblastoma cells: additive effect without potentiation.

The aim of this in-vitro study was to evaluate the combination of busulfan with radiotherapy on TE-671 human medulloblastoma cells since unexpected clinical toxicity of busulfan was reported during the treatment of brain tumors, suggesting a possible radiopotentiation. The cytotoxicity of busulfan was determined by using colony forming assays, and doses inducing growth inhibitions of 10, 20 and 50% were selected to be tested in association: 6, 12 and 32 mumol/l for busulfan and 0.5, 1 and 3 Gy for irradiation. All possible combinations were considered within this frame and the results showed that the combination of busulfan with radiotherapy exerted an additive effect without potentiation.

Busulfan↗
PubMed1991

[Mixed mullerian tumours of the endometrium. Retrospective study, with prognostic aims, comparing their evolution to that of adenocarcinomas of the endometrium].

Mixed Mullerian Tumours (MMT) of the endometrium have a bad reputation as far as prognosis is concerned. We have studied 34 cases of MMT treated between 1976 and 1988 and have compared their outcome with a matched series of 68 cases of adenocarcinoma (ADC). These were taken out of 880 cases of ADC treated during this period of time after matching them for the stage, the type of treatment, the year of treatment and the age of the patient. The curves of survival and the totals of survival were determined using Kaplan-Meier's method and also compared using Logrank's test. The 5-years overall survival was 18% for MMT as against 55% for ADC (p less than 0.001). The difference was equally significant statistically in terms of specific survival without recurrences. The 16 patients in stages I and II who were treated with the same protocol as used for ADC were matched against 32 cases of ADC taken out of the 680 cases ADC in stages I and II and treated by the same protocol (84%). After five years MMT had a higher number of survivors (35% overall, 45% with specific survival and 35% without recurrences), but the difference with survival of ADC was as significant (respectively 75, 85, 85%). Recurrences of MMT were frequent (62%), with metastases in 9 out of 10 and early (50%), in every respect opposed with recurrences of ADC (16%) which were in three out of five cases localized and late (after 10 months). These figures make one have to think of modifying the way MMT is treated. External pelvic radiotherapy should be carried out before any other treatment. The place for other methods of therapy is to be discussed.

Adenocarcinoma↗
PubMed1991

[Role of radiotherapy in the treatment of brain tumors].

Tumors of the central nervous system represent about 25% of malignant tumors in children. They differ by their histological subtypes and evolution. Surgery is often incomplete and chemotherapy has not yet demonstrated its efficiency. Thus, radiotherapy (Rt), in spite of its late effects on the normal brain, remains widely used. The most severe complications of Rt can be avoided by precise multidisciplinary indications, judicious choice of volume to be irradiated, use of specific X-rays with a precise technology. Indications of radiotherapy are residual tumor after surgery and all malignant tumors, even if completely removed. The maximum tolerable doses are well known, but the volumes to be irradiated remain of debate for some types especially taking into account the risk of dissemination to cerebro spinal fluid. Overall 5-year survival rate is about 50% with great variations from one histological type to another. Brachytherapy may sometimes be useful but is a very sophisticated technique.

Brain Neoplasms↗
PubMed1990

DL-3,3-difluoroglutamate: an enhancer of folylpolyglutamate elongation.

The effect of 3,3-difluoroglutamate (F2Glu) on the reaction catalyzed by rat liver folypolyglutamate synthetase was investigated. F2Glu was a potent, concentration-dependent inhibitor of poly(gamma-glutamylation) using [3H]Glu and either methotrexate (4-NH2-10-CH3PteGlu) or tetrahydrofolate as substrates. It was determined that F2Glu acted as an alternate substrate, but in contrast to the previously characterized alternate substrate 4-fluoroglutamate (McGuire, J.J., and Coward, J.K. (1985) J. Biol. Chem. 260, 6747-6754), it did not terminate polyglutamate chain elongation. Instead, F2Glu promoted chain elongation. Thus, synthesis of products from [3H]methotrexate containing 1 and 2 additional amino acid residues occurred at a substantially higher rate in the presence of F2Glu when compared to identical reactions in the presence of Glu; this was more pronounced for the product containing 2 additional residues. Identities of the products were established by their respective chromatographic elution positions and by limit digestion with gamma-glutamyl hydrolases. Ligation of Glu to 4-NH2-10-CH3PteGlu-gamma-(3,3-difluoroglutamate) was also enhanced. These results are consistent with F2Glu enhancing the synthesis of poly(gamma-glutamate) metabolites at the level of either the incoming amino acid (glutamate analog) or the gamma-glutamyl acceptor species. F2Glu is thus the first glutamate analog which enhances chain elongation catalyzed by folypolyglutamate synthetase.

Animals↗
PubMed1990

The inhibition of human neutrophil elastase and cathepsin G by peptidyl 1,2-dicarbonyl derivatives.

Neutrophil elastase and cathepsin G are serine proteases that can damage connective tissue and trigger other pathological reactions. Compounds containing a peptide sequence to impart specificity and bearing an alpha-dicarbonyl unit (alpha-diketone or alpha-keto ester) at the carboxy terminus are potent inhibitors of the neutrophil serine proteases (human neutrophil elastase: R-Val-COCH3, Ki = 0.017 microM; R-Val-COOCH3, Ki = 0.002 microM; human neutrophil cathepsin G: R-Phe-COCH3, Ki = 0.8 microM; R-Phe-COOCH3, Ki = 0.44 microM; R = N-(4-[(4-chlorophenyl)sulfonylaminocarbonyl]phenylcarbonyl)+ ++ValylProlyl).

Animals↗
PubMed1990

Synthesis of peptidyl fluoromethyl ketones and peptidyl alpha-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G.

Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

Amino Acid Sequence↗
PubMed1990

Polyamine analogues with antitumor activity.

A series of tetraamines derived from 1,8-diaminooctane was prepared and tested as antitumor agents. The reaction of 1,8-diaminooctane with acrylonitrile gave N,N'-bis(cyanoethyl)-1,8-diaminooctane, which was reduced to tetraamine 20. Alkylation of the terminal nitrogen atoms of the tetra-Boc derivative of this compound by methyl or ethyl halide followed by removal of the Boc groups gave the bis(alkyl)polyamines 26a and 26b, respectively. These three compounds exhibit promising antitumor activity in the mouse L1210 leukemia model. Coadministration of a polyamine oxidase inhibitor potentiated the antitumor activity.

Animals↗
PubMed1990

The mechanism of inhibition of S-adenosyl-L-homocysteine hydrolase by fluorine-containing adenosine analogs.

(Z)-4',5'-Didehydro-5'-deoxy-5'-fluoroadenosine (I), 5'-deoxy-5'-difluoroadenosine (II), and 4',5'-didehydro-5'-deoxy-5'-fluoroarabinosyl-adenosine (III) are inhibitors of rat liver S-adenosyl-L-homocysteine hydrolase. Compounds I and II are time-dependent and irreversible inhibitors of the enzyme. Both I and II are oxidized by E.NAD to produce E.NADH, and fluoride anion is formed in the inactivation reaction (0.7 to 1.0 mole fluoride/mole of enzyme subunit, and 1.7 moles fluoride/mole of enzyme subunit from I and II, respectively). The enzyme is stoichiometrically labeled with [8-3H]-I, but the label is lost upon denaturation of the protein either with or without treatment of the labeled complex with sodium borohydride. The compound III, the arabino derivative of I, is a competitive inhibitor of the enzyme. The mechanism of the inhibition of S-adenosyl-L-homocysteine hydrolase by these inhibitors is discussed.

Adenosine↗
PubMed1990

Use of electrons for radiation therapy in France.

The development of high energy radiotherapy equipments in France between 1950 and 1990 is analyzed. The use of betatrons after a growth between 1960-1970 decreased progressively from 1975 in favour of linear accelerators (133 in 1989). Cobalt-therapy, rapidly grown up between 1960 and 1980, has reached a plateau phase with a trend to being progressively substituted by low energy linac. The dosimetric aspects are considered: calibration of electron beams, quality control and treatment planning. About 22000 cancer patients were treated in 16 Centres in 1983; of these only 23% (mean value) received electron therapy, but the number varies greatly from one center to another (9-45%). The major indications for electrons in France are: neck nodes, operated breast, internal mammary chain. The general trend is to restrict their use to lesions not deeper than 4-5 cm and first of all to employ them as a boosting treatment, after an X ray irradiation.

Electrons↗