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Biomedical subjects

A Roussel

Publications and source records attributed to A Roussel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Recurrences of rectal cancers: results of a multimodal approach with intraoperative radiation therapy. French Group of IORT. Intraoperative Radiation Therapy.

PURPOSE: Prognosis of recurrent rectal cancer remains poor, mainly because of the difficulties of achieving a satisfactory local control. Intraoperative radiation therapy (IORT) allows for the delivery of a complementary single dose to the tumor residues or to the tumor bed and could be useful jn a multimodal treatment. In an attempt to evaluate this interest, a retrospective analysis of patients treated with IORT in six French hospitals has been performed. METHODS AND MATERIALS: Data have been collected in 73 patients (41 men), with a mean age of 62 years, treated with IORT. Initial rectal tumors were large (mean diameter: 45 mm), partially or totally fixed to the contiguous structures in 39%, and with nodal involvement in 50% of the cases. Initial surgery had been a sphincter-sparing surgery in 67%; external radiation therapy had been delivered in 52%, and a chemotherapy had been given in 10% of the patients. Recurrences were isolated (without metastases) in 86%, and were posterior or posterolateral in 55% of the cases. Surgery allowed for a complete macroscopical resection in 57%, a partial resection with gross residual disease in 29%, and no resection in 14% of the recurrences. Intraoperative radiation therapy was delivered in a dose of 10 to 25 Gy (mean 18.5) through localizators of a mean diameter of 75 mm (60 to 110). External radiation therapy, either preoperative or postoperatively was given to 30 patients without prior radiation therapy. Ten patients received additional chemotherapy with 5-fluorouracil. RESULTS: Four postoperative deaths occurred. Postoperative morbidity occurred in 16 patients and some complications were probably related to the IORT procedure. Four long-term complications were observed. Overall actuarial survival occurred in 72.4% of the patients at 1 year, in 44.6% at 2 years, and in 30.6% at 3 years. Twenty-one local failures have been observed. Actuarial local control occurred in 71.3% of the patients at 1 year, 47.7% at 2 years, and 31.3% at 3 years. CONCLUSION: Intraoperative radiation therapy is a complementary treatment for recurrences of rectal cancer. It provides encouraging results, particularly in some selected situations, when patients have not previously been treated with external radiation therapy. Further studies of multimodal treatments are necessary.

Adult↗
PubMed1996

Intraoperative radiation therapy in recurrent carcinoma of the uterine cervix: report of the French intraoperative group on 70 patients.

PURPOSE: To evaluate the feasibility and oncologic results of intraoperative radiation therapy (IORT) for recurrent uterine cervical carcinoma in a cohort of patients treated in seven French institutions. METHODS AND MATERIALS: From 1985 to 1993, 70 patients with pelvic recurrences underwent IORT with/ without external radiation therapy (ERT) and chemotherapy (CT). Treatment modalities for recurrence were IORT alone (40 out of 70), IORT + ERT (30 out of 70), additional chemotherapy (20 out of 70). Gross complete resection (CR) was performed in 30 out of 70 cases, partial resection (PR) in 37 out of 70, and unspecified surgery in 3 out of 70. Sixty-five patients had electron beam IORT and 5, 100 KV photon IORT. Mean IORT cone size, electron beam energy, and dose (calculated at the 90% isodose line) were, respectively, 75 mm (40 to 90), 12 MeV (6 to 20), and 18 Gy (10 to 25) after CR and 80 mm (45 to 100), 15 MeV (7 to 24), and 19 Gy (10 to 30) after PR. RESULTS: Mean follow-up after IORT was 15 months (2 to 69). One, 2- and 3-year overall survival rates were 47, 17, and 8%, respectively; median survival was 11 months and local control, 21%. Median survival and local control rates increased after CR (13 months, 27%) vs. PR (10 months, 17%) and when initial treatment consisted of surgery (S) alone (15 months, 25%) vs. radiation therapy (RT +/- S) (10 months, 16%). However, these differences were not statistically significant. No death-related toxicity was observed. Grade 2 or 3 toxicity was observed in 19 out of 70 patients (27%), including 9 not directly IORT-related complications (13%) (three digestive tract fistulas, one rectal stricture, three urinary fistulas, two infections) and 10 directly IORT-related complications (14%) (five neuropathies, four ureteral obstructions, and one rectal stricture). CONCLUSION: This retrospective study demonstrates the feasibility of IORT. The usefulness of IORT still needs to be evaluated in primary treatment of advanced stages of cervical carcinoma.

Adult↗
PubMed1994

Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations.

BACKGROUND: The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease free survival. METHODS: Ninety-three resected specimens from patients treated with cis-dichloro-diamino cisplatin and irradiation before surgery were examined on semiserial sections. Patients selected for surgery were all Status 1 according to the World Health Organization (WHO) classification. Histologic typing was based on the WHO classification. Tumor regression grade (TRG) was quantitated in five grades: TRG 1 (complete regression) showed absence of residual cancer and fibrosis extending through the different layers of the esophageal wall; TRG 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; TRG 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; TRG 4 showed residual cancer outgrowing fibrosis; and TRG 5 was characterized by absence of regressive changes. Survival curves were estimated according to the Kaplan-Meier method. A quantification of the relationship between treatment failure and confounding variables (age, tumor location, tumor size, esophageal wall involvement by residual cancer and/or regressive changes, histology, treatment, adequacy of surgery, pathologic lymph node status, and tumor regression grade) was done using Cox's proportional hazards model. RESULTS: Forty-two percent of specimens were TGR 1-2; 20%, TGR 3; and 33%, TGR 4-5. Univariate analysis found that tumor size, pathologic lymph node status, tumor regression grade, and esophageal wall involvement were highly correlated with disease free survival (P < 0.05). After multivariate analysis, only tumor regression (i.e., TRG 1-3 versus TRG 4-5) remained a significant (P < 0.001) predictor of disease free survival. CONCLUSIONS: This study highlights the importance of tumor regression in the survival of patients with esophageal carcinoma treated with preoperative chemoradiotherapy. These findings suggest that tumor regression grade should be considered when evaluating therapeutic results.

Adult↗
PubMed1994

Lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure: consequences for heparin binding and catalysis.

Lipoprotein lipase and pancreatic lipase have about 30% sequence identity, suggesting a similar tertiary fold. Three-dimensional models of lipoprotein lipase were constructed, based upon two recently determined x-ray crystal structures of pancreatic lipase, in which the active site was in an open and closed conformation, respectively. These models allow us to propose a few hypotheses on the structural determinants of lipoprotein lipase which are responsible for heparin binding, dimer formation, and phospholipase activity. The folding of the protein assembles a number of positive charge clusters at the back of the molecule, opposite the active site. These clusters probably form the heparin binding site, as confirmed by recent site-directed mutagenesis experiments. The active sites of lipoprotein lipase and pancreatic lipase look very similar, except for the lid (a surface loop covering the catalytic serine in the inactive state). A different open (active) conformation of the lid in both enzymes may be responsible for their differing substrate specificities. Predictions of the nature of the lipoprotein lipase dimer remain elusive, although our model enabled us to propose a few possibilities.

Amino Acid Sequence↗
PubMed1993

A hypothetical complex between crystalline flavocytochrome b2 and cytochrome c.

Flavocytochrome b2 and cytochrome c are physiological electron transfer partners in yeast mitochondria. The formation of a stable complex between them has been demonstrated both in solution and in the crystalline state. On the basis of the three-dimensional structures, using molecular modeling and energy minimization, we have generated a hypothetical model for the interaction of these redox partners in the crystal lattice. General criteria such as good charge and surface complementarity, plausible orientation, and separation distance of the prosthetic groups, as well as more specific criteria such as the stoichiometry determined in the crystal, and the involvement of both domains and of more than one subunit of flavocytochrome b2 led us to discriminate between several possible interaction sites. In the hypothetical model we present, four cytochrome c molecules interact with a tetramer of flavocytochrome b2. The b2 and c hemes are coplanar, with an edge-to-edge distance of 14 A. The contact surface area is ca. 800 A2. Several electrostatic interactions involving the flavin and the heme domains of flavocytochrome b2 stabilize the binding of cytochrome c.

Computer Graphics↗
PubMed1992

Solution conformation of human neuropeptide Y by 1H nuclear magnetic resonance and restrained molecular dynamics.

The solution structure of human neuropeptide Y has been solved by conventional two-dimensional NMR techniques followed by distance-geometry and molecular-dynamics methods. The conformation obtained is composed of two short contiguous alpha-helices comprising residues 15-26 and 28-35, linked by a hinge inducing a 100 degree angle. The first helix (15-26) is connected to a polyproline stretch (residues 1-10) by a tight hairpin (residues 11-14). The helices and the polyproline stretch are packed together by hydrophobic interactions. This structure is related to that of the homologous avian pancreatic polypeptide and bovine pancreatic polypeptide. The C- and N-terminii, known to be involved in the biological activity for respectively the receptor binding and activation, are close together in space. The side chains of residues Arg33, Arg35 and Tyr36 on the one hand, and Tyr1 and Pro2 on the other, form a continuous solvent-exposed surface of 4.9 mm2 which is supposed to interact with the receptor for neuropeptide Y.

Amino Acid Sequence↗
PubMed1990

Conformational flexibility of a scorpion toxin active on mammals and insects: a circular dichroism study.

Three scorpion toxins have been analyzed by circular dichroism in water and in 2,2,2-trifluoroethanol (TFE) solutions. These toxins were chosen because they are representative of three kinds of pharmacological activities: (1) toxin AaH IT2, an antiinsect toxin purified from the venom of Androctonus australis Hector, which is able to bind to insect nervous system preparation, (2) toxin Css II, from the venom of Centruroides suffusus suffusus, which is a beta-type antimammal toxin capable of binding to mammal nervous system preparation, and (3) the toxin Ts VII from the venom of Tityus serrulatus, which is able to bind to both types of nervous systems. In order to minimize bias, CD data were analyzed by a predictive algorithm to assess secondary structure content. Among the three molecules, Ts VII presented the most unordered secondary structure in water, but it gained in ordered forms when solubilized in TFE. These results indicated that the Ts VII backbone is the most flexible, which might result in a more pronounced tendency for this toxin molecule to undergo conformational changes. This is consistent with the fact that it competes with both antiinsect and beta-type antimammal toxins for the binding to the sodium channel.

Amino Acid Sequence↗
PubMed1990

Three-dimensional structures of complexes of Lathyrus ochrus isolectin I with glucose and mannose: fine specificity of the monosaccharide-binding site.

The structure of the methyl-alpha-D-mannopyranoside-LOL I complex has been solved by the molecular replacement method using the refined saccharide-free LOL I coordinates as starting model. The methyl-alpha-D-mannopyranoside-LOL I complex was refined by simulated annealing using the program X-PLOR. The final R-factor value is 0.182 [Fo greater than 1 sigma(Fo)]. The isostructural methyl-alpha-D-glucopyranoside-LOL I complex was refined by X-Ray coupled energy minimization using the methyl-alpha-D-mannopyranoside-LOL I structure as a starting model to an R factor of 0.179 (all data). In both crystal forms, each dimer binds two molecules of sugar in pockets found near the calcium ions. The two saccharide moieties, which are in the C1 chair conformation, establish the same hydrogen bond pattern with the lectin. However, the van der Waals contacts are different between the O2, C2, C6, and O6 atoms of the two molecules and the backbone atoms of residues 208-211. Mannose, due to its axial C2 conformation, encloses the backbone atoms of the protein in a clamplike way. Van der Waals energy calculations suggest that this better complementarity of the mannoside molecule with the lectin could explain its higher affinity for isolectin I.

Binding Sites↗
PubMed1990

CRYStallize: a crystallographic symmetry display and handling subpackage in TOM/FRODO.

We have implemented in TOM/FRODO a protein crystallographic symmetry display and handling package, called CRYStallize. This package is designed as an aid in solving protein structures by molecular replacement methods. It allows the rotation/translation solutions provided by molecular replacement programs to be checked in a fast and easy way. Using CRYStallize, approximate solutions can also be improved by manual modifications. Symmetry-related objects, represented as surfaces, can be generated and handled in the same way as the reference molecules, thus permitting an efficient analysis of crystal packing and site accessibility. This program is available in the TOM/FRODO software release, which runs on the Silicon-Graphics workstations.

Computer Graphics↗
PubMed1989

Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexate: final results of a controlled clinical trial.

Between May 1976 and January 1982, 170 patients were entered in a randomized study comparing a combined treatment consisting of methotrexate followed by irradiation versus radiotherapy alone in patients with non metastatic inoperable oesophageal cancer. Methotrexate was administered subcutaneously in 4 days to a total dose of 24 mg/m2. Radiotherapy was performed, in both groups, at a dose of 56.25 Gy in 25 fractions (5 weeks). The administration of methotrexate did not lead to an increased intolerance to radiotherapy but severe hematological toxicities were observed in 7.8% of the cases. No difference in the duration of survival was detected. Initial performance status of the patients and their weight loss prior to entry on trial were the factors that were most predictive of the patient's prognosis.

Adult↗
PubMed1989

[Hydrocholecystitis in children and newborn infants. Apropos of 3 cases].

We report two cases of hydrocholecystitis in children and one in a neonate. One child had hepatitis A and the other had typhoid fever. A beta-hemolytic group B streptococcal infection was found in the neonate. In all three cases, the first manifestation was an abdominal mass and treatment of the causative disease ensured recovery. These three observations provided us with the opportunity for reviewing the literature. Isolated hydrocholecystitis is distinguished from hydrocholecystitis as a symptom. The clinical evaluation and diagnostic investigations are described in detail; special attention is given to abdominal ultrasonography. Etiology and pathophysiology, as well as management are discussed. Our three cases and the review of the literature confirm the benign prognosis of this condition.

Child, Preschool↗
PubMed1989

[Adjuvant radiochemotherapy in operable cancers of the thoracic esophagus. Preliminary results of a multicenter study. A study of 119 cases].

119 operable patients with an oesophageal squamous cell carcinoma were treated preoperatively by a combination of radiotherapy (37 Gy in two courses) and chemotherapy by cisplatin (delivered before each course of radiation). The response was evaluated on the resected specimen. 111 patients underwent operation and 101 tumours were resected. The toxicity was acceptable by reducing the Cisplatin dosage from 100 mg/m2 to 80 mg/m2 for the last 67 patients. A complete response was observed in 24 patients and a partial response in 46. The preliminary results show a 57% eighteen-month survival in the group of resected patients. A controlled study is needed to compare this combined regimen versus surgery alone in curatively resectable patients.

Adult↗
PubMed1989

Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC.

One hundred and fifteen patients with curative and palliative surgery for gastric cancer were randomized to receive radiotherapy alone (1) or in combination with short-term (ST) 5-FU (2), long-term (LT) 5-FU (3), ST and LT 5-FU (4). The ST 5-FU was given at a daily dose of 575 mg/m2, every 4-6 h during the first 4 days of treatment before starting irradiation. The LT 5-FU was given at a dosage of 750 mg/m2 every 2 weeks for 18 months or until progression. The median survival times for treatment 1 to 4 was respectively 12, 10, 15 and 18 months. There was a statistically significant overall difference between the four treatments (P = 0.041). However, when the comparisons were adjusted for the most significant prognostic factors, the difference in survival disappeared. Moreover, no difference was found between treatments in terms of time progression. Nevertheless, among 22 patients with residual tumour, the three who were still alive without disease progression (with survivals of 19+, 49+ and 90+ months at the time of this analysis) had been treated with radiotherapy combined with ST and LT 5-FU.

Adenocarcinoma↗