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Biomedical subjects

F Mornex

Publications and source records attributed to F Mornex.

At least 91 records · Page 5Linked to original sources

Characterization of double minute chromosomes' DNA content in a human high grade astrocytoma cell line by using comparative genomic hybridization and fluorescence in situ hybridization.

The presence of double minute chromosomes (dmin) in cancer cells is known to be correlated with gene amplifications. In human high grade astrocytomas or glioblastomas, about 50% of cytogenetically characterized cases display dmin. G5 is a cell line which has been established from a human glioblastoma containing multiple dmin. In order to identify the DNA content of these dmin, three techniques were successively used: conventional cytogenetic analysis, comparative genomic hybridization (CGH). and fluorescent in situ hybridization (FISH). The karyotype of G5 cells showed numerical chromosome changes (hypertriploidy), several marker chromosomes, and multiple dmin. CGH experiments detected two strong DNA amplification areas located in 9p21-22 and 9p24, as well as an underrepresentation of chromosomes 6, 10, 11, 13, 14, and 18q. By using FISH with a chromosome 9-specific painting probe to metaphase chromosomes of the G5 cell line, dmin were shown to contain DNA sequences originating from chromosome 9. This study demonstrates the usefulness of a combination of classical karyotyping, CGH, and FISH to identify the chromosomal origin of amplified DNA sequences in dmin.

Astrocytoma↗

Clinical and radiological aspects of Villaret's syndrome.

A 68-year-old man with a history of large cell lung carcinoma presented 1 year after surgical management of the initial lesion, with a complete unilateral IX-XII cranial nerve palsy with Horner's sign. This rare multiple cranial nerve palsy is called Villaret's syndrome. It suggests an extracranial lesion located in the retroparotid space. Complete basal skull radiology work up including computed tomography and magnetic resonance imaging confirmed the location of the causal lesion in the retroparotid space.

Aged↗

Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy. METHODS AND MATERIALS: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based. RESULTS: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors. CONCLUSION: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Adolescent↗

[Exposure of patients to radiation risk in common medical practice].

Medical radiation includes radiodiagnosis, nuclear medicine, and radiation therapy. This radiation exposure differs from occupational public exposure, since a direct benefit is conferred upon the patient. The theoretical risks include genetic mutations, carcinogenesis and teratogenesis. In radiodiagnosis and nuclear medicine, the absorbed doses are very low, and no hazardous effect has been observed. In radiation therapy however, where high doses are delivered to a small number of patients, radio-induced carcinogenesis is well documented. It is by no means sure that the nuclear risk must be taken into account, and fully justifies the accomplishments and recommendations of the French radiation protection programs. There is no question that the nuclear risk-benefit equation resulting from medical exposure is tipped heavily in favor of benefit.

Humans↗

Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer.

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.

Adolescent↗

[Radiotherapy of thymoma. Study of the literature apropos of a retrospective and multicenter series of 149 cases].

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p < 0.0001). Metastases occurred in 26 patients. Seven patients developed grade 3-4 pulmonary and heart complications. One patient developed a malignant lymphoma after 24 cycles of chemotherapy. Disease-free survival (DFS) rates were of five years 92%, 75%, 60%, 39% and 48% in stage I, II, IIIA, IIIB and IVA patients, respectively. After complete resection, partial resection and biopsy alone, these rates were 74%, 60% and 38%, respectively. With a multivariate analysis, DFS rates were influenced by the extent of surgery (p < 0.001) and by chemotherapy (p < 0.001). Three other factors could predict a worse DFS: young age (p < 0.006), stages III-IV (p < 0.04) and mediastinal symptoms (p < 0.001), "GETT" staging correlated well with local control and survival. After complete resection, a 50 Gy postoperative radiation therapy can be recommended in patients with invasive thymomas. Despite a 65% local control rate after partial resection or biopsy alone in this series, a higher dose of radiation (> 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

Adolescent↗

[The effect of radiation on malignant cells].

Mechanisms of death following irradiation of malignant cells are incompletely understood. Radiation-induced lesions and their consequences on the cancer cell are described. Factors conditioning malignant cell response to radiation are discussed, as well as the mechanisms of radiation-induced carcinogenesis. Finally, the recent molecular biology contributions to gene regulation during cell growth are presented.

Cell Cycle↗

Toxicity of combined radiation and chemotherapy in non-small cell lung cancer.

The present paper reviews the different acute and late effects due to radiation and chemotherapy on the different organs lying within the chest (lung, esophagus, spinal cord, heart and skin) using available experimental and clinical data. Some specific issues are stressed, such as the problem of time interval between drug and radiation, the latency period for late effects, and the necessity to use an actuarial method to evaluate the real risk of late effects.

Actuarial Analysis↗

[Radiation-induced cancer after treatment of mediastinal seminoma. Apropos of a case].

Radiation-induced cancer is a rare complication of radiotherapy. The diagnosis relies on chronological, topographical and histological data distinguishing the lesion from tumoural relapse. We report the case of a second cancer, meeting the criteria of radiation-induced malignancy, and attempt to define the frequency, clinical situations and risk man. In addition to gentic mechanisms, other factors appear to play a role in the genesis of radiation-induced cancer.

Fatal Outcome↗

[Non small-cell bronchial cancers: toxicity of the association radiotherapy-chemotherapy. Review of the literature].

Radiation therapy is the elective treatment of inoperable non small cell lung cancer, but is potentially curative only for a few of them: failures result from distant metastases and/or from progressive local disease. During the last years, following the progress in chemotherapy, combining radiation and drugs is becoming a more common approach. Nevertheless, one of the main concerns remains the potential interference between both modalities leading to an increased toxicity, which may outweigh all potential benefit. Several organs can be a target for acute or late toxicity: lung (pneumonitis and fibrosis), esophagus (acute esophagitis, stenosis), heart (pericarditis, impaired ventricular functions, heart failure, coronary stenosis), spinal cord (transient myelopathy, radiation myelitis), skin (moist desquamation, fibrosis, telangiectasia). The current published trials combining drug and radiation appear to be a rather safe approach especially when avoiding concomitant treatment. However, several points remain unsolved: the optimal combination scheme, the real risk of late damage observation including the second cancer occurrence risk. This risk is uneasy to evaluate due to the long latency period. The way of describing the late damage is crucial, seeking for a more precise system of evaluating, recording and reporting late effects, taking into account objective damage as well as the patient's symptoms. Therefore, combining drug and radiation should preferentially be performed within prospective studies, with precise evaluation procedures.

Antineoplastic Combined Chemotherapy Protocols↗

Phase I pharmacokinetics study of high-dose fotemustine and its metabolite 2-chloroethanol in patients with high-grade gliomas.

The pharmacokinetics of high-dose fotemustine followed by autologous bone-marrow transplantation during a phase I-II clinical trial in 24 patients with glioblastoma or astrocytoma (grade III-IV) was investigated. Plasma levels of fotemustine were determined by high-performance liquid chromatography (HPLC) and UV detection. The metabolite, 2-chloroethanol, was simultaneously followed in six patients by gag liquid chromatography and electron capture detection (GLC-ECD) assay. The drug was given as a 1-h infusion on 2 consecutive days. In all, 40 pharmacokinetic determinations of fotemustine were made at dose levels ranging from 2 x 300 to 2 x 500 mg/m2. Plasma drug elimination was best described by a bi-exponential model, with short distribution and elimination half-lives of 4.15 +/- 2.57 and 28.8 +/- 12.1 min being observed, respectively. No significant difference in half-lives or clearance was seen between the first and the second administration. During dose escalation, the mean area under the concentrationtime curve (AUC) increased from 5.96 +/- 2.89 to 12.22 +/- 3.95 mg l-1 h. Drug clearance was independent of the dose given and equal to 109 +/- 65 l/h, indicating no possible saturation of metabolism and elimination mechanisms at these high-dose levels. The metabolite 2-chloroethanol appeared very early in plasma samples. Its elimination was rapid and rate-limited by the kinetics of the parent compound, giving the same apparent terminal half-life. A close relationship between AUC and C45 values was evidenced (r = 0.890). Associated with the stability of fotemustine kinetic parameters, this could be used in future studies for individual dose adjustment, particularly for high-dose fractionated regimens.

Adult↗

Radiation therapy for malignant astrocytomas in adults.

High grade (or malignant) astrocytomas remain a formidable therapeutic challenge. The main prognostic factors are patient age, patient performance status, tumor grade, the extent of surgical resection and the presence of fits. These factors could help to identify different groups of patients and should be an advantage in deciding on treatment strategies. Modern imaging techniques provide a more precise idea of tumor volume. The study of tumor recurrence shows that they occur in the immediate vicinity of the primary site. Surgery aside, radiotherapy remains the most important treatment modality. Currently, its standards concerning optimal dose and target volume appear to be accepted overall. There is no doubt that a dose-response relation exists; however, doses exceeding 60 Gy increase morbidity. Therefore 60 Gy is the dose most often cited in the literature. Furthermore, as whole brain irradiation does not decrease the risk of recurrence, a focal irradiation including a defined mean volume is generally used today. Radiosensitizers and heavy particles have not fulfilled their initial promise. Brachytherapy remains an interesting alternative for a limited number of patients. Nevertheless, it seems to increase recurrence at a distance from the primary site and to lead to severe focal lesions. Interstitial thermoradiotherapy may minimize local doses and thus help avoid serious local necrosis. Amongst the other therapeutic alternatives, intravenous chemotherapy using nitrosoureas provides a certain but modest benefit. Other administration modalities are currently undergoing evaluation. These include intra-arterial chemotherapy or high dose chemotherapy with auto-bone marrow transplantation. The interest of this latter is concerned mainly with anaplastic astrocytomas. Finally, among the future alternatives, gene therapy appears to hold the most promise. Intensive therapies, combined modality treatments, with the recent help of biological innovations, should be proposed to favorable groups of patients.

Adult↗