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P Lagarde

Publications and source records attributed to P Lagarde.

At least 19 recordsLinked to original sources
PubMed2006

Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells.

Unr (upstream of N-ras) is a cytoplasmic RNA-binding protein involved in the regulation of messenger RNA stability and internal initiation of translation. We have used Unr-deficient murine embryonic stem (ES) cells to analyse Unr role in cell proliferation and response to stress. Disruption of both unr gene copies had no effect on ES cell proliferation. However, after ionizing radiation (IR), clonogenic survival of unr(-/-) ES cells was approximately 3-fold enhanced as compared to unr(+/+) cells. We further determined that IR-induced apoptosis was decreased in unr(-/-) ES cells, and that reintroduction of the unr gene in unr(-/-) cells restored normal IR-induced apoptosis. Three pro-apoptotic genes, p53, caspase-3 and Gadd45gamma, were downregulated in unr(-/-) ES cells, indicating that Unr, as other cytoplasmic RNA-binding proteins, regulates a complex genetic program, promoting cell death after IR. In contrast, in the human hepatoma cell line HuH7, Unr knockdown using unr-specific small interfering RNAs induced apoptosis, both in untreated and gamma-irradiated cells. Thus, our results establish that Unr acts as a positive or negative regulator of cell death, depending on the cell type. Manipulating the level of Unr may constitute a specific approach to sensitize cancer cells to anticancer treatments.

Animals↗
PubMed2006

[Conservative and functional management for soft tissue sarcomas of the extremities: role of radiotherapy].

Recent publications have permitted to quantify the benefit of radiotherapy in the conservative treatment of soft tissue sarcoma of the limbs. The aim of this review is to focus on aspects of radiotherapy witch influence local control and functional outcome for early and late normal tissue damage. The evaluation of late effects is performed according to Soma-Lent (Subjective-Objective-Management-Analytic-Late Effects of Normal Tissues) classification. About complications, neurological complications are probably under estimated and are related to total dose of radiation therapy.

Arm↗
PubMed2005

[Adjuvant radiation therapy for soft tissue sarcoma of the extremities: analysis of local control according to volume and dose].

PURPOSE: To evaluate retrospectively the anatomical definition of target volumes in the treatment of soft tissue sarcomas of the limbs and to study the radiation dose in the local control and toxicity. METHODS AND PATIENTS: Seventy-seven patients were consecutively treated for primary soft tissue sarcoma of the extremity with limb sparing surgery and external beam radiotherapy (EBRT) in the same institution. The median follow up was 56 months (17-89 months). RESULTS: Fifty-two patients (67%) had clear microscopic surgical margin (R0 resection), 23 (30%) had histologically positive microscopic margin (R1 resection), 2 had a macroscopic residual disease (R2 resection). An anatomical definition of target volumes has been realised. The mean dose was 50 Gy in 25 or 28 fractions; 23 patients received a boost restricted to the tumor bed: 13 with EBRT, 10 with brachytherapy (BRT). Thirty-four patients had an adjuvant chemotherapy. The overall 5 year local relapse rate was 10%. Seven local relapses were described, five of the high-grade tumours, and five in patients with positive margin. In univariate analysis, quality of surgery shows a significant effect for local control. By using LENT-SOMA scale for late toxicity, a significant difference was found for neurological complications for patients receiving a boost. CONCLUSIONS: The results of the series validate the concept of anatomical definition of the initial target volume. A boost should be realised for positive margin tumors and may be for high-grade tumors. Neurological toxicity must be considered for the evaluation of the prescribed dose.

Chemotherapy, Adjuvant↗
PubMed2005

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)].

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

Carcinoma, Squamous Cell↗
PubMed2004

[Comparison of intensity-modulated postoperative radiotherapy with conventional postoperative conformal radiotherapy for retroperitoneal sarcoma].

External postoperative radiation therapy for retroperitoneal sarcoma is an example of treatment using large fields for complex shaped volumes of irradiation. Prescribed dose is limited by tolerance of adjacent organs at risk (OAR). From a recent case treated by conventional conformal radiotherapy (3D-CRT), we evaluate the benefit of five theoretical IMRT plans. Criteria used are calculated from DVH related to delineated PTV and OAR. IMRT should permit to enhance the prescribed dose without increasing dose in the OAR (especially residual kidney, spinal cord and small bowel). This theoretical study show the feasibility of a dose escalation from a treatment dose of 45 Gy delivered by 3D-CRT up to a planning dose of 54 Gy calculated by IMRT with: for the PTV: an improvement of the dose homogeneity about 5% (range 2-6%) and moreover the coverage factor (CF) about 13% (range 9-16%); for the OAR: an improvement of the protection factor (PF) about 20% (range 11-24%); and thus an improved conformity index (CI = CF x PF) about 25% (range 15-32%).

Feasibility Studies↗
PubMed2002

Churg-Strauss syndrome in two patients receiving montelukast.

OBJECTIVE: Churg-Strauss syndrome (CSS) has been described in association with the treatment of asthmatic patients with leukotriene receptor antagonist. The main mechanism proposed to explain this condition is the unmasking of CSS after the leukotriene receptor antagonist has allowed corticosteroid tapering. Other hypotheses might be proposed. METHODS: We describe two patients who developed CSS after starting treatment with montelukast, a new antileukotriene drug. RESULTS: Both patients presented with CSS after 4-5 months of treatment with montelukast. Neither patient received long-term systemic steroids for asthma, but both were on inhaled steroids. One patient had a myocardial involvement and experienced a stroke. Our two patients were treated with systemic steroids and cyclophosphamide. CONCLUSIONS: CSS does not appear to relate to steroid tapering in our patients. The other hypotheses are a coincidence or a direct adverse effect of the antileukotriene. Long-term data on these drugs are lacking and leukotriene's role in vasculitis remains to be elucidated.

Acetates↗
PubMed2002

[Surgical methods of removal of T4 nasopharyngeal malignancies. A preliminary report on 18 cases].

OBJECTIVES: To describe the technique and evaluate postoperative sequelae and results of transfacial surgical removal of T4N0 nasopharyngeal malignant neoplasms. MATERIAL AND METHODS: Eighteen cases of surgically-treated nasopharyngeal cancers, managed between january 1993 and october 2000, were retrospectively studied. Three patients were non-responders to neoadjuvant chemotherapy, 6 suffered local recurrence following standard treatment and 7 were operated first either because of a huge and osteolytic tumor or because of an uncommon histolopathology. RESULTS: Preoperative Vth nerve neuralgia (8 cases) was alleviated (4 cases) or cured (3 cases). At the time of diagnosis, ophthalmoplegia was observed in 3 cases. It disappeared postoperatively in 2 cases and after following radiation therapy in one. Median follow-up of the series was of 31.8 mths. Four patients were died of disease; one of them from distant metastases 4 years post-surgery. One patient is alive with distant metastases. The 13 last (72.2%) are alive without disease with a 35.6 mths median follow-up (6-77 mths). DISCUSSION: This short and heterogeneous series cannot lead to any evidence-based conclusion. But mid-term free-of-disease survival of 4 of the 5 patients suffering local recurrence and of patients presenting with so-called non-radiation-sensitive tumors is to be considered. In comparison with the high risk of neurological sequels following reirradiation, absence of specific toxicity of surgery observed in this series is to be underlined. CONCLUSION: In selected cases surgical treatment does not demonstrate any toxicity and is able to offer mid-term local control of the disease. Its role is to be evaluated further before inclusion in the therapeutic algorithm of these very bad prognosis-associated tumors.

Adult↗
PubMed2001

[Definitions of target volumes in soft tissue sarcomas of the extremities].

Soft tissue sarcomas of the extremities are currently treated with more conservative and functional approaches, combining surgery, radiotherapy and chemotherapy. The role of external beam radiotherapy and brachytherapy has been defined through randomised studies performed in the 80's and 90's. However, the ubiquity of tumour location for these tumours makes difficult a systematic definition of local treatments. Tumour volume definition is based on pre and post surgical imaging (MRI) and on described pathological report. The clinical target volume will take into account quality of the resection and anatomical barriers and will be based on an anatomy and not only on safety margins around the tumour bed. General rules for this irradiation (doses, volumes) and principal results will be presented.

Brachytherapy↗
PubMed2000

Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975-1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates for survival without recurrence were 54% and 32%, respectively. CONCLUSION: The results confirm the beneficial effect of surgery. Further study is needed to explore the roles of combined treatments.

Adolescent↗
PubMed1999

[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?].

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.

Age Factors↗
PubMed1998

[Chemotherapy of soft tissue sarcoma in the adult].

The goal of postoperative treatment in adult soft tissue sarcoma is local control, and in high-risk patients prevention of distant failures. Radiation therapy is essential after non-radical surgery. The role of adjuvant chemotherapy on improvement of overall survival remains to be evidenced; however, recent meta-analysis data have confirmed its impact on both local and metastatic evolution of the disease. Because for both radiotherapy and chemotherapy, delay of treatment may be crucial for efficacy following tumor excision, concomitant radiochemotherapy should be considered. Review of the literature as well as personal results showed the feasibility of postoperative radiochemotherapy in adult soft tissue sarcoma, even when the chemotherapeutic associations used included an anthracycline. Prospective study of radiochemotherapy should be performed in order to assess its real impact in terms of efficacy and toxicity.

Adult↗
PubMed1997

Differential stabilization of topoisomerase-II-DNA cleavable complexes by doxorubicin and etoposide in doxorubicin-resistant rat glioblastoma cells.

Using the technique of alkaline filter elution, we have evaluated the DNA damage induced by doxorubicin and etoposide in a rat glioblastoma cell line, C6, and its doxorubicin-selected resistant variant, C6 0.5. DNA damage paralleled drug-induced cytotoxicity, but it appeared that the same DNA damage generated much less cytotoxicity in resistant cells than in sensitive ones, resistant cells being able to tolerate more DNA damage than sensitive cells. We have then quantified the doxorubicin- and etoposide-induced complexes between topoisomerase II (topoII) DNA with the technique of SDS/KCl precipitation. Etoposide produced a concentration-dependent increase in topoII-DNA complexes, which was higher in resistant cells at equitoxicity, just as was DNA damage. In contrast, doxorubicin-induced topoII-DNA complexes, which were much less abundant than those induced by etoposide, were not differently produced in sensitive and resistant cells. This indicates that the DNA damage occurring in resistant cells at high doxorubicin concentrations might originate from source other than topoII-DNA complex formation. When verapamil was added during drug exposure, it restored doxorubicin intracellular accumulation to the level reached in sensitive cells, partially reversed both doxorubicin and etoposide resistance, increased the formation of etoposide-induced topoII-DNA complexes, but not those induced by doxorubicin. Immunoblot analysis of topoII as well as the measure of its catalytic activity in nuclear extracts revealed a quantitative defect of this enzyme in the resistant line. When inhibiting this activity by doxorubicin and etoposide, we observed that the concentrations of etoposide required for a given inhibition of kinetoplast DNA decatenation are much higher that those of doxorubicin. The topoII extracted from both cell lines is, therefore, much more sensitive to doxorubicin than to etoposide, but no difference in drug sensitivity was evident between sensitive and resistant cells, indicating that no qualitative alteration in topoII catalytic activity was likely to occur.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Radiotherapy of spinal metastases in breast cancer. Apropos of a series of 108 patients].

PURPOSE: Retrospective analysis of analgesic, decompressive and remineralization effects of radiation therapy for spinal metastases in breast cancer. PATIENTS AND METHODS: From January 1990 to December 1992, 108 patients with breast cancer were treated by irradiation at the Bergonié Institute for a first spinal metastasis. Three patients had undergone previous surgery (laminectomy and Doves' frame). The indication of radiation therapy was analgesic (102 patients) or decompressive (six patients). The usual irradiation scheme was 30 Gy/10 fractions/2 weeks. RESULTS: The analgesic effect was considered as 'complete' or 'almost complete' (83%), 'moderate' (13%) or absent (4%). The mean time to the maximum analgesic response was 35 days. The duration of both the analgesic response and remineralization effects could not be retrospectively assessed due to lack of data. Decompressive effects were complete in five cases and absent in one case. A second spinal radiation therapy was necessary 78 times (eight times in junction field within 6 months following the first treatment). Spinal cord compression occurred either out of (three cases) or within (one case) the irradiated field. CONCLUSION: Radiation therapy for spinal metastases in breast cancer remains a palliative analgesic treatment. Indication for decompression is rare. However, assessment of compressive 'risk' leads to discussion of radiological staging (contribution of magnetic resonance imaging) and possible previous treatment (vertebroplasty or osteosynthesis).

Adult↗