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P Richaud

Publications and source records attributed to P Richaud.

At least 19 recordsLinked to original sources

Genome-wide transcriptome profiling of the early cadmium response of Arabidopsis roots and shoots.

Transcriptional regulation in response to cadmium treatment was investigated in both roots and leaves of Arabidopsis, using the whole genome CATMA microarray containing at least 24,576 independent probe sets. Arabidopsis plants were hydroponically treated with low (5 microM) or high (50 microM) cadmium concentrations during 2, 6, and 30 hours. At each time point, Cd level was determined using ICP-AES showing that both plant tissues are able to accumulate the heavy metal. RT-PCR of eight randomly selected genes confirmed the reliability of our microarray results. Analyses of response profiles demonstrate the existence of a regulatory network that differentially modulates gene expression in a tissue- and kinetic-specific manner in response to cadmium. One of the main response observed in roots was the induction of genes involved in sulfur assimilation-reduction and glutathione (GSH) metabolism. In addition, HPLC analysis of GSH and phytochelatin (PC) content shows a transient decrease of GSH after 2 and 6 h of metal treatment in roots correlated with an increase of PC contents. Altogether, our results suggest that to cope with cadmium, plants activate the sulfur assimilation pathway by increasing transcription of related genes to provide an enhanced supply of GSH for PC biosynthesis. Interestingly, in leaves an early induction of several genes encoding enzymes involved in the biosynthesis of phenylpropanoids was observed. Finally, our results provide new insights to understand the molecular mechanisms involved in transcriptional regulation in response to cadmium exposure in plants.

Arabidopsis↗

Phosphate deficiency promotes modification of iron distribution in Arabidopsis plants.

Phosphate (Pi) is an essential element for plant development and metabolism. Due to its low availability and mobility in soils, it is often a limiting nutrient for their growth. This phenomenon is reinforced by the formation of insoluble complexes in the environment with many cations, affecting the solubility of both phosphate and associated ions. This interaction is investigated here for iron, a strong phosphate chelator. Depleting the medium in phosphate clearly resulted in an increase of iron content in Arabidopsis. These modifications triggered molecular responses linked with iron status (transport, homeostasis and accumulation). Interestingly, physiological modifications affecting iron storage were also observed. The accumulation of phosphate/iron complexes in the vacuoles of plants grown in Pi-rich medium disappeared in Pi-depleted medium in favor of accumulation of iron inside the chloroplasts, likely associated with ferritin.

Arabidopsis↗

[Standards, options, and recommendation for external radiotherapy of prostatic cancer: evaluation of the effect of dosage].

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.

Humans↗

[Hormono-radiotherapy of non-metastatic prostate cancers].

Patients presenting with non-metastatic cancer of prostate have a high probability of relapse if they are treated by either surgery alone or irradiation alone, when poor prognosis factors are present. Clinical stage (> or = T3a), Gleason score, and PSA level (> 20 ng/mL) are the more significant factors. It is likely that many patients can draw benefit of combined androgenic suppression and radiotherapy. However, despite results of European and American trials published the last decade, a number of questions remain without a clear response, especially on the modalities of treatment according to the characteristics of the disease.

Adenocarcinoma↗

[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↗

Antibodies to the CFTR modulate the turgor pressure of guard cell protoplasts via slow anion channels.

The plasma membrane guard cell slow anion channel is a key element at the basis of water loss control in plants allowing prolonged osmolite efflux necessary for stomatal closure. This channel has been extensively studied by electrophysiological approaches but its molecular identification is still lacking. Recently, we described that this channel was sharing some similarities with the mammalian ATP-binding cassette protein, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel [Leonhardt, N. et al. (1999) Plant Cell 11, 1141-1151]. Here, using the patch-clamp technique and a bioassay, consisting in the observation of the change in guard cell protoplasts volume, we demonstrated that a functional antibody raised against the mammalian CFTR prevented ABA-induced guard cell protoplasts shrinking and partially inhibited the slow anion current. Moreover, this antibody immunoprecipitated a polypeptide from guard cell protein extracts and immunolabeled stomata in Vicia faba leaf sections. These results indicate that the guard cell slow anion channel is, or is closely controlled by a polypeptide, exhibiting one epitope shared with the mammalian CFTR.

Animals↗

[Standards, Options, and Recommendations for brachytherapy in patients with prostate cancer: efficacy and toxicity].

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

Antineoplastic Agents, Hormonal↗

[Competitive morbidity ant its impact on life expectancy: evaluation and inclusion in the therapeutic decision regarding localized prostatic cancer].

OBJECTIVES: The treatment decision taken by a multidisciplinary meeting for patients with localized prostate cancer must take into account the clinical stage of the cancer and its histological characteristics, but also the patient's age, general state and any concomitant diseases, as treatment is only beneficial when it induces a reduction of morbidity and specific mortality. The specific survival with or without recurrence after treatment for localized prostate cancer is long, at least more than 10 years. Curative treatment is generally not proposed to men with localized prostate cancer when his probability of survival related to a competitive morbidity (intercurrent medical disease) is estimated to be less than 10 years. The objective of this study was to measure the increase or reduction of the survival probability of a patient with localized prostate cancer according to his competitive morbidity, based on the mean life expectancy of the general population. METHODS: Review of the literature. RESULTS: Studies describing the natural history of prostate cancer show that the impact of treatment on morbidity of the cancer (local and/or metastatic) requires a life expectancy of about 8 to 10 years. The impact of a treatment on specific survival requires a life expectancy of about 13 to 15 years. The exact prevalence of diseases coexisting with prostate cancer is unknown. In the USA, The Index of Coexisting Disease (ICD), which takes into account 14 diseases, appears to be the most reliable tool to measure the competitive morbidity in patients with localized prostate cancer. Each disease is classified into 4 levels of severity (score 0 to 3). A table indicates estimated life expectancies by age-group and by ICD score. All men with a high score (2 to 3) die within 10 years after diagnosis, men with a score of 0 have a better estimated life expectancy according to age than that of the general population. CONCLUSION: The upper age limit, theoretically set at 70 years, in order to propose curative treatment for localized prostate cancer needs to be reviewed (the mean life expectancy for a 70-year-old man is 12.9 years in France). According to the ICD, the life expectancy at 70 years is 14.8 years in the case of a score of 0 and 8.4 years in the case of a score of 2. In the case of a score of 2, the impact of curative treatment on localized prostate cancer would be real on morbidity, but not on specific mortality.

Humans↗

ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative group of radiotherapy of the european organization for research and treatment of cancer (EORTC).

BACKGROUND: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance. AIM: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck. METHODS: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n=10), and AF with both carbogen and nicotinamide (n=17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions. RESULTS: No significant difference in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaired when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, in an unselected group of patients. More than 20% of patients experienced grade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentages of objective response at 2 months were 81, 70 and 87%, respectively. CONCLUSION: Future ARCON trials should target selected head and neck tumor localizations and stages, and a lower nicotinamide dose is needed to reduce severe upper gastro-intestinal toxicity.

Adult↗

Follicular lymphomas--a review of treatment modalities.

Follicular lymphoma is the most common low-grade non Hodgkin's lymphoma and represent an homogeneous entity as defined by pathological, molecular and clinical data. This indolent disease is characterised by a slow growth pattern with possible spontaneous regression, is often disseminated but remains incurable with available treatments when disseminated. For localised stages, involved field radiotherapy remains the standard choice but other approaches remain to be investigated. In advanced disease, chemotherapy has been demonstrated to produce high response rates but recent trials with new treatment strategies including interferon and monoclonal antibodies may improve the current situation. In this article, we will review treatment of follicular lymphomas, specially emphasising published phase III trials.

Humans↗

Current treatment of Hodgkin's disease.

In spite of the fact that Hodgkin's disease (HD) remains still an enigma its management and treatment yield a cure rate of about 80% of all patients. However, this management has two limits: on one side favourable cases which should not be overtreated because of unacceptable side-effects, and on the other side very unfavourable cases which should be treated differently because of a very high rate of failure and/or relapse. Then it becomes necessary to precise as thoroughly as possible these two limits in order to choose the adequate treatment for the patient. Prognostic factors based on patient and disease characteristics allow a relatively exact classification of favourable and unfavourable cases. This distinction in two prognostic groups has therapeutic implications in terms of chemotherapy (regimen, duration) and radiotherapy (extension, doses). Other specific situations have to be considered, e.g. pediatric cases, pregnancy, old age and HIV-infected patients who need an adapted management according to very different situations.

Antineoplastic Combined Chemotherapy Protocols↗

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↗

Competitive polymerase chain reaction to quantify tumor cells in peripheral blood of patients with T(14;18)-bearing follicular non-Hodgkin's lymphoma: an exploratory study in 8 patients.

Detection of residual disease in follicular lymphoma is hampered by the observation of t(14;18)-bearing cells in the blood of healthy adult humans. To overcome this problem, we decided to validate a quantification method of t(14;18)-bearing cells and test it in t(14;18)-bearing follicular lymphomas (FL). We designed a competitive PCR method to quantify t(14;18)-bearing cells in peripheral blood. First, we controlled overall reliability (specificity, sensitivity, reproducibility, precision and accuracy); then we used our method to study 16 peripheral blood samples collected in 8 patients with t(14;18)-bearing FL. There were considerable variations in the number of circulating tumor cell (CTC) in FL patients, ranging from zero to 17,813 cells/ml. In 2 patients who were sampled before and after treatment and who attained complete remission (CR), a significant decrease in the number of CTC was observed. In 3 patients with detectable CTC during CR, relapse occurred 4 to 11 months later. Of 3 patients with no detectable CTC, 2 remain in CR 35 and 95 months later, but one relapsed 11 months after sample collection. These preliminary results suggest that quantification of CTC may be worthwhile in follicular lymphoma. It may improve our ability to predict relapse occurrence, but also may help in understanding this peculiar disease. Int. J. Cancer (Pred. Oncol.) 84:558-561, 1999.

Chromosomes, Human, Pair 14↗

ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC.

BACKGROUND: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours. AIM: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours. METHODS: The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11 ) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy. RESULTS: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively. CONCLUSION: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps.

Administration, Inhalation↗

Nitrite and nitrous oxide reductase regulation by nitrogen oxides in Rhodobacter sphaeroides f. sp. denitrificans IL106.

We have cloned the nap locus encoding the periplasmic nitrate reductase in Rhodobacter sphaeroides f. sp. denitrificans IL106. A mutant with this enzyme deleted is unable to grow under denitrifying conditions. Biochemical analysis of this mutant shows that in contrast to the wild-type strain, the level of synthesis of the nitrite and N(2)O reductases is not increased by the addition of nitrate. Growth under denitrifying conditions and induction of N oxide reductase synthesis are both restored by the presence of a plasmid containing the genes encoding the nitrate reductase. This demonstrates that R. sphaeroides f. sp. denitrificans IL106 does not possess an efficient membrane-bound nitrate reductase and that nitrate is not the direct inducer for the nitrite and N(2)O reductases in this species. In contrast, we show that nitrite induces the synthesis of the nitrate reductase.

Cloning, Molecular↗

[Adult's anaplastic CD30+ large cell lymphomas].

Anaplastic large-cell lymphomas were recognized by Stein in 1985. Less than fifteen years were necessary to confirm this entity, as well as her phenotype and to characterize the t(2;5) (p23;q35) chromosomal abnormality. This rare subgroup of non-Hodgkin's lymphomas (15% of peripheral T cell lymphomas and 8% of all diffuse aggressive lymphomas) is individualized in the Real classification. This disease, which had a bimodal age distribution, is clinically characterized by a diffuse nodal involvement and the frequency of extranodal involvement, especially skin and lungs. Primitive cutaneous anaplastic large cell lymphomas belong to the cutaneous CD30+ lymphoproliferative diseases spectrum. Among peripheral T cell and diffuse aggressive lymphomas, they have the better prognosis. We present in this paper a review of the recent advances in the knowledge, treatment and prognosis of this peculiar entity.

Adult↗

Plasmid content and localization of the genes encoding the denitrification enzymes in two strains of Rhodobacter sphaeroides.

Plasmid content and localization of the genes encoding the reductases of the denitrification pathway were determined in the photosynthetic bacterium Rhodobacter sphaeroides forma sp. denitrificans by transverse alternating-field electrophoresis (TAFE) and hybridization with digoxigenin-labeled homologous probes. Two large plasmids of 102 and 115 kb were found. The genes encoding the various reductases are not clustered on a single genetic unit. The nap locus (localized with a napA probe), the nirK gene and the norCB genes encoding the nitrate, nitrite and nitric oxide reductases, respectively, were found on different AseI and SnaBI digested chromosomal DNA fragments, whereas the nos locus (localized with a nosZ probe), encoding the nitrous oxide reductase, was identified on the 115-kb plasmid. Furthermore, the genes encoding two proteins of unknown function, one periplasmic and the other cytoplasmic, but whose synthesis is highly induced by nitrate, were found on a different chromosomal fragment. For comparison, the same experiments were carried out on the well-characterized strain Rhodobacter sphaeroides 2.4.1.

Blotting, Southern↗