Search PubMed⌕ Search

Biomedical subjects

N Mounier

Publications and source records attributed to N Mounier.

At least 37 records · Page 2Linked to original sources
PubMed1998

A multivariate analysis of the survival of patients with aggressive lymphoma: variations in the predictive value of prognostic factors during the course of the disease. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The International Prognostic Index (IPI) was recently developed to predict patient survival on the basis of pretreatment clinical features. However, classical multivariate regression models such as the IPI fail to detect time-dependent changes in the predictive value of covariates. In this study, an extension of the Cox proportional hazards model was used to determine whether the value of prognostic factors might decay over time. METHODS: A total of 1271 patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of overall survival and monthly risk of dying. By a standard method, prognostic factors were identified in a training sample and confirmed in a validation sample. The independently significant covariates were then included in a step-function regression model (3-step) that permitted determination of their value in predicting the short term and long term survival of the entire population. RESULTS: During the entire follow-up period (median, 5.5 years), lactate dehydrogenase level, tumor stage, performance status, and number of extranodal sites remained independently predictive of overall survival. However, these covariates had nonproportional hazard functions. The study of their time-dependent effect with the 3-step model confirmed that they were predictive of overall survival during the short term follow-up period of 3 months to 2 years. However, during the induction period of 0-3 months and the long term follow-up period of 2-10 years, there was only 1 independently predictive factor for each of these periods: performance status and tumor stage, respectively. CONCLUSIONS: The IPI factors are relevant to short term follow-up and permit the selection of routine or experimental therapeutic regimens. In contrast, only performance status is predictive of a patient's ability to tolerate induction chemotherapy, and only tumor stage is predictive of long term survival.

Antineoplastic Agents↗
PubMed1998

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas. Groupe d'Etude des Lymphomes de l'Adulte.

The objectives of this study were to evaluate the outcome after polychemotherapy for patients with primary cutaneous large-cell lymphomas (PCLL) and to validate the recently proposed immunohistologic classification of cutaneous lymphomas. Among 140 patients with positive skin biopsies included in the LNH87 protocol (for treatment of aggressive lymphomas), 49 patients met the criteria of PCLL. Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52), peripheral lymph nodes, n=22; diffuse disease, n=12; median tumor size, 4.5 cm; elevated lactate dehydrogenase, n=9; ECOG: 0/1, n=49. Histology was: follicular center B cell, n=23; B-lymphoblastic, n=1; anaplastic large-cell lymphoma, n=14 (T cell phenotype n=8); CD30- T cell lymphoma, n=11. All patients received polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation for 6 months) n=25; mBACOD (eight cycles) n=16; over 70 years, C(T)VP (six cycles) n=8. Radiation therapy was not included in the protocol. With a median follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event-free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%. Significant adverse prognostic factors were: histology (CD30- T cell lymphoma) and diffuse cutaneous disease (>10% of skin). The presence of nodal involvement was only significant for EFS. When compared to 140 non-cutaneous lymphoma patients included in the same trial and fully matched for the main clinical characteristics, OS was similar. In conclusion, PCLL behaves like other localized B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG, age) except for CD30+ PCLL which have a very good prognosis.

Adolescent↗
PubMed1998

Conditioning regimens before transplantation in patients with aggressive non-Hodgkin's lymphoma.

Substantial progress has been made in understanding the role of autotransplantation in aggressive non-Hodgkin's lymphoma. At present, the clinical indications for high-dose therapy include patients with relapsed or poor prognosis disease. Hematopoietic reconstitution with peripheral stem cells has rendered transplantation less toxic but the optimal preparative regimen remains to be found. It should combine a high antitumor activity with acceptable toxicity to normal tissues. The literature, on combinations of drugs with or without total body irradiation, was reviewed with regard to this objective. BEAM, CBV and ICE, the most common chemotherapy regimens can be considered safe as they cause low transplant-related morbidity. The combination of fractionated TBI and etoposide or cyclophosphamide was not found to be superior. However, it must be kept in mind that comparisons were made on registry data or retrospectively. In every case, relapse of the residual primary disease argue for the need for more effective strategies such as tandem transplantation or sequential high-dose chemotherapy with stem-cell support. To obtain an objective evaluation, these new preparative regimens need to be tested in controlled trials with treatment groups stratified for known prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Localized or metastatic cancer of the prostate: review of new treatment modalities].

Amongst men, prostatic adenocarcinoma is the most common cancer and the second most frequent cause of deaths. Widespread PSA measurement have led to earlier diagnosis. Recent clinical trials have tried to show an improvement in the prognosis. Early stages are mainly treated surgically even if local control results are similar with radiotherapy. Radiotherapy is the main stay of treatment for more locally advanced disease, either conventionally or conformational. Adjuvant hormonotherapy has been shown to improve survived as opposed to neoadjuvant hormonotherapy which only has local effects. The treatment of metastatic disease is palliative with the use of antiandrogens. In case of relapse, a second line of hormonotherapy or a chemotherapy is given. However the problem is the lack of effective drugs. Response rates to the main drug treatment are around 10 to 20%. New therapeutic approaches are now based on antimicrotubules agents but it is difficult to evaluate their efficacity. Further clinical trials will provide more information about improvement in survival rates and in quality of life.

Humans↗
PubMed1997

Structural comparisons of muscle and nonmuscle actins give insights into the evolution of their functional differences.

Actin is a highly conserved protein although many isoforms exist. In vertebrates and insects the different actin isoforms can be grouped by their amino acid sequence and tissue-specific gene expression into muscle and nonmuscle actins, suggesting that the different actins may have a functional significance. We ask here whether atomic models for G- and F-actins may help to explain this functional diversity. Using a molecular graphics program we have mapped the few amino acids that differ between isoactins. A small number of residues specific for muscle actins are buried in internal positions and some present a remarkable organization. Within the molecule, the replacements observed between muscle and nonmuscle actins are often accompanied by compensatory changes. The others are dispersed on the protein surface, except for a cluster located at the N-terminus which protrudes outward. Only a few of these residues specific for muscle actins are present in known ligand binding sites except the N-terminus, which has a sequence specific for each isoactin and is directly implicated in the binding to myosin. When we simulated the replacements of side chains of residues specific for muscle actins to those specific for nonmuscle actins, the N-terminus appears to be less compact and more flexible in nonmuscle actins. This would represent the first conformational grounds for proposing that muscle and nonmuscle actins may be functionally distinguishable. The rest of the molecule is very similar or identical in all the actins, except for a possible higher internal flexibility in muscle actins. We propose that muscle actin genes have evolved from genes of nonmuscle actins by substitutions leading to some conformational changes in the protruding N-terminus and the internal dynamics of the main body of the protein.

Actins↗
PubMed1997

Transfected muscle and non-muscle actins are differentially sorted by cultured smooth muscle and non-muscle cells.

We have analyzed by immunolabeling the fate of exogenous epitope-tagged actin isoforms introduced into cultured smooth muscle and non-muscle (i.e. endothelial and epithelial) cells by transfecting the corresponding cDNAs in transient expression assays. Exogenous muscle actins did not produce obvious shape changes in transfected cells. In smooth muscle cells, transfected striated and smooth muscle actins were preferentially recruited into stress fibers. In non-muscle cells, exogenous striated muscle actins were rarely incorporated into stress fibers but remained scattered within the cytoplasm and frequently appeared organized in long crystal-like inclusions. Transfected smooth muscle actins were incorporated into stress fibers of epithelial cells but not of endothelial cells. Exogenous non-muscle actins induced alterations of cell architecture and shape. All cell types transfected by non-muscle actin cDNAs showed an irregular shape and a poorly developed network of stress fibers. beta- and gamma-cytoplasmic actins transfected into muscle and non-muscle cells were dispersed throughout the cytoplasm, often accumulated at the cell periphery and rarely incorporated into stress fibers. These results show that isoactins are differently sorted: not only muscle and non-muscle actins are differentially distributed within the cell but also, according to the cell type, striated and smooth muscle actins can be discriminated for. Our observations support the assumption of isoactin functional diversity.

Actins↗
PubMed1993

Expression of a Bombyx cytoplasmic actin gene in cultured Drosophila cells: influence of 20-hydroxyecdysone and interference with expression of endogenous cytoplasmic actin genes.

The expression of the Bombyx cytoplasmic actin A3 gene and its response to 20-hydroxyecdysone are studied after transfection in hormone responsive Drosophila cells and are compared to the expression of homologous resident genes. The host cells accumulate correct transcripts of the Bombyx gene in a gene dosage dependent way. The relative amount of endogenous cytoplasmic actin mRNAs is decreased in transfected cells, whether the transgene is integrated into the genome or not. When 20-hydroxyecdysone is added to the culture medium, the accumulation of the foreign mRNA is decreased whereas those of endogenous cytoplasmic actin transcripts are increased. These results are discussed in terms of competition for transcription and regulatory factors.

Actins↗
PubMed1993

A cytoplasmic actin gene from the silkworm Bombyx mori is expressed in tissues of endodermal origin and previtellogenic germ cells of transgenic Drosophila.

A cytoplasmic actin gene from Bombyx mori introduced into Drosophila melanogaster by P-element mediated transformation, is efficiently transcribed in larvae, pupae and adults of the host. The exogenous mRNA has the same size as the one observed in the Bombyx cells and the intron located within the coding region is properly excised, indicating a correct recognition of the exogenous sequences by the Drosophila transcriptional and splicing machineries. The expression of the Bombyx gene in Drosophila tissues was determined by transforming flies with a hybrid gene in which a large part of the Bombyx actin coding sequences was replaced by those of the bacterial lac Z gene. This chimaeric gene is specifically and highly expressed, from the embryo to the adult of the transgenic lines, in tissues of endodermal origin, the midgut and its derivatives, i.e. gastric caeca, the outer layer of the proventriculus, and in the Malpighian tubules. This gene is also expressed, at a lower level, in germ cells but restricted to the sixteen cell cysts during previtellogenesis. The expression of the Bombyx gene during development of transgenic flies was compared to that of the two Drosophila endogenous cytoplasmic actin genes and the results are discussed.

Actins↗
PubMed1992

Insect muscle actins differ distinctly from invertebrate and vertebrate cytoplasmic actins.

Invertebrate actins resemble vertebrate cytoplasmic actins, and the distinction between muscle and cytoplasmic actins in invertebrates is not well established as for vertebrate actins. However, Bombyx and Drosophila have actin genes specifically expressed in muscles. To investigate if the distinction between muscle and cytoplasmic actins evidenced by gene expression analysis is related to the sequence of corresponding genes, we compare the sequences of actin genes of these two insect species and of other Metazoa. We find that insect muscle actins form a family of related proteins characterized by about 10 muscle-specific amino acids. Insect muscle actins have clearly diverged from cytoplasmic actins and form a monophyletic group emerging from a cluster of closely related proteins including insect and vertebrate cytoplasmic actins and actins of mollusc, cestode, and nematode. We propose that muscle-specific actin genes have appeared independently at least twice during the evolution of animals: insect muscle actin genes have emerged from an ancestral cytoplasmic actin gene within the arthropod phylum, whereas vertebrate muscle actin genes evolved within the chordate lineage as previously described.

Actins↗
PubMed1986

Isolation of actin genes in Bombyx mori: the coding sequence of a cytoplasmic actin gene expressed in the silk gland is interrupted by a single intron in an unusual position.

To study the regulation of the gene(s) coding for the actin present in the microfilaments involved in the secretion of silk, we have probed a Bombyx mori genomic library with a Drosophila actin cDNA clone and selected 16 recombinant phages. They correspond to 3 different genomic fragments each containing a distinct actin coding sequence. Southern blots of genomic DNA probed with the cloned genes show that in Bombyx mori, there are at least 5 different actin genomic sequences. Two cloned genes A1 and A2 hybridize to a 1.7 kb long mRNA abundant in the carcass of the larva and thus probably code for muscle type actin. The third cloned gene, A3, hybridizes to two mRNAs of about 1.8 kb present in the silk gland and thus probably encodes a cytoplasmic actin. The coding sequence of this gene has been sequenced: it is almost identical to the Drosophila cytoplasmic actin genes but it has a single intron of 92 nucleotides within the codon 116, a position not observed in any other organism.

Actins↗
PubMed1980

A cytogenetical analysis of sterile mutants in Caenorhabditis elegans.

The regulation of gametogenesis in the hermaphrodite and proterandrous nematode Caenorhabditis elegans is introduced here through the analysis of nonconditional sterile mutants. To investigate the mechanisms which allow the two gametogenetic phases to succeed each other in the same ovotestis, three mutants were studied cytogenetically. Two of the mutants exhibit only the spermatocyte phase and the third shows a greatly reduced and disturbed oogenesis. These three mutations all produce large decreases in ovotestis size and gonocyte number. Each of the three is monofactorial, recessive, autosomal and independent. Homozygous mutant males are also sterile. The gametogenesis phases which could be disturbed by mutation were determined by cytological analysis of the ovotestis of 12 other sterile strains. These phases occur during mitotic divisions of the genital primordium, zygotene chromosome pairing, male meiosis and spermiogenesis, oogenesis induction and oocyte maturation. These steps of gametogenesis need a wild-type genic activity to occur normally. It appears that spermatogenesis and oogenesis are two genetically independent processes, and that oogenesis is rather autonomous and its induction would depend on a hormonal factor.

Animals↗
PubMedDate not supplied

[Radiotherapy-induced solid tumors: review of the literature and risk assessment].

Although the first radiation-induced solid tumor was reported as early as 1902, the risk of second tumor has been underestimated by radiation oncologists who treated large numbers of patients with either benign or malignant diseases. Since then, numerous epidemiological studies yielded better knowledge of the risks of radiation-induced malignancies. For instance, radiation-induced tumors are the first cause of death 10 years after treatment for Hodgkin's disease. We present here a literature review of the risks of radiation-tumors in various organs, related to the irradiation dose, age, and associated diseases. The most sensitive organs are the thyroid, central nervous system, breast, bone, and lung, especially in smokers. Higher risks are observed with increasing doses, the shape of the dose-response curve depending on the tumor type, when the irradiation is performed in children or young adults and in patients with retinoblastomas. The risk of radiation-induced tumors should lead the radiation oncology committee to reconsider the dose and technique of irradiation and to reduce the use of ionizing radiation in benign diseases.

Age Factors↗