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J Couturier

Publications and source records attributed to J Couturier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice.

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.

Animals↗
PubMed1999

hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors.

The chromatin-remodeling hSNF5/INI1 gene has recently been shown to act as a tumor suppressor gene in rhabdoid tumors (RTs). In an attempt to further characterize the main chromosomal mechanisms involved in hSNF5/INI1 inactivation in RTs, we report here the molecular cytogenetic data obtained in 12 cell lines harboring hSNF5/INI1 mutations and/or deletions in relation to the molecular genetic analysis using polymorphic markers extended to both extremities of chromosome 22q. On the whole, mitotic recombination occurring in the proximal part of chromosome 22q, as demonstrated in five cases, and nondisjunction/duplication, highly suspected in two cases (processes leading respectively to partial or complete isodisomy), appear to be major mechanisms associated with hSNF5/INI1 inactivation. Such isodisomy accompanies each of the RTs exhibiting two cytogenetically normal chromosomes 22. This results in homozygosity for the mutation at the hSNF5/INI1 locus. An alternate mechanism accounting for hSNF5/INI1 inactivation observed in these tumors is homozygous deletion in the rhabdoid consensus region. This was observed in each of the four tumors carrying a chromosome 22q abnormality and, in particular, in the three tumors with chromosomal translocations. Only one case of our series illustrates the mutation/deletion classical model proposed for the double-hit inactivation of a tumor suppressor gene.

Chromosomal Proteins, Non-Histone↗
PubMed1999

Two new cases of papillary renal cell carcinoma with t(X;1)(p11;q21) in females.

Two cases of papillary renal cell carcinoma (RCC) with a karyotype 46,X,t(X;1)(p11.2;q21) in two female patients aged 9 and 29 years are reported. These observations, and the review of the 17 reported cases with a translocation at band Xp11 confirm that this abnormality delineates a clinicopathological entity within the classical papillary RCC, characterized by the early age of occurrence and, probably, distinct histological features. Including these two new female cases, the sex ratio in cases with t(X;1) appears similar to that observed in the other papillary RCC.

Carcinoma, Papillary↗
PubMed1999

[Herceptin, a monoclonal humanized antibody anti-HER2: a major therapeutic progress in breast cancers overexpressing this oncogene?].

HER2 is overexpressed in about 25% to 30% of breast cancers and associated with poor prognosis, resistance to hormonotherapy and lack of sensitivity to CMF-based adjuvant chemotherapy. Herceptin (trastuzumab), a humanized monoclonal antibody, administered as a single agent, produces objective responses in phase II trials in patients with metastatic breast cancers overexpressing HER2. It has shown a substantial benefit in a phase III trial which compares a standard first line chemotherapy (doxorubicin and cyclophosphamide or taxol alone) to the same chemotherapy with Herceptin in metastatic breast cancer. The Herceptin arm had significantly higher response rate (+ 53%), an improvement in the median duration of response (+ 57%) as well as in time to progression (+ 65%) compared to chemotherapy alone.

Antibiotics, Antineoplastic↗
PubMed1999

A possible tetracycline-risperidone-sertraline interaction in an adolescent.

A 15-year-old adolescent male, with Asperger's disorder, Tourette's disorder and obsessive-compulsive disorder, on a tetracycline-risperidone-sertraline treatment regimen, had an acute exacerbation of motor and vocal tics. The increase in tics may have resulted from either a tetracycline-risperidone interaction leading to decreased levels of risperidone, or a tetracycline-sertraline interaction leading to increased levels of sertraline or the natural course of the Tourette's disorder. The sertraline dose was increased with no concomitant increase in tics, and subsequent discontinuation of tetracycline resulted in an improvement in tics, which indicates an interaction between tetracycline and risperidone. The addition of antibiotics to psychotropic medications requires close monitoring due to the potential interactions.

Adolescent↗
PubMed1999

[Renal medullary carcinoma, a new clinico-pathological entity. Immunohistochemical, ultrastructural, flow cytometric and cytogenetic study of a case].

The renal medullary carcinoma is a rare tumor. We report a case in a black patient with sickle cell trait. The tumor was located in the lower pole of the left kidney. It had a tubular and microcystic architecture. It was composed of large eosinophilic cells with vesicular nuclei containing prominent nucleoli, in a desmoplastic and inflammatory stroma. By immunohistochemistry, the tumoral cells were positive for cytokeratin and Ulex europaeus lectin. Electron microscopy revealed small intracytoplasmic lumina with microvilli. The flow cytometric study showed DNA-multiploidy. The cytogenetic study revealed tetraploidy without structural abnormality. The renal medullary carcinoma is often reported in young black patients with sickle cell trait. Its microscopic, immunohistochemical and ultrastructural features favor its identification as a particular variety of Bellini duct carcinoma. Its link with sickle cell trait has to be defined.

Adult↗
PubMed1998

Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome.

Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month-old female with a terminal deletion of the long arm of chromosome 2 [46,XX,del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the 2q37 deletion syndrome, the present observation raises the question of whether a tumor susceptibility gene maps to chromosome 2q37 and suggests giving consideration to the possible occurrence of Wilms' tumor in the course of disease.

Abnormalities, Multiple↗
PubMed1998

Mechanisms of acid-base regulation in migrant sea lampreys (Petromyzon marinus) following exhaustive exercise

The life cycle of the sea lamprey (Petromyzon marinus) is characterized by a terminal upstream spawning migration that may be associated with brief bursts of high-intensity swimming. Such activity usually leads to pronounced blood acid-base disturbances in fishes, but lampreys rapidly correct these perturbations within 1 h. In the present study, patterns of post-exercise H+ excretion (JHnet) and ion movements were followed in sea lampreys to test the hypothesis that dynamic manipulation of Na+ versus Cl- movements across the animal's body surface, presumably at the gills, accounted for the rapid restoration of blood pH following exercise. The first hour of post-exercise recovery in sea lampreys was associated with marked stimulation of JHnet (equivalent to base uptake), which approached -500 micromol kg-1 h-1. After 1 h, JHnet patterns had returned to resting rates. Analyses of net Na+ and Cl- movements (JNanet, JClnet) suggested that elevated net Cl- losses, which greatly exceeded net Na+ losses, accounted for most of the JHnet. Subsequent experiments, using radiotracers (22Na+, 36Cl-), indicated that differential increases in Cl- versus Na+ permeability accounted for the greater post-exercise Cl- losses and the corresponding stimulation of net proton excretion. Finally, metabolic acid budget analyses confirmed our hypothesis that rapid excretion of metabolic protons was the primary means used by sea lampreys to correct post-exercise extracellular acidosis.

Journal Article↗
PubMed1997

A new member of the ETS family fused to EWS in Ewing tumors.

As a result of chromosome translocations, the EWS gene is fused to a variety of transcription factors in human solid neoplasia. In Ewing tumors EWS can be fused to four different members of the ETS family, namely FLI-1, ERG, ETV1 and E1AF. We have identified a new member of the ETS family, called FEV, which is fused to EWS in a subset of Ewing tumors. FEV encodes a 238 amino acid protein which contains an ETS DNA binding domain closely related to that of FLI-1 and ERG. However, the N-terminal portion of FEV is only 42 amino acids long which suggests that FEV is lacking important transcription regulatory domains contained in FLI-1 and ERG N-terminal parts. The C-terminal end of FEV is rich in alanine residues which may indicate that FEV is a transcription repressor. The FEV gene is encoded by three exons and is located on chromosome 2. FEV expression was only detected in adult prostate and small intestine but not in other adult nor in fetal tissues, thus indicating that FEV has a restricted expression pattern. Following a scheme similar to previously described translocations in Ewing tumors, a t(2;22) chromosome translocation fuses the N-terminal domain of EWS to the ETS DNA binding domain of FEV.

Adult↗
PubMed1997

Pleomorphic medium-sized T-cell lymphoma following Hodgkin's disease (nodular sclerosis type).

We describe a 32-year-old woman who presented with Hodgkin's disease, nodular sclerosis type II, subtype I, which necessitated several treatments over 11 years. The patient then developed pleomorphic, medium-sized T-cell lymphoma, which had a fatal outcome within 13 months. The role of radiotherapy, splenectomy, and chemotherapy in second tumor induction is compared with other sequential T-cell lymphomas. The significance of rare Epstein-Barr virus-infected cells during the T-cell lymphoma extension is discussed.

Adult↗
PubMed1996

[Severe 5-fluorouracil toxicity in a woman treated for breast cancer with concurrent osteogenesis imperfecta and dehydrogenase deficiency].

Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme involved in the catabolism of 5 fluorouracil (5 FU). The clinical importance of DPD has recently been demonstrated wit the identification of rare cases presenting a severe toxicity to 5 FU related to proven DPD deficiency. We report a new case in a patient with concurrent congenital osteogenesis imperfecta. We were surprised to find another similar association reported by Lyss. It is tempting to speculate that DPD activity may be abnormally regulated in osteogenesis imperfecta patients.

Anemia, Aplastic↗
PubMed1995

Integration of viral sequences into the c-myc gene in two mammary adenocarcinomas induced by polyomavirus in athymic nude mice.

We report the analysis of polyomavirus (Py) DNA integration into chromosomal DNA of two Py-induced mammary adenocarcinomas of athymic nude mice. Prior observations had established that these tumors had high levels of episomal Py DNA, making analysis of integration sites difficult. Propagation of tumor cells in culture allows the isolation of lines which have lost episomal Py DNA but are still tumorigenic and thus can be used for in situ and Southern analysis of Py sequences. The data reported here support the conclusion that Py DNA integrated into and next to the c-myc gene, adding further importance to this tumor system which, in its modifications of c-myc expression, appears to be similar to some human mammary cancers. In situ hybridization experiments on metaphase chromosomes of tumor cells showed that (i) in both cases, there was a single integration site at the same position on the same chromosome in all cells of a given tumor, and (ii) integration sites were different in the two tumors; in one, it was located on chromosome 15, near the c-myc proto-oncogene, and in the other, it was situated in the distal part of chromosome 1. We have demonstrated a probable rearrangement between chromosome 1 and chromosome 15, in the region of Py insertion, thus suggesting that a specific site on chromosome 15 is involved in tumorigenesis. The discovery that Py DNA was integrated at specific sites in host chromosomes raised the questions of whether such integrations were correlated with the activation of specific oncogenes. The rearrangements of the c-myc proto-oncogene observed on Southern blot analysis for both tumors, along with similar integration patterns of Py sequences, the overexpression of the c-myc gene, and the synthesis of abnormal oversized hybrid transcripts between c-myc and Py genes, favor this hypothesis. Finally, the analysis of episomal Py DNA in various tumors shows viral populations presenting a specific deletion in a part of the Py late region. This deleted region in the episomal virus genome was systematically found integrated in chromosomal DNA, thus arguing for the importance of Py integration in the induction of mammary tumor.

Adenocarcinoma↗
PubMed1995

A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors.

The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors.

Cell Line↗
PubMed1994

Evidence for long-range oncogene activation by hepadnavirus insertion.

Insertional mutagenesis of host genes, a common oncogenic strategy of slow transforming retroviruses, has recently been described for a DNA virus of the hepadnavirus group: the woodchuck hepatitis virus. This virus causes insertional activation of myc genes, mainly the intronless N-myc2 oncogene, in > 50% of woodchuck liver tumours. In most remaining tumours, N-myc2 is overexpressed without any apparent genetic alteration. To elucidate the role of the virus in such cases, we have cloned and analysed single integration sites in four woodchuck tumours carrying wild-type myc alleles. All sites were clustered within < 20 kb in a single locus, in which scarce unique sequences showed no detectable transcriptional activity. By fluorescent in situ hybridization, N-myc2 and the new locus (win) were localized to the same region of the long arm of the woodchuck X chromosome, and a 150-180 kb intervening distance was deduced from pulse-field gel analysis. The detection of viral integrations in win in additional tumours that produced abundant N-myc2 transcripts further substantiates the link between these two loci in woodchuck tumorigenesis. We propose that efficient activation of the N-myc2 promoter by the hepadnavirus enhancer acting over a long distance might operate in liver cell transformation.

Animals↗
PubMed1993

Aneuploidy in human lymphocytes: an extensive study of eight individuals of various ages.

Data on aneuploidy from a prospective study on a large number of lymphocyte metaphases (over 1000 in 72-h and 100 in 48-h cultures) per individual from eight healthy donors of various ages are reported. Chromosome losses were dependent on culture time, being significantly more frequent in 72-h than in 48-h cultures. All donors exhibited various degrees of aneuploidy which increased with age in women. This increase resulted essentially from X chromosome losses, as previously reported. Although the rate of aneuploidy limited to autosomes was similar in newborns and in adults, the distributions of the missing autosomes were different. In the two newborns studied, autosome aneuploidy was random. In the adults, a significant inverse correlation with autosome lengths was observed. The inverse correlation between chromosome lengths and losses may be explained by selective pressure against monosomic cells in the adults.

Adult↗
PubMed1993

[Demonstration and electrophysiological analysis of the blinking reflex in the rat. Value of the animal model].

The authors have developed an animal model for the electrophysiological investigation of the blink reflex. The justification for such investigations and the experimental protocol were presented. The authors studied the blick reflex with electromyographic recordings obtained after the stimulation of the supra orbital nerve (V1) in the awake rat and in the anaesthesized rat. Two components of the reflex, R1 and R2 were observed. The early component, R1 was ipsilateral to the stimulus. It was observed whatever the degree of anaesthesia. The R2 component came later and was only observed in awake or weakly anaesthesized rats. It appeared to be isolated and unprecedented by an R1 component when the contralateral supra orbital nerve was stimulated. The R1 responses were facilitated by prior ipsilateral or contralateral stimulation of V1.

Anastomosis, Surgical↗
PubMed1992

Constitutional balanced translocations in patients with solid tumors.

In a sample of 329 patients with a solid tumor (colon and breast adenocarcinoma, cervical carcinoma, and meningioma), four balanced constitutional translocations were observed. Two were t(13q14q), and two were reciprocal translocations. Comparison with surveys of newborns showed a significant excess of translocations in our sample.

Adenocarcinoma↗