PubMed Health⌕ Search

Biomedical subjects

P Anglard

Publications and source records attributed to P Anglard.

34 records · Page 2Linked to original sources
PubMed1993

Molecular genetic studies of sporadic and familial renal cell carcinoma.

Renal cell carcinoma (RCC) occurs predominantly as a sporadic disease but has familial forms. Cytogenetic and DNA deletion analyses show that both sporadic and familial RCC tumors arise as the result of chromosomal deletions in the 3p13-p26 region. von Hippel-Lindau (VHL) disease is a hereditary, multifocal syndrome that includes, among several affected organs, multiple, bilateral renal cysts and RCC. Although the VHL disease gene maps to chromosome 3p25-p26, data indicate that the VHL and sporadic RCC disease genes are likely to be independent. The authors hypothesize that VHL disease manifestations are controlled by mutations in the VHL disease gene and that the onset of VHL-associated kidney cancer is due to a second mutation of the linked sporadic RCC gene.

Carcinoma, Renal Cell↗
PubMed1992

Stimulation of glycolysis by corticotropin and phorbol ester in cultured neurons.

Incubation of cultured neurons from chick embryo forebrain with corticotropin (ACTH) or the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) stimulates the production of lactate. The stimulation is seen after 2 h of treatment and is maximal after 12 h. Both ACTH (1-24) and TPA increase the concentration of fructose 2,6-bisphosphate (Fru-2,6-P2), a metabolic activator of 6-phosphofructo-1-kinase (PFK-1). This effect is concentration-dependent and is maximal after 4 h of treatment. PFK-1 activity is increased in a dose-dependent manner by ACTH (1-24) or TPA. This increase is not visible during the first 6 h and reaches its maximum after 18 h of treatment. The stimulation of PFK-1 activity is not due the increase of Fru-2,6-P2 by ACTH (1-24) or TPA, since saturating concentrations of Fru-2,6-P2 are present in the PFK-1 assay medium. Thus, it appears that ACTH (1-24) and TPA regulate glycolysis through two modes with different time responses: increase in Fru-2,6-P2 is the main mechanism operating during the first 6 h following the treatments and increase in the amount, or stable increase in activity of PFK-1, takes place during the later phase. It is suggested that the action of corticotropin on glycolysis is part of the mechanism of the neurotrophic activity of this hormone.

Adenosine Triphosphate↗
PubMed1992

Molecular and cellular characterization of human renal cell carcinoma cell lines.

Recent studies have suggested that a tumor suppressor gene located in the region 3p21-26 of chromosome 3 is essential to the genesis of sporadic renal cell carcinoma (RCC) and that other tumor suppressor genes located on other chromosomes may be involved with progression of this malignancy. The cellular heterogeneity of solid tumors complicates their analysis. In order to analyze a homogeneous population of tumor cells and identify genetic changes associated with histology in renal cortical tumors, we have established and characterized 35 RCC lines derived from tumor tissue from 31 patients with renal cell carcinomas. The overall success rate in establishing these cell lines from fresh or frozen specimens was 75% (18 of 24) and 35% (17 of 48), respectively. These lines differed in their morphology, growth rates, and tumorigenicity in athymic nude mice. Molecular characterization utilizing DNA fingerprinting and restriction fragment length polymorphism deletion analysis was performed to detect somatic mutations and loss of heterozygosity on the short arm of chromosome 3. Analysis revealed loss of heterozygosity on chromosome 3p in 25 cell lines derived from 28 informative nonpapillary forms of RCC (89%). Deletion-mapping analysis showed the retention of the distal locus, D3S18, in one of the RCC cell lines, which further localized the position of the putative tumor suppressor gene to the region proximal to D3S18. Although deletions on chromosome 3 have been recently suggested to be specific to the clear cell-type phenotype, our results revealed no correlation between loss of heterozygosity and clear or granular cell types.

Animals↗
PubMed1991

Somatic allelic deletion of nm23 in human cancer.

Tumor progression to the metastatic phenotype is accompanied in certain cell types by reduced expression of the nm23 gene. We have localized human nm23-H1 to chromosome 17 by somatic cell hybrid analysis. Regional localization in the CEPH database and in situ hybridization is reported. Somatic allelic deletion of nm23-H1 was observed in human breast, renal, colorectal, and lung carcinoma DNA samples, as compared to DNA from matched normal tissues. A homozygous deletion of nm23-H1 was observed in a lymph node metastasis of a colorectal carcinoma, indicating that nm23-H1 can be recessively inactivated. The data identify nm23-H1 as a novel, independent locus for allelic deletion in human cancer, a characteristic shared with previously described suppressor genes.

Alleles↗
PubMed1991

Molecular analysis of genetic changes in the origin and development of renal cell carcinoma.

Renal cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 which suggests the presence of a tumor suppressor gene at this location. In order to more precisely define the location of the renal cell carcinoma gene and to differentiate molecular changes occurring in early stages of renal neoplasia versus those occurring later in malignant progression, DNA from normal and tumor tissue from 60 patients with various stages of renal cell carcinoma was analyzed for loss of alleles at different chromosomal loci. In tumor tissue from 51 of 58 evaluable patients (88%) there was loss of heterozygosity at one or more of 10 loci tested on chromosome 3 independently of tumor stage. Analysis of the genotypes identified the distal portion of 3p bounded by D3S2 and D3S22 (3p21-26) as the region of the disease gene. In tumor tissue from patients with advanced renal cell carcinoma, we found loss of heterozygosity on chromosome 11p in 5 of 21 (24%), on chromosome 13 in 3 of 9 (33%), and on chromosome 17 in 2 of 19 (11%). We found no loss of heterozygosity at the loci on chromosomes 11, 13, or 17 in tumor tissue from patients with localized renal cell carcinoma (N = 5). These data suggest the existence of a tumor suppressor gene on chromosome 3p which may be essential to the genesis of sporadic renal cell carcinoma and that other tumor suppressor genes are associated with progression of this malignancy.

Adult↗
PubMed1991

The effect of suramin, tumor necrosis factor and interferon gamma on human prostate carcinoma.

Suramin, an antiparasitic agent which has been shown to block the stimulatory effect of growth factors on certain cancers, is currently being evaluated in clinical trials and as an antineoplastic agent in patients with advanced prostate carcinoma. Preliminary studies suggested that suramin inhibits the growth in vitro of human prostate carcinoma. The present study was performed in order to evaluate the effect of suramin, recombinant human tumor necrosis factor (TNF), interferon gamma and the combination of suramin plus TNF or interferon gamma on proliferation of PC-3, a human, hormone unresponsive prostate carcinoma cell line. In medium containing 2% fetal calf serum (FCS) suramin, at doses of 10 microM, 30 microM and 100 microM (levels readily achievable in humans) inhibited proliferation of PC-3. TNF, at a concentration of 500 units/ml., induced an approximately 50% inhibition of growth of PC-3. The combination of suramin plus TNF induced a greater inhibition of growth than did either agent alone, even at the low dose of 10 microM suramin. Interferon gamma, 500 units/ml., inhibited PC-3 growth. However, the combination of interferon gamma plus suramin (30 microM) induced less inhibition of proliferation than did interferon gamma alone. These results may serve as a rationale for clinical trials employing the combination of TNF plus suramin in patients with advanced prostate carcinoma.

Antineoplastic Agents↗
PubMed1990

Epidermal growth factor receptor gene analysis in renal cell carcinoma.

The epidermal growth factor receptor binds the mitogens epidermal growth factor and transforming growth factor-alpha. Increased expression of the epidermal growth factor receptor has been noted in many types of tumors and is associated with gene amplification in several including epidermoid carcinoma, lung carcinoma, breast carcinoma and glioblastoma. We have recently observed increased expression of the epidermal growth factor receptor messenger RNA in neoplastic tissue relative to normal kidney tissue from patients with renal cell carcinoma. To determine if epidermal growth factor receptor gene amplification was present in renal cell carcinoma, DNA was extracted from renal cell carcinoma cell lines and from normal kidney and renal cell carcinoma tissues derived from radical nephrectomy specimens from thirty patients. DNA was analyzed by Southern blot hybridization. There was no epidermal growth factor receptor gene amplification detected in the renal cell carcinoma samples studied, indicating the increased epidermal growth factor gene expression observed in renal cell carcinoma does not occur through gene amplification. Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.

Adenocarcinoma↗
PubMed1989

Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma.

Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.

Autoradiography↗
PubMed1989

Genetic changes in human adrenocortical carcinomas.

Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1989

Improved detection of allele loss in renal cell carcinomas after removal of leukocytes by immunologic selection.

We used immunologic selection to remove contaminating leukocytes from primary renal cell carcinomas and to improve detection of chromosome 3p allele loss. Leukocytes were removed from disaggregated renal cell carcinomas by a double-antibody, magnetic bead separation technique. Before immunologic selection, the preparations contained 26% +/- 15% (SD) tumor cells (n = 7); after immunologic selection, the preparations contained 76% +/- 12% tumor cells. The recovery of tumor cells in the purified preparations was about 10%. Detection of allele deletion was facilitated by immunologic selection. This method may be useful in allele deletion analysis of other human solid tumors that are contaminated with host leukocytes and, with appropriate modification, may be applied to tumors that are contaminated with other cell types.

Alleles↗
PubMed1986

Modulation of cytosolic protein kinase C activity by ferricyanide: priming event seems transmembrane redox signalling. A study on transformed C3H/10T1/2 cells in culture.

Transformed 3T3/10T1/2 cultured cells incubated with ferricyanide caused a decrease of 2 mM EDTA extractable cytosolic protein kinase C activity in 2 min, whereas 5 or 20 min ferricyanide treatment reverted the enzyme activity to that observed without ferricyanide. The ferricyanide effect in 2 min was abolished by amiloride and sustained by ouabain. Thus, deactivation-activation of cytosolic protein kinase C is attributed to an unknown signal generation during H+ accumulation coupled with the Na+/H+ exchange phase. In this mechanism the priming event concerns the transmembrane redox process shedding H+ into the cell interior while impermeant ferricyanide acts as a unique electron acceptor.

Animals↗
PubMed1986

[Neurotropic action of adrenocorticotropic hormone].

The adrenocorticotropic hormone (ACTH) is produced within the cell body of hypothalamic neurons by proteolytic cleavage of its large precursor molecule, pro-opiomelanocortin. These neurons distribute ACTH-containing nerve endings throughout the central nervous system. ACTH is able to evoke motor and behavioural responses and to modify neuronal metabolism. Since ACTH has been shown to regulate glucose uptake and utilization, its implication in the adaptative response to stress situations, such as cerebral hypoxia, deserves further investigations.

Adrenocorticotropic Hormone↗
PubMed1985

Regulation of cyclic AMP and cyclic GMP levels by adrenocorticotropic hormone in cultured neurons.

The effect of adrenocorticotropic hormone (ACTH) on the intracellular concentration of cyclic nucleotides was studied in cultures of neurons from embryonic chick cerebral hemispheres. Incubation of neurons with ACTH(1-24) in the presence of phosphodiesterase inhibitor isobutylmethylxanthine resulted in a sustained increase in cyclic AMP while rise in cyclic GMP level was transient. The values obtained for half-maximal stimulation were 0.5 microM and 0.03 nM for cyclic AMP and cyclic GMP respectively. Concomitantly, ACTH(1-24) stimulated guanylate cyclase activity (half-maximal stimulation at 0.02 nM). These results suggest the existence of two distinct populations of ACTH receptors in neurons and provide the first evidence that cyclic GMP does mediate the action of ACTH in neurons.

Adrenocorticotropic Hormone↗
PubMed1985

Regulation of deoxyglucose uptake by adrenocorticotropic hormone in cultured neurons.

The influence of ACTH and some of its N-terminal related peptides was investigated on the uptake of (3H)-2-deoxy-D-glucose in pure cultures of neurons from chick embryo cerebral hemispheres. ACTH influences deoxyglucose uptake in a time and dose-dependent fashion. The stimulation of deoxyglucose uptake is observed after a delay of 6-8 h and requires active protein synthesis. ACTH does not affect deoxyglucose in non-neuronal cells (astroglial cells, hepatocytes, myoblasts, fibroblasts). The effect of various peptide hormones, neuropeptides and growth factors, active in the central nervous system or other tissues, has also been examined. None of these were able to stimulate deoxyglucose uptake, suggesting that the regulation of hexose uptake in neurons is specific for the ACTH-related peptides.

Adrenocorticotropic Hormone↗
PubMed1983

Long-term culture of neurones from human cerebral cortex in serum-free medium.

A method for cultivating neurones from the fetal human central nervous system in the absence of glial cells is described. Brain cells from 15-18-week-old human fetuses are plated on polylysine-coated surfaces and grown in a serum-free hormonally-defined medium. About 98% of the cells were identified as neurones using tetanus toxin as a marker. The cultures survive for up to 7 weeks and develop an extremely complex network of neurites.

Cells, Cultured↗