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N Andrieu

Publications and source records attributed to N Andrieu.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparative study of the metabolic pools of sphingomyelin and phosphatidylcholine sensitive to tumor necrosis factor.

The metabolism and localization of the pools of sphingomyelin and phosphatidylcholine (PtdCho) which are hydrolyzed upon activation of the sphingomyelin signal transduction pathway were studied in human skin fibroblasts treated with tumor necrosis factor alpha (TNF-alpha). In a first series of experiments, cellular phospholipids were labeled with [3H]choline under conditions that inhibit the vesicular traffic to the plasma membrane. Thus, in human fibroblasts metabolically labeled in the presence of brefeldin A, monensin or at 20 degree C, the arrival of newly synthesized sphingomyelin to the cell surface was prevented, supporting previous conclusions for a vesicular mechanism of sphingomyelin transport to the plasma membrane. Under these conditions, TNF-alpha induced the hydrolysis of PtdCho but did not promote the hydrolysis of 3H-labeled sphingomyelin, suggesting that the sphingomyelin signaling pool resides in a compartment distal to the Golgi apparatus, and possibly in the plasma membrane. TNF was also unable to trigger the breakdown of a radioactive sphingomyelin, [ceramide-3H]sphingomyelin, exogenously added to the cells to label the exoplasmic side of the cell surface. However, TNF caused PtdCho and sphingomyelin degradation in fibroblasts that had been treated with bacterial sphingomyelinase to degrade the sphingomyelin pool of the external leaflet of the plasma membrane. A similar result was obtained at 4 degree C, i.e. under conditions which inhibit endocytosis, thereby excluding the endosomes as a potential site for TNF-induced sphingomyelin hydrolysis. Altogether, these results strongly argue for a localization of the sphingomyelin signaling pool at the inner leaflet of the plasma membrane, but neither in the endolyso-somal nor the Golgi compartments. In addition, when [3H]choline-labeled fibroblasts were treated under non-lytic conditions with bacterial phospholipase C to degrade the external pool of PtdCho, TNF was still able to stimulate the hydrolysis of PtdCho. This demonstrates that the pool of PtdCho involved in TNF-alpha signaling (and which is hydrolyzed concurrently with sphingomyelin to generate diacylglycerol), is not located in the outer leaflet of the plasma membrane.

Brefeldin A↗
PubMed1996

Use of relatives of cases as controls to identify risk factors when an interaction between environmental and genetic factors exists.

BACKGROUND: The difficulty in detecting relevant risk factors for chronic diseases (such as breast and colon cancer) may be due to heterogeneity in the populations of studied cases, and one source of heterogeneity may be differential genetic susceptibility predisposing to differential environmental sensitivity. METHODS: The purpose of this investigation is to determine whether the estimates of odds ratios are modified by using relatives as controls when risk factors interact with an underlying genetic factor. RESULTS: We demonstrate that using relative controls in matched case-control studies produces odds ratios different from population-based odds ratios. This difference is dependent on the amount of interaction between the genetic and environmental factors and on the genetic correlation between relatives. CONCLUSIONS: In the case of a common disease, the use of relatives as controls could be helpful in detecting interaction between an exposure and an underlying genetic factor when the genetic factor is common.

Case-Control Studies↗
PubMed1995

Low temperatures and hypertonicity do not block cytokine-induced stimulation of the sphingomyelin pathway but inhibit nuclear factor-kappa B activation.

In order to better understand the significance of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)-receptor internalization in the sphingomyelin pathway signal transduction, we investigated receptor signaling under conditions in which receptor internalization is blocked. We demonstrate that human recombinant TNF-alpha and IL-1 beta both induced sphingomyelin and phosphatidylcholine hydrolysis at either 4, 14, or 37 degrees C in human skin fibroblasts and U937 monocytic cells. Cytokine-induced sphingomyelin degradation also occurred when endocytosis was inhibited by incubating the cells in hypertonic medium. While internalization was not required for the production of ceramide, activation of the transcription factor NF-kappa B was strongly reduced when cells were stimulated with TNF at low temperature or in hypertonic medium. Under these conditions, activation of NF-kappa B by the cell-permeant C2- ceramide (N-acetylsphingosine), by exogenous sphingomyelinase or by phorbol myristate acetate was also inhibited. These results suggest that low temperature and hypertonicity, two inhibitors of receptor internalization: (i) do not affect the TNF-alpha- or IL-1 beta-induced sphingomyelin hydrolysis, but (ii) do inhibit a step distal to ceramide of the intracellular signaling pathway leading to NF-kappa B activation.

Cell Line↗
PubMed1995

Degradation of fluorescent and radiolabelled sphingomyelins in intact cells by a non-lysosomal pathway.

The aim of the present study was to investigate the role of the entitled neutral, sphingomyelinase in the non-lysosomal pathway of sphingomyelin degradation by intact cells (Spence et al. (1983) J. Biol. Chem. 258, 8595-8600; Levade et al. (1991) J. Biol. Chem. 266, 13519-13529). The uptake and degradation of sphingomyelin by intact living cells was studied using cell lines exhibiting a wide range of activity levels of acid, lysosomal and neutral sphingomyelinases as determined in vitro on cell homogenates by their respective standard assays. For this purpose, neuroblastoma, skin fibroblasts, lymphoid and leukemic cell lines, some of them derived from patients with Niemann-Pick disease (deficient in the acid, lysosomal sphingomyelinase) were incubated with radioactive, [oleoyl-3H]sphingomyelin or fluorescent, pyrene-sulfonylaminoundecanoyl-sphingomyelin. Either compound was taken up by a pathway which was not receptor-mediated and hydrolyzed by all intact cells, including those derived from Niemann-Pick disease patients. Moreover, their degradation by the intact cells was not inhibited by treatment with chloroquine, indicating hydrolysis by a non-lysosomal sphingomyelinase. The intracellular sphingomyelin degradation rates showed no correlation with the activity of the 'classical' neutral sphingomyelinase as determined in vitro. In particular, fibroblasts derived from Niemann-Pick patients lacking the lysosomal sphingomyelinase, and having no detectable in vitro activity of the 'classical' neutral sphingomyelinase, were able to degrade the exogenously supplied sphingomyelins. Indeed, in vitro these cells were shown to exhibit neutral, magnesium- and dithiothreitol-dependent sphingomyelinase activities, that might contribute to the non-lysosomal pathway for sphingomyelin degradation to ceramide in intact cells.

Bridged-Ring Compounds↗
PubMed1995

Familial risk, abortion and their interactive effect on the risk of breast cancer--a combined analysis of six case-control studies.

In a previous study in France, we reported that the relative risk of breast cancer associated with a family history of breast cancer was higher in those subjects with a history of abortions. The present study was undertaken to check the existence of this interaction in other studies and to investigate whether the interaction is modified by the time at which abortions occur. Data were obtained from six case-control studies in France, Australia and Russia, with information on family history of breast cancer and abortion for 2693 breast cancer cases and 3493 controls. The interaction effect was estimated in each study separately, then combined using a multivariate weighted average. The relative risk conferred by a family history of breast cancer increased with the number of abortions (1.8 for no abortion, 1.9 for one abortion, 2.8 for two or more). There was a significant interaction between total number of abortions and family history (P = 0.04), but this was no longer significant when adjusted for other risk factors. The familial risk was highest for those who had had an abortion before first childbirth (1.9 for abortion after first childbirth, 2.7 for abortion before first childbirth). The adjusted risk associated with family history was significantly higher in those with an abortion before first childbirth (P = 0.04). Our findings suggest a synergism between familial factors and abortion. The interaction was not substantially modified by the type of abortion (spontaneous or induced) but was modified by the time at which it occurred in relation to first childbirth. This suggests an effect of abortion itself rather than predisposition to abortion. Further studies of breast cancer cases, particularly among BRCA1 gene carriers and their families, could improve our understanding of this effect.

Abortion, Induced↗
PubMed1994

Evidence against involvement of the acid lysosomal sphingomyelinase in the tumor-necrosis-factor- and interleukin-1-induced sphingomyelin cycle and cell proliferation in human fibroblasts.

The hydrolysis of sphingomyelin (SPM) has been reported to mediate a number of responses to extracellular agents, including cytokines. The so-called SPM cycle may result from the activation of different types of sphingomyelinases (SPMases). We investigated the hypothetical contribution of acid lysosomal SPMase in the SPM signal-transduction pathway. We examined the ability of human skin fibroblasts with a genetic deficiency of acid lysosomal SPMase activity to respond to tumour necrosis factor alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). We report that both cytokines promoted SPM hydrolysis in fibroblasts derived from patients with Niemann-Pick disease or I-cell disease, similar to that observed in normal cells. Treatment of normal fibroblasts with cationic amphiphilic drugs resulted in inhibition of acid SPMase activity, but had no effect on cytokine-induced SPM turnover. In addition, TNF-alpha and IL-1 beta stimulated [3H]thymidine incorporation in Niemann-Pick fibroblasts, as in normal cells. Thus our results argue against a role for acid endolysosomal SPMase in mediating the cytokine-induced SPM signalling cascade.

Cell Division↗
PubMed1994

Familial risk of breast cancer in a French case-control study.

The relationship between a family history of cancer and the risk of breast cancer was investigated in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in families. This relationship increased linearly with both the number of the affected relatives and with the degree of kinship between the affected relative and the case. The highest risk was observed when a sister was affected by breast cancer. This could be explained by longer common environmental exposures between sisters than between mother and daughter. This could also be explained by a genetic factor segregating under a recessive model. The risk of breast cancer associated with colon, uterus, ovary, and prostate cancer in the family was not significantly different from one. However, the estimated odds ratios associated with a family history of colon cancer increased with the degree of kinship between the affected relative and the case in a similar manner to those of breast cancer. A relationship between the risk of breast cancer and a family history of colon cancer would support the existence of a common familial factor (be it genetic or not) for these cancers. Further genetic epidemiological studies might help to define the mode of inheritance of the same susceptibility to cancer at different sites.

Adult↗
PubMed1994

Familial risk of breast cancer and abortion.

We found that the risk of breast cancer associated with a family history of breast cancer increased with the number of abortions (induced as well as spontaneous) in a study of 495 breast cancer cases and 785 controls aged 20 to 56 years. For the women who had undergone at least two abortions, the risk associated with a family history did not seem to depend on the type of abortion. This finding suggests that the effect of a family history on the risk of breast cancer is modified by event(s) resulting from abortions. Further epidemiological studies should be conducted to verify the existence of this interaction.

Abortion, Induced↗
PubMed1993

Variations in the risk of breast cancer associated with a family history of breast cancer according to age at onset and reproductive factors.

In a case-control study of 495 breast cancer patients and 785 controls between 20 and 56 years of age, the risk of breast cancer associated with a family history of breast cancer was studied according to age and reproductive factors. The familial risk of breast cancer was not significantly modified by age at onset, age at menarche, number of children, age at first full-term pregnancy, menstrual cycle length or age at menopause. However, the familial risk significantly increased with the number of abortions (p < 0.05) and seemed to decrease after a natural menopause (p = 0.08). These results suggest that a familial predisposition to breast cancer exerts the same influence during the first six decades of life, except maybe when there are isolated or repeated events such as abortions or artificially imposed menopause, in which case the risk is apparently greater.

Adolescent↗
PubMed1991

Association between breast cancer and family malignancies.

In a case-control study, the relationship between a family history of cancer of the breast, ovary, colon, uterus or prostate and the risk of breast cancer was investigated. The data consisted of family histories from 495 breast cancer cases and 785 controls aged 20-56 years. A positive association was found between the occurrence of breast cancer and a history of breast cancer in the families of the subjects affected. This relationship increased linearly with both the degree of kinship of the affected relatives and with their number. The risk of breast cancer associated with other types of cancer in the family was not significantly different from unity.

Adult↗
PubMed1991

Oral contraceptives and breast cancer: a French case-control study.

The relationship between the risk of breast cancer and oral contraceptive use was investigated in a case-control study conducted in France between 1983 and 1987 in five public hospitals. Some 464 cases aged 25 to 56 years and 542 matched controls were interviewed about their history of the use of oral contraceptives (OC). Results are given for the entire population and for the subgroup of 358 and 379 premenopausal cases and controls. The multivariate relative risk estimate, for ever user, was 1.5 (p less than 0.01) in the whole group as well as in the premenopausal subgroup (p less than 0.02). However, there was no evidence that the effect varied appreciably according to duration of use, age at first use, use before first full-term pregnancy (FFTP) and time since first or last use. The risk was not altered for any particular brand of OC. We conclude that, because of the widespread attention given to the relationship between OC use and breast cancer, information bias might be responsible for part of the excess in risk observed among OC ever users.

Adenocarcinoma↗
PubMed1990

Strong association between c-myb and oestrogen-receptor expression in human breast cancer.

Previous articles have reported that the c-myb proto-oncogene was activated in various types of tumours of the hematopoietic system suggesting that this gene plays a role in the development of these malignancies. However no studies of the c-myb gene have as yet been performed in solid primary tumours. In the present study we have analysed in breast cancer the c-myb gene with the aim to determine its involvement in tumour progression. Expression of the c-myb oncogene was analysed from 169 carcinoma specimens obtained from untreated patients with non-inflammatory breast cancer (NBC) (112 patients) and inflammatory breast cancer (IBC) (57 patients). A 3.5 kb c-myb transcript band was detected in 108 (64%) tumours. c-myb expression was found to be associated with good prognostic factors (lowest histopathologic grade (P = 0.01), oestrogen and progesterone receptor status (P less than 10(-4)) and pS2 gene expression (P less than 10(-4)) and negatively correlated with breast cancers of poorer prognosis, namely IBC (P = 0.03) and NBC with multiple involved nodes (P = 0.15). Other genes (c-myc, c-erbB2, c-fos and epidermal growth factor receptor) were also studied. The c-myb gene expression was found to be inversely correlated (P less than 0.03) with only c-erbB2 overexpression in NBC. When data were analysed with a logistic regression model using a stepwise procedure, c-myb expression was found to be associated only with the oestrogen receptor status (P less than 10(-4)). In conclusion, our data indicate that analysis of c-myb expression in breast cancer could allow the characterization of a new class of oestrogen-dependent tumours.

Breast Neoplasms↗
PubMed1989

Familial susceptibility to breast cancer: a complex inheritance.

The main results of segregation analysis aimed at identifying a major genetic factor involved in susceptibility to breast cancer are reviewed. They show that the existence of a single major gene is not sufficient to explain the distribution of the disease observed in the families concerned and suggest that the genetic inheritance involved is heterogeneous and complex. Heterogeneity has been explored in various studies according to epidemiological criteria. From these analyses, genetically homogeneous subgroups emerged (for instance families with breast cancer only or with affected males). The study of such homogeneous subgroups might help to better locate the susceptibility gene(s) on the chromosome map by analysis of genetic linkage using different markers. The results of segregation analysis depend on how epidemiological factors are taken into account. It is of major importance that epidemiological data on the proband (i.e., the individual prompting selection of a family) as well as on the members of his/her family are taken into consideration to improve understanding of the complexity of breast cancer transmission.

Breast Neoplasms↗
PubMed1989

Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance.

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.

Breast Neoplasms↗
PubMed1988

Genetic analysis of human breast cancer: implications for family study designs.

Genetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and gene-environment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.

Breast Neoplasms↗