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C Saura

Publications and source records attributed to C Saura.

At least 19 recordsLinked to original sources
PubMed2026

Impact of BRCA2 pathogenic variants on outcomes to first-line CDK4/6 inhibitors plus endocrine therapy in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain. PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH). RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors. CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

Humans↗
PubMed2001

[Impact of the exclusion of donors who have stayed in the United Kingdom on the residual risk of HIV transmission by blood transfusion].

BACKGROUND: One of the measures aimed at reducing the risk of transmission of the agent responsible for the new variant of Creutzfeldt-Jakob disease was to exclude blood donors having stayed in the United Kingdom between 1980 and 1996. The objective of the study was to estimate the impact on the residual risk of HIV transmission of recruiting extra first-time donors to replace donors having stayed in the United Kingdom. METHODS: The residual risk of HIV transmission due to donations made during the window period was estimated in all donations made in France during the 3-year period 1996-1998 by a linear combination of residual risks in repeat donors and first-time donors. In repeat donors, the estimate is based on the incidence rate of HIV in this population and in first-time donors on the "detuned assay" method. Seven simulations of the impact on the residual risk were made using various percentages of donors which would be excluded (from -5% to -35%). RESULTS: In all donations made in France during the 1996-1998 period, the residual risk of HIV transmission was estimated at 0.70 per million donations, which represents five to six donations made during the window period. If all the donors who had stayed in the United Kingdom were excluded from the donation (35%) and replaced by first-time donors, the residual risk of HIV transmission would be increased from 0.70 to 0.86 per million donations. This increase of 24% would represent one or two extra cases of post-transfusion HIV infection over a 3-year period. CONCLUSION: The results of this study show that the exclusion of a large number of blood donors, replaced by first-time donors, would have a low but quantifiable impact on the residual risk of HIV transmission. This increase of risk was one of the factors that led to the decision of not excluding donors having stayed in the United Kingdom between 1980 and 1996.

Blood Donors↗
PubMed2000

[Screening for markers of infections transmitted by transfusions in the blood collected in France from 1996 to 1998].

From 1996 to 1998, a decrease in positive donation rates has been observed for HIV, HCV and HBs Ag in first-time donors, while these rates remained stable for HTLV. In repeat donors, the same decrease was observed for HCV and HBs Ag while the rates remained stable for HIV. No HTLV-positive donations from repeat donors were noted in 1998. About half of the HIV-positive repeat donors were regular donors (less than two years between the two donations), as well as 88% of HBV-infected repeat donors. Inversely, only 20% of HCV-positive repeat donors were regular donors. Anti-HBc antibodies have been found in 20% of HIV-infected donors, in 22% of HCV-infected donors, and were associated with HBs Ag in 99% of the cases. Elevated ALT was observed in 47% of donors with anti-HCV and in 10% of donors with HBs Ag. The major risk factors are at-risk sexual behavior for HIV and use of intravenous drugs and nosocomial infections for HCV. Being a native of an endemic country has been found to be the major risk for HBV. The major HTLV risk factor was directly or indirectly linked to the Caribbean area.

Biomarkers↗
PubMed1998

[Prevalence of HIV, HTLV, and hepatitis B and C viruses in blood donors in France, 1992-1996].

The prevalence of HIV, HTLV, HBV and HCV infections has been calculated by age and sex of blood donors and not, as generally done, according to the number of donations. This study has been conducted on the basis of two surveys. The first one collected information about the sex and age of the seropositive donors. A second survey, begun in 1992, collected information about the demographic characteristics of blood donors. This population has a higher male to female sex ratio (1:2 versus 1:0) and is younger than the general population. Thus, the prevalence of these viral infections has been determined according to sex, age and type of donors (first-time or repeat) from 1992 to 1996 and the trends have been analysed. The main results are the following: a decreasing prevalence of HIV in first-time donors from 1992 to 1996, more marked in men than in women and in the 18-29 year age group than in the other age groups; a slighter decrease in prevalence of HBV and HCV in first-time donors from 1992 to 1996 with no difference in this decrease between sex and age groups. HBs Ag prevalence in first-time donors was twice as high in men than in women and was highest in donors aged from 40 to 49 years in both sexes. Prevalence of antibodies to HCV in first-time donors was comparable in both sexes but varied greatly with age. In men, a peak was observed in the 30-39 age group and in women, the highest prevalence was seen in the 50-65 age group.

Adult↗
PubMed1998

HTLV testing in blood transfusion.

To improve the safety of the blood supply, HTLV screening of blood donations became mandatory in different countries. In Japan and in Europe, the majority of HTLV-infected donors are HTLV-1 whereas in the USA more than half of them are HTLV-II-positive. The prevalence of HTLV-infected donors is low in European Countries as is the rate of seroconversion. Consequently, to test donors only once would have a high efficiency. This procedure is already in use in certain countries. Furthermore, if the use of leucodepleted cell concentrates is generalized, the policies of HTLV screening will still be further modified.

Blood Donors↗
PubMed1997

Cell surface adenosine deaminase: much more than an ectoenzyme.

During the last 10 years, adenosine deaminase (ADA), an enzyme considered to be cytosolic, has been found on the cell surface of many cells, therefore it can be considered an ectoenzyme. EctoADA, which seems to be identical to intracellular ADA and has a globular structure, does not interact with membranes but with membrane proteins. Two of these cell surface receptors for ectoADA have been identified: CD26 and A1 adenosine receptors (A1R). Apart from degradation of extracellular adenosine another functional role of ectoADA has been assigned. EctoADA is able to transmit signals when interacting with either CD26 or A1R. In this way, it acts as a co-stimulatory molecule which facilitates a variety of specific signalling events in different cell types. The heterogeneous distribution of the enzyme in the nervous system indicates that ectoADA may be a neuroregulatory molecule. On the other hand, ectoADA might act as a bridge between two different cells thus raising the possibility that it may be important for the development of the nervous system.

Adenosine Deaminase↗
PubMed1997

[Screening for markers of blood-borne diseases in donated units collected in France from 1993 to 1995].

A decrease of positive donation rates for antibodies to HIV, to HCV and for HBs Ag has been observed between 1993 and 1995 both in first-time and regular donations. In first-time donors, the most important decrease has been observed for HIV and in regular donors for HCV and HBs Ag. The interval between the negative and the positive donations was inferior to 1 year for 50% of regular donors and was superior to 2 years for 20 to 30%. About 30% of HIV positive donations were positive for other markers: 23% for anti-HBc and 10% for anti-HCV. About 40% of HCV positive donations had an elevated ALT level. Risk factors related to HIV heterosexual transmission appear to be the most difficult to identify during the donor selection and the least often associated with other markers. In recently HCV-infected donors, the main risk factors were IV drug addiction (25%) and nosocomial infection (30%). The major HTLV risk factor was directly or indirectly linked to the Caribbean area. Important differences between continental France and overseas territories were observed for HIV and HBs Ag rates.

AIDS Serodiagnosis↗
PubMed1997

Ligand-induced phosphorylation, clustering, and desensitization of A1 adenosine receptors.

Through immunocytochemistry with the use of antibodies against A1 adenosine receptors (A1Rs) and confocal microscopy, we show that stimulation of A1Rs by the agonist (R)-phenylisopropyladenosine [(R)-PIA] caused a rapid (5-15 min) aggregation (clustering) of receptor molecules on the surface of DDT1MF-2 cells. Internalization of the chronically stimulated receptor was slower and occurred concomitantly, with a time-dependent decrease (50%) in the number of cell surface [3H](R)-PIA binding sites. The reduction of binding sites was due partly (30%) to internalization and partly (20%) to the presence of desensitized cell surface receptor molecules that were unable to bind the ligand. Chronic exposure of DDT1MF-2 cells to 50 nM (R)-PIA produced functional desensitization, as deduced from second messenger production assays. Quantification of the content of A1Rs by immunoblotting and flow cytometry in cells pretreated with 50 nM (R)-PIA indicates a time-dependent slow down-regulation of the receptor. Receptor clustering and agonist-induced receptor phosphorylation, which occurred in serine and tyrosine, were simultaneous. The finding that activators of protein kinase A or C were able to induce functional desensitization of A1Rs, phosphorylate A1Rs in serine and threonine, and trigger clustering of the receptor suggests that phosphorylation of A1Rs in serine/threonine is involved in desensitization-related events.

Adenosine↗
PubMed1996

Adenosine deaminase affects ligand-induced signalling by interacting with cell surface adenosine receptors.

Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be found as an ecto-enzyme. At the plasma membrane, an adenosine deaminase binding protein (CD26, also known as dipeptidylpeptidase IV) has been identified but the functional role of this ADA/CD26 complex is unclear. Here by confocal microscopy, affinity chromatography and coprecipitation experiments we show that A1 adenosine receptor (A1R) is a second ecto-ADA binding protein. Binding of ADA to A1R increased its affinity for the ligand thus suggesting that ADA was needed for an effective coupling between A1R and heterotrimeric G proteins. This was confirmed by the fact that ASA, independently of its catalytic behaviour, enhanced the ligand-induced second messenger production via A1R. These findings demonstrate that, apart from the cleavage of adenosine, a further role of ecto-adenosine deaminase on the cell surface is to facilitate the signal transduction via A1R.

Adenosine Deaminase↗
PubMed1996

Adenosine deaminase interacts with A1 adenosine receptors in pig brain cortical membranes.

Adenosine deaminase is an enzyme of purine metabolism that has largely been considered to be cytosolic. A few years ago, adenosine deaminase was reported to appear on the surface of cells. Recently, it has been demonstrated that adenosine deaminase interacts with a type II membrane protein known as either CD26 or dipeptidylpeptidase IV. In this study, by immunoprecipitation and affinity chromatography it is shown that adenosine deaminase and A1 adenosine receptors interact in pig brain cortical membranes. This is the first report in brain demonstrating an interaction between a degradative ectoenzyme and the receptor whose ligand is the enzyme substrate. By means of this interaction adenosine deaminase leads to the appearance of the high-affinity site of the receptor, which corresponds to the receptor-G protein complex. Thus, it seems that adenosine deaminase is necessary for coupling A1 adenosine receptors to heterotrimeric G proteins.

Adenosine Deaminase↗
PubMed1987

Albendazole and thiabendazole in murine strongyloidiasis.

The activity of albendazole and thiabendazole, two derivatives of benzimidazole, were tested in an experimental model of Strongyloides ratti infestation in the rat. Two series of seven consecutive daily negative parasitic plate cultures, separated by four weeks of steroid therapy, confirmed cure of the infestation. Both drugs were inactive against larvae in the tissue phase, but completely effective in the intestinal phase.

Albendazole↗
PubMed1986

Role of icosanoids in alveolar macrophage phagocytosis and aggregation.

Rat alveolar macrophages (AM) collected by bronchoalveolar lavage were incubated in the presence or absence of various icosanoids or inhibitors of the arachidonic acid cascade with either chrysotile asbestos (50 micrograms/ml) to determine cell aggregation, or human red blood cells (Rh+; preincubated with anti-D globulin) to measure phagocytosis. Phorbol myristate acetate (PMA) and ionophore A23187, two agents which stimulate arachidonic acid metabolism, reduced red blood cell phagocytosis by AM whereas arachidonic acid had no effect on this cellular event. Neither arachidonic acid nor its metabolites (prostaglandins E2, I2, F2 alpha, the thromboxane mimick U44069 and leukotrienes A4, B4, C4, D4) had a significant effect on phagocytosis. Inhibition of the synthesis of cyclooxygenase products with various concentrations of indomethacin, aspirin and OKY-1581 or of lipoxygenase products with eicosatetraynoic acid, BW755c, diethylcarbamazine and phenidone did not affect phagocytosis either. On the other hand, asbestos-induced aggregation was significantly reduced by nordihydroguaiaretic acid (NDGA), BW755C, benoxaprofen, and high concentrations of indomethacin but not by aspirin. These results suggested that metabolites of arachidonic acid (especially lipoxygenase products) play a modulatory role in non specific alveolar macrophage aggregation but not in specific, Fc receptor-mediated phagocytosis.

Animals↗