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Biomedical subjects

F Andre

Publications and source records attributed to F Andre.

At least 19 recordsLinked to original sources
PubMed2006

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

BACKGROUND: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. METHODS: Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. RESULTS: After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.

Adult↗
PubMed2006

Evidence that urinary excretion of thiouracil in adult bovine submitted to a cruciferous diet can give erroneous indications of the possible illegal use of thyrostats in meat production.

Thyrostats have been banned for use as veterinary drugs in Europe since 1981 because of their carcinogenic and teratogenic properties. Until now, the identification of thiouracil in animal biological matrices has been interpreted as the consequence of an illegal administration. The present paper studies the influence of a cruciferous-based feed on the occurrence of thiouracil as a residue in urine. Urine samples collected from two heifers fed on cabbage or rapeseed cakes were analysed for the presence of thiouracil by 3-iodobenzylbromide derivatization and liquid chromatography-electrospray ionization tandem mass spectroscopy (LC-ESI(-)-MS/MS) analysis. Urine collected after cabbage or rapeseed feeding showed thiouracil concentrations in the range 3-7 and 2-9 microg l-1, respectively, demonstrating a relationship between a diet based on cruciferous vegetables and the occurrence of thiouracil in urine. Thiouracil was excreted in urine in the hours following cruciferous intake. Complete elimination (<0.8 microg l-1) of the compound occurred within 5 days. The precursors in cruciferous vegetables responsible for the thiouracil excretion in urine were proved not to be thiouracil itself.

Animal Feed↗
PubMed2005

Application of stable carbon isotope analysis to the detection of 17beta-estradiol administration to cattle.

The use of anabolic agents in food producing animals is prohibited within the EU since 1988 (96/22/EC directive). The control of the illegal use of natural steroid hormones in cattle is still an exciting analytical challenge as far as no definitive method and non-ambiguous analytical criteria are available. The ability of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to demonstrate the administration of 17beta-estradiol to bovine has been investigated in this paper. By comparison of 13C/12C isotopic ratio of main urinary estradiol metabolite, i.e. 17alpha-estradiol, with two endogenous reference compounds (ERCs), i.e. dehydroepiandrosterone (DHEA) and 5-androstene-3beta,17alpha-diol, the differentiation of estradiol metabolite origin, either endogenous or exogenous, has been proved to be achievable. After treatment, the delta(13)C(VPDB)-values of 17alpha-estradiol reached -27 per thousand to -29 per thousand, whereas delta13CVPDB-values of DHEA remained between -13 per thousand and -20 per thousand depending on the diet, maize and grass, respectively. A significant difference of delta13CVPDB between ERCs and 17alpha-estradiol was measurable over a period of 2 weeks after estradiol ester administration to the animal.

Androstenediol↗
PubMed2004

Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome.

BACKGROUND: The expression of CXCR4 has been implicated in metastatic dissemination in different models of breast cancer and melanoma. In the present study, we evaluated CXCR4 expression in non-small-cell lung cancer (NSCLC) and the relationship between CXCR4 expression and the prognosis of stage I disease. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed CXCR4 expression in specimens from 61 patients with completely resected pathologically confirmed stage I NSCLC for whom clinical follow-up data were available. RESULTS: In the present study, we have shown that: CXCR4 is expressed by tumor cells in stage I NSCLC; CXCR4 is located in the nucleus and/or in the cytoplasm of tumor cells; strong nuclear staining was observed in 17 cases (29.8%); patients whose tumors had CXCR4-positive nuclear staining had a significantly longer duration of survival than patients whose tumors had no nuclear expression (P = 0.039, log-rank test). Interestingly, the 5-year metastasis rates were 23.5% and 34.1% in patients with CXCR4-positive and CXCR4-negative nuclear expression, respectively (P = 0.2). CONCLUSION: Strong CXCR4-positive nuclear staining was associated with a significantly better outcome in early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.

Adult↗
PubMed2004

Risk factors for brain relapse in patients with metastatic breast cancer.

BACKGROUND: The occurrence of brain metastases is an emerging problem in patients with metastatic breast cancer. In the present study, we looked at risk factors for brain metastasis among patients with metastatic breast cancer. PATIENTS AND METHODS: The risk factors for brain metastasis were first determined in a series of 215 patients with metastatic breast cancer. Risk factors identified in the multivariate analysis were re-evaluated in a confirmatory series of 199 patients with metastatic breast cancer. All the patients had been included in prospective randomized trials that evaluated chemotherapy or endocrine therapy in an adjuvant setting. RESULTS: In the first series, the presence of lung metastases (hazard ratio = 4.3, 95% CI: 1.9-9.3, P=0.0003) and negative hormone receptor status (hazard ratio = 4.2, 95% CI: 1.7-11, P=0.002) were the only predictive factors associated with the occurrence of brain metastases in the multivariate analysis. The second series confirmed that the presence of lung metastases and negative hormone receptor status were associated with the occurrence of brain metastases. CONCLUSION: The presence of lung metastases as the first site of relapse and a negative hormone receptor status are predictive for the occurrence of brain metastases in patients with metastatic breast cancer. A prophylactic treatment should be evaluated in these subsets of patients.

Adult↗
PubMed2003

A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer.

With the availability of chemotherapy agents for first- and second-line treatment of advanced non-small-cell lung cancer (NSCLC), the patient population that requires subsequent chemotherapy is increasing. This retrospective analysis was performed to describe the clinical course after two standard or approved chemotherapy agents in patients with good overall performance status. Data were selected from patients with advanced NSCLC who had received third- or fourth-line chemotherapy after two prior chemotherapy regimens that included platinum and docetaxel given concurrently or sequentially. Prior regiments had failed due to discase progression within 90 days of chemotherapy, or unacceptable toxicity. Examination of over 700 patient records between January 1993 and January 2000 at one US and one European cancer centre revealed 43 patients that fulfilled the inclusion criteria. Response rates decreased with each line of treatment: first line, 20.9%; second line, 16.3%; third line, 2.3%; and fourth line, 0%. The disease control rate (response plus stable disease) also decreased dramatically from first- to fourth-line treatment, although it was higher for second-line treatment (74.4%) than for first-line treatment (62.8%). The median overall survival time from diagnosis was 16.4 months. The median overall survival time from the start of the last treatment (either third or fourth line) was 4 months. Patients with stage III disease at diagnosis had a longer overall survival from diagnosis than patients with stage IV disease (P=0.02). This review highlights the need for novel therapy approaches for patients with recurrent NSCLC who have failed second-line therapy and provides a baseline for the statistical design of such studies.

Adult↗
PubMed2001

Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy: should prophylactic cranial irradiation be reconsidered?

BACKGROUND: Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall-cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients. METHODS: In this study, the authors compared the patterns of relapse in 81 patients with clinically detectable N2 NSCLC who had been treated with preoperative chemotherapy with the relapse patterns of 186 comparable patients who had been treated with primary surgery. Clinically detectable N2 (cN2) denotes mediastinal lymph node enlargement on computed tomography scan, which then is confirmed by mediastinoscopy. RESULTS: Overall 20% of patients developed a locoregional recurrence. Chemotherapy decreased the risk of visceral metastasis as 28% of the patients preoperatively treated and 38%of those not treated with preoperative chemotherapy presented a visceral metastasis (P < 0.05). Preoperative chemotherapy and adenocarcinoma subtypes were associated with a higher rate of brain metastasis (P < 0.05). Thirty-two percent of the patients treated preoperatively and 18% of those not treated with preoperative chemotherapy presented a brain metastasis (P < 0.05), which was isolated in 22% and 11% of the patients, respectively (P < 0.05). CONCLUSION: The current study found that preoperative chemotherapy for cN2 decreases the risk of visceral metastasis but is associated with a high rate of isolated brain metastases. Prophylactic cranial irradiation may need to be reinvestigated in clinical trials, especially in patients who present with an adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Multi-residue extraction-purification procedure for corticosteroids in biological samples for efficient control of their misuse in livestock production.

A fast and efficient multi-residue extraction-purification procedure was developed for 12 corticosteroids in biological matrices (hair, urine and meat), in order to control their illegal use as growth promoters in cattle. Detection and identification of the analytes were achieved using a previously described LC-MS-MS method based on negative electrospray ionisation and a triple quadrupole analyser. The presented procedures included acid (hair) or enzymatic (urine and meat) hydrolysis, C18 reversed-phase SPE, Na2CO3 liquid-liquid clean-up and SiOH normal-phase SPE. The detection limits of the developed methods were between 2.9 and 9.3 pg/mg (ppb) for hair samples and in the 40 - 70 pg/g (ppt) range for the urine or meat samples. The acid hydrolysis used for corticosteroid extraction in hair was optimised using an experimental design and response surface methodology. Achieved performances were linked to a physico-chemical approach based on the corticosteroids specific C17 side-chain. This original multi-residue and multi-matrices analytical methodology will be used for further metabolism studies.

Adrenal Cortex Hormones↗
PubMed2001

Brain metastases at the time of presentation of non-small cell lung cancer: a multi-centric AERIO analysis of prognostic factors.

A multi-centre retrospective study involving 4 French university institutions has been conducted in order to identify routine pre-therapeutic prognostic factors of survival in patients with previously untreated non-small cell lung cancer and brain metastases at the time of presentation. A total of 231 patients were recorded regarding their clinical, radiological and biological characteristics at presentation. The accrual period was January 1991 to December 1998. Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The median survival of the whole population was 28 weeks. Univariate analysis (log-rank), showed that patients affected by one of the following characteristics proved to have a shorter survival in comparison with the opposite status of each variable: male gender, age over 63 years, poor performance status, neurological symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml(-1), high serum alkaline phosphatase level, high serum LDH level and serum sodium level below 132 mmol l(-1). In the Cox's model, the following variables were independent determinants of a poor outcome: male gender: hazard ratio (95% confidence interval): 2.29 (1.26-4.16), poor performance status: 1.73 (1.15-2.62), age: 1.02 (1.003-1.043), a high serum NSE level: 1.72 (1.11-2.68), neurological symptoms: 1.63 (1.05-2.54), and a low serum sodium level: 2.99 (1.17-7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC patients, whatever the metastatic site (namely sex, age, gender, performance status and serum sodium level) this study discloses 2 determinants specifically resulting from brain metastasis: i.e. the presence of neurological symptoms and a high serum NSE level. The latter factor could be in relationship with the extent of normal brain tissue damage caused by the tumour as has been demonstrated after strokes. Additionally, the observation of a high NSE level as a prognostic determinant in NSCLC might reflect tumour heterogeneity and understimated neuroendocrine differentiation.

Adult↗
PubMed2000

Characterization of exogenous testosterone in livestock by gas chromatography/combustion/isotope ratio mass spectrometry: influence of feeding and age.

The detection of exogenous testosterone in bovine urine was investigated by using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The carbon isotopic ratio measurement of epitestosterone, etiocholanolone (testosterone metabolite) and DHEA (testosterone precursor) in female bovine urines after testosterone enanthate administration was carried out. An important modification in the 13C/12C ratio of testosterone metabolites was observed, such that significant differences between precursor and metabolites of testosterone occurred until three weeks after intramuscular administration of testosterone enanthate. The factors influencing the 13C/12C of endogenous steroids were studied especially through cattle feeding and age. The DHEA mean delta13C value was found to vary between -25 and -26/1000 when hay and concentrate diet were used for fattening. On the other hand the delta13C value observed when maize silage was used increased to -20/1000. Testosterone metabolites showed the same delta13C increase as their precursor. Moreover, we observed a clear relationship between age and efficiency of misuse determination. Indeed, because of the lower concentration of natural hormones in young animals, the contribution of exogenous molecules increases significantly compared with older subjects. Consequently, demonstration of administration is easier to achieve in calves than in mature animals.

Aging↗
PubMed2000

Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of 19-norandrosterone and 19-noretiocholanolone in human urine.

For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping.

Adult↗
PubMed2000

Biosynthesis of 6beta-hydroxymethyltestosterone using bovine hepatocyte cultures.

Usually performed to investigate biotransformations of xenobiotics, in vitro liver models could become useful tools for the synthesis of not commercially available compounds. In this study, bovine hepatocyte cultures were used to biosynthesise, on the laboratory scale, one major metabolite of methyltestosterone: 6beta-hydroxymethyltestosterone. After incubation of bovine hepatocytes with methyltestosterone for 24 h, culture medium was removed and stored at -20 degrees C until analysis. The sample was extracted and purified on a reversed-phase HPLC system. The metabolite of interest was then analysed in LC-MS and GC-MS for structural identification. The purity and the isomery of the 6 and 17 positions were confirmed by NMR analyses. This first success in producing purified 6beta-hydroxymethyltestosterone from bovine hepatocyte cultures allowed us to consider that in vitro liver models could be reliable tools for standard biosynthesis.

Animals↗
PubMed2000

Peritoneal carcinomatosis in germ-cell tumor: relations with retroperitoneal lymph node dissection.

Peritoneal carcinomatosis from germ-cell tumor has rarely been described, and thus remains largely unknown. We report here five cases involving this entity. All five patients had embryonal carcinoma in their primary germ-cell tumor. Four of them had undergone retroperitoneal lymph node dissection (RPLND), and viable malignant cells were found. RPLND was performed for relapses (n = 3) and as primary therapy for stage II disease (n = 1). The peritoneum was the only site of relapse in three patients, and was associated with pleural effusion in one. The time to relapse after RPLND ranged from 6 to 14 months. One patient sustained injury to lymph nodes during RPLND, and another patient had a peritoneal xanthelasma. The only three patients already described in the literature underwent RPLND or surgical biopsy. All these observations suggest a striking relation between RPLND and occurrence of subsequent peritoneal carcinomatosis.

Adult↗
PubMed2000

Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications.

PURPOSE: Patients who suffer from non-small-cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (N2) belong to a heterogeneous subgroup of patients. We analyzed the prognosis of patients with resected N2 NSCLC to propose homogeneous patient subgroups. PATIENTS AND METHODS: The present study comprised 702 consecutive patients from six French centers who underwent surgical resection of N2 NSCLC. Initially, two groups of patients were defined: patients with clinical N2 (cN2) and those with minimal N2 (mN2) disease were patients in whom N2 disease was and was not detected preoperatively at computed tomographic scan, respectively. RESULTS: The median duration of follow-up was 52 months (range, 18 to 120 months). A multivariate analysis using Cox regression identified four negative prognostic factors, namely, cN2 status (P <. 0001), involvement of multiple lymph node levels (L2+; P <.0001), pT3 to T4 stage (P <.0001), and no preoperative chemotherapy (P <. 01). For patients treated with primary surgery, 5-year survival rates were as follows: mN2, one level involved (mN2L1, n = 244): 34%; mN2, multiple level involvement (mN2L2+, n = 78): 11%; cN2L1 (n = 118): 8%; and cN2L2+ (n = 122): 3%. When only patients with mN2L1 disease were considered, the site of lymph node involvement according to the American Thoracic Society numbering system had no prognostic significance (P =.14). Preoperative chemotherapy was associated with a better prognosis for those with cN2 (P <.0001). Five-year survival rates were 18% and 5% for cN2 patients treated with and without preoperative chemotherapy, respectively. CONCLUSION: This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests different therapeutic approaches according to the subgroup profile.

Adolescent↗