2.3.1 Synthèse et destruction cycliques de protéines 2.3.2 Complexes CDK4 et CDK6-cycline D 2.3.3... more 2.3.1 Synthèse et destruction cycliques de protéines 2.3.2 Complexes CDK4 et CDK6-cycline D 2.3.3 Protéines pRB et E2Fs 2.3.4 Complexes CDK2-cyclines A et E 2.3.5 Autres complexes enzymatiques 2.3.6 Protéine p21 CIP1 2.3.7 Protéine p27 KIP1 2.3.8 Protéines p16 INK4a , p15 INK4b , p18 INK4c , et p19 INK4d 2.3.9 Protéine p53 2.4 Synthèse et Réparation de l'ADN 2.4.1 Transmission de l'information génétique 2.4.2 Structure des nucléotides 2.4.3 Structure des acides nucléiques 2.4.4 Réplication de l'ADN 2.4.5 Réparation de l'ADN 2.5 Régulation Allostérique de la Synthèse des Nucléotides 2.6 Inhibition de la Synthèse de Thymidine 2.7 La 5-Iodo-2'-désoxyuridine 2.7.1 Synthèse et radiomarquage 2.7.2 Radioisotopes de l'iode 2.7.3 Considérations sur une application clinique 2.7.4 Les glioblastomes comme cibles potentielles 2.8 Objectifs du Travail
Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer ch... more Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer chemotherapy outcome. We aimed to investigate the effects of fish oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5-fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax+/+) and LS174T (Bax-/-) cells were co-treated for 24-72 h with 1 μm-5-FU, 1 μm-OX or 10 μm-IRI and/or FOE dilution corresponding to 24 μm-EPA and 20·5 μm-DHA. Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell viability, apoptosis and nuclear morphological changes were evaluated by cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'-diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was used to evaluate mitochondrial dysfunction, and protein expression involved in mitochondrial apoptosis was determined by ...
The effects of polyunsaturated fatty acids and lipid peroxidation on LM fibroblast plasma membran... more The effects of polyunsaturated fatty acids and lipid peroxidation on LM fibroblast plasma membrane individual leaflet sterol distribution and structural order were examined. The cytofacial (inner) leaflet was more rigid and contained more sterol than the exofacial (outer) leaflet. The static (limiting anisotropy) and dynamic (rotational relaxation time) structural components of diphenylhexatriene (DPH) motion in each leaflet were determined by phase and modulation fluorometry measurements combined with leaflet-specific quenching by trinitrophenyl groups. Polyunsaturated fatty acids, incorporated into the membrane phospholipids by culture medium supplementation, decreased the limiting anisotrophy of DPH in the cytofacial but not the exofacial leaflet thereby abolishing the transbilayer difference in fluidity. Peroxidation by Fe(II) + H2O2 resulted in a rigidification (increase in limiting anisotropy and rotational relaxation time) of the plasma membrane exofacial leaflet, regardless of whether the membranes contained saturated and monounsaturated fatty acids or were enriched in either linoleate or linolenate. The structure of the cytofacial leaflet reported by DPH was unaffected. Plasma membrane transbilayer sterol distribution, measured by leaflet-specific quenching of dehydroergosterol fluorescence, indicated that 20-28% of the sterol was localized in the exofacial leaflet. Polyunsaturated fatty acid supplementation of LM fibroblasts resulted in a complete reversal of plasma membrane transbilayer sterol distribution (72-76% exofacial leaflet). Sterol transbilayer distribution between the membrane leaflets was completely resistant to alteration by exposure to crosslinking agents and peroxidation in control plasma membranes and by peroxidation in linoleate- or linolenate-supplemented membranes.
It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergist... more It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and ...
Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despit... more Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despite few randomized controlled studies, therapeutic fasting is prescribed in various chronic diseases, as diabetes, hypertension and also cancer. Fasting is applied to lose weight in overweight and obese patients. However, weight loss is often associated with fat-free mass loss. Chronic caloric restriction has been associated with longevity in animal studies, while it has been poorly studied in humans to date. Good quality studies are needed to better understand the effects of fasting on health and diseases.
Nutritional status has a prognostic value in the clinical evolution of patients who are malnouris... more Nutritional status has a prognostic value in the clinical evolution of patients who are malnourished, are becoming malnourished or are in process of being rehabilitated. The evaluation of nutritional status is based on a comprehensive approach, and includes body composition measurement by bio-impedance analysis (BIA). BIA determines the quantity of body fat-free and fat mass and has a precision around 4%. The reliability of BIA depends on the use of body composition prediction equations that are adapted to the subjects studied and on the inclusion of various anthropometric parameters (weight, height, sex, age, race, etc). BIA remains imprecise in the presence of abnormal distribution of body compartments (ascites, dialysis, lipodystrophy) or of extreme weights (cachexia, severe obesity). Multi-frequency or segmental BIA were developed to overcome hydration abnormalities and variations in body geometry. However, these techniques require further validation. This review discusses the indications and limitations of BIA.
In the industrialised countries, the sedentary life and the ageing process of the population, as ... more In the industrialised countries, the sedentary life and the ageing process of the population, as well as the more frequent chronic diseases and heavy treatments, increase the incidence of protein-energy malnutrition (PEM). The insidious nature and harmful outcome of the PEM on the recovery process requires careful attention of the practitioner to the clinical signs of PEM. Their detection includes an anamnesis, anthropometric examinations, and assessments of the nutritional intakes and the impact of disease and medico-surgical treatments. However, the loss of muscle mass, which is the main indicator of the PEM, is often only assessed by the measurement of the body composition using bioelectrical impedance analysis. The advantage of this method is to distinguish fat-free mass, including muscle mass, from fat mass, when the loss of muscle is hidden by an increase of fat mass and/or body water. Using these different tools allows the practitioner to early detect PEM, to identify its causes, and to establish an appropriate nutritional schedule, in order to prevent from PEM or correct it.
MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy to use by any t... more MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy to use by any trained care-giver and valid for any adult patient. It considers body mass index, weight change and acute disease effect equally and determines a malnutrition risk score. If necessary, anthropometric measures may be simpliyfied by alternative methods. MUST is reliable between different healthcare settings et promotes detection and management of malnutrition during the patient medical course.
2.3.1 Synthèse et destruction cycliques de protéines 2.3.2 Complexes CDK4 et CDK6-cycline D 2.3.3... more 2.3.1 Synthèse et destruction cycliques de protéines 2.3.2 Complexes CDK4 et CDK6-cycline D 2.3.3 Protéines pRB et E2Fs 2.3.4 Complexes CDK2-cyclines A et E 2.3.5 Autres complexes enzymatiques 2.3.6 Protéine p21 CIP1 2.3.7 Protéine p27 KIP1 2.3.8 Protéines p16 INK4a , p15 INK4b , p18 INK4c , et p19 INK4d 2.3.9 Protéine p53 2.4 Synthèse et Réparation de l'ADN 2.4.1 Transmission de l'information génétique 2.4.2 Structure des nucléotides 2.4.3 Structure des acides nucléiques 2.4.4 Réplication de l'ADN 2.4.5 Réparation de l'ADN 2.5 Régulation Allostérique de la Synthèse des Nucléotides 2.6 Inhibition de la Synthèse de Thymidine 2.7 La 5-Iodo-2'-désoxyuridine 2.7.1 Synthèse et radiomarquage 2.7.2 Radioisotopes de l'iode 2.7.3 Considérations sur une application clinique 2.7.4 Les glioblastomes comme cibles potentielles 2.8 Objectifs du Travail
Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer ch... more Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer chemotherapy outcome. We aimed to investigate the effects of fish oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5-fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax+/+) and LS174T (Bax-/-) cells were co-treated for 24-72 h with 1 μm-5-FU, 1 μm-OX or 10 μm-IRI and/or FOE dilution corresponding to 24 μm-EPA and 20·5 μm-DHA. Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell viability, apoptosis and nuclear morphological changes were evaluated by cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'-diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was used to evaluate mitochondrial dysfunction, and protein expression involved in mitochondrial apoptosis was determined by ...
The effects of polyunsaturated fatty acids and lipid peroxidation on LM fibroblast plasma membran... more The effects of polyunsaturated fatty acids and lipid peroxidation on LM fibroblast plasma membrane individual leaflet sterol distribution and structural order were examined. The cytofacial (inner) leaflet was more rigid and contained more sterol than the exofacial (outer) leaflet. The static (limiting anisotropy) and dynamic (rotational relaxation time) structural components of diphenylhexatriene (DPH) motion in each leaflet were determined by phase and modulation fluorometry measurements combined with leaflet-specific quenching by trinitrophenyl groups. Polyunsaturated fatty acids, incorporated into the membrane phospholipids by culture medium supplementation, decreased the limiting anisotrophy of DPH in the cytofacial but not the exofacial leaflet thereby abolishing the transbilayer difference in fluidity. Peroxidation by Fe(II) + H2O2 resulted in a rigidification (increase in limiting anisotropy and rotational relaxation time) of the plasma membrane exofacial leaflet, regardless of whether the membranes contained saturated and monounsaturated fatty acids or were enriched in either linoleate or linolenate. The structure of the cytofacial leaflet reported by DPH was unaffected. Plasma membrane transbilayer sterol distribution, measured by leaflet-specific quenching of dehydroergosterol fluorescence, indicated that 20-28% of the sterol was localized in the exofacial leaflet. Polyunsaturated fatty acid supplementation of LM fibroblasts resulted in a complete reversal of plasma membrane transbilayer sterol distribution (72-76% exofacial leaflet). Sterol transbilayer distribution between the membrane leaflets was completely resistant to alteration by exposure to crosslinking agents and peroxidation in control plasma membranes and by peroxidation in linoleate- or linolenate-supplemented membranes.
It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergist... more It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and ...
Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despit... more Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despite few randomized controlled studies, therapeutic fasting is prescribed in various chronic diseases, as diabetes, hypertension and also cancer. Fasting is applied to lose weight in overweight and obese patients. However, weight loss is often associated with fat-free mass loss. Chronic caloric restriction has been associated with longevity in animal studies, while it has been poorly studied in humans to date. Good quality studies are needed to better understand the effects of fasting on health and diseases.
Nutritional status has a prognostic value in the clinical evolution of patients who are malnouris... more Nutritional status has a prognostic value in the clinical evolution of patients who are malnourished, are becoming malnourished or are in process of being rehabilitated. The evaluation of nutritional status is based on a comprehensive approach, and includes body composition measurement by bio-impedance analysis (BIA). BIA determines the quantity of body fat-free and fat mass and has a precision around 4%. The reliability of BIA depends on the use of body composition prediction equations that are adapted to the subjects studied and on the inclusion of various anthropometric parameters (weight, height, sex, age, race, etc). BIA remains imprecise in the presence of abnormal distribution of body compartments (ascites, dialysis, lipodystrophy) or of extreme weights (cachexia, severe obesity). Multi-frequency or segmental BIA were developed to overcome hydration abnormalities and variations in body geometry. However, these techniques require further validation. This review discusses the indications and limitations of BIA.
In the industrialised countries, the sedentary life and the ageing process of the population, as ... more In the industrialised countries, the sedentary life and the ageing process of the population, as well as the more frequent chronic diseases and heavy treatments, increase the incidence of protein-energy malnutrition (PEM). The insidious nature and harmful outcome of the PEM on the recovery process requires careful attention of the practitioner to the clinical signs of PEM. Their detection includes an anamnesis, anthropometric examinations, and assessments of the nutritional intakes and the impact of disease and medico-surgical treatments. However, the loss of muscle mass, which is the main indicator of the PEM, is often only assessed by the measurement of the body composition using bioelectrical impedance analysis. The advantage of this method is to distinguish fat-free mass, including muscle mass, from fat mass, when the loss of muscle is hidden by an increase of fat mass and/or body water. Using these different tools allows the practitioner to early detect PEM, to identify its causes, and to establish an appropriate nutritional schedule, in order to prevent from PEM or correct it.
MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy to use by any t... more MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy to use by any trained care-giver and valid for any adult patient. It considers body mass index, weight change and acute disease effect equally and determines a malnutrition risk score. If necessary, anthropometric measures may be simpliyfied by alternative methods. MUST is reliable between different healthcare settings et promotes detection and management of malnutrition during the patient medical course.
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Papers by Yves Dupertuis