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Biomedical subjects

L Vincent

Publications and source records attributed to L Vincent.

At least 19 recordsLinked to original sources

Activation of FGFR1beta signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells.

Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1beta signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1beta results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1beta signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1beta supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.

Acute Disease↗

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness.

In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased.

Breast Neoplasms↗

Fenofibrate inhibits angiogenesis in vitro and in vivo.

Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, used as a normolipidemic agent, is thought to offer additional beneficial effects in atherosclerosis. Since angiogenesis is involved in plaque progression, hemorrhage, and instability, the main causes of ischemic events, this study was designed to evaluate the action of fenofibrate on angiogenesis. Our results show that fenofibrate (i) inhibits endothelial cell proliferation induced by angiogenic factors, followed at high concentrations by an increase in apoptosis, (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo. Concerning the mechanism of action, the inhibition of endothelial cell migration by fenofibrate can be explained by a disorganization of the actin cytoskeleton. At the molecular level, fenofibrate markedly decreased basic fibroblast growth factor-induced Akt activation and cyclooxygenase 2 gene expression. This inhibition of angiogenesis could participate in the beneficial effect of fenofibrate in atherosclerosis.

Actins↗

Acute renal failure in the tropics: emerging trends from a tertiary care hospital in South India.

AIM: To study epidemiology, laboratory parameters, outcome and factors determining outcome of patients presenting with acute renal failure in our hospital. MATERIALS AND METHODS: A prospective study between December 1997-December 1999 in which all patients presenting with acute renal failure were included. Demographics, laboratory parameters, etiology, outcome and prognostic factors determining outcome were studied. RESULTS: 642 patients were part of the study. The predominant underlying cause for ARF was sepsis (153/642); overall mortality was 26.5%. Patients who had sepsis were admitted in the ICU, and patients with oliguria had poorer outcome. CONCLUSION: Sepsis continues to be the predominant cause of ARF. Overall mortality of our patients is better, because of the case mix, a large percentage of patients had acute gastroenteritis as a cause of CRF.

Acute Kidney Injury↗

Renal failure in a patient with primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APLA) is a syndrome complex characterized by recurrent arterial or venous thrombosis, recurrent fetal wastage, thrombocytopenia and presence in serum of antibodies against negatively charged phospholipids like lupus anticoagulant (LA), anticardiolipin antibody (ACLA) and subgroups. These are classified further as primary (wherein this occurs in isolation) and secondary (associated with infection, drugs and malignancies). It is uncommon to find both LA and ACLA in primary APLA syndrome (unlike as in the secondary form). Renal manifestations which include renal arterial and venous occlusion and infarction and thrombotic microangiopathy have also been infrequently described. We hereby present a case of primary APLA syndrome with unusual features of LA and ACLA occurring together and also the presence of renal failure due to left renal artery thrombosis and right renal artery occlusion.

Antiphospholipid Syndrome↗

The effect of group psychosocial support on survival in metastatic breast cancer.

BACKGROUND: Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival. METHODS: In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires. RESULTS: Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]). CONCLUSIONS: Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.

Adult↗

Inhibition of endothelial cell migration by cerivastatin, an HMG-CoA reductase inhibitor: contribution to its anti-angiogenic effect.

Recent studies have suggested that inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (statins) can play a role in protection against vascular risk, which is independent of cholesterol reduction. It could act by inhibiting the synthesis of isoprenoids (farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP)), which are respectively essential for membrane attachment and biological activity of GTPases Ras and RhoA. This study demonstrates that a statin (cerivastatin) inhibits angiogenesis. This effect was due to a decrease in endothelial cell locomotion which was reversed by GGPP. It was mainly related to delocalization of RhoA from cell membrane to cytoplasm, responsible for the disorganization of actin stress fibers. Furthermore, a decrease in MMP-2 secretion, involved in cell invasion, was also observed. This effect is rather due to Ras inhibition as it was reversed by FPP. This anti-angiogenic activity could explain the beneficial effect of statins on atherosclerosis and on cancer prevention as shown by clinical studies.

Actins↗

Fibrinogen: a vascular risk factor, why? Contributing effect of oncostatin M on both fibrinogen biosynthesis by hepatocytes and participation in atherothrombotic risk related to modifications of endothelial cells.

Fibrinogen is a vascular risk factor. We suggest that it is a marker of cytokine secretion that simultaneously stimulates fibrinogen biosynthesis and vascular modifications responsible for atherothrombosis. Among these cytokines, oncostatin M (OSM) is the most potent cytokine for inducing fibrinogen biosynthesis by hepatocytes, and it could contribute to endothelial cell anomalies involved in the atherothrombotic process. Here we show that OSM acts (1) by inducing the secretion involved in invasion of the vessel wall by monocytes; (2) by inducing angiogenesis it promotes plaque destabilization, rupture, and consequently thrombosis; and (3) by decreasing fibrinolysis on macrovascular endothelial cells.

Arteriosclerosis↗

[Neoadjuvant chemoradiotherapy and peroperative radiotherapy for non-small-cell lung cancer of the apex. A study of 5 cases].

The management of superior sulcus tumors with Pancoast 's syndrome is not well defined, especially in view of their low frequency. Even if surgery performed by "en bloc" resection of the tumor and the chest wall is recommended, neoadjuvant treatment could have a potential benefit on the resecability and pain control. We report five cases of Pancoast tumors (NSCLC), treated by radiotherapy and chemotherapy before surgery. Four tumors was on stage IIIb. A regimen with radiotherapy (50 Gy) and chemotherapy (cisplatinum + etoposide) was initially performed. Four tumors were resected, with 2 complete pathologic responses and good control on pain. Three patients received radiotherapy during surgery. No toxic reaction was observed. This regimen may be discussed with locally advanced tumors and poor prognosis.

Aged↗

Influencing nurses' knowledge, attitudes, and practice in cancer pain management.

The purpose of this study was to explore the effects of an education intervention on nurses' knowledge, attitudes, and practice in pain assessment and management over 3 months. The education intervention program was designed to change knowledge and influence the attitudes of registered nurses through a values clarification process using a conceptual framework based on a theory of reeducation. Participants in this descriptive, exploratory study were 53 nurses from six oncology units. Data were collected on their knowledge, attitudes, documentation practices, and analgesic choices in defined patient situations. The intervention was effective in changing the knowledge, attitudes, and behaviors of nurses in the study, but the effect was not maintained over time. Study findings suggest that further educational and organizational support is needed for effective practice in pain assessment and management. Further research should explore education programs that will maintain new knowledge over time. In addition, assessment of the effect that new knowledge has on the achievement of improved pain relief for patients should be explored in the future.

Attitude of Health Personnel↗

[Digestive disorders and Legionnaires' lung disease. Accompanying signs or visceral location?].

Digestive disorders in Legionella pneumophila pneumonia such as nausea, vomiting, diarrhoea, are common; they are clinical arguments to suspect this bacteria to be responsible for this pneumonia. In this case-report, a patient with pneumonia due to Legionella pneumophila serogroup I presented in the follow-up with signs of enteritis with ascites. We looked ahead in literature who made us discover the multiple organ involvement that may happen in Legionnaires' disease. Diagnostic procedures consist in simple tests as ultrasonography, abdominal computerised tomography, that show inflammatory disease signs and sometimes ascites. Exceptionally, Legionella pneumophila has been demonstrated with direct immunofluorescent microscopic study, in inflammatory colitis pieces with haemorrhagic necrosis in different stage processes. Pathogenesis could be explained by the systemic spread of the organism and formation at distance of necrotising enteritis focus. It is initiated by necrotising factors of bacterial origin and hypersensitivity reactions (type I and III).

Adult↗

Pulmonary mucormycosis in a diabetic patient.

We present the case of a 54 year-old male from Moldavia with diabetes mellitus (type II diabetic), admitted to hospital in January 1999, with ketoacidosis and consolidation of the lower left lobe. The diagnosis of mucormycosis was confirmed by identification of large, nonseptate hyphae of the order Mucorales. A strain of Rhizopus oryzae (Rhizopus arrhizus) was isolated from culture on sabouraud medium. The patient was treated by systemic amphotericin B, associated with surgical debridement (lobectomy). The treatment with amphotericin B was stopped after ten days and the patient was completely asymptomatic and returned to Moldavia. Mucormycoses are rare, and tend to be encountered in individuals with predisposing factors such as malignant blood disorders (immunocompromised patients) or diabetes mellitus. Prognosis is poor, resembling infection with Aspergillus, despite aggressive treatment as in the present case. The gravity of the condition can be accounted for by the thrombotic and necrosing nature of the fungal invasion of lung vessels.

Diabetes Complications↗

Cyclooxygenase-2 activity is necessary for the angiogenic properties of oncostatin M.

Macrophages play a major role in angiogenesis. We recently reported that oncostatin M (OSM), a cytokine of the interleukin (IL)-6 family secreted by macrophages, has a potent angiogenic activity on human microvascular endothelial cells (HMEC-1), but has no effect on macrovascular cells (human umbilical vein endothelial cells (HUVECs)). In this work, we show that in HMEC-1, OSM (0.5-2.5 ng/ml), leukemia inhibitory factor (LIF) (25 ng/ml), bFGF (25 ng/ml) and IL-1beta (5 ng/ml) induced production of cyclooxygenase (COX)-2. In contrast, in HUVECs, neither OSM nor LIF induced COX-2 mRNA, suggesting that COX-2 might be implicated in the angiogenic activity of OSM. This was confirmed by the inhibiting effect on OSM-induced HMEC-1 proliferation of specific COX-2 inhibitors. In vivo studies confirmed this findings. We conclude that induction of COX-2 by OSM is necessary for its angiogenic activity, but is not sufficient since IL-1beta, which also induces COX-2 in HMEC-1, has only a poor proliferative effect.

Animals↗

Fatigue in women with breast cancer receiving radiation therapy.

Fatigue is a common complaint of individuals receiving treatment for cancer. There is a dearth of rigorous research investigating the clinical course and prognosis of fatigue over the course of radiation therapy. Seventy six patients with breast cancer receiving external radiation therapy were followed longitudinally from the onset of treatment to 6 months post-treatment. Fatigue significantly increased over the course of treatment, was highest at the last week of treatment, and returned to pretreatment levels by 3 months after treatment. Fatigue was not influenced by the patient's age, stage of disease, time since surgery, weight, and length of time since diagnosis. Fatigue was significantly related to symptom distress, psychologic distress, and self-reported fatigue relief strategies. The most frequently reported self-relief strategies were "sit" and "sleep." Fatigue had a negative impact on the patient's quality of life. Impairment in quality of life was evident by the end of treatment, with improvement by 3 and 6 months after treatment. The second week through to the last week of radiation therapy are critical times to target interventions for the management of fatigue. The amelioration of concomitant symptoms is a supportive approach that might be helpful. Self-help strategies focusing on the cessation of activity and increasing rest were reported as successful by patients.

Activities of Daily Living↗

[Percutaneous closure of an right-left interatrial shunt acquired after pneumonectomy].

Right to left shunt through a patent foramen ovale after pneumonectomy is a rare complication. Its clinical presentation is a severe dyspnea with posture dependency. The diagnosis is easily confirmed by contrast echocardiography. The purpose of this article is to expose the interest of interventional catheterization and transcatheter closure. This method appears to be a viable alternative to surgery for those patients with precarious respiratory function.

Cardiac Catheterization↗

Attitudes of Canadian oncology practitioners toward psychosocial interventions in clinical and research settings in women with breast cancer.

The aim of this study was to survey Canadian oncology practitioners' attitudes toward psychosocial concerns and issues in women with breast cancer. Surveys were mailed to 351 medical, radiation and surgical oncologists and 375 oncology nurses. Standard questionnaires assessed attitudes towards psychosocial issues in women with primary and metastatic breast cancer and evaluated the practitioners' willingness to refer women to psychosocial intervention trials in the presence and absence of competing drug trials. Responses were obtained from 74% of those surveyed. Respondents reported being aware of the common occurrence of psychosocial problems in women with metastatic breast cancer, however, physicians were less likely than nurses to offer these women psychosocial support on a prophylactic basis (p < 0.0001) and they expressed greater concern than nurses about scientific validity of (p = 0.0003), and potential psychological damage from (p = 0.005), psychosocial support groups. Nurses were more likely than physicians to favour a study investigating group psychosocial support over competing drug studies (p < or = 0.003) in the metastatic setting. Physicians were less likely than nurses to deal with weight problems prophylactically in women with primary breast cancer (p = 0.0009) and they expressed greater concern over scientific validity of psychosocial interventions addressing weight than nurses (p = 0.0008); nurses were more concerned about excessive expectations of patients regarding potential benefits of such interventions (p < 0.0001). Regardless, nurses were more likely than physicians to favour a psychosocial intervention study focused on weight management over drug studies in pre- (p = 0.0006) and postmenopausal women (p = 0.05) with primary breast cancer. Canadian oncology practitioners are aware of the common occurrence of psychosocial distress in women with breast cancer. Physicians and nurses assigned differing priorities to psychosocial interventions in both clinical and research situations.

Adult↗