Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia.

Neuropilin-1 (NRP-1), a vascular endothelial growth factors and semaphorin receptor functioning as mediator of angiogenesis and neuronal guidance, is expressed by various solid tumors. The importance of NRP-1 in hematological malignancies such as acute myeloid leukemia (AML) remains to be elucidated. Therefore, we determined NRP-1 expression by immunohistochemical analysis of bone marrow biopsies of patients with newly diagnosed, untreated AML. The expression of NRP-1 was significantly increased in AML patients (n = 76; median 12.9 arbitrary units (a.u.)) as compared with controls (n = 38; median 2.75 a.u.). Survival was significantly poorer in patients with high (> median) versus low (< or = median) NRP-1 expression levels with 5-year overall survival rates of 16.9 versus 49.6% (P = 0.050). In conclusion, our data provide evidence of increased NRP-1 expression in AML with significant correlation to survival. Thus, NRP-1 might constitute a promising target for antileukemic and antiangiogenic treatment strategies in AML.     

Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors

In acute myeloid leukemia (AML), receptor tyrosine kinase ligands promote growth and survival and contribute to AML-associated marrow neoangiogenesis. We have tested simultaneous inhibition of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptor signaling by novel indolinone derivatives using 14 myeloid, including 11 human leukemic, cell lines. Compounds inhibited colony formation of all cell lines in a dose-dependent fashion. Inhibitory concentrations for 50% of the colony formation/survival (IC50) for BIBF1000 were <100 nmol/L for 3 of 11, 相似文献   

Dietary change, nutrition education and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a prevalent and serious condition. Nutrition might play a role in COPD prevention and is definitely important in COPD management. There are some indications from epidemiological studies that dietary factors such as ample consumption of fruit and fish may decrease COPD risk. The available evidence is, however, not substantial enough to warrant dietary recommendations for primary prevention of COPD. Substantial evidence does point to the conclusion that, regardless of disease severity, weight loss is related to decreased exercise capacity, health status and mortality as well as to increased morbidity among patients with moderate to severe COPD. Current nutritional support strategies have primarily focussed on treatment of severely underweight and disabled patients. In an in-patient setting or when incorporated in a pulmonary rehabilitation programme, nutritional support has proved effective in inducing weight gain and related functional improvements. However, such interventions are only feasible for a selected group of patients and are very laborious. Therefore, opportunities for dietary and nutrition interventions in COPD management should be explored, aiming at early detection, prevention and early treatment of involuntary weight loss. This means expanding the target group to include COPD out-patients and primary care patients before they have become underweight, and putting more emphasis on dietary change than on medically prescribed supplementation. Successful intervention assumes (voluntary) adjustment of dietary behaviour, and health professionals may play an essential role in encouraging patients to make and maintain these changes. Achieving dietary change among COPD patients may require a combination of diet counselling and self-management. A model for such a combination is presented.     

Long-term secondary prophylaxis in children, adolescents and young adults with von Willebrand disease. Results of a cohort study

In patients with von Willebrand disease (VWD) replacement therapy with factor VIII/von Willebrand (VWF) concentrates is increasingly applied as prophylactic regimen. Since 2000, 82 consecutively enrolled patients with clinically relevant bleeding episodes (spontaneous, peri- or postoperative) were diagnosed with VWD [type 1: 42/82; type 2: 24/82; type 3: 13/82; acquired: 3/82]. In all patients, decision for initiating prophylaxis was based on a bleeding score > 2 prior to diagnosis, concomitant with recurrent bleeds associated with anaemia in patients with on-demand VWD therapy. We report results on secondary prophylactic VWF replacement therapy applied in 32 patients [children n=13; adolescents n=7; adults n=12] with VWD [type 1: 4; type 2: 15; type 3: 13], 15 of which were females, and nine of these at the reproductive period. Eight patients were treated with Humate P? or Wilate? (n=24). Median [min-max] dose [vWF:RCo] was 40 [20-47] IU/kg, 23 patients were given substitution therapy twice weekly, seven patients three times a week, and two children four times per week. Within a 12-month-period haemoglobin concentrations returned to normal values. Median duration of prophylaxis was three years. Recurrent bleeding episodes stopped in 31 of 32 patients, whereas inhibitors developed in one. Following a 12-month observation period the monthly bleeding frequency and the bleeding score was significantly reduced [3 vs. 0.07; 3 vs. 0: p< 0.001], compared to the pre-prophylaxis/pre-diagnostic values. The use of secondary prophylactic VWF replacement therapy is an effective tolerated treatment modality, highly beneficial for patients with VWD, who present with recurrent bleeding events during on-demand therapy.     

Tailored Print Communication and Telephone Motivational Interviewing Are Equally Successful in Improving Multiple Lifestyle Behaviors in a Randomized Controlled Trial

Background  

Computer tailoring and motivational interviewing show promise in promoting lifestyle change, despite few head-to-head comparative studies.     

Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile

tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.