Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line

<p>Abstract</p> <p>Background</p> <p>Troglitazone (TGZ) is a potential anticancer agent. Little is known about the effect of this agent on cancer cell migration.</p> <p>Methods</p> <p>Human ovarian carcinoma cell line, ES-2 cells were treated with various concentrations of TGZ. Cell migration was evaluated by wound-healing and Boyden chamber transwell experiments. PPARγ expression was blocked by PPARγ small interfering RNA. The effects of TGZ on phosphorylation of FAK, PTEN, Akt were assessed by immunoblotting using phospho-specific antibodies. The cellular distribution of paxillin, vinculin, stress fiber and PTEN was assessed by immunocytochemistry.</p> <p>Results</p> <p>TGZ dose- and time-dependently impaired cell migration through a PPARγ independent manner. TGZ treatment impaired cell spreading, stress fiber formation, tyrosine phosphorylation of focal adhesion kinase (FAK), and focal adhesion assembly in cells grown on fibronectin substratum. TGZ also dose- and time-dependently suppressed FAK autophosphorylation and phosphorylation of the C-terminal of PTEN (a phosphatase). At concentration higher than 10 μM, TGZ caused accumulation of PTEN in plasma membrane, a sign of PTEN activation.</p> <p>Conclusion</p> <p>These results indicate that TGZ can suppress cultured ES-2 cells migration. Our data suggest that the anti-migration potential of TGZ involves in regulations of FAK and PTEN activity.</p

Effects of body position on autonomic regulation of cardiovascular function in young, healthy adults

Background: Analysis of rhythmic patterns embedded within beat-to-beat variations in heart rate (heart rate variability) is a tool used to assess the balance of cardiac autonomic nervous activity and may be predictive for prognosis of some medical conditions, such as myocardial infarction. It has also been used to evaluate the impact of manipulative therapeutics and body position on autonomic regulation of the cardiovascular system. However, few have compared cardiac autonomic activity in supine and prone positions, postures commonly assumed by patients in manual therapy. We intend to redress this deficiency. Methods: Heart rate, heart rate variability, and beat-to-beat blood pressure were measured in young, healthy non-smokers, during prone, supine, and sitting postures and with breathing paced at 0.25 Hz. Data were recorded for 5 minutes in each posture: Day 1 - prone and supine; Day 2 - prone and sitting. Paired t-tests or Wilcoxon signed-rank tests were used to evaluate posture-related differences in blood pressure, heart rate, and heart rate variability. Results: Prone versus supine: blood pressure and heart rate were significantly higher in the prone posture (p &lt; 0.001). Prone versus sitting: blood pressure was higher and heart rate was lower in the prone posture (p &lt; 0.05) and significant differences were found in some components of heart rate variability. Conclusion: Cardiac autonomic activity was not measurably different in prone and supine postures, but heart rate and blood pressure were. Although heart rate variability parameters indicated sympathetic dominance during sitting (supporting work of others), blood pressure was higher in the prone posture. These differences should be considered when autonomic regulation of cardiovascular function is studied in different postures

Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma

Fifteen patients with relapsed osteosarcoma were treated with an intensive combination chemotherapy schedule. Ifosfamide 2.5 g m−2 daily and etoposide 150 mg m−2 daily coincidentally for 3 days and high-dose methotrexate 8 g m−2 (with folinic acid rescue) on days 10–14 in a planned 21-day cycle. Feasibility, toxicity and response to this alternative combination for the treatment of relapsed osteosarcoma was assessed. There were 98 evaluable cycles for toxicity and tolerability. The majority of cycles were well tolerated. Haematological toxicity of grade 3/4 (common toxicity criteria) was seen in all courses. Renal tubular loss of electrolytes, particularly magnesium, occurred in 71% of cycles. Thirteen per cent of cycles were repeated within 21 days and 61% within 28 days. In the thirteen patients evaluable for response, a partial response rate of 31% was seen after two cycles. However, patients with stable disease continued on therapy, and an overall consequent response rate of 62% was observed. Four patients were alive with no evidence of disease at 8–74 months. Three are alive with disease (at 8–19 months). There were six deaths, all disease related. This regimen exhibits an encouraging response rate in a group of children with poor prognosis disease, with a tolerable toxicity profile. © 1999 Cancer Research Campaig

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Beyond equilibrium climate sensitivity

ISSN:1752-0908ISSN:1752-089