Fluoxetine Inhibits STAT3-mediated Survival and Invasion of Osteosarcoma Cells.

BACKGROUND/AIM: Osteosarcoma (OS) is a common primary malignancy of bone in adolescents. Its highly metastatic characteristics can lead to treatment failure and poor prognosis. Although standard treatments, including surgery, radiotherapy, and chemotherapy, have progressed in the past decade, treatment options to overcome metastatic progression remain sparse. Fluoxetine, an anti-depressant, has been widely used in patients with cancer for their mental issues and was reported to possess antitumor potential. However, the effect of fluoxetine on OS remains unclear. MATERIALS AND METHODS: In this study, we used cell viability, invasion/migration transwell, wound-healing and aortic ring assays to identify the effects of fluoxetine on metastasis and progression in OS. RESULTS: Fluoxetine induced cytotoxicity in OS cells by activating both extrinsic/intrinsic apoptosis signaling pathways. Proliferation and anti-apoptosis-related factors such as cyclin D1 and X-linked inhibitor of apoptosis were suppressed by fluoxetine. Additionally, fluoxetine suppressed the invasive/migratory abilities of OS and inhibited the development of angiogenesis by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Metastasis-associated factors, vascular endothelial growth factors, matrix metallopeptidase 2 and -9, were all reduced in OS cells by fluoxetine treatment. CONCLUSION: Fluoxetine not only induces cytotoxicity and apoptosis of OS cells, but also suppresses metastasis and angiogenesis by targeting STAT3.

Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome.

OBJECTIVE: This study was undertaken to evaluate the pregnancy and perinatal outcomes of pregnant women with severe acute respiratory syndrome (SARS). STUDY DESIGN: All pregnant women (12) who presented with SARS in Hong Kong between February 1 and July 31, 2003, were included. The pregnancy and perinatal outcomes were collected. Evidence of perinatal transmission of virus was assessed with the SARS-associated coronavirus reverse-transcriptase polymerase chain reaction on cord blood, placenta tissue, and subsequent follow-up of the neonate on serology. RESULTS: Three deaths occurred among the 12 patients, giving a case fatality rate of 25%. Four of the 7 patients (57%) who presented in the first trimester had spontaneous miscarriage. Four of the 5 patients who presented after 24 weeks were delivered preterm. Two mothers recovered without delivery, but their ongoing pregnancies were complicated by intrauterine growth restriction. No newborn infant had clinical SARS and all investigations were negative for SARS. CONCLUSION: SARS during pregnancy is associated with high incidences of spontaneous miscarriage, preterm delivery, and intrauterine growth restriction. There is no evidence of perinatal SARS infection among infants born to these mothers.

Limitation of life support: frequency and practice in a Hong Kong intensive care unit.

OBJECTIVE: To examine the frequency and the decision-making processes involved in limiting (withdrawing and withholding) life support therapy in critically ill Chinese patients in the intensive care unit. DESIGN: Prospective survey of patients who had life support limited between April 1997 and March 1999. SETTING: Medical and surgical intensive care unit of a teaching hospital. PATIENTS: All patients admitted to the intensive care unit of the Prince of Wales Hospital who subsequently died and/or had life support limited. Brain-dead patients were excluded from analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 490 patients who died in the intensive care unit, limitation of life support occurred in 288 (58.8%). Relatives or patients requested limitation of life support in 32 cases (11%). The family and/or patient concurred with limitation of life support in 273 occasions (95%). Therapy was withheld in 30.8% and withdrawn in 28.0% of deaths. Therapy limited included inotropes, additional oxygen, and renal replacement therapy. CONCLUSIONS: Limitation of therapy in dying Chinese patients occurs frequently in intensive care patients, and both patients and relatives concur with medical decisions to limit therapy in these patients. Withholding therapy rather than withdrawing therapy occurs more frequently than in Western populations.

Left ventricular long-axis changes in early diastole and systole: impact of systolic function on diastole.

Impaired long-axis motion is a sensitive marker of systolic myocardial dysfunction, but no data are available that relate long-axis changes in systole with those in diastole, particularly in subjects with diastolic dysfunction and a 'normal' left ventricular (LV) ejection fraction. A total of 311 subjects (including 105 normal healthy volunteers) aged 20-89 years with variable degrees of systolic function (LV ejection fraction range 0.15-0.84) and diastolic function were studied using tissue Doppler echocardiography and M-mode echocardiography to determine mean mitral annular amplitude and peak velocity in systole and early and late diastole. The LV systolic mitral annular amplitude (S(LAX), where LAX is long-axis amplitude) and peak velocity (S(m)) correlated well with the respective early diastolic components (E(LAX) and E(m)) and late diastolic (atrial) components (A(LAX) and A(m)). A non-linear equation fitted better than a linear relationship (non-linear model: S(LAX) against E(LAX), r(2)=0.67; S(m) against E(m), r(2)=0.60; S(LAX) against A(LAX) and S(m) against A(m), r(2)=0.42). After adjusting for age, sex and heart rate, linear relationships of early diastolic (E(LAX), r(2)=0.70; E(m), r(2)=0.60) and late diastolic (A(LAX), r(2)=0.61; A(m), r(2)=0.64) long-axis amplitudes and velocities with the respective values for S(LAX) and S(m) were found, even in those subjects with apparently 'isolated' diastolic dysfunction. Long-axis changes in systole or diastole did not correlate with Doppler mitral velocities. We conclude that ventricular long-axis changes in early diastole are closely related to systolic function, even in subjects with diastolic dysfunction. 'Pure' or isolated diastolic dysfunction is uncommon.