Characterisation and manipulation of docetaxel resistant prostate cancer cell lines.

Background: There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel.

Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation.

Background: Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis.

Methods: cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting.

Neonatal encephalopathy is associated with altered perinatal systemic neutrophil apoptosis.

Systemic hypoxia-ischemia at birth may alter the neonatal neutrophil phenotype. In this study, we evaluated alterations in perinatal neutrophil phenotype following systemic hypoxia-ischemia compared with normal controls. Neutrophils from adults (n = 15), normal newborns (n = 20), newborns requiring resuscitation at birth (n = 17), and their respective maternal samples were incubated alone or with lipopolysaccharide (LPS).

Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults.

Background: Dysfunctional inflammatory responses have been implicated in several neonatal inflammatory disorders following infection and hypoxia.

Objectives: We aimed to study the effects of in vitro hypoxia and heat shock (HS) on normal adult and newborn neutrophil migration (CD11b) and persistence (apoptosis) following lipopolysaccharide (LPS) stimulation.

Methods: The mechanism for altered LPS responses was assessed at the level of the LPS signalling receptors, Toll-like receptor-4 (TLR-4), TLR-2 and CD14 expression in normal neonates and adults.

TGF-beta1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation.

Apoptosis and epithelial-mesenchymal transdifferentiation (EMT) occur in stressed tubular epithelial cells and contribute to renal fibrosis. Transforming growth factor (TGF)-beta(1) promotes these responses and we examined whether the processes were interdependent in vitro. Direct (caspase inhibition) and indirect [epidermal growth factor (EGF) receptor stimulation] strategies were used to block apoptosis during TGF-beta(1) stimulation, and the subsequent effect on EMT was assessed.

Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function.

Neutropenia is a common sequela of neonatal sepsis. Recent clinical trials have shown the beneficial effects of colony-stimulating factors (CSFs) on outcome in this group, but the exact mechanism remains unknown. Neonates and mothers who were at high-risk for infection were recruited for cord blood sampling in a university tertiary referral maternity hospital.

Gene expression profile of inflammatory neutrophils: alterations in the inhibitors of apoptosis proteins during spontaneous and delayed apoptosis.

Inflammatory mediators delay neutrophil apoptosis, which contributes to the persistence of inflammation. The mechanisms responsible for this delay and resistance to Fas antibody-induced apoptosis are unknown but are dependent on protein synthesis. These proteins have been shown to inhibit caspase activity central to the induction of apoptosis.

Aspirin preserves neutrophil apoptosis after cardiopulmonary bypass.

The aim of this study was to test the hypothesis that ongoing aspirin therapy preserves neutrophil apoptosis after cardiac surgery with cardiopulmonary bypass (CPB) by a cyclooxygenase mechanism. Twenty patients undergoing coronary revascularization with CPB were enrolled in a prospective cohort study. Patients who had continued taking 300 mg of aspirin until the day before surgery (n = 10) were compared with 10 patients not taking aspirin or who had discontinued it more than 5 days before surgery.

Labor promotes neonatal neutrophil survival and lipopolysaccharide responsiveness.

Labor is a mild proinflammatory state that is associated with fetal leukocytosis. Elective cesarean section has been linked with increased neonatal morbidity, which may be partially immune mediated. We hypothesized that labor may alter neutrophil phenotype and thereby decrease neonatal complications.

Labor induces a maternal inflammatory response syndrome.

Objective: We studied the effect of labor on maternal neutrophil phenotype.

Study Design: Neutrophil apoptosis with inflammatory cytokines and the expression of CD11b, CD34 and toll-like receptor 4 (TLR4) were assessed with flow cytometry in women at uncomplicated vaginal delivery (VD), and elective cesarean section (ElCS) without labor, emergency cesarean section with (EmCSL+) or without (EmCSL-) labor.

Results: Spontaneous neutrophil apoptosis is delayed in maternal neutrophils after VD, EmCSL+ or EmCSL- versus ElCS.

Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone.

Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed.

The apoptosome pathway to caspase activation in primary human neutrophils exhibits dramatically reduced requirements for cytochrome C.

Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the "apoptosome" as a result of the cell stress-associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain.

Endothelin in unilateral ureteral obstruction: vascular and cellular effects.

Purpose: Unilateral ureteral obstruction results in decreased blood flow and tissue loss in the obstructed kidney. This condition is compensated by increased perfusion and trophic changes in the contralateral kidney. Vascular mediators' effects are central to these changes and of these mediators endothelin is the most potent vasoconstrictor known.

Androgen-mediated resistance to apoptosis.

Background: Previous studies demonstrate that androgen is capable of exerting a protective effect in the androgen-sensitive human prostate cancer cell line LNCaP. Limited studies, however, have addressed the underlying mechanisms involved, in particular the effects of androgen on both pro- and anti-apoptotic gene expression.

Methods: We investigated the effects of androgen on apoptotic sensitivity and the expression of the caspases and specific members of the Bcl-2 family in the LNCaP cell line.

Cytoprotective effects of nitrates in a cellular model of hydronephrosis.

Background: The earliest insult to the kidney following the onset of ureteral obstruction is a marked elevation in collecting system pressure. This imparts a mechanical stress that is transmitted directly from the collecting system to the kidney substance. Renal tubular injury is the principal functional and histological change encountered, with glomerular changes being less marked and occurring later.

Inhibitors of apoptosis proteins in prostate cancer cell lines.

Background: The caspases are the central executioners of apoptosis. The inhibitors of apoptosis proteins (IAPs) are a family of recently described caspase inhibitors. We hypothesised that tumor resistance to apoptosis could be due in part to IAP expression.