Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.

FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain.

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BACKGROUND: This study assessed the long‐term safety and tolerability of fentanyl buccal tablet (FBT) in opioid‐tolerant patients with cancer and breakthrough pain (BTP) who were either naive to FBT or had completed 1 of 2 previous double‐blind, placebo‐controlled FBT studies (rollover patients). METHODS: Patients who were FBT‐naive underwent titration to find a successful FBT dose. Rollover patients used a previously identified successful dose of FBT. Patients who achieved a successful dose were eligible to enter a maintenance phase (≥12 months). Safety assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory tests. RESULTS: Two hundred thirty‐two patients were enrolled. A total of 112 entered titration; 79 identified a successful FBT dose, and 77 of these patients entered the maintenance phase along with 120 rollover patients (n = 197). AEs resulted in discontinuation of therapy for 33% of patients. The most common AEs were generally typical of opioids administered to cancer patients. All serious AEs were considered to be related to the patients' underlying conditions, except for 1 incident of FBT‐related drug withdrawal syndrome. Sixty patients died after enrollment because of disease progression. Fifteen (6%) patients experienced ≥1 application‐site AE, all of which were considered by investigators to be related to FBT. CONCLUSIONS: FBT was generally well tolerated and had a favorable safety profile in the long‐term (≥12 months) management of patients with persistent cancer pain and BTP. No unexpected AEs occurred. Safety and tolerability was similar to that observed in short‐term studies. Cancer 2009. © 2009 American Cancer Society.

FBT resulted in more rapid onset of analgesia and was generally well tolerated in comparison with oxycodone for the treatment of BTP in opioid-tolerant patients.

Inactivation of p53-mediated cell death pathways is a central component of cancer progression. ASPP2 (apoptosis stimulated protein of p53-2) is a p53 binding protein that specially stimulates pro-apoptosis function of p53. Down-regulation of ASPP2 is observed in many human cancers and is associated with poor prognosis and metastasis. In this study, ASPP2 was found to enhance L-OHP-induced apoptosis in HCT116 p53−/− cells in a p53-independent manner. Such apoptosis-promoting effect of ASPP2 was achieved by inhibiting autophagy. Further experiments with ASPP2 RNA interference and autophagy inhibitor (3-methyladenine, 3-MA) confirmed that ASPP2 enhanced HCT116 p53−/− cell apoptosis via inhibiting the autophagy. The association of cell death and autophagy was also found in ASPP2+/− mice, where colon tissue with reduced ASPP2 expression displayed more autophagy and less cell death. Finally, colorectal tumours and their adjacent normal tissues from 20 colorectal cancer patients were used to examine ASPP2 expression, p53 expression and p53 mutation, to understand their relationships with the patients' outcome. Three site mutations were found in p53 transcripts from 16 of 20 patients. ASPP2 mRNA expressions were higher, and autophagy level was lower in the adjacent normal tissues, compared with the tumour tissues, which was independent of both p53 mutation and expression level. Taken together, ASPP2 increased tumour sensitivity to chemotherapy via inhibiting autophagy in a p53-independent manner, which was associated with the tumour formation, suggesting that both p53 inactivation and ASPP2 expression level were involved in the sensitivity of colorectal cancer to chemotherapy.

BackgroundOur previous work demonstrated that persistent peripheral nociception (PPN) leads to synaptic plasticity and functional changes in the rat hippocampus. The protein kinase mTOR is a critical regulator of protein synthesis-dependent synaptic plasticity in the hippocampus as well as synaptic plasticity associated with central and peripheral pain sensitization. We examined the role of mTOR signaling in pain-associated entorhinal cortex (EC) - hippocampal synaptic plasticity to reveal possible cellular mechanisms underlying the effects of chronic pain on cognition and emotion.ResultsSubcutaneous injection of bee venom (BV) into one hind paw to induce PPN resulted in sustained (> 8 h) mTOR phospho-activation and enhanced phosphorylation of the mTOR target p70 S6 kinase (S6K) in the hippocampus. The magnitude and duration of long-term potentiation (LTP) in both EC - dentate gyrus (DG) and EC - CA1 synaptic pathways were elevated in BV-treated rats as measured by microelectrode array recording. Moreover, the number of potentiated synapses in the hippocampus was markedly upregulated by BV-induced PPN. Both elevated mTOR-S6K signaling and enhanced LTP induced by BV injection were reversed by systemic injection of the mTOR inhibitor rapamycin (RAPA). Rats injected with BV exhibited markedly reduced ambulation and exploratory activity in the open field (signs of depression and anxiety) compared to controls, and these effects were also reversed by RAPA.ConclusionWe suggest that PPN-induced enhancement of synaptic plasticity in EC - hippocampal pathways and the behavioral effects of PPN are dependent on mTOR-S6K signaling.

FBT was generally safe and well tolerated, with self-reported functional improvement observed in most of the opioid-tolerant patients with BTP in association with chronic noncancer pain.