Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review.

BACKGROUND: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. METHODS: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. RESULTS: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. CONCLUSIONS: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

Evidence of strong earthquake shaking in the lower wabash valley from prehistoric liquefaction features.

Earthquake-induced liquefaction features in Holocene sediments provide evidence of strong prehistoric shaking, magnitude m(b) 6.2 to 6.7, in the Wabash Valley bordering Indiana and Illinois. The source of the one or more earthquakes responsible was almost certainly in or near the Wabash Valley. The largest event is interpreted to have occurred between 7500 and 1500 years ago on the basis of archeological, pedological, and stratigraphic relations.

Long-lasting poloidal ULF waves observed by multiple satellites and high-latitude SuperDARN radars.

Poloidal ultra-low frequency (ULF) waves between 5-10 mHz were observed by multiple satellites and three high-latitude Super Dual Auroral Radar Network (SuperDARN) radars during the recovery phase of a moderate geomagnetic storm on Jan 24-27, 2016. The long-lasting ULF waves were observed in the magnetic field and energetic particle flux perturbations during three successive passes by two Geostationary Operational Environmental Satellites (GOES) through the dayside magnetosphere, during which plasmasphere expansion and refilling were observed by two Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes. The radial magnetic field oscillation was in phase (~ 180° out of phase) with the northward (southward) moving proton flux oscillation at 95 keV, consistent with high-energy drift-bounce resonance signatures of protons with second harmonic poloidal standing Alfvén waves. The longitudinal extent of the waves approached 10 hours in local time on the dayside and gradually decreased with time. High-time resolution (~ 6 s) data from three high-latitude SuperDARN radars show that the wave intensification region was localized in latitude with a radial extent of ~ 135-225 km in the subauroral ionosphere. No signature of these waves were observed by ground-based magnetometers colocated with the GOES satellites suggesting that the poloidal waves were high-m mode and thus screened by the ionosphere. During this interval one of the THEMIS probes observed a bump-on-tail ion distribution at 1-3 keV which we suggest is the source of the long-lasting second harmonic poloidal ULF waves.

The rex genes of bacteriophage lambda can inhibit cell function without phage superinfection.

The rexA and rexB genes of bacteriophage lambda are expressed from the prophage and cause the exclusion of many superinfecting mutant phages. We cloned the rexA and rexB genes into a multicopy plasmid so that they were overexpressed from the inducible tac promoter. No obvious phenotypes were associated with overexpressing both rexA and rexB or overexpressing rexA in the absence of rexB expression. However, induction of rexA in the presence of limiting rexB activity caused an immediate cessation of cell growth. All macromolecular synthesis abruptly ceased and amino acid transport was severely inhibited. Intracellular levels of adenosine 5'-triphosphate also dropped. These phenotypes are similar to those observed after phage superinfection, leading us to propose that at least some of the exclusion caused by the Rex proteins could be due to a change in their ratio following superinfection.

Fast-acting fentanyl preparations and pain management.

Cancer-related pain is a common clinical problem, experienced by ∼90% of patients with cancer. The mainstay of treatment remains opioids and the WHO analgesic ladder. Following the principles of the analgesic ladder, 80% of patients can achieve pain control. However, breakthrough pain remains a form of cancer-related pain that is particularly difficult to manage in both specialist and generalist settings. The focus of this article is the mismatch between the temporal characteristics of the majority of cancer-related breakthrough pain which is fast onset and resolution, with the pharmacological profile of oral morphine. The contribution of fast-acting fentanyl preparations to the treatment of breakthrough pain and the evidence for the various commercially available preparations will be considered.

A non-essential domain of Escherichia coli RNA polymerase required for the action of the termination factor Alc.

An evolutionarily nonconserved region of approximately 250 amino acids can be deleted from the amino-terminal part of the beta subunit of Escherichia coli RNA polymerase without effect on the enzyme's basic function. The non-essential segment is located between two highly conserved motifs and is flanked by sequences participating in the rifampicin-binding site. The results define the second non-essential domain in the beta subunit, in addition to the more distal dispensable segment identified previously. The Alc protein of bacteriophage T4 participates in the host transcription shutoff after infection by causing premature termination of transcription on E. coli DNA. Point mutations which prevent Alc action in vivo change amino acids in the non-essential NH2-terminal domain of the beta subunit. These point mutations as well as deletions which remove the non-essential region also prevent Alc action. Thus, in the RNA polymerase molecule, the proximal non-essential domain of beta may function as an acceptor of Alc or other regulatory factors.

Genetic element from human surfactant protein SP-C gene confers bronchiolar-alveolar cell specificity in transgenic mice.

Transgenic mice bearing chimeric genes consisting of 5'-sequences derived from the human surfactant protein C (SP-C) gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were generated. Analysis of CAT activity was utilized to demonstrate tissue-specific and developmental expression of chimeric genes containing 3.7 kb of sequences from the human SP-C gene. Lung-specific expression of the 3.7 SP-C-CAT transgene was observed in eight distinct transgenic mouse lines. Expression of the 3.7 SP-C-CAT transgene was first detected in fetal lung on day 11 of gestation and increased dramatically with advancing gestational age, reaching adult levels of activity before birth. In situ hybridization demonstrated that expression of 3.7 SP-C-CAT mRNA was confined to the distal respiratory epithelium. Antisense CAT hybridization was detected in bronchiolar and type II epithelial cells in the adult lung of the 3.7 SP-C-CAT transgenic mice. In situ hybridization of four distinct 3.7 SP-C-CAT transgenic mouse lines demonstrated bronchiolar-alveolar expression of the chimeric CAT gene, although the relative intensity of expression at each site varied within the lines studied. Glucocorticoids increased murine SP-C mRNA in fetal lung organ culture. Likewise, expression of 3.7 SP-C-CAT transgene increased during fetal lung organ or explant culture and was further enhanced by glucocorticoid in vitro. The 5'-regions of human SP-C conferred developmental, lung epithelial, and glucocorticoid-enhanced expression of bacterial CAT in transgenic mice. The increased expression of SP-C accompanying prenatal lung development and exposure to glucocorticoid is mediated, at least in part, at the transcriptional level, being influenced by cis-active elements contained within the 5'-flanking region of the human SP-C gene.