Hydrocarbon Anions in Interstellar Clouds and Circumstellar Envelopes

The recent detection of the hydrocarbon anion C6H- in the interstellar medium has led us to investigate the synthesis of hydrocarbon anions in a variety of interstellar and circumstellar environments. We find that the anion/neutral abundance ratio can be quite large, on the order of at least a few percent, once the neutral has more than five carbon atoms. Detailed modeling shows that the column densities of C6H- observed in IRC +10 216 and TMC-1 can be reproduced. Our calculations also predict that other hydrocarbon anions, such as C4H- and C8H-, are viable candidates for detection in IRC +10 216, TMC-1, and photon-dominated regions such as the Horsehead Nebula

The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK

Monitoring of Gene Expression in Bacteria during Infections Using an Adaptable Set of Bioluminescent, Fluorescent and Colorigenic Fusion Vectors

A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ). The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective conditions. Transcriptional and translational fusions to the reporter genes gfpmut3.1, amCyan, dsRed2, luxCDABE, phoA or lacZ can be constructed, and presence of identical multiple cloning sites in the vector system facilitates the interchange of promoters or reporter genes between the plasmids of the series. The promoter of the constitutively expressed gapA gene of Escherichia coli was included to obtain fluorescent and bioluminescent expression constructs. A combination of the plasmids allows simultaneous detection and gene expression analysis in individual bacteria, e.g. in bacterial communities or during mouse infections. To test our vector system, we analyzed and quantified expression of Yersinia pseudotuberculosis virulence genes under laboratory conditions, in association with cells and during the infection process

ZD6474 – clinical experience to date

ZD6474 selectively targets two key pathways in tumour growth by inhibiting vascular endothelial growth factor (VEGF)-dependent tumour angiogenesis and epidermal growth factor (EGF)-dependent tumour cell proliferation and survival. Phase I clinical evaluation has shown ZD6474 to be generally well tolerated, with a pharmacokinetic profile appropriate for once-daily oral dosing. Phase II evaluation of ZD6474 at doses of 100−300 mg is ongoing in a range of patient types in single and combination regimens. These include three randomised studies of patients with non-small-cell lung cancer. In one of these trials, the efficacy of ZD6474 monotherapy is being compared with that of the EGF receptor tyrosine kinase inhibitor gefitinib (Iressa™) in previously treated patients. In the other two trials, the efficacy of ZD6474 in combination with certain standard chemotherapy regimens is being compared with that of standard chemotherapy alone: one with carboplatin and paclitaxel in previously untreated patients, and the second with docetaxel in patients who progressed after platinum-containing therapy. The advent of novel molecular-targeted agents such as ZD6474 has necessitated a re-evaluation of conventional cancer study design in order to optimise appraisal of this new generation of anticancer agents. The specific considerations of the ZD6474 clinical programme are discussed

Role of novel targeted therapies in the clinic

The number and variety of novel, molecular-targeted agents offers realistic hope for significant advances in cancer treatment. The potential of these new treatment approaches is unquestionable, but the reality is something that only thorough clinical evaluation and experience can reveal. Clinical experience of targeted therapies is at an early stage but it is likely that we will have an increasing number of treatment options available to us in the near future. This manuscript explores our current understanding of molecular-targeted therapies and considers: What approach should be used? (single vs multitarget agents); When should they be administered? (identifying the optimal point for intervention); How should they be used? (monotherapy or combination therapy regimens); and Who should we be giving them to? (acknowledging the need for patient selection)

Impact of effective prevention and management of febrile neutropenia

Chemotherapy-induced febrile neutropenia is costly in both financial and human terms. The associated costs can be reduced substantially through the development and implementation of national policies and locally agreed protocols for the prevention and management of febrile neutropenia. Patients, the NHS, healthcare professionals and the broader community all stand to benefit from a commitment to effective management of this common and predictable side effect of some chemotherapy regimens for early-stage breast cancer