Polo like kinase 2 tumour suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer

The polo-like kinase PLK2 has recently been identified as a potential theranostic marker in the management of chemotherapy sensitive cancers. The methylation status of the PLK2 CpG island varies with sensitivity to paclitaxel and platinum in ovarian cancer cell lines. Importantly, extrapolation of these in vitro data to the clinical setting confirms that the methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin and paclitaxel chemotherapy. A second cell cycle regulator, p57Kip2, is also subject to epigenetic silencing in carboplatin resistance in vitro and in vivo, emphasising that cell cycle regulators are important determinants of sensitivity to chemotherapeutic agents and providing insights into the phenomenon of collateral drug sensitivity in oncology. Understanding the mechanistic basis and identification of robust biomarkers to predict collateral sensitivity may inform optimal use of chemotherapy in patients receiving multiple lines of treatment

Identification of genes induced by BRCA1 in breast cancer cells

Cataloged from PDF version of article.Inherited mutations of the BRCA1 gene predispose to breast, ovarian, and other cancers. The role of the BRCA1 gene in the maintenance of chromosomal integrity is linked to a number of biological properties of its protein product, including transcriptional regulation. In the present study, we have used suppression subtractive hybridisation (SSH) to identify genes induced by BRCA1 by comparing control MCF7 breast carcinoma cells (driver) with MCF7 cells ectopically expressing BRCA1 (tester) and generated a forward subtracted cDNA library. We screened 500 putative positive clones from this library. Two hundred and ten of these clones were positive by differential screening with forward and reverse subtracted probes and the 65 cDNA clones which showed more than fivefold increase were selected for sequencing analysis. We clustered 46 different genes that share high homology with sequences in the GenBank/EMBL databases. Among these, 30 were genes whose function had been previously identified while the remaining 16 clones were genes with,unknown functions. Of particular interest, BRCA1 gene induces the expression of genes encoding DNA repair proteins RAD21 and MSH2, ERBB2/HER2 interacting protein ERBIN, meningioma-associated protein MAC30, and a candidate ovarian tumour-suppressor OVCA1. Northern and Western blot analyses confirmed that the expression of these five genes are up-regulated following BRCA1 overexpression in MCF7 and UBR60-bcl2 cells. This is the first study reporting a set of BRCA1-induced genes in breast carcinoma cells by the SSH technique. We suggest that some known genes identified in this study may provide new insights into the tumour-suppressor function of BRCA1. (C) 2002 Elsevier Science (USA). All rights reserved

Protection of mice against cancer by immunization with membranes but not purified virions from virus infected cancer cells.

The life span of C57/Bl mice inoculated with Lewis lung carcinoma cells was prolonged if the mice were pre-immunized with membranes from these cells infected in vitro with influenza virus. Likewise, BALB/c mice were protected against the malignant tumour WEHI-11 by prior immunization with extracts of cultured WEHI-11 cells which had been infected with influenza virus or Semiliki Forest virus (SFV). Partially purified SFV grown in WEHI-11 cells also protected mice from cancer grafts but neither highly purified SFV nor the glycoprotein from the envelope of this virus protected the mice. It is concluded that SFV-induced immunopotentiation against cancer is not due to covalent linkage of tumour specific transplantation antigen (TSTA) to viral envelope protein but more probably is due to the apposition of viral glycoprotein and cellular TSTA in the plasma membrane of the cancer cell

The role of interspecific variability and herbicide pre-adaptation in the cinmethylin response of Alopecurus myosuroides

BACKGROUND: Cinmethylin is an inhibitor of plant fatty acid biosynthesis, with in-plant activity caused by its binding to fatty acid thioesterases (FAT). The recent registration of cinmethylin for pre-emergence herbicidal use in the UK represents a new mode of action (MOA) for control of the grassweed blackgrass (Alopecurus myosuroides). To date there is little published information on the extent of blackgrass’ inter-population variability in sensitivity to cinmethylin, nor on any potential effect of existing non-target-site resistance (NTSR) mechanisms on cinmethylin efficacy. RESULTS: Here we present a study of variability in cinmethylin sensitivity amongst 97 UK blackgrass populations. We demonstrate that under controlled conditions, a UK field-rate dose of 500 g ha-1 provides effective control of the tested populations. Nevertheless, we reveal significant inter-population variability at doses below this rate, with populations previously characterised as strongly NTSR displaying the lowest sensitivity to cinmethylin. Assessment of paired resistant “R” and sensitive “S” lines from standardised genetic backgrounds confirms that selection for NTSR to the acetyl-CoA-carboxylase inhibitor fenoxaprop, and the microtubule assembly inhibitor pendimethalin, simultaneously results in reduced sensitivity to cinmethylin at doses below 500 g ha-1. Whilst we find no resistance to the field-rate dose, we reveal that cinmethylin sensitivity can be further reduced through experimental selection with cinmethylin. CONCLUSION: Cinmethylin therefore represents a much-needed further MOA for blackgrass control, but needs to be carefully managed within a resistance monitoring and integrated weed management (IWM) framework to maximise the effective longevity of this compound

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

Background Exposure to metal working fluid (MWF) has been associated with outbreaks of EAA in the US, with bacterial contamination of MWF being a possible cause, but was uncommon in the UK. Twelve workers developed extrinsic allergic alveolitis (EAA) in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. This had three aims:- • To measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases. • To provide case-detection so that those affected can be treated. • To provide epidemiological data to identify the cause of the outbreak. Methods The outbreak was investigated in a three-phase cross-sectional survey of the workforce. Phase I A respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. Phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481(94.4%) responded along with 48/50(96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). Phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results 87 workers (10.4% of workforce) met case definitions for occupational lung disease, comprising EAA(19), occupational asthma(74) and humidifier fever(7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using metal working fluid (MWF) from a large sump(27.3%) compared with working all over the manufacturing area (7.9%) (OR=4.39,p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Conclusions Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF, there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance

Catalog of Nearby Isolated Galaxies in the Volume z<0.01

We present a catalog of 520 most isolated nearby galaxies with radial velocities V_LG<3500 km/s covering the entire sky. This population of "space orphans" makes up 4.8% among 10900 galaxies with measured radial velocities. We describe the isolation criterion used to select our sample, called the "Local Orphan Galaxies" (LOG), and discuss their basic optical and HI properties. A half of the LOG catalog is occupied by the Sdm, Im and Ir morphological type galaxies without a bulge. The median ratio M_gas/M_star in the LOG galaxies exceeds 1. The distribution of the catalog galaxies on the sky looks uniform with some signatures of a weak clustering on the scale of about 0.5 Mpc. The LOG galaxies are located in the regions where the mean local density of matter is approximately 50 times lower than the mean global density. We indicate a number of LOG galaxies with distorted structures, which may be the consequence of interaction of isolated galaxies with massive dark objects

Hybrid Vibrio vulnificus

Hybridization between natural populations of Vibrio vulnificus results in hyperinvasive clone

Binary Galaxies in the Local Supercluster and Its Neighborhood

We report a catalog of 509 pairs identified among 10403 nearby galaxies with line-of-sight velocities V_LG < 3500 km/s.We selected binary systems in accordance with two criteria (bounding and temporal), which require the physical pair of galaxies to have negative total energy and its components to be located inside the zero-velocity surface. We assume that individual galaxy masses are proportional to their total K-band luminosities, M = L_K x 6M/L. The catalog gives the magnitudes and morphological types of galaxies and also the projected (orbital) masses and pair isolation indices. The component line-of-sight velocity differences and projected distances of the binary systems considered have power-law distributions with the median values of 35 km/s and 123 kpc, respectively. The median mass-to-K-band luminosity ratio is equal to 11 M/L, and its uncertainty is mostly due to the errors of measured velocities. Our sample of binary systems has a typical density contrast of d ro/ro_c ~ 500 and a median crossing time of about 3.5 Gyr. We point out the substantial fraction of binary systems consisting of late-type dwarf galaxies, where the luminosities of both components are lower than that of the Small Magellanic Cloud. The median projected distance for 41 such pairs is only 30 kpc, and the median difference of their line-of-sight velocities is equal to 14 km/s which is smaller than the typical error for radial-velocity (30 km/s). This specific population of gas-rich dwarf binary galaxies such as I Zw 18 may be at the stage immediately before merging of its components. Such objects, which are usually lost in flux-limited (and not distance-limited) samples deserve a thorough study in the HI radio line with high spatial and velocity resolution.Comment: published in Astrophysical Bulletin, 2008, Vol. 63, No. 4, pp. 299-34

Electron-beam propagation in a two-dimensional electron gas

A quantum mechanical model based on a Green's function approach has been used to calculate the transmission probability of electrons traversing a two-dimensional electron gas injected and detected via mode-selective quantum point contacts. Two-dimensional scattering potentials, back-scattering, and temperature effects were included in order to compare the calculated results with experimentally observed interference patterns. The results yield detailed information about the distribution, size, and the energetic height of the scattering potentials.Comment: 7 pages, 6 figure