Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer

D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 μg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 μg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders. © 2000 Cancer Research Campaig

NREL Combined Experimental Final Report--Phase II

Predicting peak power and loads on a fixed-pitch wind turbine. How does the performance of the airfoil in the wind tunnel differ from the performance of an operating horizontal-axis wind turbine (HAWT)

Trade unions and the challenge of fostering solidarities in an era of financialisation

This articles re-examines evidence that trade unions in the UK have struggled to renew themselves despite considerable investment of time and effort. It argues that financialisation in the realms of capital accumulation, organisational decision making and everyday life has introduced new barriers to building the solidarities within and between groups of workers that would be necessary to develop a stronger response to the catastrophic effects on labour of financialisation in general, and the financial crisis specifically. The crisis highlighted the weaknesses of trade unions as institutions of economic and industrial democracy, but has also given some opportunities to establish narratives of solidarity in spaces and platforms created within a financialised context

IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas

High grade gliomas (HGGs) are aggressive primary brain tumours with local invasive growth and poor clinical prognosis. Clinical outcome is compounded by resistance to standard and novel therapeutics. We have evaluated reformulated aspirin (IP1867B) alone and in combination with conventional and novel anti-aHGG agents. We show that recent biopsy-derived aHGG models were highly resistant to conventional therapeutics although show sensitivity to IP1867B, a reformulated "liquid" aspirin. IP186713 treatment mediated a potent suppression of the IL6/STAT3 and NF-kappa B pathways and observed a significant reduction in EGFR transcription and protein expression. We observed the loss of the insulin-like growth factor 1 and insulin-like growth factor 1 receptor expression at both the transcript and protein level post IP1867B treatment. This increased sensitivity to EGFR inhibitors. In vivo, IP1867B was very well tolerated, had little-to-no gastric lesions versus aspirin and, directed a significant reduction of tumour burden with suppression of EGFR, IGF1 and IGFR1. With EGFR inhibitors, we noted a potent synergistic response in aHGG cells. These data provide a rationale for further investigation of IP1867B with a number of anti-EGFR agents currently being evaluated in the clinic.Brain Tumour ResearchHeadcase Cancer TrustOllie Young FoundationFCT Investigator contract from the Foundation for Science and Technology (FCT), Portugal [IF/00614/2014]FCTPortuguese Foundation for Science and Technology [IF/00614/2014/CP12340006, UID/BIM/04773/2013CBMR1334]Innovate Pharmaceutical

Corrigendum to IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas (vol 458C, pg 29, 2019)

info:eu-repo/semantics/publishedVersio

Retraction notice to " IP1867B suppresses the Insulin-like Growth Factor 1 Receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas” [Canc. Lett., 458 (2019) pages 29–38]

This article has been retracted at the request of the Editor-in-Chief due to concerns regarding the legitimacy of images and data presented in the paper. Though a corrigendum (Can. Lett. Vol. 469, 2020, pages 524–535) was previously published to address some of these concerns, this corrigendum has also been found to contain errors and therefore cannot stand. Specific concerns are listed below.info:eu-repo/semantics/publishedVersio

Functional modelling of a novel mutation in BBS5.

BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy disorder with 18 known causative genes (BBS1-18). The primary clinical features are renal abnormalities, rod-cone dystrophy, post-axial polydactyly, learning difficulties, obesity and male hypogonadism. RESULTS: We describe the clinical phenotype in three Saudi siblings in whom we have identified a novel mutation in exon 12 of BBS5 (c.966dupT; p.Ala323CysfsX57). This single nucleotide duplication creates a frame shift results in a predicted elongated peptide. Translation blocking Morpholino oligonucleotides were used to create zebrafish bbs5 morphants. Morphants displayed retinal layering defects, abnormal cardiac looping and dilated, cystic pronephric ducts with reduced cilia expression. Morphants also displayed significantly reduced dextran clearance via the pronephros compared to wildtype embryos, suggesting reduced renal function in morphants. The eye, kidney and heart defects reported in morphant zebrafish resemble the human phenotype of BBS5 mutations. The pathogenicity of the novel BBS5 mutation was determined. Mutant mRNA was unable to rescue pleiotropic phenotypes of bbs5 morphant zebrafish and in cell culture we demonstrate a mislocalisation of mutant BBS5 protein which fails to localise discretely with the basal body. CONCLUSIONS: We conclude that this novel BBS5 mutation has a deleterious function that accounts for the multisystem ciliopathy phenotype seen in affected human patients

Functional modelling of a novel mutation in <em>BBS5</em>

Background: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy disorder with 18 known causative genes (BBS1-18). The primary clinical features are renal abnormalities, rod-cone dystrophy, post-axial polydactyly, learning difficulties, obesity and male hypogonadism.Results: We describe the clinical phenotype in three Saudi siblings in whom we have identified a novel mutation in exon 12 of BBS5 (c.966dupT; p.Ala323CysfsX57). This single nucleotide duplication creates a frame shift results in a predicted elongated peptide. Translation blocking Morpholino oligonucleotides were used to create zebrafish bbs5 morphants. Morphants displayed retinal layering defects, abnormal cardiac looping and dilated, cystic pronephric ducts with reduced cilia expression. Morphants also displayed significantly reduced dextran clearance via the pronephros compared to wildtype embryos, suggesting reduced renal function in morphants. The eye, kidney and heart defects reported in morphant zebrafish resemble the human phenotype of BBS5 mutations. The pathogenicity of the novel BBS5 mutation was determined. Mutant mRNA was unable to rescue pleiotropic phenotypes of bbs5 morphant zebrafish and in cell culture we demonstrate a mislocalisation of mutant BBS5 protein which fails to localise discretely with the basal body.Conclusions: We conclude that this novel BBS5 mutation has a deleterious function that accounts for the multisystem ciliopathy phenotype seen in affected human patients. \ua9 2014 Al-Hamed et al.; licensee BioMed Central Ltd

Trade unions and precariat in Europe : representative claims

Trade unions have been charged with neglecting labour market ‘outsiders’, while alternative actors have emerged to represent these. In response, unions have stepped up their claim to be representative of all workers, without distinction. We review the theoretical and policy debates on this issue, and argue that representation as such has been under-theorized. We draw on Saward’s concept of ‘representative claims’ to analyse the different grounds for competing assertions of representativeness. We identify four main forms of claims, and illustrate these with empirical examples. We conclude that these different claims are mutually reinforcing in stimulating attention to the outsiders, and in their interaction with institutional settings, they have a performative effect in defining new social actors

Chronic nonpuerperal uterine inversion and necrosis: a case report

<p>Abstract</p> <p><b>Introduction</b></p> <p>Inversion of the non-pregnant uterus is rare.</p> <p><b>Case presentation</b></p> <p>A 56-year-old African American woman presented to our emergency center with complaints of a mass protruding from her vagina. She subsequently underwent vaginal myomectomy, abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathologic examination revealed a necrotic fibroid and endometrium. At the time of laparotomy an inverted uterus was diagnosed when a 3 cm dimple containing bilateral round ligaments, infundibulopelvic ligaments and bladder was observed.</p> <p>Conclusion</p> <p>Chronic nonpuerperal inversion of the uterus is rare. Infection should be suspected and appropriate broad spectrum antibiotics begun while planning surgery. An attempt at vaginal restoration and removal is difficult. Abdominal hysterectomy may be necessary taking care to locate the distal urinary collecting system.</p