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  • 1
    Keywords: EXPRESSION ; GENE ; PROTEIN ; HIGH-RISK ; POOR-PROGNOSIS ; AKT ; IMMUNOHISTOCHEMICAL DETECTION ; PTEN/MMAC1 ; SUPPRESSOR ; FISH ANALYSIS
    Abstract: The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naive and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P 〈 0.0001), high Gleason grade (P 〈 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P 〈 0.0001), presence of ERG gene fusion (P 〈 0.0001), and nuclear p53 accumulation (P 〈 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P 〈 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers.
    Type of Publication: Journal article published
    PubMed ID: 22705054
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  79. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20080430-20080504; Bonn; DOC08hnod414 /20080422/
    Publication Date: 2008-04-21
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Exogenous application of either indolylacetic acid or gibberellic acid to the leaves or flower buds of plants kept in short days failed to induce the bud abscission experienced in long days3'4. In contrast, however, it has now been found6 that application of synthetic abscisic acid (ABA) to the ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 227 (1970), S. 628-629 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Previous work on the effects of photoperiod on flower bud development in plants has concentrated on initiation3'4. In cases where day length was shown to cause flower bud abscission little attempt was made to analyse the physiological basis of the effect5-8. We wish to report two of a series of ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 179 (1957), S. 206-207 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Most of these proteins crystallize in plates or in various types of needles. All have sedimentation constants falling along the same line and extrapolating to an S20Mc=0) of about 3-0 (Fig. 1). On the basis of amino-acid composition, the tropomyosin of mammalian striated muscle can be ...
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2018-05-16
    Description: Introduction Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant’s fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. Trial registration number NCT02730338 .
    Keywords: Open access, Oncology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 8
    Publication Date: 2018-03-29
    Description: Objectives To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs. Setting A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. Participants A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed. Primary and secondary outcome measures Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up. Data analysis Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale. Results Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P〈0.001, I 2 =40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P〈0.001, I 2 =72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I 2 =59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I 2 =91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction =0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, P interaction 〈0.001). Conclusion Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura. PROSPERO registration number CRD42016052460 .
    Keywords: Open access, Cardiovascular medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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