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  • 1
    Keywords: DISEASE ; POPULATION ; RISK ; POLYMORPHISMS ; IDENTIFICATION ; METAANALYSIS ; telomere length ; LOCI ; GENOME-WIDE ASSOCIATION ; 5P15.33
    Abstract: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 x 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 x 10(-5)), rs4583925 (p = 4.0 x 10(-5)) and rs2735948 (p = 5.0 x 10(-5)). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants. What's new? Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools.
    Type of Publication: Journal article published
    PubMed ID: 25940397
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  • 2
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Summary An investigation was conducted to determine the effects of relatively low power density microwave exposures on various serum components of the Dutch rabbit. Both continuous wave and pulsed mode exposures at 2.45 GHz were used at power densities of 25, 10 and 5 mW/cm2. Studies of 10 serum components were performed. Additional studies were conducted on changes in sleeping times of pentobarbital-sedated rabbits at various power densities. Gross and histopathological examinations were performed on representative samples of animals. Changes in the blood chemistry of irradiated animals were consistent with a dose-dependent response to a non-specific thermal stress at all power densities used. Observed physiological response, as well as rectal temperature measurements, indicated that the thermoregulatory capability of the rabbits was sufficient to compensate for the thermal burden at 5 and 10 mW/cm2, but could be overridden by a 2 h exposure at 25 mW/cm2. Pathology findings included a mild, repairable nephrosis in animals exposed at a power density of 25 mW/cm2. A further investigation of analeptic effects at power densities varying from 5 mW/cm2 to 50 mW/cm2 resulted in a statistically significant decrease in sleeping times, apparently proportional to power density below 15 mW/cm2.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 1 (1980), S. 345-352 
    ISSN: 0197-8462
    Keywords: electromagnetic pulsed (EMP) fields ; pentobarbital-induced sleeping time ; serum chemistry ; serum triglycerides ; creatine phosphokinase (CPK) ; Dutch rabbits ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Dutch rabbits were acutely exposed to electromagnetic pulsed (EMP) fields (pulse duration 0.4μs, field strengths of 1-2 kV/cm and pulse repetition rates in the range of 10 to 38 Hz) for periods of up to two hours. The dependent variables investigated were pentobarbital-induced sleeping time and serum chemistry (including serum triglycerides, creatine phosphokinase (CPK) isoenzymes, and sodium and potassium). Core temperature measured immediately pre-exposure and postexposure revealed no exposure-related alterations. Over the range of field strengths and pulse durations investigated no consistent, statistically significant alterations were found in the end-points investigated.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0197-8462
    Keywords: 27-MHz radiation ; 2,450-MHz RF radiation ; isothermal exposure ; mouse spermatozoa ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Mouse spermatozoa were exposed in vitro for 1 h to 27- or 2,450-MHz CW RF radiation at SARs of 0 to 90 W/kg under isothermal (37 ± 0.2 °C) conditions. Exposure at either frequency to RF radiation at SARs of 50 W/kg or greater resulted in a statistically significant reduction in the ability of irradiated sperm to fertilize mouse ova in vitro (P 〈 .05). Over the range of SARs there was no apparent difference in the effects of 27- vs. 2,450-MHz RF radiation. There were no readily detectable exposure effects on spermatozoan morphology, ultrastructure, or capacitation. The reduction of in vitro fertilization is attributed to a direct effect of RF radiation on spermatozoa rather than to heating.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Bioelectromagnetics 3 (1982), S. 453-466 
    ISSN: 0197-8462
    Keywords: microwaves ; whole blood ; washed red cells ; permeability alterations ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Rabbit erythrocytes were exposed in vitro to continuous wave (CW) and pulse-modulated X-band microwaves in wave guide exposure chambers. Erythrocytes were exposed as whole (hep-arinized) blood suspensions or as washed cells in 1:1 isotonic buffered K+-free saline suspensions. Statistically significant increases in K+ efflux relative to thermal controls were detected when red cells were exposed in whole blood suspensions to either CW or pulsed 8.42-GHz microwaves at SARs that resulted in equilibrium sample temperatures of approximately 24 °C. Under the same exposure conditions, no statistically significant K+ efflux occurred in the case of 1:1 red cell suspensions. Measured differences in sample heating rates and temperature gradients between microwave-exposed and heated control suspensions may account in part for the differential effect of microwave exposure but such effects do not appear to explain the results of this study fully.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cleary, Allison S -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1174-5. doi: 10.1126/science.aad7103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pennsylvania State University College of Medicine, Hershey PA 17078, USA. acleary@hmc.psu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785463" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/genetics/metabolism/*pathology ; Clone Cells/metabolism/pathology ; Female ; Mammary Neoplasms, Experimental/genetics/metabolism/*pathology ; Mice ; Neoplasms, Basal Cell/genetics/metabolism/pathology ; Wnt1 Protein/genetics/*metabolism ; ras Proteins/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-04-04
    Description: Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050741/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050741/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cleary, Allison S -- Leonard, Travis L -- Gestl, Shelley A -- Gunther, Edward J -- R01 CA152222/CA/NCI NIH HHS/ -- England -- Nature. 2014 Apr 3;508(7494):113-7. doi: 10.1038/nature13187.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA [2] Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA. ; 1] Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA [2] Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA [3] Department of Medicine (Hematology/Oncology), Pennsylvania State University College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695311" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Lineage ; Cell Proliferation ; Clone Cells/metabolism/pathology ; Disease Models, Animal ; Female ; Mice ; Mosaicism ; Mutation ; Neoplasm Recurrence, Local/genetics/metabolism/pathology ; Neoplastic Stem Cells/metabolism/pathology ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Wnt Signaling Pathway ; Wnt1 Protein/deficiency/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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