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  • 1
    Publication Date: 2015-05-02
    Description: Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly. Centrinone treatment caused centrosome depletion in human and other vertebrate cells. Centrosome loss irreversibly arrested normal cells in a senescence-like G1 state by a p53-dependent mechanism that was independent of DNA damage, stress, Hippo signaling, extended mitotic duration, or segregation errors. In contrast, cancer cell lines with normal or amplified centrosome numbers could proliferate indefinitely after centrosome loss. Upon centrinone washout, each cancer cell line returned to an intrinsic centrosome number "set point." Thus, cells with cancer-associated mutations fundamentally differ from normal cells in their response to centrosome loss.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764081/" 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/PMC4764081/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Yao Liang -- Anzola, John V -- Davis, Robert L -- Yoon, Michelle -- Motamedi, Amir -- Kroll, Ashley -- Seo, Chanmee P -- Hsia, Judy E -- Kim, Sun K -- Mitchell, Jennifer W -- Mitchell, Brian J -- Desai, Arshad -- Gahman, Timothy C -- Shiau, Andrew K -- Oegema, Karen -- GM074207/GM/NIGMS NIH HHS/ -- GM089970/GM/NIGMS NIH HHS/ -- GM103403/GM/NIGMS NIH HHS/ -- R01 GM089970/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1155-60. doi: 10.1126/science.aaa5111. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. ; Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. ; Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. ; Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. koegema@ucsd.edu ashiau@ucsd.edu. ; Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. koegema@ucsd.edu ashiau@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931445" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation ; Centrioles/*drug effects ; Humans ; Mice ; Piperazines/pharmacology ; Protein Kinase Inhibitors/chemistry/*pharmacology ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors ; Pyrimidines/chemistry/*pharmacology ; Sulfones/chemistry/*pharmacology
    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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  • 2
    ISSN: 1432-0533
    Keywords: Meningioma ; Bromodeoxyuridine ; Cell kinetics ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-six patients with intracranial meningiomas and two with hemangiopericytic variants received a 30-min intravenous infusion of bromodeoxyuridine (BrdUrd), 200 mg/m2, before tumor removal. Excised tumor specimens were stained by the indirect immunoperoxidase method to determine the BrdUrd labeling index (LI), or percentage of cells in DNA synthesis. The BrdUrd LI was 〈 1% in 63 (86.3%) of 73 nonmalignant meningiomas and 〈 1% in 20 (87%) of 23 malignant meningiomas. Of 23 malignant meningiomas 11 were recurrent tumors; 8 patients had recurrence 3 to 33 months after the study. The recurrence rate was 100% (five of five) in patients whose tumors had a BrdUrd LI 〉 5%, 44% (11 of 25) in those with a BrdUrd LI 1% to 5%, and 6.1% (4 of 66) in those with an LI 〈 1%. Thus, meningiomas with a BrdUrd LI 〉 1% may grow faster and recur more frequently. Among patients with malignant mengngiomas, the mean time to recurrence after the study was 7.5 months in those with a BrdUrd LI 〉 5% and 20.2 months for those with an LI 1% to 5%. The mean time to recurrence was 97.8 months in patients with nonmalignant meningiomas. Both hemangiopericytic variants were recurrent and showed LIs of 0.5% and 4.1%; the former tumor recurred 8 years after complete resection, while the latter recurred three times in 3.5 years. Thus, the proliferative potential of intracranial meningiomas as reflected by the BrdUrd LI appears to be a prognostic variable that can help to elucidate the biological behavior of individual meningiomas.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Pituitary adenoma ; Monoclonal antibody Ki-67 ; Anti-DNA polymerase α monoclonal antibody ; Bromodeoxyuridine ; Nucleolar organizer regions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase α monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase α and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase α PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P〈0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P〈0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P〈0.005). These results suggest that the Ki-67 and DNA polymerase α PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 73 (1987), S. 138-144 
    ISSN: 1432-0533
    Keywords: Giant axonal neuropathy ; Intermediate filaments ; Rosenthal fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Giant axonal neuropathy (GAN) is a disease characterized by a slowly progressive neuropathy and signs of central involvement, manifested by visual impairment, corticospinal tract dysfunction, ataxia, and dementia. Pathological hallmarks of the disease include axonal swellings packed with neurofilaments in both peripheral and central nervous systems, and accumulations of intermediate filaments in Schwann cells, fibroblasts, melanocytes, endothelial, and Langerhans cells. Rosenthal fibers, sometimes appearing in masses and mimicking Alexander's disease, emerge as a conspicuous characteristic in longstanding GAN.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Glioblastoma ; Proliferative potential ; Bromodeoxyuridine ; Ki-67 ; Nucleolar organizer region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate intratumoral differences in indices of tumor cell proliferation, we measured the bromodeoxyuridine labeling index (BrdUrd LI), the Ki-67 protein proliferating cell indices (PCIs) determined by monoclonal antibody MIB 1 in microwave-processed paraffin sections (MIB 1 PCI) and in some eases by monoclonal antibody in frozen sections (Ki-67 PCI), and counts of argyrophilic nucleolar organizer regions (AgNORs) in 20 glioblastomas. In the most actively proliferating areas, MIB 1 and Ki-67 PCIs correlated well with the BrdUrd LI and with each other, while AgNOR counts correlated less strongly with these indices. In less active areas, the MIB 1 PCI and BrdUrd LI changed concomitantly from one area to another within a tumor except in areas of pseudopalisading with necrosis; in these areas the BrdUrd LI decreased significantly compared with neighboring tumor tissue, while the MIB 1 PCI did not. There was very little staining of gemistocytic nuclei with either anti-BrdUrd or MIB 1 monoclonal antibodies; this supports the concept that gemistocytes are mainly quiescent cells. AgNORs in all of the above-mentioned areas varied from tumor to tumor, which suggests that they may indicate some cellular activity other than proliferation. The close correlation between the BrdUrd LI and Ki-67 protein PCIs in corresponding regions of glioblastomas suggests that MIB 1 staining of microwave-processed paraffin sections can be used to evaluate the growth potential of individual glioblastomas and possibly of other gliomas as well.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: Key words AML ; CNS ; Mucormycosis ; Fungus ; CVA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 74-year-old man with newly diagnosed acute myelogenous leukemia unexpectedly suffered a massive cerebral infarct on day 2 of induction chemotherapy. Clinically, the hemorrhagic infarct was thought to be due to leukostasis and thrombocytopenia. Necropsy, however, revealed that Zygomycetes-type hyphae had infiltrated cerebral vessels in and near the infarct. The fungal infection was clinically silent otherwise, although fungal elements were also identified in the lung at autopsy. This case illustrates how closely fungal infection may resemble a leukemia-associated cerebrovascular accident.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0711
    Keywords: Key words Pregnancy ; Sumatriptan ; Adverse events ; Pharmacovigilance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Sumatriptan is an acute treatment for migraine which is often used by women in their child-bearing years, and who become unexpectedly pregnant. Within the context of the post-marketing use of sumatriptan injection for the acute treatment of migraine, and in compliance with approved labeling, we wished to compare perinatal pregnancy outcomes in women who did and did not use the drug after conception. Methods: Open-label, prospective study conducted in 12,339 migraineurs (including 9,861 women) whose demography and consumption pattern of sumatriptan injections were typical, and were predicted to include 150 pregnancies. Outcome of pregnancy was the end-point. Results: There were 168 of 173 pregnancies that were well-documented. Sumatriptan was only used prior to conception in 92 cases. There were 76 first trimester exposures to sumatriptan. There were no differences in pregnancy outcome between the two groups. Conclusions: Perinatal and pregnancy outcome did not differ between patients who had and had not used sumatriptan after conception, at the resolution of these sample sizes. This study design complements the ongoing pregnancy registry, which is now widened to patients exposed to all formulations of sumatriptan.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 43 (1987), S. 1675-1677 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Inorganic chemistry 13 (1974), S. 101-105 
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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