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  1. Article ; Online: Daylight saving time and mortality-proceed with caution.

    Klerman, Elizabeth B / Weaver, Matthew D / Roenneberg, Till / Malow, Beth A / Johnson, Karin G

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1576

    MeSH term(s) Seasons ; Circadian Rhythm
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Letter
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45837-4
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  2. Article ; Online: A survey of chromosomal instability measures across mechanistic models.

    Lynch, Andrew R / Bradford, Shermineh / Zhou, Amber S / Oxendine, Kim / Henderson, Les / Horner, Vanessa L / Weaver, Beth A / Burkard, Mark E

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 16, Page(s) e2309621121

    Abstract: Chromosomal instability (CIN) is the persistent reshuffling of cancer karyotypes via chromosome mis-segregation during cell division. In cancer, CIN exists at varying levels that have differential effects on tumor progression. However, mis-segregation ... ...

    Abstract Chromosomal instability (CIN) is the persistent reshuffling of cancer karyotypes via chromosome mis-segregation during cell division. In cancer, CIN exists at varying levels that have differential effects on tumor progression. However, mis-segregation rates remain challenging to assess in human cancer despite an array of available measures. We evaluated measures of CIN by comparing quantitative methods using specific, inducible phenotypic CIN models of chromosome bridges, pseudobipolar spindles, multipolar spindles, and polar chromosomes. For each, we measured CIN fixed and timelapse fluorescence microscopy, chromosome spreads, six-centromere FISH, bulk transcriptomics, and single-cell DNA sequencing (scDNAseq). As expected, microscopy of tumor cells in live and fixed samples significantly correlated (R = 0.72;
    MeSH term(s) Humans ; Cell Line, Tumor ; Chromosomal Instability/genetics ; Neoplasms ; Centromere ; Karyotyping ; Gene Expression Profiling ; Chromosome Segregation ; Aneuploidy
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2309621121
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  3. Article ; Online: How Taxol/paclitaxel kills cancer cells.

    Weaver, Beth A

    Molecular biology of the cell

    2014  Volume 25, Issue 18, Page(s) 2677–2681

    Abstract: Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, ... ...

    Abstract Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, recent evidence demonstrates that intratumoral concentrations of paclitaxel are too low to cause mitotic arrest and result in multipolar divisions instead. It is hoped that this insight can now be used to develop a biomarker to identify the ∼50% of patients that will benefit from paclitaxel therapy. Here I discuss the history of paclitaxel and our recently evolved understanding of its mechanism of action.
    MeSH term(s) Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Antineoplastic Agents, Phytogenic/therapeutic use ; Cell Cycle Checkpoints/drug effects ; Humans ; Neoplasms/drug therapy ; Paclitaxel/pharmacology ; Paclitaxel/therapeutic use
    Chemical Substances Antineoplastic Agents, Phytogenic ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2014-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E14-04-0916
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  4. Article ; Online: Chromosome Missegregation as a Modulator of Radiation Sensitivity.

    Cosper, Pippa F / Copeland, Sarah E / Tucker, John B / Weaver, Beth A

    Seminars in radiation oncology

    2021  Volume 32, Issue 1, Page(s) 54–63

    Abstract: Chromosome missegregation over the course of multiple cell divisions, termed chromosomal instability (CIN), is a hallmark of cancer. Multiple causes of CIN have been identified, including defects in the mitotic checkpoint, altered kinetochore-microtubule ...

    Abstract Chromosome missegregation over the course of multiple cell divisions, termed chromosomal instability (CIN), is a hallmark of cancer. Multiple causes of CIN have been identified, including defects in the mitotic checkpoint, altered kinetochore-microtubule dynamics, centrosome amplification, and ionizing radiation. Here we review the types, mechanisms, and cellular implications of CIN. We discuss the evidence that CIN can promote tumors, suppress them, or do neither, depending on the rates of chromosome missegregration and the cellular context. Very high rates of chromosome missegregation lead to cell death due to loss of essential chromosomes; thus elevating CIN above a tolerable threshold provides a mechanistic opportunity to promote cancer cell death. Lethal rates of CIN can be achieved by a single insult or through a combination of insults. Because ionizing radiation induces CIN, additional therapies that increase CIN may serve as useful modulators of radiation sensitivity. Ultimately, quantifying the intrinsic CIN in a tumor and modulating this level pharmacologically as well as with radiation may allow for a more rational, personalized radiation therapy prescription, thereby decreasing side effects and increasing local control.
    MeSH term(s) Centrosome/metabolism ; Centrosome/pathology ; Chromosomal Instability/genetics ; Chromosome Segregation ; Humans ; Kinetochores/metabolism ; Kinetochores/pathology ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/radiotherapy ; Radiation Tolerance/genetics
    Language English
    Publishing date 2021-12-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1146999-7
    ISSN 1532-9461 ; 1053-4296
    ISSN (online) 1532-9461
    ISSN 1053-4296
    DOI 10.1016/j.semradonc.2021.09.002
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    Zs.A 3654: Show issues Location:
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  5. Article ; Online: Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference.

    Lynch, Andrew R / Arp, Nicholas L / Zhou, Amber S / Weaver, Beth A / Burkard, Mark E

    eLife

    2022  Volume 11

    Abstract: Chromosomal instability (CIN)-persistent chromosome gain or loss through abnormal mitotic segregation-is a hallmark of cancer that drives aneuploidy. Intrinsic chromosome mis-segregation rate, a measure of CIN, can inform prognosis and is a promising ... ...

    Abstract Chromosomal instability (CIN)-persistent chromosome gain or loss through abnormal mitotic segregation-is a hallmark of cancer that drives aneuploidy. Intrinsic chromosome mis-segregation rate, a measure of CIN, can inform prognosis and is a promising biomarker for response to anti-microtubule agents. However, existing methodologies to measure this rate are labor intensive, indirect, and confounded by selection against aneuploid cells, which reduces observable diversity. We developed a framework to measure CIN, accounting for karyotype selection, using simulations with various levels of CIN and models of selection. To identify the model parameters that best fit karyotype data from single-cell sequencing, we used approximate Bayesian computation to infer mis-segregation rates and karyotype selection. Experimental validation confirmed the extensive chromosome mis-segregation rates caused by the chemotherapy paclitaxel (18.5 ± 0.5/division). Extending this approach to clinical samples revealed that inferred rates fell within direct observations of cancer cell lines. This work provides the necessary framework to quantify CIN in human tumors and develop it as a predictive biomarker.
    MeSH term(s) Aneuploidy ; Bayes Theorem ; Chromosomal Instability/genetics ; Chromosome Aberrations ; Chromosome Segregation/genetics ; Humans ; Karyotype ; Neoplasms/genetics ; Systems Analysis
    Language English
    Publishing date 2022-04-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.69799
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  6. Article: A survey of CIN measures across mechanistic models.

    Lynch, Andrew R / Bradford, Shermineh / Zhou, Amber S / Oxendine, Kim / Henderson, Les / Horner, Vanessa L / Weaver, Beth A / Burkard, Mark E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Chromosomal instability (CIN) is the persistent reshuffling of cancer karyotypes via chromosome mis-segregation during cell division. In cancer, CIN exists at varying levels that have differential effects on tumor progression. However, mis-segregation ... ...

    Abstract Chromosomal instability (CIN) is the persistent reshuffling of cancer karyotypes via chromosome mis-segregation during cell division. In cancer, CIN exists at varying levels that have differential effects on tumor progression. However, mis-segregation rates remain challenging to assess in human cancer despite an array of available measures. We evaluated measures of CIN by comparing quantitative methods using specific, inducible phenotypic CIN models of chromosome bridges, pseudobipolar spindles, multipolar spindles, and polar chromosomes. For each, we measured CIN fixed and timelapse fluorescence microscopy, chromosome spreads, 6-centromere FISH, bulk transcriptomics, and single cell DNA sequencing (scDNAseq). As expected, microscopy of tumor cells in live and fixed samples correlated well (R=0.77; p<0.01) and sensitively detect CIN. Cytogenetics approaches include chromosome spreads and 6-centromere FISH, which also correlate well (R=0.77; p<0.01) but had limited sensitivity for lower rates of CIN. Bulk genomic DNA signatures and bulk transcriptomic scores, CIN70 and HET70, did not detect CIN. By contrast, single-cell DNA sequencing (scDNAseq) detects CIN with high sensitivity, and correlates very well with imaging methods (R=0.83; p<0.01). In summary, single-cell methods such as imaging, cytogenetics, and scDNAseq can measure CIN, with the latter being the most comprehensive method accessible to clinical samples. To facilitate comparison of CIN rates between phenotypes and methods, we propose a standardized unit of CIN: Mis-segregations per Diploid Division (MDD). This systematic analysis of common CIN measures highlights the superiority of single-cell methods and provides guidance for measuring CIN in the clinical setting.
    Language English
    Publishing date 2023-06-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.15.544840
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  7. Article ; Online: Tuning Chromosomal Instability to Optimize Tumor Fitness.

    Burkard, Mark E / Weaver, Beth A

    Cancer discovery

    2017  Volume 7, Issue 2, Page(s) 134–136

    Abstract: Low rates of chromosomal instability (CIN) are weakly tumor promoting, whereas high rates of CIN cause cell death and tumor suppression. In this context, Sansregret and colleagues show that one mechanism to restrain excessive CIN in tumor cells and ... ...

    Abstract Low rates of chromosomal instability (CIN) are weakly tumor promoting, whereas high rates of CIN cause cell death and tumor suppression. In this context, Sansregret and colleagues show that one mechanism to restrain excessive CIN in tumor cells and increase fitness is through mutations in the anaphase promoting complex/cyclosome. This serves to delay mitotic progression and decrease the rate of chromosome missegregation. Cancer Discov; 7(2); 134-6. ©2017 AACRSee related article by Sansregret et al., p. 218.
    MeSH term(s) Anaphase-Promoting Complex-Cyclosome/genetics ; Cell Death ; Cell Line, Tumor ; Chromosomal Instability ; Humans
    Chemical Substances Anaphase-Promoting Complex-Cyclosome (EC 2.3.2.27)
    Language English
    Publishing date 2017-02-06
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-16-1415
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    Zs.A 6916: Show issues Location:
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  8. Article ; Online: Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles

    Amber S. Zhou / John B. Tucker / Christina M. Scribano / Andrew R. Lynch / Caleb L. Carlsen / Sophia T. Pop-Vicas / Srishrika M. Pattaswamy / Mark E. Burkard / Beth A. Weaver

    PLoS Biology, Vol 21, Iss

    2023  Volume 10

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Mad1 at the Golgi apparatus: a story beyond kinetochores.

    Wan, Jun / Weaver, Beth A

    Cell cycle (Georgetown, Tex.)

    2015  Volume 14, Issue 12, Page(s) 1763–1764

    MeSH term(s) Cell Cycle Checkpoints ; Cell Cycle Proteins/physiology ; Cell Movement/genetics ; Golgi Apparatus/metabolism ; Humans ; Integrins/metabolism ; Nuclear Proteins/physiology
    Chemical Substances Cell Cycle Proteins ; Integrins ; Nuclear Proteins
    Language English
    Publishing date 2015-05-28
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.1080/15384101.2015.1032639
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    Zs.A 5881: Show issues Location:
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  10. Article ; Online: Evaluating an engaging and coach-assisted online cognitive behavioral therapy for depression among adolescent and young adult cancer survivors: A pilot feasibility trial.

    Zhang, Anao / Weaver, Addie / Walling, Emily / Zebrack, Brad / Jackson Levin, Nina / Stuchell, Beth / Himle, Joseph

    Journal of psychosocial oncology

    2022  Volume 41, Issue 1, Page(s) 20–42

    Abstract: Objectives: Technology-assisted Cognitive Behavioral Therapy (tCBT) has significant potentials to provide engaging and accessible depression treatment for adolescents and young adults (AYAs) coping with cancer. This study evaluated the feasibility and ... ...

    Abstract Objectives: Technology-assisted Cognitive Behavioral Therapy (tCBT) has significant potentials to provide engaging and accessible depression treatment for adolescents and young adults (AYAs) coping with cancer. This study evaluated the feasibility and preliminary efficacy of an engaging and tailorable tCBT - Mind Your Total Health (MYTH) - for AYA cancer survivors' depression.
    Methods: Seventeen AYAs diagnosed with cancer were randomly assigned to either the intervention (MYTH) or control group. The intervention group (n = 10) received eight weekly 30-35 minutes coach-assisted tCBT (MYTH), while the control group (n = 7) received active control, BeatingtheBlues (BtB).
    Results: Eight out of ten participants in the MYTH group completed at least six out of eight sessions, suggesting strong feasibility (80% completion rate) among AYAs with cancer. Efficacy outcomes indicated that participants in the MYTH group reported significant pre- and post-treatment reduction in depression,
    Discussion: This engaging, tailorable, and coach-assisted tCBT intervention is promising in alleviating depression and anxiety among AYA cancer survivors. Future research needs to include larger sample size and a more diverse patient population.
    MeSH term(s) Adolescent ; Humans ; Young Adult ; Anxiety/psychology ; Cancer Survivors ; Cognitive Behavioral Therapy ; Depression/therapy ; Feasibility Studies ; Neoplasms/therapy ; Neoplasms/psychology ; Pilot Projects
    Language English
    Publishing date 2022-01-18
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 605892-9
    ISSN 1540-7586 ; 0734-7332
    ISSN (online) 1540-7586
    ISSN 0734-7332
    DOI 10.1080/07347332.2021.2011530
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