Cell
 2011
DOI: 10.1016/j.cell.2011.01.017
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Identification of Aneuploidy-Selective Antiproliferation Compounds

Yun‐Chi Tang
1
,
Bret R. Williams
2
,
Jake J. Siegel
3
et al.

Abstract: Aneuploidy, an incorrect chromosome number, is a hallmark of cancer. Compounds that cause lethality in aneuploid, but not euploid, cells could therefore provide new cancer therapies. We have identified the energy stress-inducing agent AICAR, the protein folding inhibitor 17-AAG, and the autophagy inhibitor chloroquine as exhibiting this property. AICAR induces p53-mediated apoptosis in primary mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19. AICAR and 17-AAG, especially when combine… Show more

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Cited by 332 publications

(399 citation statements)
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“…We then removed the drug and monitored their proliferation over time either in the absence ( Figure 1A-C) or in the presence of a chemotherapeutic agent ( Figure 1D-G). In agreement with previous reports Williams et al 2008;Sheltzer et al 2017;Stingele et al 2012;Santaguida et al 2017;Tang et al 2011), induction of CIN led to decreased proliferation ( Figure 1B, C). To test the effects of CIN on cell proliferation in the presence of a chemotherapeutic agent, cancer cell lines were exposed to a battery of chemotherapeutic drugs, after reversine removal ( Figure 1D, E).…”
Section: Resultssupporting
confidence: 93%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…We then removed the drug and monitored their proliferation over time either in the absence ( Figure 1A-C) or in the presence of a chemotherapeutic agent ( Figure 1D-G). In agreement with previous reports Williams et al 2008;Sheltzer et al 2017;Stingele et al 2012;Santaguida et al 2017;Tang et al 2011), induction of CIN led to decreased proliferation ( Figure 1B, C). To test the effects of CIN on cell proliferation in the presence of a chemotherapeutic agent, cancer cell lines were exposed to a battery of chemotherapeutic drugs, after reversine removal ( Figure 1D, E).…”
Section: Resultssupporting
confidence: 93%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Lower CQ doses were less effective, likely due to the already high basal levels of autophagy in TSCs. Our findings align with Tang et al, who reported increased basal autophagy in aneuploid MEFs following chromosomal mis-segregation and noted that aneuploid cells were more sensitive to autophagy inhibition 69 .…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Then, we tried to add selective pressure by exposing high passage T21‐iPSC cultures to the Hsp90 inhibitor 17‐AAG. Contrary to a previous report that had failed to identify an increased sensitivity of T21‐iPSCs to this proteotoxic agent , as can be seen in Figure , we were able to reproduce previous work demonstrating that aneuploid cells are more sensitive than euploid cells to proteotoxic stress . However, even after exposing high passage T21‐iPSC cultures to 9 days of treatment with 80 nM 17‐AAG, which killed over 95% of the T21‐iPSC colonies, we still could not detect a single euploid iPSC in the surviving colonies.…”
Section: Discussionsupporting
(Expert classified)
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
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