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51.
Alexander J McIntyre Charlotte Z Angel James S Smith Amy Templeman Katherine Beattie Shannon Beattie Alice Ormrod Eadaoin Devlin Charles McGreevy Chloe Bothwell Sharon
L Eddie Niamh
E Buckley Rich Williams Paul
B Mullan 《Nucleic acids research》2022,50(11):6154
Chromosome 17q23 amplification occurs in 20% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours. 相似文献
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Edward B. Blanchard Maria L. Peters Christiane Hermann Shannon M. Turner Todd C. Buckley Kristine Barton Mark P. Dentinger 《Applied psychophysiology and biofeedback》1997,22(4):227-245
In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA),
70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization
of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of
expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received
12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and
4 weeks after treatment, HA Index was significantly (p=.003) reduced as was HA medication consumption. There were no differential
reducations in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the
end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a
specific effect of TBF for hand warming on vascular HA activity. 相似文献
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