Balancing the yin and yang of SINE

Pluthero, Fred G.; Kahr, Walter H A

doi:10.1182/blood-2017-07-793398

Cited by 2 publications

(2 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We hypothesize that this favorable drug interaction may also be due to the combined G1/S and G2/M phase arrests, in which G2/M phase arrest is consistent with published literature on paclitaxel [55]. Another explanation might otherwise be due to the synergy between inhibited microtubules due to paclitaxel and inhibited centromere formation via XPO1 inhibition [56]. The mechanism underlying the observed synergistic interaction between these two compounds is currently ongoing and beyond the scope of this manuscript.…”

Section: Discussionsupporting

confidence: 84%

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer

Sexton

Zaid

Chaudhury

et al. 2019

IJMS

View full text Add to dashboard Cite

Gastric cancer remains an unmet clinical problem in urgent need of newer and effective treatments. Here we show that the nuclear export protein, Exportin 1 (XPO1, chromosome region maintenance 1 or CRM1), is a promising molecular target in gastric cancer. We demonstrate significant overexpression of XPO1 in a cohort of histologically diverse gastric cancer patients with primary and metastatic disease. XPO1 RNA interference suppressed gastric cancer cell growth. Anti-tumor activity was observed with specific inhibitor of nuclear export (SINE) compounds (selinexor/XPOVIO), second-generation compound KPT-8602/eltanexor, KPT-185 and +ve control Leptomycin B in three distinct gastric cancer cell lines. SINE compounds inhibited gastric cancer cell proliferation, disrupted spheroid formation, induced apoptosis and halted cell cycle progression at the G1/S phase. Anti-tumor activity was concurrent with nuclear retention of tumor suppressor proteins and inhibition of colony formation. In combination studies, SINE compounds enhanced the efficacy of nab-paclitaxel in vitro and in vivo. More significantly, using non-coding RNA sequencing studies, we demonstrate for the first time that SINE compounds can alter the expression of non-coding RNAs (microRNAs and piwiRNAs). SINE treatment caused statistically significant downregulation of oncogenic miR-33b-3p in two distinct cell lines. These studies demonstrate the therapeutic significance of XPO1 in gastric cancer that warrants further clinical investigation.

show abstract

Section: Discussionsupporting

confidence: 84%

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer

Sexton

Zaid

Chaudhury

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…The key to breaking this stalemate was to give patients a Selinexor "holiday" that is long enough (8 -21 days) to allow some of their MK progenitors to pass through the drug-sensitive stage and, in some cases, with the added benefit of treatment with TPO mimetics. This tactic produced a substantial recovery in platelet counts (81).…”

Section: Figure 2 Regulation Of Steady-state Thrombopoiesismentioning

confidence: 90%

The Birth and Death of Platelets in Health and Disease

Pluthero

Kahr

2018

Physiology

Self Cite

View full text Add to dashboard Cite

Blood platelets are involved in a wide range of physiological responses and pathological processes. Recent studies have considerably advanced our understanding of the mechanisms of platelet production and clearance, revealing new connections between the birth and death of these tiny, abundant cells. Key insights have also been gained into how physiological challenges such as inflammation, infection, and chemotherapy can affect megakaryocytes, the cells that produce platelets.

show abstract

Balancing the yin and yang of SINE

Cited by 2 publications

References 10 publications

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer

The Birth and Death of Platelets in Health and Disease

Contact Info

Product

Resources

About