Group items tagged

the mortality rate of EOC has not been significantly changed for several decades

Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer

Low-prevalence but statistically significant mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12 were also identified, but the majority of genes were mutated at low frequency, making it difficult to distinguish between driver and passenger mutations

KPNB1 inhibition via any of three KPNB1 siRNAs or importazole treatment induced apoptosis in human EOC cell lines (Fig. 3 A–F and Fig. S4), and was accompanied by an increase in the expression levels of the proapoptotic proteins BAX and cleaved caspase-3

Stable overexpression of KPNB1 in SKOV3 and OVCAR3 (Fig. S6) significantly accelerated cell proliferation/survival (Fig. 5 A–C), confirming that KPNB1 functions as an oncogene in EOC

KPNB1 overexpression significantly decreased caspase-3/7 activity (Fig. 5D), in addition to the expression levels of cleaved caspase-3 and BAX proteins (Fig. 5E). KPNB1 overexpression also decreased p21 and p27 protein levels (Fig. 5E), as opposed to their increase by KPNB1 inhibition

KPNB1 functions as an antiapoptotic and proproliferative oncogene in EOC.

Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1

KPNB1 acts as an oncogene in human EOC and represents a promising therapeutic target.

ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC

ivermectin also induced apoptosis

ivermectin increased the expression levels of BAX, and cleaved PARP, as well as p21 and p27

KPNB1 inhibition is responsible for the antitumor effect of ivermectin

we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells

Single treatment of ivermectin or paclitaxel reduced tumor growth in nude mice, but, notably, combination treatment of ivermectin and paclitaxel almost completely suppressed tumor growth

ERBB2, is amplified and overexpressed in many cancers, including breast (31), ovary (31), colon (32), bladder (33), non-small-cell lung (34), and gastric cancer (35), and is a poor prognostic factor in certain cancer types

KPNB1 was the second-highest-ranked gene identified in our screen

Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1’s oncogenic potential in these tumor types

our findings suggest that KPNB1 might serve as a master regulator of cell cycle by regulating several cell cycle-related proteins, including p21, p27, and APC/C family members

higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans

none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event

we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone