Single-session endovascular treatment with MAT as the first-line thrombus removal method is feasible, safe, and effective for IVCS with secondary acute isolated iliofemoral DVT. Although limited, our experience suggests that patients thought to be at high risk of bleeding may be candidates for the present single-session endovascular protocol.
PLE sclerotherapy under fluoroscopic guidance is safe and effective for the treatment of orbital venous malformations and can be used as one of the treatment alternatives.
Taken together, ALS induces autophagy and cell cycle arrest in HepG2 cells via PI3K/Akt/mTOR-mediated pathway. Autophagy inhibition may promote the anticancer effect of ALS and sensitize the chemotherapy in HepG2 cells.
Melanoma is one of the most malignant and aggressive cancers with high cancer-related deaths. However, it is unclear whether Ku80 regulates tumor growth in human melanoma. In this study, we screened a siRNA library targeting 6024 human genes and identified Ku80 as a potential therapeutic target in melanoma cells. Knockdown of Ku80 significantly suppressed melanoma cell proliferation and induced apoptosis, as well as enhanced the antitumor effect of melatonin in melanoma in vitro and in vivo. Overexpression of Ku80, however, promoted melanoma growth and increased the insensitivity of melanoma cells to melatonin. Mechanistically, we found that Ku80 bound to the PDK1 promoter and activated the transcription of PDK1. Moreover, we showed that the binding of Ku80 at the PDK-1 promoter was HIF1-α dependent, and melatonin degraded HIF1-α in melanoma cells. Furthermore, clinical data revealed that the expression of Ku80 and PDK-1 proteins were positively correlated and elevated in the tumor tissues of melanoma patients, and high expression of Ku80 predicted a poor prognosis in melanoma. Collectively, our study demonstrated that Ku80 promoted melanoma growth and regulated antitumor activity of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway, suggesting that Ku80 may be a potential molecular target for melanoma treatment.
Hepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is an important hallmark in cancers, but the mechanism by which TERT is activated differentially in cancers is poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as a new modulator of TERT expression and tumor growth in HCC. NACO3 specifically binds to the TERT promoter at the -234 to -144 region and transcriptionally activates TERT expression. NCOA3 promotes HCC cell growth and tumor progression in vitro and in vivo through upregulating the TERT signaling. Knockdown of NACO3 suppresses HCC cell viability and colony formation, whereas TERT overexpression rescues this suppression. NCOA3 interacts with and recruits SP1 binding on the TERT promoter. Knockdown of NCOA3 also inhibits the expression of the Wnt signaling-related genes but has no effect on the Notch signaling-targeting genes. Moreover, NCOA3 is positively correlated with TERT expression in HCC tumor tissues, and high expression of both NCOA3 and TERT predicts a poor prognosis in HCC patients. Our findings indicate that targeting the NCOA3-SP1-TERT signaling axis may benefit HCC patients.
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, but the overall prognosis remains disappointing especially in the advanced-stage patients. Aberration expression of Aurora kinases is tumorigenic and thus it has attracted interests as therapeutic targets in cancer treatment. Here, we investigated the proteomic response of HCC Hep3B cells to danusertib (Danu), a pan-Aurora kinase inhibitor, and then validated the proteomic results based on stable-isotope labeling by amino acids in cell culture (SILAC). The proteomic data identified that Danu modulated the expression of 542 protein molecules (279 up-regulated; 260 down-regulated; 3 stable). Ingenuity pathway analysis (IPA) and KEGG pathway analysis identified 107 and 24 signaling pathways were regulated by Danu, respectively. IPA analysis showed cellular growth and proliferation, and cell death and survival were among the top five molecular and cellular functions regulated by Danu. The verification experiments showed that Danu inhibited the proliferation of Hep3B cells with a 24-hr IC50 value of 22.03 µM. Danu treatment also arrested Hep3B cells in G2/M phase via regulating the expression of key cell cycle regulators and induced apoptosis via mitochondria-dependent pathway in a dose-dependent manner. Besides, Danu induced a marked autophagy, and inhibition of autophagy enhanced the anticancer effects of Danu, indicating a cyto-protective role of Danu-induced autophagy. Our proteomic data and Western blotting assays showed the PI3K/Akt/mTOR signaling pathway was involved in the inducing effect of Danu on apoptosis and autophagy. Collectively, our findings have demonstrated that the Aurora kinases inhibition with danusertib results in global proteomic response and exerts anticancer effects in Hep3B cells involving regulation of cell cycle, apoptosis and autophagy and associated signaling pathways.
Objective Population-based epidemiological data on left common iliac vein (LCIV) compression is scarce. This study aimed to investigate the prevalence of LCIV compression in an asymptomatic population and patients with left iliofemoral deep vein thrombosis (IF-DVT). Materials and Methods Nonprobability sampling method was used in this multicenter cross-sectional study. The minimum diameter of LCIV and right common iliac vein minimum were measured. The percentage of LCIV compression (LCIV-CP) was calculated. Compression severity (CS) was classified as mild (CP ≤ 50%), moderate (50% < CP ≤ 70%), and severe (CP > 70%). Results In all, 896 subjects constituted the asymptomatic population and 93 patients constituted the IF-DVT population. In the asymptomatic population, LCIV-CP ranged from 1.1% to 89.9% (mean 44.0%), and people with mild, moderate, and severe CS accounted for 62.3%, 28.2%, and 9.5%, respectively. In the IF-DVT population, the mean LCIV-CP was 71.1% (range 42.2%–95.2%), and patients with severe CS accounted for 75.3%. Gender and age differences in LCIV-CP and CS distribution were observed in the asymptomatic population. Females, the young- and middle-aged group had higher LCIV-CPs. In the population with moderate-severe CS, the middle-aged group accounted for a larger proportion. Middle-aged females comprised the highest percentage of patients with moderate or severe CS. Sex and age affected the LCIV-CP and CS distribution. No gender and age differences were observed in the IF-DVT population. Conclusions LCIV compression is common in population. Middle-aged females are the predominant population with moderate-severe compression. Overlapping of LCIV-CP in the asymptomatic and IF-DVT population is significant and other risk factors should be integrated into the consideration when assessing the risk of IF-DVT secondary to LCIV compression.
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