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It has been reported that miR-21 is upregulated in hepatocellular carcinoma (HCC), and overexpressed miR-21 plays a key role in promoting cell cycle progression, reducing cell death and favoring angiogenesis and invasion. Overexpr...
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It has been reported that miR-21 is upregulated in hepatocellular carcinoma (HCC), and overexpressed miR-21 plays a key role in promoting cell cycle progression, reducing cell death and favoring angiogenesis and invasion. Overexpression of hepatocellular carcinoma, downregulated 1 (HEPN1) exhibits an antiproliferative effect on HepG2 cells, suggesting that silencing of HEPN1 may contribute to carcinogenesis of hepatocytes. In silico analysis revealed that HEPN1 may be a potential target of miR-21. Using quantitative reverse transcription PCR and Western blot, we found that HEPN1 was strikingly downregulated in both mRNA (fold change was 33.5, P<0.0001) and protein levels in human HCC tumor tissues, in comparison with the adjacent non-tumor tissues. More importantly, the expression level of HEPN1 was inversely correlated with the expression of miR-21 in HCC (R-2=0.442, P<0.0001). The combination between the 3' untranslated region (UTR) of HEPN1 with miR-21 was experimentally verified by a miRNA luciferase reporter approach. The suppressed cell proliferation upon stimulation of miR-21 inhibitor could be partially abolished by knocking down HEPN1, so inhibition of miR-21 expression in HCC cells profoundly suppressed cell proliferation partially by upregulating HEPN1 expression. Taken together, the current study suggested an underlying mechanism that miR-21 directly target HEPN1 and inhibit its expression during the carcinogenesis of HCC. HEPN1 may thus be a candidate as a therapeutic target for patients with HCC.
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Eight protoberberine-type alkaloids and two indole alkaloids were isolated from the MeOH extracts of the herb Corydalis saxicola BUNTING (Papaveraceae). Their structures were identified as clehydrocavidine (1), dehydroapocavidine ...
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Eight protoberberine-type alkaloids and two indole alkaloids were isolated from the MeOH extracts of the herb Corydalis saxicola BUNTING (Papaveraceae). Their structures were identified as clehydrocavidine (1), dehydroapocavidine (2), dehydroisoapocavidine (3), berberine (4), dehydroiso-corypalmine (5), coptisine (6), tetradehydroscoulerine (7), berbinium (8), 1-formyl-5-methoxy-6-methylindoline (9), and 1-formyl-2-hydroxy-5-methoxy-6-methylindoline (10). Compounds 3, 9, and 10 are new alkaloids. All compounds were tested for anti-HBV activity against the 2.2.15 cell line in vitro. Dehydrocavidine (1), dehydroapocavidine (2), and dehydroisoapocavidine (3) exhibited inhibitory activity against HBsAg and HBeAg, but no cytotoxicity against the 2.2.15 cell line.
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BACKGROUND. Ultrasound LI-RADS version 2017 recommends that patients with US-2 subthreshold observations undergo repeat surveillance ultrasound in 3-6 months and return to routine surveillance if the observation shows no growth fo...
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BACKGROUND. Ultrasound LI-RADS version 2017 recommends that patients with US-2 subthreshold observations undergo repeat surveillance ultrasound in 3-6 months and return to routine surveillance if the observation shows no growth for 2 years. However, outcomes of US-2 observations are unknown. OBJECTIVE. The purpose of this article was to determine imaging outcomes of US-2 observations detected on surveillance ultrasound examinations. METHODS. This retrospective study included 175 patients (median age, 59 years; 70 women, 105 men) at high risk for hepatocellular carcinoma (HCC) with US-2 observations (i.e., subcentimeter observations) on surveillance ultrasound. Observations were classified on follow-up ultrasound performed 2 or more years later as showing no correlate, stable (if remaining subcentimeter), or progressed (if measuring >= 10 mm, meeting US-3 criteria). Observations were classified on follow-up multiphasic CT or MRI (stratified as < 2-year vs >= 2-year follow-up) as showing no correlate or, if showing a correlate, using CT/MRI LI-RADS version 2018. RESULTS. A total of 111 patients had follow-up ultrasound after 2 or more years and 106 had follow-up CT or MRI (79 before 2 years, 27 after 2 years). On the basis of final follow-up examinations, 173 of 175 observations were stable on follow-up ultrasound 2 or more years later (n = 68); showed no correlate on follow-up ultrasound, CT, or MRI (n = 88); or were classified as LR-1 or LR-2 on CT or MRI (n = 17). The remaining 2 of 175 observations were LR-3 on CT or MRI. No observations progressed to US-3 on follow-up ultrasound or were classified as LR-4 or greater on CT or MRI. A correlate was observed in 25 of the 106 follow-up CT or MRI examinations (LR-1 or LR-2 in 23; LR-3 in two). Eight patients developed HCC at a median of 2.0 years after initial US-2 observation detection; all HCCs were in separate locations from the baseline observations and were preceded by a surveillance ultrasound that could not reidentify the baseline observation. In three patients who underwent liver transplant, the explant showed no dysplastic nodule or HCC. CONCLUSION. US-2 subthreshold observations are unlikely to progress or become HCC and commonly have no correlate on follow-up imaging. CLINICAL IMPACT. Because of the low progression rate of US-2 subthreshold observations, it is unclear if an extended period of intensive surveillance, as recommended by multiple professional societies, is warranted.
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Background & Aims: Intermediate hepatocellular carcinoma (HCC) treatment has become complicated due to the development of various molecular-targeted agents (MTAs). We aimed to determine whether the administration of MTAs in patients with intermediate-stage HCC contributed to the prevention of progression to an advanced stage. Methods: We enrolled and retrospectively examined 289 patients with Child-Pugh class A who had been diagnosed with intermediate-stage HCC and underwent initial trans-arterial chemoembolization (TACE). Patients were classified into 2 groups: a group in which MTAs were administered to patients whose condition was refractory to TACE (n = 65) and a group in which MTAs were not administered (n = 65) at intermediate-stage HCC after propensity score matching (PSM). Time to stage progression (TTSP) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Results: TTSP and OS of the group with MTA administration were significantly longer than those of the group without MTA administration (TTSP: 36.4 vs. 17.9 months, p < 0.001; median survival time [MST]: 44.6 vs. 26.6 months, p = 0.001). Within the up-to-seven criteria and administration of MTAs at the intermediate-stage HCC were identified as independent factors for TTSP and OS in the multivariate analysis. TTSP and OS in the era of the multi-MTA group were significantly longer than those in the era of the mono-MTA group (TTSP: 44.8 vs. 27.4 months, p = 0.01; MST: 53.4 vs. 33.3 months, p = 0.01). Conclusion: The administration of MTAs in patients with intermediate-stage HCC contributes to the prevention of stage progression and prolongs OS....
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Background & Aims: Intermediate hepatocellular carcinoma (HCC) treatment has become complicated due to the development of various molecular-targeted agents (MTAs). We aimed to determine whether the administration of MTAs in patients with intermediate-stage HCC contributed to the prevention of progression to an advanced stage. Methods: We enrolled and retrospectively examined 289 patients with Child-Pugh class A who had been diagnosed with intermediate-stage HCC and underwent initial trans-arterial chemoembolization (TACE). Patients were classified into 2 groups: a group in which MTAs were administered to patients whose condition was refractory to TACE (n = 65) and a group in which MTAs were not administered (n = 65) at intermediate-stage HCC after propensity score matching (PSM). Time to stage progression (TTSP) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Results: TTSP and OS of the group with MTA administration were significantly longer than those of the group without MTA administration (TTSP: 36.4 vs. 17.9 months, p < 0.001; median survival time [MST]: 44.6 vs. 26.6 months, p = 0.001). Within the up-to-seven criteria and administration of MTAs at the intermediate-stage HCC were identified as independent factors for TTSP and OS in the multivariate analysis. TTSP and OS in the era of the multi-MTA group were significantly longer than those in the era of the mono-MTA group (TTSP: 44.8 vs. 27.4 months, p = 0.01; MST: 53.4 vs. 33.3 months, p = 0.01). Conclusion: The administration of MTAs in patients with intermediate-stage HCC contributes to the prevention of stage progression and prolongs OS.
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