Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2β expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2β/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.
Participants were randomly assigned to receive treatment with a self-expandable metallic stent (SEMS) placement combined with intraluminal I seed strands brachytherapy (brachytherapy group) or a SEMS without brachytherapy (control group). The outcomes were measured in terms of technical success, clinical success, stent patency, complications related to the procedure, and patient survival. A P value of less than 0.05 indicated a significant difference. Results There were no significant differences in technical and clinical success between brachytherapy and control group (100 vs. 100%-100 vs. 93.3%). During the median 273.4 ± 154.6 days follow-up time, the median stent patency time in the brachytherapy group was longer than those in the control group (368.0 ± 42.4 vs. 220.0 ± 34.8 days), and the duration of survival in the brachytherapy groups was higher than those in the control group (355.0 ± 71.5 vs. 209.0 ± 17.2 days). There were no significant differences in the complications between the two groups. Conclusions SEMS placement combined with intraluminalI seed strands brachytherapy are feasible and effective for malignant biliary obstruction, and seems to prolong the stent patency and survival time.
AimTo evaluate the type of venous involvement in Chinese Budd-Chiari syndrome (BCS) patients and the relative diagnostic accuracy of the different imaging modalities.MethodsUsing digital subtraction angiography (DSA) as a reference standard, color Doppler ultrasound (CDUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) were performed on 338 patients with BCS. We analyzed the course of the main and any accessory hepatic veins (HVs) and the inferior vena cava (IVC) to assess the etiology of obstructed segments and diagnostic accuracy of CDUS, CTA and MRA.ResultsAmong the 338 cases, there were 8 cases (2.4%) of isolated IVC membranous obstruction, 45 cases (13.3%) of isolated HV occlusion, and 285 cases (84.3%) with both IVC membranous obstruction and HV occlusion. Comparing with DSA, CDUS, CTA had a diagnostic accuracy of 89.3% and 80.2% in detecting BCS, and 83.4% of cases correctly correlated by MRA.ConclusionIn Henan Province, most patients with BCS have complex lesions combining IVC and HV involvement. The combination of CDUS and CTA or MRI is useful for diagnosis of BCS and guiding therapy.
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are demonstrated to be potent regulators in the development of various types of human cancers, including non-small cell lung cancer (NSCLC). In the present study, the level of circRNA-HIPK3 were measured by Taq-man based quantitative real-time PCR (qRT-PCR) analysis in both NSCLC patient specimens and cells, which showed that circRNA-HIPK3 was upregulated in both NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), migration and flow-cytometry assays indicated that circRNA-HIPK3 participated in the regulation of the proliferation, migration, invasion and apoptosis of NSCLC cells. MiR-193a expression was increased by circHIPK3 silencing. We then showed that miR-149 interacts with FOXM1 by binding to the 3ʹuntranslated region (UTR). Further, ectopic overexpression of miR-149 by transfecting miR-149 mimics significantly inhibited growth, migration and invasion of HSCLCs, which was found to be mediated through FOXM1. Moreover, miR-149 overexpression decreases the viability and proliferation of HSCLCs. Therefore, our data suggest that circHIPK3 regulates the function of NSCLCs through miR-149-mediated FOXM1 expression regulation, potentially providing a novel insight into the pathogenesis of NSCLC.
Dense extracellular matrix (ECM) severely impedes the spread of
drugs in solid tumors and induces hypoxia, reducing chemotherapy efficiency.
Different proteolytic enzymes, such as collagenase (Col) or bromelain,
can directly attach to the surface of nanoparticles and improve their
diffusion, but the method of ligation may also impair the enzymatic
activity due to conformational changes or blockage of the active site.
Herein, a “nanoenzyme capsule” was constructed by combining
collagenase nanocapsules (Col-nc) with heavy-chain ferritin (HFn)
nanocages encapsulating the chemotherapy drug doxorubicin (DOX) to
enhance tumor penetration of the nanoparticles by hydrolyzing collagen
from the ECM. Col-nc could protect the activity of the enzyme before
reaching the site of action while being degraded under mildly acidic
conditions in tumors, and the released proteolytic enzyme could digest
collagen. In addition, HFn as a carrier could effectively load DOX
and had a self-targeting ability, enabling the nanoparticles to internalize
into cancer cells more effectively. From in vivo and in vitro studies,
we found that collagen was effectively degraded by Col-nc/HFn(DOX)
to increase the accumulation and penetration of nanoparticles in the
solid tumor site and could alleviate hypoxia inside the tumor to enhance
the antitumor effects of DOX. Therefore, the strategy of increasing
nanoparticle penetration in this system is expected to provide a potential
approach for the clinical treatment of solid tumors.
PTCB is safe, feasible, and simple, with a high true positive rate for definitive diagnosis of OJ causes. Well differentiated adenocarcinoma was the predominant pathologic type.
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