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1.
Medicine (Baltimore) ; 103(7): e37179, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38363898

ABSTRACT

Lung adenocarcinoma (LUAD) is usually diagnosed at advanced stages. Hence, there is an urgent need to seek an effective biomarker to predict LUAD status. Long noncoding RNAs (lncRNAs) play key roles in the development of tumors. However, the relationship between LINC00921 and LUAD remains unclear. The gene expression data of LUAD were downloaded from the Cancer Genome Atlas database to investigate the expression level of LINC00921 in LUAD. Diagnostic ability analysis, survival analysis, tumor mutational burden analysis, and immune cell infiltration analysis of LINC00921 in LUAD patients were performed simultaneously. According to the median expression value of LINC00921, patients were divided into LINC00921 high- and low-expression groups. The function of LINC00921 in LUAD was identified through difference analysis and enrichment analysis. Moreover, drugs that may be relevant to LUAD treatment were screened. Finally, blood samples were collected for real-time polymerase chain reaction. LINC00921 was significantly lower in LUAD tumor tissues. Notably, patients with low expression of LINC00921 had a shorter median survival time. Decreased immune cell infiltration in the tumor microenvironment in the low LINC00921 expression group may contribute to poorer patient outcomes. Tumor mutational burden was significantly different in survival between the LINC00921 high- and low-expression groups. In addition, LINC00921 may exert an influence on cancer development through its regulation of target genes transcription. Glyceraldehyde-3-phosphate dehydrogenase-related drugs may be more likely to be therapeutically effective in LUAD. LINC00921 was able to be used as the potential diagnostic indicator for LUAD.


Subject(s)
Adenocarcinoma , Lung Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Biomarkers , Real-Time Polymerase Chain Reaction , Lung , Lung Neoplasms/genetics , Tumor Microenvironment/genetics
2.
FEBS Open Bio ; 11(1): 133-145, 2021 01.
Article in English | MEDLINE | ID: mdl-33176070

ABSTRACT

Sorafenib, the first-line agent for treatment of advanced hepatocellular carcinoma (HCC), improves median overall survival by approximately 3 months. In the present study, we investigated whether sorafenib combined with cucurbitacin B (CuB), a natural tetracyclic triterpenoid isolated from Cucurbitaceae, exerts enhanced antitumor effects against HCC. Cell viability and colony formation ability were detected by cell-counting kit-8 and colony formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression was detected by western blotting. HepG2 xenografts in nude mice were used to evaluate in vivo antitumor effects. We report that sorafenib and CuB exhibited synergistic effects on cellular proliferation inhibition and cell apoptosis induction, but not on cell cycle arrest. Furthermore, combination treatment enhanced levels of cleaved caspase 3 and cleaved caspase 9, but suppressed phosphorylation of STAT3. Epidermal growth factor, a potent stimulator of signal transducer and activator of transcription-3 (STAT3), promoted cell viability and colony formation ability, whereas combination treatment exerted inhibitory effects on epidermal growth factor-induced STAT3 phosphorylation. Finally, HepG2 xenograft mice cotreated with sorafenib and CuB exhibited reduced tumor progression without notable weight loss. In conclusion, sorafenib and CuB exert synergistic antitumor effects through a pathway that may involve STAT3 phosphorylation, and this may represent a promising therapeutic approach for treatment of HCC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Sorafenib/pharmacology , Triterpenes/pharmacology , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Survival/drug effects , Drug Synergism , Female , Hep G2 Cells , Humans , Liver Neoplasms/pathology , Mice , Phosphorylation/drug effects , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Sorafenib/therapeutic use , Triterpenes/therapeutic use , Xenograft Model Antitumor Assays
3.
Cancer Gene Ther ; 28(1-2): 126-140, 2021 02.
Article in English | MEDLINE | ID: mdl-32616906

ABSTRACT

Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the first-line systemic therapy for advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to play critical roles in the initiation, progression, and drug resistance of HCC. In this study, we aimed to identify sorafenib-induced miRNAs and demonstrate their regulatory roles. First, we identified that the expression of the tumor-suppressive miRNA miR-375 was significantly induced in hepatoma cells treated with sorafenib, and miR-375 could exert its antiangiogenic effect partially via platelet-derived growth factor C (PDGFC) inhibition. Then, we demonstrated that sorafenib inhibited PDGFC expression by inducing the expression of miR-375 and a transcription factor, achaete-scute homolog-1 (ASH1), mediated the induction of miR-375 by sorafeinb administration in hepatoma cells. Finally, we verified that the expression of miR-375 was reduced in sorafenib-resistant cells and that the restoration of miR-375 could resensitize sorafenib-resistant cells to sorafenib partially by the degradation of astrocyte elevated gene-1 (AEG-1). In conclusion, our data demonstrate that miR-375 is a critical determinant of HCC angiogenesis and sorafenib tolerance, revealing a novel miRNA-mediated mechanism underlying sorafenib treatment.


Subject(s)
Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/blood supply , Liver Neoplasms/drug therapy , MicroRNAs/metabolism , Sorafenib/pharmacology , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Drug Resistance, Neoplasm , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Mice , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Rats, Sprague-Dawley
4.
Proc Inst Mech Eng H ; 233(2): 232-243, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30565501

ABSTRACT

In this work, an uncertainty optimization approach for dental implant is proposed to reduce the stress at implant-bone interface. Finite element method is utilized to calculate the stress at implant-bone interface, and support vector regression is used to replace finite element method to ease the computational cost. Deterministic optimization based on support vector regression is conducted, which demonstrates that the method using support vector regression replacing finite element method in dental implant optimization is efficient and reliable. Global sensitivity analysis based on support vector regression is used to assign different uncertainties (manufacturing errors) to different design variables to save the manufacturing cost. Two popular uncertainty optimization methods, k-sigma method and interval method, are used for the uncertainty optimization of dental implant. The results indicate that the stress at implant-bone interface is reduced greatly considering the uncertainties in design variables with the manufacturing cost increasing a little. This approach can be promoted to other types of bio-implants.


Subject(s)
Dental Implants , Dental Prosthesis Design/methods , Finite Element Analysis , Support Vector Machine , Uncertainty , Regression Analysis
5.
Small ; 13(35)2017 09.
Article in English | MEDLINE | ID: mdl-28639331

ABSTRACT

The lack of stable and efficient techniques to synthesize high-quality large-area thin films is one of the major bottlenecks for the real-world application of the 2D transition metal dichalcogenides. In this work, the growth of molybdenum disulfide (MoS2 ) on sapphire substrates by sulfurizing the MoO3 film deposited by atomic layer deposition (ALD) is reported. The advantages of the ALD method can be well inherited, and the synthesized MoS2 films exhibit excellent layer controllability, wafer-scale uniformity, and homogeneity. MoS2 films with desired thickness can be obtained by varying MoO3 ALD cycles. The atomic force microscope and Raman measurements demonstrate that the ALD-based MoS2 has good uniformity. Clear Raman shift as a function of the film thickness is observed. Field-effect transistor devices are fabricated through a transfer-free and top-down process. High On/Off current ratio (≈104 ) and medium-level electron mobilities (≈0.76 cm2 V-1 s-1 for monolayer, and 5.9 cm2 V-1 s-1 for four-layer) are obtained. The work opens up an attractive approach to realize the application of wafer-scale 2D materials in integrated circuits and systems.

6.
Anal Chem ; 86(18): 8922-6, 2014 Sep 16.
Article in English | MEDLINE | ID: mdl-25144468

ABSTRACT

Compact disc-based bioassays have been developed as novel point-of-care (POC) tools for various applications in chemical analysis and biomedical diagnosis. For the fabrication of assay discs, the surface patterning and sample introduction have been restricted to manual delivery that is unfavorable for on-demand high throughput medical screening. Herein, we have adapted a conventional inkjet printer to prepare bioassays on regular DVD-Rs and accomplished quantitative analysis with a multimode DVD/Blu-Ray optical drive in conjunction with free disc diagnostic software. The feasibility and accuracy of this method have been demonstrated by the quantitative analysis of inkjet-printed biotin-streptavidin binding assays on DVD, which serves as a trial system for other complex, medically relevant sandwich-format or competitive immunoassays.


Subject(s)
Biological Assay , Biotin/metabolism , Streptavidin/metabolism , Biotin/chemistry , Compact Disks , Point-of-Care Systems , Printing , Protein Binding , Streptavidin/chemistry
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