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1.
Cells ; 13(7)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38607055

ABSTRACT

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.


Subject(s)
Biomarkers , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Proto-Oncogene Proteins c-myc , Receptors, Interleukin-6 , Humans , Apoptosis , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use
2.
Adv Healthc Mater ; 12(25): e2300670, 2023 10.
Article in English | MEDLINE | ID: mdl-37220874

ABSTRACT

Programmed death ligand-1 (PD-L1) and donor antigens are critical for donor immature dendritic cells (DCs) targeting donor-specific T cells to induce transplant tolerance. This study aims to clarify whether DC-derived exosomes (DEX) with donor antigens (H2b) and high levels of PD-L1 expression (DEXPDL1+ ) can help to suppress graft rejection. In this study, it is demonstrated that DEXPDL1+ presents donor antigens, as well as PD-L1 co-inhibitory signals, directly or semi-directly via DCs to H2b-reactive T cells. This dual signal presentation can prolong the survival of heart grafts from B6 (H2b) mice but not from C3H (H2k) mice by inhibiting T cell activation, inducing activated T cell apoptosis, and modulating the balance of T cell differentiation from inflammatory to regulatory. Additionally, even though DEXPDL1+ treatment cannot induce tolerance after short-term treatment, this study provides a new vehicle for presenting co-inhibitory signals to donor-specific T cells. This novel strategy may facilitate the realization of donor-specific tolerance via the further optimization of drug-loading combinations and therapeutic regimens to elevate their killing ability.


Subject(s)
Exosomes , T-Lymphocytes , Mice , Animals , B7-H1 Antigen , Transplantation, Homologous , Mice, Inbred C57BL , Mice, Inbred C3H , Immunosuppression Therapy , Antigens , Dendritic Cells
3.
BMC Oral Health ; 23(1): 298, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37194034

ABSTRACT

BACKGROUND: Few studies have evaluated the effects of the crown-to-implant (C/I) ratio on the marginal bone level (MBL) and bone density in non-splinted single implants. The aim of this study was to assess the effect of C/I ratio on MBL and density of peri-implant bone in non-splinted posterior implants. METHODS: The C/I ratio, MBL, and grayscale values (GSVs) for bone density were measured from X-rays. Four areas of interest (two at the apical area and two at the middle of the peri-implant area) and two control areas were selected for evaluation. Follow-up radiographs were calibrated according to the control areas. RESULTS: In all, 117 non-splinted posterior implants in 73 patients followed up for a mean duration of 36.23 ± 10.40 (range 24-72) months were considered. The mean anatomical C/I ratio was 1.78 ± 0.43 (range 0.93 to 3.06). The mean change in MBL was 0.28 ± 0.97 mm. There were no significant associations between the C/I ratio and MBL changes (r = -0.028, p = 0.766). Pearson correlation showed a significant correlation between changes in GSV and the C/I ratio in the middle peri-implant area (r = 0.301, p = 0.001) and apical area (r = 0.247, p = 0.009). CONCLUSIONS: A higher C/I ratio of single non-splinted posterior implants is associated with increased peri-implant bone density, but not correlated with changes in MBL.


Subject(s)
Alveolar Bone Loss , Dental Implants , Humans , Bone Density , Cross-Sectional Studies , Alveolar Bone Loss/diagnostic imaging , Crowns , Follow-Up Studies , Dental Prosthesis, Implant-Supported , Dental Prosthesis Design
4.
Cancers (Basel) ; 14(14)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35884570

ABSTRACT

EGFR-mutated non-small cell lung cancer (NSCLC) patients can be effectively treated with tyrosine kinase inhibitors (TKI) but frequently present with an EGFR T790M resistance mutation at relapse. We aimed to screen for T790M in pre-treatment formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients with a confirmed T790M mutation at progression. We analyzed 33 pre-treatment DNA samples of NSCLC patients who progressed upon TKI between 2013 to 2019. To establish storage-time dependent formalin fixation-induced background levels for C>T mutations, we analyzed DNA isolated from archival (stored >1 year, n = 22) and recently generated (stored <1 month, n = 11) FFPE samples and included DNA isolated from white blood cells (WBC) (n = 24) as controls. DNA samples were analyzed by droplet digital (dd)PCR, and positivity was defined by outlier detection according to Grubb's criterion. The T790M background allele frequency levels were 0.160% in DNA isolated from archival-FFPE, 0.100% in fresh FFPE, and 0.035% in WBC. Progression-free survival (PFS) time of the single T790M positive patient was 9 months, while T790M negative patients had a median PFS of 10 months (range 2−27). Proper storage time matched FFPE control samples are essential for reliable detection of T790M mutation at low VAF. The presence of EGFR T790M mutations in pre-TKI samples is rare, even in patients who progressed with EGFR T790M mutations.

5.
J Fungi (Basel) ; 8(1)2022 Jan 04.
Article in English | MEDLINE | ID: mdl-35049989

ABSTRACT

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016-2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

6.
J Cancer ; 12(18): 5562-5572, 2021.
Article in English | MEDLINE | ID: mdl-34405017

ABSTRACT

The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) plays a critical role in tumorigenesis as well as drug resistance in various cancers. However, the molecular mechanism by which HOTAIR induces gefitinib resistance in non-small cell lung cancer is to date unclear. In the present study, we revealed that HOTAIR is upregulated in gefitinib-resistant lung cancer cells and over-expression of HOTAIR enhances gefitinib resistance in lung cancer cells. In addition, the overexpression of HOTAIR promotes cell cycle progression through epigenetic regulation of EZH2/H3K27. Silencing of EZH2 by either siRNA or inhibitors sensitized the lung cancer cells to gefitinib. Inhibition of EZH2 induces expression of p16 and p21, whereas levels of CDK4, cyclinD1, E2F1, and LSD1 are significantly decreased in PC-9 cells overexpressing HOTAIR. ChIP-PCR experiments indicate that HOTAIR increases H3K27me3 recruitment to the promoter of p16 and p21 in PC-9 lung cancer cells overexpressing HOTAIR. In xenograft mouse models, overexpressing HOTAIR in lung cancer tissues decreased p16 and p21 proteins. Taken together, these data suggest that HOTAIR contributes to gefitinib resistance by regulating EZH2 and p16 and p21. Targeting HOTAIR may be a novel therapeutic strategy for treating gefitinib-resistance in non-small cell lung cancer.

7.
Macromol Rapid Commun ; 42(19): e2100327, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34288205

ABSTRACT

Conjugated polymer sorting is currently the best method to select large-diameter single-walled carbon nanotubes (SWCNTs) with tunable narrow chirality in the adaption of highly desired electronics applications. The acceleration on conjugated polymers-SWCNTs interaction with long-term stability through different molecular designs; for example, longer alkyl side-chains or conjugation moieties have been extensively developed in recent years. However, the importance of the macromolecules with abundant van der Waals (VDW) interaction in the conjugated-based block copolymer system acting during SWCNTs sorting is not clearly demonstrated. In this work, a conjugated diblock copolymer involving polyisoprene (PI) and highly dense π-interaction of poly (9,9-dioctylfluorene) (PFO) is utilized to investigate the impact of natural rubber PI physical interaction on sorting effectiveness and stability. Through the rational design of diblock copolymer, PFO with ≈1200 isoprene units can remarkably enhance SWCNTs sorting ability and selected few chiralities with a diameter of ≈0.83-1.1 nm and highly stable solution for more than 1 year. The introduction of long-chain PI system is attributed not only to form weak VDW force with SWCNTs and strengthen the wrapping of PFO around the semiconducting SWCNTs but also to act as a barrier among nanotubes to prevent reaggregation of sorted SWCNTs.


Subject(s)
Nanotubes, Carbon , Electronics , Polymers
8.
Sensors (Basel) ; 21(3)2021 Jan 28.
Article in English | MEDLINE | ID: mdl-33525633

ABSTRACT

This paper introduces a real-time processing and classification of raw sensor data using a convolutional neural network (CNN). The established system is a microcontroller-unit (MCU) implementation of an intelligent gripper for shape identification of grasped objects. The pneumatic gripper has two embedded accelerometers to sense acceleration (in the form of vibration signals) on the jaws for identification. The raw data is firstly transferred into images by short-time Fourier transform (STFT), and then the CNN algorithm is adopted to extract features for classifying objects. In addition, the hyperparameters of the CNN are optimized to ensure hardware implementation. Finally, the proposed artificial intelligent model is implemented on a MCU (Renesas RX65N) from raw data to classification. Experimental results and discussions are introduced to show the performance and effectiveness of our proposed approach.

9.
BMC Cancer ; 20(1): 1189, 2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33276757

ABSTRACT

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In traditional anti-cancer therapy, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been proven to be beneficial for patients with EGFR mutations. However, patients with EGFR wild-type NSCLC were usually not respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2) is a key molecular in the PRC2 complex and plays an important role in epigenetic regulation and is overexpressed in variant tumors. EZH2 inhibitors have been reported to sensitize variant tumor cells to anticancer drugs. This study aimed to investigate whether the EZH2 inhibitors, GSK343 and DZNep when combined with gefitinib can reverse EGFR-TKIs resistance in EGFR wild-type NSCLC cells. METHODS: The RNA-sequencing data of patients with NSCLC [502 patients with lung squamous cell carcinoma, including 49 paracancerous lung tissues and 513 patients with lung adenocarcinoma (LUAD), including 59 paracancerous lung tissues] from the Cancer Genome Atlas (TCGA), were analyzed for EZH2 expression. EZH2 expression was verified in 40 NSCLC tissue cancer samples and their corresponding paracancerous tissues from our institute (TJMUGH) via RT-PCR. A549 and H1299 cells treated with siRNA or EZH2 inhibitors were subjected to cell viability and apoptosis analyses as well to EGFR pathway proteins expression analyses via western blotting. RESULTS: EZH2 was upregulated in human NSCLC tissues and correlated with poor prognosis in patients with LUAD based on data from both TCGA and TJMUGH. Both GSK343 and DZNep sensitized EGFR wild-type LUAD cells (A549 and H1299) to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and by inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted a stronger inhibitory effect on tumor activity, cell proliferation and cell migration than single drug administration in vitro and in vivo. CONCLUSIONS: These data suggest that the combination of EZH2 inhibitors with EGFR-TKIs may be an effective method for treating NSCLC-patients with EGFR-wild type, who do not want to undergo traditional treatment with chemotherapy.


Subject(s)
Adenosine/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/pathology , Drug Resistance, Neoplasm/drug effects , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Gefitinib/pharmacology , Genes, erbB-1 , Indazoles/pharmacology , Lung Neoplasms/drug therapy , Neoplasm Proteins/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Pyridones/pharmacology , Adenosine/pharmacology , Adult , Aged , Animals , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Cell Cycle/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Drug Screening Assays, Antitumor , Drug Synergism , Enhancer of Zeste Homolog 2 Protein/biosynthesis , Enhancer of Zeste Homolog 2 Protein/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , RNA Interference , RNA, Neoplasm/biosynthesis , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Signal Transduction/drug effects
10.
Protein Expr Purif ; 175: 105688, 2020 11.
Article in English | MEDLINE | ID: mdl-32681953

ABSTRACT

BST2 is a single-pass type II transmembrane (TM) protein, which has a cytoplasmic domain, a transmembrane domain, and an extracellular domain, each domain is important for biologic function of BST2. BST2 is a host restriction factor that can effectively inhibit retrovirus release. Rhesus monkeys are considered as relevant natural animal models for studying AIDS in humans. In order to recognize rhesus BST2 (RhBST2) protein and detect its function accurately, we prepared a polyclonal antibody (pAb) especially for RhBST2. Meanwhile, we constructed RhBST2 proteins with the addition of an HA-tag at the N-terminus (RhBST2-NHA) or inside of the ectodomain (RhBST2-IHA) to compare the recognition ability of rabbit anti-RhBST2 pAb and anti-HA mAb. The results showed that the anti-HA mAb and rabbit anti-RhBST2 pAb had the same ability to identify RhBST2. RhBST2 demonstrated antiviral activity and the ability to activate NF-κB. Moreover, the N-glycosylation states, cell surface level and intracellular localization of RhBST2 were detected. However, HA tags relatively changed part of the biological function of RhBST2. These results show that the RhBST2 polyclonal antibody is more suitable for analyzing the properties and functions of RhBST2, and the natural domain of RhBST2 is very important for its function.


Subject(s)
Antibodies/immunology , Antigens, CD , Antiviral Agents , Acquired Immunodeficiency Syndrome , Animals , Antigens, CD/biosynthesis , Antigens, CD/chemistry , Antigens, CD/immunology , Antiviral Agents/chemistry , Antiviral Agents/immunology , Antiviral Agents/metabolism , GPI-Linked Proteins/biosynthesis , GPI-Linked Proteins/chemistry , GPI-Linked Proteins/immunology , HEK293 Cells , HIV-1/immunology , Humans , Macaca mulatta , Protein Domains , Rabbits
11.
Front Microbiol ; 11: 1230, 2020.
Article in English | MEDLINE | ID: mdl-32595622

ABSTRACT

Human BCA2/RNF115/Rabring7 (hBCA2) is a RING type E3 ubiquitin ligase with the ability of autoubiquitination or promoting protein ubiquitination. It also acts as a host restriction factor has BST2-dependent and BST2-independent antiviral activity to inhibit the release of HIV-1. In a previous study, we demonstrated that feline BCA2 (fBCA2) also has E3 ubiquitin ligase activity, although its antiviral mechanism remained unclear. In this study, we showed that fBCA2 can interact with feline BST2 (fBST2) and exhibits an fBST2-independent antiviral function, and the RING domain is necessary for the antiviral activity of fBCA2. fBCA2 could degrade HIV-1 Gag and restrict HIV-1 transcription to counteract HIV-1 but not promote the degradation of HIV-1 through lysosomal. Furthermore, for both fBCA2 and hBCA2, restricting viral transcription is the main anti-FIV mechanism compared to degradation of FIV Gag or promoting viral degradation. Consequently, transcriptional regulation of HIV or FIV by BCA2 should be the primary restriction mechanism, even though the degradation mechanism is different when BCA2 counteracts HIV or FIV. This may be due to BCA2 has a special preference in antiviral mechanism in the transmission of primate or non-primate retroviruses.

12.
ACS Omega ; 4(25): 21178-21186, 2019 Dec 17.
Article in English | MEDLINE | ID: mdl-31867511

ABSTRACT

The poor compatibility of an inorganic electron transport layer with the active layer and an ultrathin film organic material becomes a great obstacle in producing high-quality polymer solar cells with high-throughput roll-to-roll (R2R) method. Novel effective polymer solar cells had been fabricated by introducing 1, 7-disubstituted perylene diimide derivatives PDIH, PDIC, and PDIN as an electron transporting layer. It was noteworthy that PDIN could obviously improve the power conversion efficiency of solar cells that incorporated a photoactive layer composed of poly[(3-hexylthiophene)-2, 5-diyl] (P3HT) and the fullerene acceptor [6, 6-phenyl-C71-butyric acid methyl ester] (PC 71 BM). The power conversion efficiency varies from 1.5% for ZnO transparent cathode-based solar cells to 2.1% for PDIN-based electron transport layer-free solar cells. This improved performance could be attributed to the following reasons: the interaction between N atom in PDIN and O atom in indium tin oxide (ITO) reduced the work function of ITO, increased the built-in electric field, and thus lowered the electron transport barrier and improved the electron extraction ability of cathode, the appropriate roughness of the active layer increased the contact area with anode interfacial layer and enhanced the hole transport efficiency. These experimental results revealed that PDIN can be a promising novel effective material with a simplified synthesis process and lower cost as an electron transporting layer.

13.
Onco Targets Ther ; 12: 10043-10055, 2019.
Article in English | MEDLINE | ID: mdl-31819500

ABSTRACT

INTRODUCTION: Immune-based and antibody-drug conjugate therapies have shown promise in the treatment of patients with small cell lung cancer (SCLC). However, better predictive biomarkers are needed for selection of the appropriate SCLC patients for these advanced therapies and also for evaluation of the efficacy of these treatments. OBJECTIVE: The aim of this study was to examine the expression of delta-like protein 3 (DLL3), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), and mesothelin (MSTN) in patients with SCLC and compare them with those patients' clinical characteristics. METHODS: Immunohistochemical analyses of DLL3, CTLA-4 and MSTN expression were performed in 38 samples from patients with SCLC. RESULTS: We found that positive expression in patients of the biomarkers was as follows: for DLL3, 100% (38/38), for CTLA-4, 89.5% (36/38) and for MSTN 81.5% (31/38). The median survival time was 17.9 months in the DLL3 high expression group and 23 months in the DLL3 low expression group. Patients with a high expression of DLL3 showed a poorer prognosis than those with a low expression of DLL3 (HR=3.4; 95% CI, 1.34-8.6; p=0.01). CONCLUSION: The expression of DLL3, CTLA-4 and MSTN was not correlated with patients' age, sex, smoking status, stage, and tumor metastasis. The fact that there was a higher expression of DLL3, CTLA-4, and MSTN in SCLC suggested that these molecules could be used as predictive biomarkers for SCLC.

14.
Medicine (Baltimore) ; 98(48): e17953, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31770203

ABSTRACT

Chronic thromboembolic pulmonary hypertension (CTEPH), a late complication of pulmonary embolism (PE), is associated with high mortality. However, whether the right ventricular (RV) echocardiographic parameters can predict - in the short- and long-term - the development of CTEPH and mortality after PE remains unknown. Herein, we aim to investigate the incidence of CTEPH after acute PE and to evaluate the risk factors of CTEPH. In this retrospective cohort, patients with PE were followed for 10 years for the onset of CTEPH. The screening was initially conducted through echocardiography and confirmed by right heart catheterization. Also, transient and permanent risk factors were identified. Among 358 patients with PE, 8 patients (4%) were subsequently diagnosed with CTEPH at a median time of 36 months and 47 died during the follow-up period. Notably, both short- and long-term RV dilatation, hypertrophy, and increased pulmonary pressure increased the incidence of CTEPH. However, RV echocardiographic parameters failed to differentiate survivors from non-survivors. Instead, malignancy, respiratory, or chronic heart failure was strongly associated with post PE mortality in the multivariable analysis. According to our findings, post PE screening of CTEPH may facilitate early diagnosis and intervention for patients at high risk of developing CTEPH. Also, RV echocardiographic parameters are associated with subsequent CTEPH, but mortality is mainly dependent on underlying comorbidities.


Subject(s)
Echocardiography/statistics & numerical data , Hypertension, Pulmonary/diagnostic imaging , Pulmonary Embolism/mortality , Ventricular Dysfunction, Right/diagnostic imaging , Aged , Chronic Disease , Female , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/mortality , Incidence , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Retrospective Studies , Risk Factors , Time Factors , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/mortality
15.
Zhongguo Fei Ai Za Zhi ; 22(5): 264-270, 2019 May 20.
Article in Chinese | MEDLINE | ID: mdl-31109435

ABSTRACT

BACKGROUND: Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism. METHODS: Lung cancer cell lines H1299 and H3255 were cultured in vitro. The effects of Apatinib on proliferation, migration and invasion of H1299 and H3255 cells were detected by cell proliferation assays wound healing assays and Transwell assays. The protein expression related to cancer angiogenesis and invasion was detected by Western blot. RESULTS: Apatinib significantly inhibited the proliferation, migration and invasion of H1299 and H3255 in a concentration-dependent manner. Western blot showed that with the increasing of drug concentration, VEGF, VEGFR2, N-cadherin, MMP9, MMP2 and Vimentin were down-regulated, and E-cadherin were up-regulated. CONCLUSIONS: Apatinib can inhibit the invasion and migration of lung adenocarcinoma cells H1299 and H3255. By regulation of epithelial-mesenchymal transition and the expression of matrix metalloproteinase-related proteins.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Lung Neoplasms/pathology , Pyridines/pharmacology , Cell Line, Tumor , Humans , Neoplasm Invasiveness
16.
Zhongguo Fei Ai Za Zhi ; 22(5): 255-263, 2019 May 20.
Article in Chinese | MEDLINE | ID: mdl-31109434

ABSTRACT

BACKGROUND: Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells. METHODS: PC9 and PC9/AB2 cells were used for this study. CCK-8 and EdU experiment were used to detect combined treatment on cell viability and proliferation activity; Wound healing assay and Transwell chamber experiment were used to determine the effects of combination therapy on cell migration ability; Flow cytometry was used to detect the effect of combination therapy on EZH2 and apoptosis; Western blot was used to observe the effect of combination therapy on epidermal growth factor receptor (EGFR) signaling pathway-related proteins expression. RESULTS: In gefitinib-resistant cell line PC9/AB2, gefitinib combined with EZH2 inhibitor GSK343 can significantly inhibit cell viability, reduce cell migration and increase cell apoptosis. At the same time, combination therapy can significantly inhibit the expression of EZH2 and phosphorylation EGFR proteins. CONCLUSIONS: The combination of EZH2 inhibitor GSK343 and gefitinib sensitize PC9/AB2 cell to gefitinib response. This study also suggests that synergistic therapy plays a role in the reversal of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) resistance in lung cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/drug effects , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , ErbB Receptors/antagonists & inhibitors , Gefitinib/pharmacology , Lung Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Synergism , Humans
17.
Zhongguo Fei Ai Za Zhi ; 22(5): 280-288, 2019 May 20.
Article in Chinese | MEDLINE | ID: mdl-31109437

ABSTRACT

BACKGROUND: Lung cancer is a malignant tumor disease with high morbidity and high mortality. The non-small cell lung cancer (NSCLC) is the most common type, among them, lung squamous cell carcinoma own special pathological type and specific treatment, is a subtype of non-small cell lung cancer and can be divided into peripheral type and central type according to clinical phenotype. This study explores the differences in gene levels and their potential values based on clinical differences between central and peripheral in lung squamous cell carcinoma. METHODS: The lung squamous cell carcinoma dataset was collected from The Cancer Genome Atlas (TCGA) database, clinical information and the corresponding gene expression profiles were downloaded. Then we further sort and analyze all these data. RESULTS: In clinical characteristics analysis, result showed that central lung squamous cell carcinoma was more likely to metastasis with lymph node than peripheral lung squamous cell carcinoma (46.2%, 67/145 vs 28.9%, 26/90; P=0.019), while there were no significant differences in gender, age, tumor size, distant metastasis, tumor node metastasis (TNM) stage, and EGFR mutation. Gene expression analysis showed 1,031 differentially expressed genes between central and peripheral lung squamous cell carcinoma, of which 629 genes were up-regulated and 402 genes were down-regulated (peripheral vs central). Further enrichment analysis showed differentially expressed genes were mainly riched in 6 signaling pathways. Among them, the neuroactive ligand-receptor interaction pathway was the main enrichment pathway of differentially expressed genes, and other differential expressed genes were mainly involved in lipid metabolism and glucose metabolism. The analysis of interaction network showed that hepatocyte nuclear factor 1 homeobox A (HNF1A) and cytochrome p450 family, Cytochrome P450 3A4 (CYP3A4) own widely effect in up-regulated genes, while ALB and APOA1 at the key positions of the network in down-regulated genes were CONCLUSIONS: Central and peripheral lung squamous cell carcinoma showed clinical phenotype difference not only reflected in the incidence of lymph node metastasis, but also in gene expression profiles. Among them, HNF1A, CYP3A4, ALB, APOA1 at the key position of the differential gene interaction network and maybe as regulatory factors in the phenotypic difference.


Subject(s)
Carcinoma, Squamous Cell/genetics , Databases, Genetic , Gene Expression Profiling , Lung Neoplasms/genetics , Aged , Female , Gene Regulatory Networks , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Smoking/genetics
18.
Clin Exp Hypertens ; 41(3): 220-230, 2019.
Article in English | MEDLINE | ID: mdl-29672166

ABSTRACT

OBJECTIVE: This study was focused on screening leech extracts to identify those with little or no anti-coagulation effect or with significant anti-endothelial dysfunction activity. METHODS: Different leech extracts were prepared by enzymolysis and microbial transformation and their cytotoxicity were measured by MTT assay. The effect of different leech extracts on mRNA expression of coagulation-related factors (PAI, vWF, tPA, PS, TFPI, TM) was quantified by RT-PCR. After identifying a leech extract with little anti-coagulatory effect, RT-PCR was then used to assess the effect of this extract on the mRNA expression of endothelial dysfunction-related molecules (ET-1, iNOS, MCP-1, IL-6). RESULTS: 8 leech extracts were obtained, including 4 enzymatic extracts (LP, PHL, PTHL, CEHL) and 4 Lactobacillus metabolites (MRS, MRS-1, MRS-2, and MRS-3). Following optimization of conditions using MTT assays, we treated EA.hy926 cells with 0, 12.5, 25, 50 µg/mL of LP, PTHL, CEHL, MRS, MRS-1 or MRS-3 extract for 24 h. We found that PHL and MRS-1 had no significant effect on coagulation-related factors. Furthermore, treatment with 50 µg/mL PHL resulted in significant decreases in ET-1, iNOS, MCP-1, and IL-6 mRNA expression by 28.06%, 33.30%, 19.80%, and 52.34%, respectively. CONCLUSIONS: In the present study, we found that PHL, a pepsin hydrolysate of leech with little anti-coagulatory effect, could significantly suppress TNF-α induced mRNA overexpression of endothelial dysfunction-related molecules (ET-1, iNOS, MCP-1, and IL-6). These results provide a reliable experimental basis for identifying new anti-atherosclerosis therapeutics for long term use and with minimal bleeding side effects.


Subject(s)
Atherosclerosis/blood , Blood Coagulation/drug effects , Endothelial Cells/drug effects , Enzymes/pharmacology , Leeches , Tissue Extracts/pharmacology , Animals , Blood Coagulation Factors/drug effects , Blood Coagulation Factors/metabolism , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Chemokine CCL2/drug effects , Chemokine CCL2/metabolism , Endothelial Cells/physiology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Humans , Real-Time Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/antagonists & inhibitors
19.
ACS Appl Mater Interfaces ; 11(7): 7235-7241, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30556999

ABSTRACT

Atomic doping is the most fundamental approach to modulating the transport properties of carbon nanotubes. In this paper, we demonstrate the enhanced thermoelectric properties of boron-substituted single-walled carbon nanotube (B-SWCNT) films. The developed two-step synthesis of large quantities of B-SWCNTs readily enables the measurements of thermoelectricity of bulk B-SWCNT films. Complementary structural characterization implies the unique configuration of boron atoms at the doping sites of SWCNTs, successfully enabling carrier doping to SWCNTs. The developed boron substitution, in combination with chemical doping, is found to substantially improve the thermoelectric properties.

20.
Acta Pharmacol Sin ; 39(11): 1797-1803, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30154526

ABSTRACT

The abnormal expression of the long noncoding RNA (lncRNA) HOX transcript intergenic antisense RNA (HOTAIR) plays an important role in the development of various cancers; however, single nucleotide polymorphisms (SNPs) in HOTAIR and their association with primary lung cancer susceptibility have not yet been reported. Here, we performed a case-control study including 262 primary lung cancer patients and 451 cancer-free control individuals to investigate the association between four haplotype-tagging SNPs (rs920778, rs12826786, rs4759314, and rs1899663) in the HOTAIR lncRNA and the risk of developing primary lung cancer. We found a significant association between the SNPs rs920778 and rs1899663 in the HOTAIR and primary lung cancer susceptibility (P < 0.05). Moreover, homozygous C/T (C/T + TT) for rs920778 (C > T) sites was significantly associated with gender, smoking history, and pathological type. In addition, linkage disequilibrium and haplotype analysis of HOTAIR gene polymorphisms for susceptibility to lung cancer revealed a high degree of linkage disequilibrium between the rs920778 and rs1899663 loci (D' = 0.86, r2 = 0.52). The population of rs920778, rs1899663, and rs4759314 had a significantly increased risk of lung cancer (P < 0.001). In summary, the present study provides persuasive evidence that SNP rs920778 is closely correlated with susceptibility to primary lung cancer. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in the development of primary lung cancer.


Subject(s)
Carcinoma, Squamous Cell/genetics , Genetic Predisposition to Disease , Lung Neoplasms/genetics , RNA, Long Noncoding/genetics , Smoking/genetics , Adenocarcinoma of Lung/genetics , Adult , Aged , Aged, 80 and over , Asian People , Female , Genetic Association Studies , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide
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