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1.
World J Clin Oncol ; 15(4): 554-565, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38689624

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

2.
Cancer Cell Int ; 24(1): 86, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402174

ABSTRACT

BACKGROUND: The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. METHOD: In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. RESULTS: Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. CONCLUSION: The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.

3.
ACS Sens ; 9(1): 171-181, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38159288

ABSTRACT

With the rapid development of the concept of the Internet of Things (IoT), gas sensors with the function of simulating the human sense of smell became irreplaceable as a key element. Among them, ammonia (NH3) sensors played an important role in respiration tests, environmental monitoring, safety, and other fields. However, the fabrication of the high-performance device with high stability and resistance to mechanical damages was still a challenge. In this work, polyurethane (PU) with excellent self-healing ability was applied as the substrate, and the sensor was designed from new sensitive material design and device structure optimization, through applying the organic molecule with groups which could absorb NH3 and the laminated structure to shorten the electronic transmission path to achieve a low resistance state and favorable sensing properties. Accordingly, a room temperature flexible NH3 sensor based on 6,6',6″-(nitrilotris(benzene-4,1-diyl))tris(5-phenylpyrazine-2,3-dicarbonitrile) (TPA-3DCNPZ) was successfully developed. The device could self-heal by means of a thermal evaporation assisted method. It exhibited a detection limit of 1 ppm at 98% relative humidity (RH), as well as great stability, selectivity, bending flexibility, and self-healing properties. The improved NH3 sensing performance under high RH was further investigated by complex impedance plots (CIPs) and density functional theory (DFT), attributing to the enhanced adsorption of NH3. The TPA-3DCNPZ based NH3 sensors proved to have great potential for application on simulated exhaled breath to determine the severity of kidney diseases and the progress of treatment. This work also provided new ideas for the construction of high-performance room temperature NH3 sensors.


Subject(s)
Smart Materials , Humans , Benzene , Temperature , Adsorption , Ammonia
4.
ISME Commun ; 3(1): 81, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37596350

ABSTRACT

Soil microbiomes play important roles in supporting agricultural ecosystems. However, it is still not well-known how soil microbiomes and their functionality respond to fertilization in various cropping systems. Here we examined the effects of 36 years of phosphorus, nitrogen, and manure application on soil bacterial communities, functionality and crop productivity in three contrasting cropping systems (i.e., continuous leguminous alfalfa (AC), continuous winter wheat (WC), and grain-legume rotation of winter wheat + millet - pea - winter wheat (GLR)) in a highland region of China's Loess Plateau. We showed that long-term fertilization significantly affected soil bacterial communities and that the effects varied with cropping system. Compared with the unfertilized control, fertilization increased soil bacterial richness and diversity in the leguminous AC system, whereas it decreased those in the GLR system. Fertilization, particularly manure application, enlarged the differences in soil bacterial communities among cropping systems. Soil bacterial communities were mostly affected by the soil organic carbon and nitrogen contents in the WC and GLR systems, but by the soil available phosphorous content in the AC system. Crop productivity was closely associated with the abundance of fertilization-responsive taxa in the three cropping systems. Our study highlights that legume and non-legume cropping systems should be disentangled when assessing the responses of soil microbial communities to long-term fertilizer application.

5.
Angew Chem Int Ed Engl ; 62(45): e202307622, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37395558

ABSTRACT

P-type polymers are polymeric semiconducting materials that conduct holes and have extensive applications in optoelectronics such as organic photovoltaics. Taking the advantage of intrinsic discontinuous light absorption of organic semiconductors, semitransparent organic photovoltaics (STOPVs) present compelling opportunities in various potential applications such as building-integrated photovoltaics, agrivoltaics, automobiles, and wearable electronics. The characteristics of p-type polymers, including optical, electronic, and morphological properties, determine the performance of STOPVs, and the requirements for p-type polymers differ between opaque organic photovoltaics and STOPVs. Hence, in this Minireview, recent advances of p-type polymers used in STOPVs are systematically summarized, with emphasis on the effects of chemical structures, conformation structures, and aggregation structures of p-type polymers on the performance of STOPVs. Furthermore, new design concepts and guidelines are also proposed for p-type polymers to facilitate the future development of high-performance STOPVs.

6.
ACS Appl Mater Interfaces ; 15(10): 13165-13175, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36877699

ABSTRACT

In recent years, graphene has been introduced into phase change materials (PCMs) to improve thermal conductivity to enhance the heat transfer efficiency in thermal energy storage. However, graphenes tend to aggregate in PCMs, leading to the low thermal conductivity efficient enhancement (TCEE), anisotropic thermal conductivity, and deterioration of mechanical performance of PCMs. In this work, we fabricated biomimetic thermally conductive solid-solid PCMs (SSPCMs) by facile blending of the graphene into well-designed polyurethane SSPCMs, in which the graphene established a controllable and highly efficient isotropic thermally conductive pathway based on the π-π stacking between the graphene and the polymer aromatic ring segment. The as-fabricated SSPCMs showed high TCEE (156.78%), excellent flexibility (328% elongation at break), high enthalpy value (>101 J/g), and solid-solid phase transition properties, under 2% loading of graphene. The proportion of in-plane to through-plane thermal conductivity can be adjusted by an elaborate design of the aromatic ring segment in polyurethane SSPCMs. We further demonstrated mechanical flexibility and photothermal property of the composites to reveal their potential in practical applications.

7.
Glob Chang Biol ; 28(20): 6086-6101, 2022 10.
Article in English | MEDLINE | ID: mdl-35808859

ABSTRACT

Afforestation is an effective approach to rehabilitate degraded ecosystems, but often depletes deep soil moisture. Presently, it is not known how an afforestation-induced decrease in moisture affects soil microbial community and functionality, hindering our ability to understand the sustainability of the rehabilitated ecosystems. To address this issue, we examined the impacts of 20 years of afforestation on soil bacterial community, co-occurrence pattern, and functionalities along vertical profile (0-500 cm depth) in a semiarid region of China's Loess Plateau. We showed that the effects of afforestation with a deep-rooted legume tree on cropland were greater in deep than that of in top layers, resulting in decreased bacterial beta diversity, more responsive bacterial taxa and functional groups, increased homogeneous selection, and decreased network robustness in deep soils (120-500 cm). Organic carbon and nitrogen decomposition rates and multifunctionality also significantly decreased by afforestation, and microbial carbon limitation significantly increased in deep soils. Moreover, changes in microbial community and functionality in deep layer was largely related to changes in soil moisture. Such negative impacts on deep soils should be fully considered for assessing afforestation's eco-environment effects and for the sustainability of ecosystems because deep soils have important influence on forest ecosystems in semiarid and arid climates.


Subject(s)
Ecosystem , Soil , Bacteria/metabolism , Carbon/analysis , China , Forests , Nitrogen/analysis , Soil Microbiology
8.
Int J Mol Sci ; 23(8)2022 Apr 13.
Article in English | MEDLINE | ID: mdl-35457111

ABSTRACT

The aberrant activation of the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway is common in pancreatic ductal adenocarcinomas (PDAC). The application of inhibitors against PI3K and AKT has been considered as a therapeutic option. We investigated PDAC cell lines exposed to increasing concentrations of MK-2206 (an AKT1/2/3 inhibitor) and Buparlisib (a pan-PI3K inhibitor). Cell proliferation, metabolic activity, biomass, and apoptosis/necrosis were evaluated. Further, whole-exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the recurrent aberrations and expression profiles of the inhibitor target genes and the genes frequently mutated in PDAC (Kirsten rat sarcoma virus (KRAS), Tumor protein p53 (TP53)). MK-2206 and Buparlisib demonstrated pronounced cytotoxic effects and limited cell-line-specific effects in cell death induction. WES revealed two sequence variants within the direct target genes (PIK3CA c.1143C > G in Colo357 and PIK3CD c.2480C > G in Capan-1), but a direct link to the Buparlisib response was not observed. RNA-seq demonstrated that the expression level of the inhibitor target genes did not affect the efficacy of the corresponding inhibitors. Moreover, increased resistance to MK-2206 was observed in the analyzed cell lines carrying a KRAS variant. Further, increased resistance to both inhibitors was observed in SU.86.86 carrying two TP53 missense variants. Additionally, the presence of the PIK3CA c.1143C > G in KRAS-variant-carrying cell lines was observed to correlate with increased sensitivity to Buparlisib. In conclusion, the present study reveals the distinct antitumor effects of PI3K/AKT pathway inhibitors against PDAC cell lines. Aberrations in specific target genes, as well as KRAS and TP53, individually or together, affect the efficacy of the two PI3K/AKT pathway inhibitors.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Aminopyridines , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Cell Proliferation , Class I Phosphatidylinositol 3-Kinases/metabolism , Heterocyclic Compounds, 3-Ring , Humans , Morpholines , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Signal Transduction , Pancreatic Neoplasms
9.
Int J Mol Sci ; 23(8)2022 Apr 16.
Article in English | MEDLINE | ID: mdl-35457227

ABSTRACT

Casein kinase II (CK2) and cyclin-dependent kinases (CDKs) frequently interact within multiple pathways in pancreatic ductal adenocarcinoma (PDAC). Application of CK2- and CDK-inhibitors have been considered as a therapeutic option, but are currently not part of routine chemotherapy regimens. We investigated ten PDAC cell lines exposed to increasing concentrations of silmitasertib and dinaciclib. Cell proliferation, metabolic activity, biomass, and apoptosis/necrosis were evaluated, and bioinformatic clustering was used to classify cell lines into sensitive groups based on their response to inhibitors. Furthermore, whole exome sequencing (WES) and RNA sequencing (RNA-Seq) was conducted to assess recurrent mutations and the expression profile of inhibitor targets and genes frequently mutated in PDAC, respectively. Dinaciclib and silmitasertib demonstrated pronounced and limited cell line specific effects in cell death induction, respectively. WES revealed no genomic variants causing changes in the primary structure of the corresponding inhibitor target proteins. RNA-Seq demonstrated that the expression of all inhibitor target genes was higher in the PDAC cell lines compared to non-neoplastic pancreatic tissue. The observed differences in PDAC cell line sensitivity to silmitasertib or dinaciclib did not depend on target gene expression or the identified gene variants. For the PDAC hotspot genes kirsten rat sarcoma virus (KRAS) and tumor protein p53 (TP53), three and eight variants were identified, respectively. In conclusion, both inhibitors demonstrated in vitro efficacy on the PDAC cell lines. However, aberrations and expression of inhibitor target genes did not appear to affect the efficacy of the corresponding inhibitors. In addition, specific aberrations in TP53 and KRAS affected the efficacy of both inhibitors.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Casein Kinase II/metabolism , Cell Line , Cell Line, Tumor , Cell Proliferation/genetics , Cyclic N-Oxides , Humans , Indolizines , Naphthyridines , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Phenazines , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/metabolism , Pyridinium Compounds , Pancreatic Neoplasms
10.
Sci Total Environ ; 831: 154944, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35367547

ABSTRACT

Salinization is an important global environmental problem influencing sustainable development of terrestrial ecosystems. Salt-tolerant halophytes are often used as a promising approach to remedy the saline soils. Yet, how rhizosphere microbes' association and functions vary with halophytes in saline ecosystems remains unclear, restricting our ability to assess the role of halophytes in remedying saline ecosystems. Herein, we examined bacterial and fungal diversities, compositions, and co-occurrence networks in the rhizospheres of six halophytes and bulk soils in a semiarid inland saline ecosystem, and related these parameters to microbial functions. The microbiomes were more diverse and complex and microbial activity and residues were higher in rhizospheres than bulk soils. The connections of taxa in the rhizosphere microbial communities increased with fungi-fungi and bacteria-fungi connections and fungal diversity. The proportion of the fungi-related central connections were larger in rhizospheres (13-73%) than bulk soils (3%). Moreover, microbial activity and residues were significantly correlated with microbial composition and co-occurrence network complexity. These results indicated that enhanced association between fungi and bacteria increased microbial co-occurring network complexity in halophytes rhizosphere, which contributed to the higher microbial functions (microbial activities and residue) in this inland saline ecosystem.


Subject(s)
Microbiota , Rhizosphere , Bacteria , Ecosystem , Fungi , Salt-Tolerant Plants/microbiology , Soil/chemistry , Soil Microbiology
11.
Cancer Cell Int ; 22(1): 54, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35109825

ABSTRACT

BACKGROUND: Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance. Cell lines are important model systems for developing new therapeutic strategies. However, as they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Therefore, a comprehensive characterization of cell lines and their original tissues is paramount. METHODS: This study compared the transcriptomes of nine canine cell lines derived from PAC, PAC metastasis and TCC to their respective original primary tumor or metastasis tissues. Special interests were laid on cell culture-related differences, epithelial to mesenchymal transition (EMT), the prostate and bladder cancer pathways, therapeutic targets in the PI3K-AKT signaling pathway and genes correlated with chemoresistance towards doxorubicin and carboplatin. RESULTS: Independent analyses for PAC, PAC metastasis and TCC revealed 1743, 3941 and 463 genes, respectively, differentially expressed in the cell lines relative to their original tissues (DEGs). While genes associated with tumor microenvironment were mostly downregulated in the cell lines, patient-specific EMT features were conserved. Furthermore, examination of the prostate and bladder cancer pathways revealed extensive concordance between cell lines and tissues. Interestingly, all cell lines preserved downstream PI3K-AKT signaling, but each featured a unique therapeutic target signature. Additionally, resistance towards doxorubicin was associated with G2/M cell cycle transition and cell membrane biosynthesis, while carboplatin resistance correlated with histone, m- and tRNA processing. CONCLUSION: Comparative whole-transcriptome profiling of cell lines and their original tissues identifies models with conserved therapeutic target expression. Moreover, it is useful for selecting suitable negative controls, i.e., cell lines lacking therapeutic target expression, increasing the transfer efficiency from in vitro to primary neoplasias for new therapeutic protocols. In summary, the dataset presented here constitutes a rich resource for canine prostate and bladder cancer research.

12.
Int J Mol Sci ; 22(23)2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34884478

ABSTRACT

Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for the treatment of B-cell lymphomas, among which, diffuse large B-cell lymphoma (DLBCL) is the most common type. Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kγ inhibitor AS-605240 in the canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed in canine B-cell leukemia GL-1 and human DLBCL cell line SU-DHL-4. While ibrutinib alone induced significant anti-proliferative effects on all cell lines in a dose-dependent manner, AS-605240 only induced anti-proliferative effects at high concentrations. Interestingly, ibrutinib and AS-605240 acted synergistically, reducing cell proliferation and increasing apoptosis/necrosis in all cell lines and inducing morphological changes in CLBL-1. Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3ß, and ERK proteins. Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL.


Subject(s)
Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Drug Synergism , Lymphoma, Large B-Cell, Diffuse/drug therapy , Phosphatidylinositol 3-Kinases/chemistry , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Piperidines/pharmacology , Adenine/pharmacology , Animals , Apoptosis , Cell Proliferation , Dogs , Drug Therapy, Combination , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Signal Transduction , Tumor Cells, Cultured
13.
Clin Respir J ; 15(6): 637-647, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33484055

ABSTRACT

OBJECTIVE: This study was conducted to evaluate the relationship between the p73 G4C14-to-A4T14 polymorphism (hereafter, G4C14-to-A4T14) and lung cancer risk. METHODS: The studies on the relationship between G4C14-A4T14 and lung cancer risk published as of November 5, 2018, were comprehensively searched in PubMed, Embase, the Cochrane Library, the Chinese Wanfang database, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM). The last update was on May 24, 2019. Statistical analysis was performed using Stata 12.0. RESULTS: The association between G4C14-A4T14 and lung cancer risk was analyzed in nine studies. The findings indicate no association between G4C14-to-A4T14 and lung cancer risk (allele model: OR = 0.90, 95% CI: 0.73-1.11, I2  = 86.0%, P = .330; dominant model: OR = 0.93, 95% CI: 0.74-1.17, I2  = 82.6%, P = .551; recessive model: OR = 0.75, 95% CI: 0.50-1.13, I2  = 75.2%, P = .165; homozygote model: OR = 0.74, 95% CI: 0.47-1.17, I2  = 79.6%, P = .199; heterozygote model: OR = 0.98, 95% CI: 0.80-1.21, I2  = 75.8%, P = .879). The heterogeneity between subgroups by cancer types and genotyping method was significantly reduced. After the deletion of suspected duplicates, no association was found between G4C14-to-A4T14 and lung cancer susceptibility. CONCLUSION: Our meta-analysis confirms that G4C14-to-A4T14 is not significantly related to lung cancer risk.


Subject(s)
Genetic Predisposition to Disease , Lung Neoplasms , Case-Control Studies , China , Humans , Lung Neoplasms/genetics , Polymorphism, Genetic , Tumor Protein p73/genetics
14.
Anticancer Res ; 40(7): 3781-3792, 2020 07.
Article in English | MEDLINE | ID: mdl-32620617

ABSTRACT

BACKGROUND/AIM: Canine B-cell lymphoma represents a useful in vivo model for human diffuse large B-cell lymphoma (DLBCL). Pan-Bromodomain and extra-terminal (BET) inhibition targeting BRD2/3/4 and selective inhibition of BRD4, as well as spleen tyrosine kinase (SYK) inhibition, are currently evaluated as haematologic cancer therapy. Herein, we characterized the differences in the biologic response of isoform-specific or pan-BET inhibition alone or in combination with SYK inhibition. MATERIALS AND METHODS: I-BET151 (pan-inhibitor) and AZD5153 (BRD4 inhibitor) were combined with Entospletinib (SYK inhibitor) and comparatively analysed in the canine DLBCL cell line CLBL-1. Dose- and time-dependent cellular responses were analysed by cell number, metabolic activity, apoptosis/necrosis, and cell morphology. The synergistic potential was evaluated through the Bliss independence model. RESULTS: I-BET151 and AZD5153 showed significant dose- and time-dependent inhibitory effects. Adding Entospletinib to I-BET151 or AZD5153 had no additional synergistic effects. CONCLUSION: Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET.


Subject(s)
Indazoles/pharmacology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Nuclear Proteins/antagonists & inhibitors , Protein Isoforms/antagonists & inhibitors , Pyrazines/pharmacology , Animals , Cell Line, Tumor , Dogs , Heterocyclic Compounds, 2-Ring/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Lymphoma, Large B-Cell, Diffuse/metabolism , Piperazines/pharmacology , Protein Serine-Threonine Kinases/metabolism , Pyrazoles , Pyridazines , Syk Kinase/metabolism
15.
Cancer Cell Int ; 20: 139, 2020.
Article in English | MEDLINE | ID: mdl-32368185

ABSTRACT

BACKGROUND: Canine prostate cancer represents a unique model for human prostate cancer. In vitro systems offer various possibilities but Xenograft in vivo imaging allows studying complex tasks as tumor progression and drug intervention longitudinal. Herein, we established three canine prostate carcinoma cell lines stably expressing fluorescent proteins allowing deep tissue in vivo imaging. METHODS: Three canine prostate carcinoma (cPC) cell lines were stably transfected with fluorescent proteins in red, far-red and near infra-red spectrum, followed by G418 selection. Fluorescent protein expression was demonstrated by microscopy, flow cytometry and a NightOWL LB 983 in vivo imaging system. Cellular and molecular characteristics of the generated cell lines were compared to the parental cell line CT1258. Cell proliferation, metabolic activity and sphere formation capacity were analyzed. Stem cell marker expression was examined by qPCR and genomic copy number variation by genomic DNA whole genome sequencing. RESULTS: Three stably fluorescent protein transfected cPC cell lines were established and characterized. Compared to the parental cell line, no significant difference in cell proliferation and metabolic activity were detected. Genomic copy number variation analyses and stem cell marker gene expression revealed in general no significant changes. However, the generated cell line CT1258-mKate2C showed uniquely no distal CFA16 deletion and an elevated metabolic activity. The introduced fluorescencent proteins allowed highly sensitive detection in an in vivo imaging system starting at cell numbers of 0.156 × 106. Furthermore, we demonstrated a similar sphere formation capacity in the fluorescent cell lines. Interestingly, the clone selected CT1258-mKate2C, showed increased sphere formation ability. DISCUSSION: Starting from a well characterized cPC cell line three novel fluorescent cell lines were established showing high cellular and molecular similarity to the parental cell line. The introduction of the fluorescent proteins did not alter the established cell lines significantly. The red fluorescence allows deep tissue imaging, which conventional GFP labeling is not able to realize. CONCLUSION: As no significant differences were detected between the established cell lines and the very well characterized parental CT1258 the new fluorescent cell lines allow deep tissue in vivo imaging for perspective in vivo evaluation of novel therapeutic regimens.

16.
Dalton Trans ; 48(7): 2430-2441, 2019 Feb 12.
Article in English | MEDLINE | ID: mdl-30688965

ABSTRACT

Considerable attention has been focused on Cu(i)-diimine-phosphine complexes because of their good room-temperature phosphorescence since 1979, but no attention has been focused on the exploration and exploitation by using them as smart acid-base responsive switching luminescent materials. Herein, the reaction of [Cu(MeCN)4]PF6, 2-(2-naphthyl)-1H-imidazo[4,5-f][1,10]phenanthroline (nimpH) and chelating diphosphine ligands bis[(2-diphenylphosphino)phenyl] ether (POP) and 9,9-dimethyl-4,5-bis(diphenylphosphino)-9H-xanthene (xantphos) or (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (BINAP) in a 1 : 1 : 1 ratio afforded three ionic [Cu(nimpH)(PP)]PF6 complexes (PP = POP, 1a; xantphos, 2a; BINAP, 3a) and three neutral [Cu(nimp)(PP)] complexes (PP = POP, 1b; xantphos, 2b; BINAP, 3b) in neutral and strong alkaline media, respectively. The non-emissive complexes 1a, 2a and 3a exhibit turn-on luminescence upon exposure to the strong base NaOH and tetrabutylammonium fluoride (TBAF), and the intensely emissive complexes 1b, 2b and 3b display turn-off luminescence upon exposure to trifluoroacetic acid (TFA) in CH2Cl2 solutions. Naked-eye repeatable off-on-off or on-off-on luminescence behaviors of these complexes are observed in CH2Cl2 with reversible base-acid or acid-base responses. On the other hand, the addition of TBAF to neutral complexes 1b, 2b and 3b results in obvious luminescence enhancement, especially for the diluted solutions and complexes with the flexible diphosphine ligand POP. The plausible mechanisms of the above results are discussed.

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