Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 521
Filtrar
1.
Biomolecules ; 10(2)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075026

RESUMO

An established pig lung transplantation model was used to study the effects of cold ischemia time, normothermic acellular ex vivo lung perfusion (EVLP) and reperfusion after lung transplantation on l-arginine/NO metabolism in lung tissue. Lung tissue homogenates were analyzed for NO metabolite (NOx) concentrations by chemiluminescent NO-analyzer technique, and l-arginine, l-ornithine, l-citrulline and asymmetric dimethylarginine (ADMA) quantified using liquid chromatography-mass spectrometry (LC-MS/MS). The expression of arginase and nitric oxide synthase (NOS) isoforms in lung was measured by real-time polymerase chain reaction. EVLP preservation resulted in a significant decrease in concentrations of NOx and l-citrulline, both products of NOS, at the end of EVLP and after reperfusion following transplantation, compared to control, respectively. The ratio of l-ornithine over l-citrulline, a marker of the balance between l-arginine metabolizing enzymes, was increased in the EVLP group prior to reperfusion. The expression of both arginase isoforms was increased from baseline 1 h post reperfusion in EVLP but not in the no-EVLP group. These data suggest that EVLP results in a shift of the l-arginine balance towards arginase, leading to NO deficiency in the lung. The arginase/NOS balance may, therefore, represent a therapeutic target to improve lung quality during EVLP and, subsequently, transplant outcomes.

2.
Eur Respir J ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060066

RESUMO

INTRODUCTION: The ex vivo lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs which has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation. MATERIALS AND METHODS: A retrospective transcriptomics analyses were performed with peripheral tissue biopsies from "donation after brain death" lungs, with 46 pre/post-transplant pairs and 49 pre/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP. RESULTS: Twenty-one pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death, and downregulation of metabolism and protein synthesis. Seven pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. Twenty-three pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism. Of the inflammatory clusters, TLR/MYD88 signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models. CONCLUSION: EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.

3.
Cell Biol Toxicol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002708

RESUMO

Androgen deprivation therapy (ADT) via surgical or chemical castration frequently fails to halt lethal castration-resistant prostate cancer (CRPC), which is induced by multiple mechanisms involving constitutive androgen receptor (AR) splice variants, AR mutation, and/or de novo androgen synthesis. The AR N-terminal domain (NTD) possesses most transcriptional activity and is proposed as a potential target for CRPC drug development. We constructed a screening system targeting AR-NTD transcription activity to screening a compound library and identified a novel small molecule compound named QW07. The function evaluation and mechanism investigation of QW07 were carried out in vitro and in vivo. QW07 bound to AR-NTD directly, blocked the transactivation of AR-NTD, blocked interactions between co-regulatory proteins and androgen response elements (AREs), inhibited the expression of genes downstream of AR, and inhibited prostate cancer growth in vitro and in vivo. QW07 was demonstrated as an AR-NTD-specific antagonist with the potential to inhibit both canonical and variant-mediated AR signaling to regress the CRPC xenografts and is proposed as a lead compound for a specific antagonist targeting AR-NTD.

4.
J Invest Dermatol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035093

RESUMO

It is known that Lgr4 plays an important role in hair follicle development, but the impact of Lgr4 on hair cycle is still unclear. In the present study, we have found that K14-Cre-mediated skin epithelia-specific deletion of Lgr4 results in delayed anagen entry during physiological hair cycle and compromised hair follicle regeneration upon transplantation. We show that while Lgr4 deletion does not appear to affect the number of quiescent hair follicle stem cells, it leads to reduced numbers of Lgr5+ and actively proliferating stem cells in the hair follicles. Moreover, Lgr4-deficient hair follicles show molecular changes consistent with decreased mTOR and Wnt signaling but upregulated BMP signaling. Importantly, the reactivation of AKT pathway by injecting Akt activator SC79 in Lgr4-/- mice can effectively reverse the hair cycle delay. Together, these data suggest that Lgr4 promotes the normal hair cycle by activating hair follicle stem cells, and by influencing the activities of multiple signaling pathways that are known to regulate hair follicle stem cells. Our study also implicates Lgr4 as a potential target for treating hair disorder in the future.

5.
Eur J Med Chem ; 190: 112141, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32078862

RESUMO

As the continuous rise in the incidence of antibiotic resistance, it is urgent to develop novel chemical scaffolds with antibacterial activities to control the spread of resistance to conventional antibiotics. In this study, a series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives were designed and synthesized by modifying the hit compound (N2-isobutyl-N4-((4-methyl-2-phenylthiazol-5-yl)methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in vitro and in vivo. Among the tested compounds, compound 14g (N4-((5-(3-bromophenyl)thiophen-2-yl)methyl)-N2-isobutylpyrimidine-2,4-diamine) displayed the best antibacterial activities, which was not only capable of inhibiting E. coli and S. aureus growth at concentrations as low as 2 and 3 µg/mL in vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound 14g was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure is challenging to induce bacterial resistance, which suggested that compound 14g may be a kind of promising alternatives to antibiotics against bacteria.

6.
Carbohydr Polym ; 232: 115788, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952596

RESUMO

Bacterial cellulose (BC) has received considerable attention as an environment-friendly, biodegradable nanomaterial. In this study, the strain Komagataeibacter sp. nov. CGMCC 17276, which showed rapid cell growth and high BC-production ability, was isolated and classified into a novel species in the Komagataeibacter genus. Four BC synthase operons were annotated using whole-genome analysis, partially explaining the high BC yield of strain CGMCC 17276. Operons bcs Ⅱ and bcs Ⅲ showed high transcriptional levels under static and agitated culture conditions, indicating their importance in BC synthesis. Of the eight suitable carbon sources identified by whole-genome analysis, the highest BC production was achieved using glycerol as a single carbon source. Finally, waste glycerol was successfully used as an eco-friendly and sustainable strategy for BC production. This study provides valuable insights into the mechanism of BC synthesis, genetic structure of BC-producing strains, and industrialization of BC production using an eco-friendly and low-cost strategy.

8.
Phytomedicine ; 67: 153160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901889

RESUMO

BACKGROUND: Increasing evidence indicated that the cannabinoid receptors were involved in the pathogenesis of organ fibrogenesis. PURPOSE: The purpose of this study was to discover novel cannabinoid receptor 2 (CB2) agonist and assess the potential of CB2 activation in treating systemic sclerosis. METHODS: A gaussia princeps luciferase-based split luciferase complementation assay (SLCA) was developed for detection of the interaction between CB2 and ß-arrestin2. A library of 366 natural products was then screened as potential CB2 agonist using SLCA approach. Several GPCR functional assays, including HTRF-based cAMP assay and calcium mobilization were also utilized to evaluated CB2 activation. Bleomycin-induced experimental systemic sclerosis was used to assess the in vivo anti-fibrotic effects. Dermal thickness and collagen content were evaluated via H&E and sirius red staining. RESULTS: Celastrol was identified as a new agonist of CB2 by using SLCA. Furthermore, celastrol triggers several CB2-mediated downstream signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, and receptor desensitization in a dose-dependent manner, and it has a moderate selectivity on CB1. In addition, celastrol exhibited the anti-inflammatory properties on lipopolysaccharide (LPS) treated murine Raw 264.7 macrophages and primary macrophages. Finally, we found that celastrol exerts anti-fibrotic effects in the bleomycin-induced systemic sclerosis mouse model accompanied by reduced inflammatory conditions. CONCLUSION: Taken together, celastrol is identified a novel selective CB2 agonist using a new developed arrestin-based SLCA, and CB2 activation by celastrol reduces the inflammatory response, and prevents the development of dermal fibrosis in bleomycin-induced systemic sclerosis mouse model.

9.
J Med Chem ; 63(2): 676-695, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31895575

RESUMO

The transcriptional repressor B-cell lymphoma 6 (BCL6) is frequently misregulated in diffuse large B-cell lymphoma (DLBCL) and has emerged as an attractive drug target for the treatments of lymphoma. In this article, a series of N-phenyl-4-pyrimidinamine derivatives were designed and synthesized as potent BCL6 inhibitors by optimizing hit compound N4-(3-chloro-4-methoxyphenyl)-N2-isobutyl-5-fluoro-2,4-pyrimidinediamine on the basis of the structure-activity relationship. Among them, compound 14j displayed the most potent activities, which significantly blocked the interaction of BCL6 with its corepressors, reactivated BCL6 target genes in a dose-dependent manner, and had better effects compared with the two positive controls. Further studies indicated that a low dose of 14j could effectively inhibit germinal center formation. More importantly, 14j not only showed potent inhibition of DLBCL cell proliferation in vitro but also strongly suppressed the growth of DLBCL in vivo.

10.
Eur J Immunol ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954378

RESUMO

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Whereas much research has focused on its regulation and function of germinal center B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that experimental autoimmune encephalomyelitis (EAE) is exacerbated in LysM Cre+/ - Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4+ Th17 cell response. In addition, LPS-induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the Il-6 (interleukin-6) promotor in macrophages, leading to a suppressed transcription of Il-6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il-6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease. This article is protected by copyright. All rights reserved.

12.
J Med Chem ; 63(2): 569-590, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31855426

RESUMO

The prostanoid EP4 receptor is one of the key receptors associated with inflammatory mediator PGE2-elicited immunosuppression in the tumor microenvironment. Blockade of EP4 signaling to enhance immunity-mediated tumor elimination has recently emerged as a promising strategy for cancer immunotherapy. In our efforts to discover novel subtype-selective EP4 antagonists, we designed and synthesized a class of 1H-1,2,3-triazole-based ligands that display low nanomolar antagonism activity toward the human EP4 receptor and excellent subtype selectivity. The most promising compound 59 exhibits single-digit nanomolar potency in the EP4 calcium flux and cAMP-response element reporter assays and effectively suppresses the expression of multiple immunosuppression-related genes in macrophage cells. On the basis of its favorable ADMET properties, compound 59 was chosen for further in vivo biological evaluation. Oral administration of compound 59 significantly inhibited tumor growth in the mouse CT26 colon carcinoma model accompanied by enhanced infiltration of cytotoxic T lymphocytes in the tumor tissue.

13.
Nanotoxicology ; : 1-14, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852291

RESUMO

Gold nanoparticles (GNPs) are extremely useful for drug delivery, due in part to their highly tunable nature. However, this variability has prevented a clear understanding of the pharmacokinetics and toxicity of GNPs for drug delivery. Here, we present the clearance, organ distribution and acute toxicity testing of our drug delivery system which uses GNPs and two penta-peptides, to deliver a rationally designed peptide drug. We found that with or without our therapeutic, the GNP/peptide hybrid cleared rapidly from the blood in rats and accumulated mostly in the liver and spleen, although it was also detectable in several other organs. There were subtle but detectable differences between the behavior of our GNP hybrids with or without the therapeutic peptide. The GNP/peptide hybrid showed no evidence of toxicity at single doses up to 16 times the therapeutic dose, as measured by a battery of tests including, blood cell makeup, levels of markers of liver, kidney and spleen function, organ mass indexes, and histology. These results underline the importance of testing the pharmacokinetics and toxicity of all GNP preparations, as even minor changes to the surface coatings of GNPs can influence their behavior. On the other hand, the results herein can help guide the design and use of similar GNP/peptide drug delivery systems.

14.
J Clin Invest ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874110

RESUMO

Oncogenic KRAS is a major driver in lung adenocarcinoma (LUAD) that has yet to be therapeutically conquered. Here we report that the SLC7A11/glutathione axis displays metabolic synthetic lethality with oncogenic KRAS. Through metabolomics approaches, we found that mutationally activated KRAS strikingly increased the intracellular cystine level and glutathione biosynthesis. SLC7A11, a cystine/glutamate antiporter conferring specificity for cystine uptake, was overexpressed in patients with KRAS-mutant LUAD and showed positive association with tumor progression. Furthermore, SLC7A11 inhibition either by genetic depletion or pharmacological inhibition by sulfasalazine resulted in selective killing across a panel of KRAS-mutant cancer cells in vitro and tumor growth inhibition in vivo, suggesting the functionality and specificity of SLC7A11 as a therapeutic target. Importantly, we further identified a potent SLC7A11 inhibitor, HG106 that markedly decreased cystine uptake and intracellular glutathione biosynthesis. Furthermore, HG106 exhibited selective cytotoxicity towards KRAS-mutant cells by increasing oxidative stress- and endoplasmic reticulum stress-mediated cell apoptosis. Of note, treatment of KRAS-mutant LUAD with HG106 in several lung cancer preclinical mouse models led to marked tumor suppression and prolonged mouse survival. Overall, our findings reveal that KRAS-mutant LUAD cells are vulnerable to SLC7A11 inhibition, providing promising therapeutic approaches to the treatment of this currently incurable disease.

15.
Esophagus ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773415

RESUMO

Esophageal cancer (EC) is one of the most lethal malignancies of the digestive tract and remains to be improved poor prognosis. Two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), are major characteristics of EC. Deep understanding about both subtypes is essential to overcome EC. Here, we focus on chemokines and their receptors as biomarkers and their current applications for the prognosis in EC. We reviewed relevant articles identified using PubMed database for the chemokines and their receptors in EC analyzed by immunohistochemistry. The primary objective is to summarize evidences for them as prognostic biomarkers in EC. A total of twenty-one articles were reviewed after exclusion. Most studies have been done in ESCC, and less in EAC. CXCL12 and its receptor CXCR4 have been shown in both subtypes as biomarkers. CXCR7, CXCL8 and its receptor CXCR2, and CCL21 and its receptor CCR7 have been examined in ESCC. Although it was a small number of reports, CXCL10, CCL4, and CCL5 have been indicated to have anti-tumor effects in ESCC. Chemokines and their receptors have the potential to be the biomarkers in EC. Comparative studies between ESCC and EAC will reveal the similarity and difference in these two subtypes of EC. These studies may indicate whether these molecules play important roles in both subtypes or are unique to one or another.

16.
Microb Biotechnol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758659

RESUMO

Ethyl-N-dodecanoyl-l-arginate hydrochloride (LAE, ethyl lauroyl arginate HCl) is a cationic surfactant used as a food preservative with broad-spectrum antibacterial activities. However, its resistance development, influences on gut microbiome and molecular target are unclear. In this study, bacteria were stimulated by LAE for 30 days to test the bacterial resistance. Several infected animal models were used to evaluate the antibacterial effect of LAE in vivo. Mice were orally treated with LAE to test its effect on animal growth. The influence of LAE on mice gut microbiome was analysed by 16S rDNA sequencing. The results indicated that Escherichia coli did not develop resistance to LAE. LAE significantly combats bacterial infection in mice, ducklings and piglets. Moreover, LAE promotes mouse weight gain without changing body composition or reducing animal vitality, and induces lower hepatotoxicity than ampicillin. In the mouse gut microbiome assessment and characterization, LAE modifies host gut microbiota structure. Mechanistically, LAE specifically binds to acidic phospholipids including phosphatidylserine, depolarizes the membrane and disrupts the bacterial membrane followed by bacterial growth inhibition. This study investigates the molecular mechanism of LAE as well as its antibacterial functions in poultry and livestock. Our data suggest LAE is a potential antibacterial agent in animal health.

17.
J Exp Clin Cancer Res ; 38(1): 422, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640758

RESUMO

BACKGROUND: Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. METHODS: Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student's t test was applied for statistical analysis. RESULTS: We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. CONCLUSIONS: Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.

18.
Bone Res ; 7: 19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646011

RESUMO

The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.

19.
PLoS Pathog ; 15(10): e1008093, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600344

RESUMO

ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein's ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation.

20.
Eur J Med Chem ; 183: 111741, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605873

RESUMO

Tumor-associated macrophages (TAMs) are one of the prominent components of the tumor microenvironment (TME). The polarization peculiarity of TAMs drives them to infiltrate and active with states between M1 (anti-tumor) and M2 (pro-tumor) phenotypes in cancers. Exploiting small molecular drugs through targeting TAMs to repolarize them into an antitumor phenotype is considered as a novel strategy for cancer treatments in recent years. For discovering novel compounds that target TAMs, a series of ureido tetrahydrocarbazole derivatives were designed, synthesized and evaluated both in vitro and in vivo. Among them, compound 23a was found to dose-dependently repolarize TAMs from M2 to M1 both in vitro and in vivo. And more importantly, the in vivo experiments also revealed that compound 23a was capable of remarkably inhibiting tumor growth of the LLC mouse model. Moreover, the synergy of compound 23a with anti-PD-1 antibody had more superior antineoplastic effects than the exclusive use of either in vivo.


Assuntos
Antineoplásicos/síntese química , Carbazóis/síntese química , Macrófagos/efeitos dos fármacos , Ureia/análogos & derivados , Ureia/síntese química , Animais , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Carbazóis/administração & dosagem , Carbazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Sinergismo Farmacológico , Feminino , Humanos , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Relação Estrutura-Atividade , Microambiente Tumoral , Ureia/administração & dosagem , Ureia/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA