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1.
Int J Gen Med ; 15: 4209-4220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480996

RESUMO

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and distinct subtype of lung cancer characterized by its aggressiveness and dismal prognosis. However, genomic landscape and immune contexture have not been fully elucidated among PSC patients. Methods: In the present study, whole-exome-sequencing (WES) analyses were performed to depict genomic landscape of 38 independent PSC samples. Tumor mutation burden (TMB) was calculated with the total number of non-synonymous SNVs and indel variants per megabase of coding regions. PD-L1 expression and CD8+ T cell density were evaluated by immunohistochemistry in PSC samples. Their associations with genomic mutation were further assessed in genes with most frequent mutation. Overall survival (OS) of PSC patients with top mutated genes and high and low TMB, PD-L1 and CD8+ TIL expressions were further compared. Subgroup analyses of OS stratified by morphology and pathological type were conducted. Their correlation with TMB, PD-L1 and CD8+ T cell were further assessed. Results: We identified a cohort of genomic and somatic mutation in PSC patients. Subgroup patients with distinct clinicopathological features were found to harbor different genomic mutations and immunologic features. Besides, genomic profiles influenced outcomes, with SARS mutation associated with worsened prognosis. Conclusion: Through the mapping of genetic and immunologic landscape, we find the heterogeneity among the subgroups of PSC. Our findings may provide opportunities for therapeutic susceptibility among Chinese PSC patients.

2.
Bioresour Technol ; 352: 127095, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367326

RESUMO

Both alkaline organosolv and formaldehyde stabilization pretreatment can yield high-quality lignin by preventing condensation. For the hydrogenolysis of the pretreated solid residues, the highest yield of C2-C4 chemicals was 66.8% under alkaline organosolv pretreatment for 60 min. Specifically, the crimped fibers and residual lignin and hemicellulose increased the surface roughness of the residue by 40.6%, the crystallinity index decreased to 44.4%, and the crystal size was reduced to 2.15 nm, which in turn promoted hydrogenolysis of the residue. However, the increase of crystallinity and crystal size and the decrease in surface roughness of the formaldehyde stabilization pretreatment residue greatly hindered the conversion of polysaccharides. In addition, residual formaldehyde on the residue may also inhibit catalyst activity. Overall, this study provides novel perspectives on the full utilization of biomass, as well as new insights into the conversion of polysaccharides.


Assuntos
Lignina , Polissacarídeos , Biomassa , Catálise , Formaldeído/química , Hidrólise , Lignina/química , Polissacarídeos/química
3.
Mar Drugs ; 20(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35447921

RESUMO

The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of the P. agarivorans strains consists of a core-genome containing 2331 genes, an accessory-genome containing 956 genes, and a unique-genome containing 1519 genes. Clusters of Orthologous Groups analyses showed that P. agarivorans harbors strain-specifically diverse metabolisms, probably representing high evolutionary genome changes. The Kyoto Encyclopedia of Genes and Genomes and reconstructed carbohydrate metabolic pathways displayed that P. agarivorans strains can utilize a variety of carbohydrates, such as d-glucose, d-fructose, and d-lactose. Analyses of differentially expressed genes showed that compared with the stationary phase (24 h), strain P. agarivorans Hao 2018 had upregulated expression of genes related to the synthesis of extracellular polysaccharides in the logarithmic growth phase (2 h), and that the expression of these genes affected extracellular polysaccharide transport, nucleotide sugar synthesis, and glycosyltransferase synthesis. This is the first investigation of the genomic and metabolic features of P. agarivorans through pan-genomic and transcriptomic analyses, and these intriguing discoveries provide the possibility to produce novel marine drug lead compounds with high biological activity.


Assuntos
Pseudoalteromonas , Transcriptoma , Carboidratos , Genoma Bacteriano/genética , Genômica , Filogenia , Pseudoalteromonas/genética , Pseudoalteromonas/metabolismo
4.
J Clin Lab Anal ; : e24419, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403268

RESUMO

BACKGROUND: Integrin ß (ITGB) superfamily plays an essential role in the intercellular connection and signal transmission. It was exhibited that overexpressing of ITGB family members promotes the malignant progression of lung adenocarcinoma (LUAD), but the relationship between ITGB superfamily and the LUAD prognosis remains unclear. METHODS: In this study, the samples were assigned to different subgroups utilizing non-negative matrix factorization clustering according to the expression of ITGB family members in LUAD. Kaplan-Meier (K-M) survival analysis revealed the significant differences in the prognosis between different ITGB subgroups. Subsequently, we screened differentially expressed genes among different subgroups and conducted univariate Cox analysis, random forest feature selection, and multivariate Cox analysis. 9-feature genes (FAM83A, AKAP12, PKP2, CYP17A1, GJB3, TMPRSS11F, KRT81, MARCH4, and STC1) in the ITGB superfamily were selected to establish a prognostic assessment model for LAUD. RESULTS: In accordance with the median risk score, LUAD samples were divided into high- and low-risk groups. The receiver operating characteristic (ROC) curve of LUAD patients' survival was predicted via K-M survival curve and principal component analysis dimensionality reduction. This model was found to have a favorable performance in LUAD prognostic assessment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes between groups and Gene Set Enrichment Analysis (GSEA) of intergroup samples confirmed that the high- and low-risk groups had evident differences mainly in the function of extracellular matrix (ECM) interaction. Risk score and univariate and multivariate Cox regression analyses of clinical factors showed that the prognostic model could be applied as an independent prognostic factor for LUAD. Then, we draw the nomogram of 1-, 3-, and 5-year survival of LUAD patients predicted with the risk score and clinical factors. Calibration curve and clinical decision curve proved the favorable predictive ability of nomogram. CONCLUSION: We constructed a LUAD prognostic risk model based on the ITGB superfamily, which can provide guidance for clinicians on their prognostic judgment.

5.
J Biochem ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35415740

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with high mortality in humans, and there is a lack of effective and convenient early diagnosis methods. By analyzing the serum miRNA expression data in ESCC tumor samples and normal samples, on the basis of the max-relevance and min-redundancy (mRMR) feature selection and the incremental feature selection (IFS) method, a random forest classifier constructed by 5 feature miRNAs was acquired in our study. The receiver operator characteristic (ROC) curve showed that the model was able to distinguish samples. Principal component analysis (PCA) and sample hierarchical cluster analysis showed that 5 feature miRNAs could well distinguish ESCC patients from healthy individuals. The expression levels of miR-663a, miR-5100 and miR-221-3p all showed a higher expression level in ESCC patients than those in healthy individuals. On the contrary, miR-6763-5p and miR-7111-5p both showed lower expression levels in ESCC patients than those in healthy individuals. In addition, the collected clinical serum samples were used for qRT-PCR analysis. It was uncovered that the expression trends of the 5 feature miRNAs followed a similar pattern with those in the training set. The above findings indicated that the 5 feature miRNAs may be serum tumor markers of ESCC. This study offers new insights for the early diagnosis of ESCC.

6.
Front Immunol ; 13: 859893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359945

RESUMO

JMJD6 is a member of the Jumonji (JMJC) domain family of histone demethylases that contributes to catalyzing the demethylation of H3R2me2 and/or H4R3me2 and regulating the expression of specific genes. JMJD6-mediated demethylation modifications are involved in the regulation of transcription, chromatin structure, epigenetics, and genome integrity. The abnormal expression of JMJD6 is associated with the occurrence and development of a variety of tumors, including breast carcinoma, lung carcinoma, colon carcinoma, glioma, prostate carcinoma, melanoma, liver carcinoma, etc. Besides, JMJD6 regulates the innate immune response and affects many biological functions, as well as may play key roles in the regulation of immune response in tumors. Given the importance of epigenetic function in tumors, targeting JMJD6 gene by modulating the role of immune components in tumorigenesis and its development will contribute to the development of a promising strategy for cancer therapy. In this article, we introduce the structure and biological activities of JMJD6, followed by summarizing its roles in tumorigenesis and tumor development. Importantly, we highlight the potential functions of JMJD6 in the regulation of tumor immune response, as well as the development of JMJD6 targeted small-molecule inhibitors for cancer therapy.


Assuntos
Carcinoma , Neoplasias Pulmonares , Carcinogênese/genética , Carcinoma/genética , Transformação Celular Neoplásica/genética , Epigênese Genética , Humanos , Imunidade , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Pulmonares/genética , Masculino
7.
ChemSusChem ; : e202200092, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35441445

RESUMO

2-Hexanol (2-HOL) is a versatile biomass-derived platform molecule for synthesis of liquid transportation fuels, lubricants, or detergents. Herein, a one-step preparation of 2-HOL using 5-hydroxymethylfurfural (HMF) as a substrate was reported for the first time. Several Au-based catalysts supported on different metal oxides were prepared to explore the relationship between carrier and catalytic activity. The results showed that the highest 2-HOL yield of 65.8 % was obtained at complete HMF conversion over the 5 %Au/ZrO2 catalyst. The 5 %Au/ZrO2 catalyst exhibited excellent durability after five consecutive recycling runs, while confirming its remarkable ring-opening hydrogenolysis on other biomass-derived furanics, furfural, with a total yield of 1-pentanol and 2-pentanol of 67.4 %. The distinguished ring-opening hydrogenolysis performance of the Au/ZrO2 catalyst originated from a synergistic effect between the interfacial Au-O-Zr oxygen vacancies-induced Lewis acidic sites (activating C-OH/C=O bonds) and metallic Au (activating H2 ). This work provides a possibility for producing 2-HOL from HMF with high yield, expanding the sustainable application of lignocellulosic biomass.

8.
J Immunother Cancer ; 10(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35296556

RESUMO

Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant treatment with sintilimab (3 mg/kg for cases <60 kg or 200 mg for those ≥60 kg on day 1) plus CapeOx (oxaliplatin at 130 mg/m2 on D1 and capecitabine at 1000 mg/m2 two times per day on D1-D14) every 21 days, for three cycles before surgical resection, followed by adjuvant treatment with three cycles of CapeOx with the same dosages after surgical resection. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included objective response rate, tumor regression grade per Becker criteria, survival and safety. As of July 30, 2020, 36 patients were enrolled. Totally 7 (19.4%) patients had GEJ cancer, and 34 (94.4%) patients were clinical stage III cases. A total of 35 (97.2%) patients completed three cycles of neoadjuvant treatment, and 1 patients received two cycles due to adverse events. All patients underwent surgery and the R0 resection rate was 97.2%. In this study, pCR and major pathological response were achieved in 7 (19.4%, 95% CI: 8.8% to 35.7%; 90% CI: 10.7% to 33.1%) and 17 (47.2%, 95% CI: 31.6% to 64.3%) patients, respectively. Thirty-one patients received adjuvant treatment. By December 20, 2021, three patients died after disease relapse, and two patients were alive with relapse. Median disease-free survival (DFS) and overall survival (OS) were not reached. The 1-year DFS and OS rates were 90.3% (95% CI: 80.4% to 100.0%) and 94.1% (95% CI: 86.5% to 100.0%), respectively. The most common (>1 patient) grade 3 treatment-related adverse events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4-5 AEs were observed. Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.


Assuntos
Adenocarcinoma , Terapia Neoadjuvante , Adenocarcinoma/patologia , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Junção Esofagogástrica/patologia , Humanos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Oxaliplatina/uso terapêutico
9.
Mar Drugs ; 20(2)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35200619

RESUMO

Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms. In a changing marine environment, EPS secretion can reduce damage from external environmental disturbances to microorganisms. Meanwhile, EPSs have promising application prospects in the fields of food, cosmetics, and pharmaceuticals. Changes in external environmental pH have been shown to affect the synthesis of EPSs in microorganisms. In this study, we analyzed the effects of different initial fermentation pHs on the production, monosaccharide composition, and antioxidant activity of the EPSs of Pseudoalteromonas agarivorans Hao 2018. In addition, the transcriptome sequence of P. agarivorans Hao 2018 under different initial fermentation pH levels was determined. GO and KEGG analyses showed that the differentially expressed genes were concentrated in the two-component regulatory system and bacterial chemotaxis pathways. We further identified the expression of key genes involved in EPS synthesis during pH changes. In particular, the expression of genes encoding the glucose/galactose MFS transporter, phosphomannomutase, and mannose-1-phosphate guanylyltransferase was upregulated when the environmental pH increased, thus promoting EPS synthesis. This study not only contributes to elucidating the environmental adaptation mechanisms of P. agarivorans, but also provides important theoretical guidance for the directed development of new products using biologically active polysaccharides.


Assuntos
Antioxidantes/isolamento & purificação , Polissacarídeos Bacterianos/isolamento & purificação , Pseudoalteromonas/metabolismo , Antioxidantes/química , Antioxidantes/farmacologia , Fermentação , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Concentração de Íons de Hidrogênio , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Pseudoalteromonas/genética
10.
Biochem Pharmacol ; 197: 114912, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35032460

RESUMO

The roots of Glycine tabacina are used to treat rheumatoid arthritis (RA) and joint infection in folk medicine. Glytabastan B (GlyB), a newly reported coumestan isolated from this species, was found to significantly attenuate IL-1ß-induced inflammation in SW982 human synovial cells at 3 and 6 µM, as evidenced by the decreased levels of pro-inflammatory mediators and matrix metalloproteinases (MMPs). GlyB also suppressed RANKL-induced osteoclastogenesis, decreased the expression of osteoclastogenic markers (NFATc1, CTSK, MMP-9) and osteoclast-mediated bone resorption. Further, GlyB administration (12.5 and 25 mg/kg) significantly inhibited inflammation, osteoclast formation and disease progression in collagen-induced arthritis (CIA) mice. Integration of network pharmacology, quantitative phosphoproteomic and experimental pharmacology results revealed that these beneficial actions were closely associated with the blockade of GlyB on the activation of MAPK, PI3K/AKT and their downstream signals including NF-κB and GSK3ß/NFATc1. Drug affinity responsive target stability (DARTS) assay, cellular thermal shift (CETSA) assay and molecular docking analysis confirmed that there were direct interactions between GlyB and its target proteins ERK2, JNK1 and class Ⅰ PI3K catalytic subunit p110 (α, ß, δ and γ), which significantly contributed to the inhibition of activation of MAPK and PI3K/AKT pathways. In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.


Assuntos
Artrite Experimental/tratamento farmacológico , Cumarínicos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Sinoviócitos/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Células Cultivadas , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Relação Dose-Resposta a Droga , Fabaceae , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Sinoviócitos/metabolismo , Sinoviócitos/patologia
11.
Bioresour Technol ; 347: 126403, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34826560

RESUMO

Herein, WOx-decorated Ir/SiO2 (W/Ir = 0.06) and HZSM-5 were coupled to selectively convert microcrystalline cellulose (MCC) into C6 alkanes. A 92.8% yield of liquid alkanes including an 85.3% yield of C6 alkanes was produced at 210 °C. Cellulose hydrolysis, glucose hydrogenation and sorbitol hydrodeoxygenation were integrated to produce alkanes via a sorbitol route. Ir-WOx/SiO2 showed high performance for hydrogenation and hydrodeoxygenation reactions after hydrolysis catalyzed by HZSM-5. The intimate contact between WOx and Ir enhanced the synergistic interaction through the electron transfer from Ir to WOx. The interaction strengthened the reduction capability of Ir for hydrogenations, as well as improved the adsorption and activation of C-O bonds on reduced WOx for deoxygenations. The monotungstate WOx species provided moderate Lewis acids to cooperate with Ir to accelerate hydrodeoxygenations with alleviated retro-aldol condensation to yield more C6 alkanes.


Assuntos
Alcanos , Dióxido de Silício , Catálise , Celulose , Irídio , Óxidos , Tungstênio
12.
Cancer Med ; 11(3): 847-863, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34841742

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown numerous clinical benefits in multiple cancer types, but good predictive biomarkers are severely lacking. Although increasing evidence has linked Hedgehog (Hh) signaling pathway with tumor development, a systematic investigation for its potential as a biomarker remains elusive. METHODS: We collected and analyzed the transcriptional data and clinical outcomes of diverse cancers from the Cancer Genome Atlas and four published ICI datasets. Hh activity was estimated by conducting a single-sample gene-set enrichment analysis (ssGSEA) for the Hh-related genes and calculating the ssGSEA score in each tumor sample. RESULTS: Our findings suggest that tumors with high Hh activity displayed multiple immunosuppressive characteristics, including lack of anti-tumor response pathways, downregulation of immune effectors, enrichment of immunosuppressive cells and chemokines, and activation of immunosuppressive signaling. Notably, patients in the non-response group had enriched Hh activity and showed worse overall survival (OS; pooled HR = 1.50, 95% CI = 1.02-2.21, p = 0.039). In the subgroup of high programmed cell death ligand 1 (PD-L1) expression, patients who harbored high Hh activity displayed a dramatically lower response rate to ICIs and a strikingly worse OS (pooled HR = 2.89, 95% CI = 1.53-5.49, p < 0.001). CONCLUSION: Increased Hh activity correlates with tumor immunosuppression across diverse cancers. Hh activity is not only a predictive biomarker for resistance to ICIs but can also better predict clinical outcomes in combination with PD-L1 expression.


Assuntos
Proteínas Hedgehog , Neoplasias , Antígeno B7-H1 , Biomarcadores , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas Hedgehog/genética , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética
13.
J Cancer ; 13(5): 1456-1467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371329

RESUMO

Purpose: Exosome component 5 (EXOSC5) is a non-catalytic component of the RNA exosome complex, which is interacted with the Zinc-finger antiviral protein to degrade the target RNA and aberrantly expressed in various malignances. We explored the molecular mechanisms and biological roles by which EXOSC5 promotes the progression of GC. Methods: We used quantitative real-time PCR, Western blotting and immunohistochemistry to analyze EXOSC5 expression in GC samples. An GC organoid-based functional model was assessed, and cancer cell CCK-8 assay, colony formation assay and flow cytometry were performed to reveal the role of EXOSC5 in GC cell proliferation and tumorigenesis. In vivo, nude mice tumorigenesis assay were performed to explore the effects of EXOSC5 knockdown on growth of GC. The roles of EXOSC5 on AKT and STAT3 signaling pathways were measured by Western blot. Results: The expression of EXOSC5 was up-regulated in GC tissues and cell lines compared with normal group, and highly expressed EXOSC5 indicated a poorer clinical outcome for GC patients and was positively correlated with tumor size and TNM stage. EXOSC5 overexpression facilitated the growth of GC cells and organoids, while EXOSC5 downregulation inhibited proliferation and induced G1/S phase transition arrest. Moreover, mechanistic studies demonstrated that EXOSC5 increased cyclinD1 expression levels and decreasing the expression levels of p21 and p27 via regulation of the AKT and STAT3 pathway. Conclusion: The expression of EXOSC5 is upregulated and correlated with tumorigenesis and poor prognosis of GC. EXOSC5 increases GC proliferation partly through activating AKT and STAT3 pathways.

14.
Gene ; 807: 145888, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371096

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a glucose intolerance condition encounters for the first time in a fraction of pregnant women. The role of different host inflammatory molecules in GDM etiology has been deciphered. Chemerin is a chemoattractant protein primarily associated with the pathogenesis of type 2 diabetes, obesity, and metabolic syndrome. However, the association of chemerin and its genetic variants with the predisposition of GDM is not clear, and our present study is aimed to address the issue. MATERIALS AND METHODS: A total of 703 Chinese women comprising of GDM (n = 303), glucose tolerant pregnant women (n = 211), and non-pregnant glucose tolerant controls (n = 189) were recruited in the present investigation. GDM was diagnosed according to the World Health Organization recommendation for diagnosis of gestational diabetes during pregnancy. Plasma levels of chemerin were quantified by an Enzyme-linked Immunosorbent Assay (ELISA). Common variants in the chemerin gene (rs4721, rs17173617, rs7806429, and rs17173608) were genotyped by using TaqMan assay. RESULTS: Plasma chemerin level was found higher in subjects with GDM as compared to glucose tolerant pregnant and non-pregnant women. Further, a positive correlation between plasma chemerin and HOMA-IR index suggesting an essential role of chemerin in mediating insulin resistance. Variants of rs4721 and rs17173608 polymorphisms were associated with lower levels of plasma chemerin and low HOMA-IR index. Furthermore, mutants of rs4721 and rs17173608 polymorphisms were associated with protection against the development of GDM in the Chinese cohort. CONCLUSIONS: Plasma chemerin is elevated in GDM patients. Genetic variation in chemerin gene associated with lower plasma levels of chemerin, HOMA-IR index and protects against the development of GDM in Chinese.


Assuntos
Quimiocinas/genética , Quimiocinas/metabolismo , Diabetes Gestacional/genética , Adulto , Glicemia/genética , Quimiocinas/sangue , China , Estudos de Coortes , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Intolerância à Glucose/genética , Humanos , Insulina/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético/genética , Gravidez
15.
Exp Hematol Oncol ; 10(1): 56, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922633

RESUMO

Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.

16.
Int J Gen Med ; 14: 6899-6906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703294

RESUMO

BACKGROUND: Combined small cell lung cancer (c-SCLC) distinguishes itself from small cell lung cancer (SCLC) due to its inclusion of both SCLC and non-small cell lung cancer (NSCLC) components. Few studies have compared clinicopathological characteristics, prognosis and factors affecting survival. We therefore addressed the issues in this study. PATIENTS AND METHODS: A total of 400 c-SCLC and 20,841 SCLC patients were enrolled using SEER database. Difference in clinicopathological characteristics of SCLC and c-SCLC patients was analyzed using chi-square. Kaplan-Meier was applied to compare their survival before and after propensity score matching (PSM). Cox regression model was adopted to assess the impact of different clinical variables on survival. Logistic regression was applied to identify risk factors for c-SCLC and SCLC patients. RESULTS: Differences in race, sex, T stage, N stage, surgery, bone, brain and liver metastasis were detected between c-SCLC and SCLC patients. c-SCLC patients had better overall survival (OS) than SCLC patients before PSM. Age, race, sex, T stage, N stage, surgery, bone, brain, liver and lung metastasis were prognostic factors affecting OS for c-SCLC and SCLC (P < 0.05). However, a significant OS benefit was not observed in c-SCLC after adjusting for clinicopathological variables (HR, 0.950; 95% CI, 0.842-1.073; P=0.411). No significant OS difference was found between c-SCLC and SCLC patients after PSM (P = 0.789). c-SCLC patients had lower risk of lymph node (OR: 0.555; 95% CI: 0.439-0.703; P < 0.001) and liver metastasis (OR: 0.591; 95% CI: 0.448-0.779; P < 0.001), whereas had no significant differences in bone and brain metastasis risks (P > 0.05) compared with SCLC patients. CONCLUSION: The prognosis of c-SCLC did not significantly differ from that of SCLC if clinicopathological characteristics are controlled. Better prognosis for c-SCLC patients over SCLC patients may be ascribed to fewer liver and lymph node metastases upon diagnosis.

17.
Front Oncol ; 11: 732841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631565

RESUMO

Lung adenocarcinomas (LUADs) harbouring epidermal growth factor receptor (EGFR) mutations are generally unable to benefit from immune checkpoint inhibitors (ICIs) due to an immunosuppressive tumour microenvironment (TME) and a lower tumour mutation burden. Currently, no gene signature can comprehensively evaluate the TME and predict the prognosis of patients with EGFR-mutant LUAD. Using the Cancer Genome Atlas database of EGFR-mutant LUAD based on the immune score derived from the ESTIMATE algorithm, we divided 80 patients with EGFR-mutant LUAD samples into high and low immune score groups with different immune microenvironments. Subsequently, we screened 396 differentially expressed immune-related genes with prognostic value. The top Gene Ontology terms were significantly enriched in biological functions related to T cell differentiation, immune response, cell cycle, and cell proliferation, which are closely related to the immune microenvironment of tumours. In addition, the KEGG pathway enrichment analysis mainly focused on cell cycle, cell adhesion molecules, and cytokine-cytokine receptor interaction, which also had a relationship with the immune response. Subsequently, we identified a three-gene signature including BTLA, BUB1B, and CENPE using the LASSO Cox regression model. The three-gene signature could accurately identify patients at risk of EGFR-mutant LUAD in the training and validation sets and high-risk patients from both the sets exhibited significantly shorter overall survival (p=0.0053 and p=0.035, respectively). CIBERSORT was used to evaluate the abundance of immune cell infiltration in the EGFR-mutant LUAD microenvironment. The immune activity of B cells and macrophages was higher in the low-risk group, while the immune activity of natural killer cells and T cells was higher in the high-risk group. Thus, the three-gene signature closely related to immunosuppressive TME could predict the risk and prognosis in patients with EGFR-mutant LUAD.

18.
J Cancer Res Clin Oncol ; 147(12): 3653-3664, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34661758

RESUMO

PURPOSE: Non-small cell lung cancer (NSCLC) accounts for about 85% in all cases of lung cancer. In recent years, molecular targeting drugs for NSCLC have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. Currently, there are three generations of EGFR-TKIs, all of which have achieved good efficacy in clinical therapy. However, most patients developed drug resistance after 6-13 months EGFR-TKIs treatment. Therefore, a comprehensive understanding of EGFR-TKIs resistance mechanisms is of vital importance for clinical management of NSCLC. METHODS: Relevant data and information about the topic were obtained by searching PubMed (Medline), Web of Science and Google Scholar using the subject headings, such as "NSCLC", "EGFR-TKIs resistance", "EGFR mutations", "human epidermal growth factor receptor-2 (HER2/erbB-2)", "hepatocyte growth factor (HGF)", "vascular endothelial growth factor (VEGF)", "insulin-like growth factor 1 (IGF-1)", "epithelial-mesenchymal transition (EMT)", "phosphatase and tensin homolog (PTEN)", "RAS mutation", "BRAF mutation", "signal transducer and activator of transcription 3 (STAT3)", and "tumor microenvironment", etc. RESULTS: The mechanisms for EGFR-TKIs resistance include EGFR mutations, upregulation of HER2, HGF/c-MET, VEGF IGF1, EMT and STAT3 pathways, mutations of PTEN, RAS and BRAF genes, and activation of other by-pass pathways. These mechanisms are interconnected and can be potential targets for the treatment of NSCLC. CONCLUSION: In this review, we discuss the mechanisms of EGFR-TKIs drug resistance and the clinical strategies to overcome drug resistance from the perspective of EGFR-TKIs combined treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular/métodos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
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