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1.
Dis Markers ; 2022: 4262600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340411

RESUMO

Background: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer. Methods: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells. Results: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells. Conclusions: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.


Assuntos
Neoplasias do Colo , Glucagon , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Glucagon/genética , Glucagon/metabolismo , Humanos
2.
Angew Chem Int Ed Engl ; 60(20): 11464-11473, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33751758

RESUMO

Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. We designed a core-satellite size transformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFß signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. T-PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hipóxia/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Estrutura Molecular , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Células Estromais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
3.
Sci Rep ; 10(1): 12873, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732993

RESUMO

Underwater machinery withstands great resistance in the water, which can result in consumption of a large amount of power. Inspired by the character that loach could move quickly in mud, the drag reduction mechanism of Paramisgurnus dabryanus loach is discussed in this paper. Subjected to the compression and scraping of water and sediments, a loach could not only secrete a lubricating mucus film, but also importantly, retain its mucus well from losing rapidly through its surface micro structure. In addition, it has been found that flexible deformations can maximize the drag reduction rate. This self-adaptation characteristic can keep the drag reduction rate always at high level in wider range of speeds. Therefore, even though the part of surface of underwater machinery cannot secrete mucus, it should be designed by imitating the bionic micro-morphology to absorb and store fluid, and eventually form a self-lubrication film to reduce the resistance. In the present study, the Paramisgurnus dabryanus loach is taken as the bionic prototype to learn how to avoid or slow down the mucus loss through its body surface. This combination of the flexible and micro morphology method provides a potential reference for drag reduction of underwater machinery.

4.
Oncol Lett ; 19(4): 3079-3088, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256808

RESUMO

microRNAs (miRNAs) have been identified to play vital roles in the development and progression of numerous different types of human malignancy, including esophageal squamous cell carcinoma (ESCC). In the present study, the biological function of microRNA-144 (miR-144) was investigated, as well as its underlying molecular mechanism in ESCC. The results revealed that miR-144 expression was significantly decreased, whereas the expression of TP53-inducible glycolysis and apoptosis regulator (TIGAR) was significantly increased in human ESCC tissues when compared with adjacent non-tumor tissues. An increase in TIGAR was significantly associated with tumor size and Tumor-Node-Metastasis staging in patients. Functional analysis revealed that the overexpression of miR-144 using lentivirus particles significantly inhibited cell proliferation and tumor colony formation, and induced cell apoptosis in EC9706 and EC109 cells. The autophagy activity was also enhanced by miR-144 activity. In addition, overexpression of miR-144 significantly inhibited tumor growth in vivo. In the present study, TIGAR was confirmed to be the downstream target of miR-144 in ESCC. siRNA-mediated downregulation of TIGAR inversely regulated the inhibition effect of miR-144 on ESCC cells. To conclude, the present study demonstrated that miR-144 inhibits proliferation and invasion in esophageal cancer by directly targeting TIGAR.

5.
Eur Radiol ; 30(5): 2692-2702, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32020400

RESUMO

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.


Assuntos
Adenocarcinoma de Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Micro-Ondas/uso terapêutico , Recidiva Local de Neoplasia/terapia , Ablação por Radiofrequência/métodos , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vinorelbina/administração & dosagem , Gencitabina
6.
ACS Appl Mater Interfaces ; 11(21): 18995-19005, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31058483

RESUMO

Cutting off the glucose supply by glucose oxidase (GOx) has been regarded as an emerging strategy in cancer starvation therapy. However, the standalone GOx delivery suffered suboptimal potency for tumor elimination and potential risks of damaging vasculatures and normal organs during transportation. To enhance therapeutic efficacy and tumor specificity, a site-specific activated dual-catalytic nanoreactor was herein constructed by embedding GOx and ferrocene in hyaluronic acid (HA)-enveloped dendritic mesoporous silica nanoparticles to promote intratumoral oxidative stress in cancer starvation. In this nanoreactor, the encapsulated GOx served as the primary catalyst that accelerated oxidation of glucose and generation of H2O2, while the covalently linked ferrocene worked as the secondary catalyst for converting the upstream H2O2 to more toxic hydroxyl radicals (•OH) via a classic Fenton reaction. The outmost HA shell not only offered a shielding layer for preventing blood glucose from oxidation during nanoreactor transportation, thus minimizing the probable oxidative damage to normal tissues, but also imparted the nanoreactor with targeting ability for facilitating its internalization into CD44-overexpressing tumor cells. After the nanoreactor was endocytosed by target cells, the HA shell underwent hyaluronidase-triggered degradation in lysosomes and switched on the cascade catalytic reaction mediated by GOx and ferrocene. The resulting glucose exhaustion and •OH accumulation would effectively kill cancer cells and suppress tumor growth via combination of starvation and oxidative stress enhancement. Both in vitro and in vivo results indicated the significantly amplified therapeutic effects of this synergistic therapeutic strategy based on the dual-catalytic nanoreactor. Our study provides a new avenue for engineering therapeutic nanoreactors that take effect in a tumor-specific and orchestrated fashion for cancer starvation therapy.


Assuntos
Ácido Hialurônico/química , Nanopartículas/química , Neoplasias/patologia , Estresse Oxidativo , Animais , Antineoplásicos/farmacologia , Catálise , Morte Celular/efeitos dos fármacos , Feminino , Glucose Oxidase/metabolismo , Células HeLa , Humanos , Ácido Hialurônico/síntese química , Radical Hidroxila/metabolismo , Camundongos Nus , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos
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