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1.
Artigo em Inglês | MEDLINE | ID: mdl-39400783

RESUMO

PURPOSE: Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment. METHODS: BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion. RESULTS: BAFF overexpression in 4T1 cells promoted tumor growth in vivo, suppressed CD8+ T cell activity, and increased IL-10-secreting CD5+ regulatory B cells in tumors. 4T1/BAFF cells directly enhanced IL-10 production in CD5+ B cells via BAFF/BAFF-receptor interactions, and IL-10 from CD5+ B cells inhibited IFN-γ secretion by T cells. B cell depletion partially reversed the tumor-promoting effects of BAFF overexpression. Our study reveals a novel mechanism by which BAFF can foster tumor progression, with the induction of IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses appearing to be a key component of BAFF's tumor-promoting activity. CONCLUSION: These findings underscore the complex immunomodulatory effects that BAFF exerts in the tumor microenvironment and point to BAFF-induced regulatory B cells as a potential new therapeutic target in breast cancer that warrants further investigation.

2.
Cancer Control ; 27(1): 1073274820978817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33345608

RESUMO

INTRODUCTION: The mechanistic basis for the development of esophageal squamous cell carcinoma (ESCC) remains poorly understood. The goal of the present study was thus to characterize mRNA and long noncoding RNA (lncRNA) expression profiles associated with ESCC in order to identify key hub genes associated with the pathogenesis of this cancer. MATERIALS AND METHODS: The GSE26866 and GSE45670 datasets from the Gene Expression Omnibus (GEO) database were used to conduct a weighted gene co-expression network analysis (WGCNA), after which Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Cytoscape was additionally used to construct lncRNA-mRNA networks, after which hub genes were identified and validated through the assessment of TCGA datasets and clinical samples. RESULTS: Two gene modules were found to be closely linked to ESCC tumorigenesis. These genes were enriched in cell cycle, MAPK signaling, JAK-STAT signaling, pyrimidine metabolism, arachidonic acid metabolism, and P53 signaling pathway activity, all of which are directly linked with the development of cancer. In total, we identified and validated 9 hub genes associated with ESCC (DDX18, DNMT1, NCAPG, WDHD1, PRR11, VOPP1, ZKSCAN5, LC35C2, and PHACTR2). CONCLUSION: In summary, we identified key gene modules and hub genes associated with ESCC development, and we constructed a lncRNA-mRNA network pertaining to this cancer type. These results provide a foundation for future research regarding the mechanistic basis of ESCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Redes Reguladoras de Genes , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
3.
Tumour Biol ; 37(1): 1289-97, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26289845

RESUMO

The Forkhead box M1 (FoxM1) transcription factor plays crucial roles in multiple biological processes, including cell proliferation, differentiation, migration, and transformation. Recent studies have reported that aberrant expression of FoxM1 was found in a variety of human cancers. However, the expression pattern of FoxM1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been well characterized to date. In this study, the expression of FoxM1 was evaluated in 46 pairs of human HCC, the adjacent non-tumorous liver tissues, and 12 pairs of normal liver tissues by immumohistochemistry. FoxM1 expression was upregulated in the HCC (76.09 %) compared with non-tumorous liver tissues (39.13 %) and normal liver tissues (8.33 %) (P < 0.05). FoxM1 expression was significantly associated with tumor stage, tumor size, tumor number, integrality of tumor encapsulation, tumor thrombus, and AFP level (P < 0.05). Functionally, enforced expression of FoxM1 in HCC cell line (HHCC) remarkably enhanced cell proliferation in vitro and in vivo. Further analysis of cell cycle-related molecules showed that FoxM1 overexpression increased expressions of cyclin B1 and cyclin D1 but reduced expressions of p27(Kip1) and p21(Cip1). Our findings suggest that FoxM1 overexpression promotes HCC cell proliferation by cell cycle regulation, which is a potential target for hepatocellular carcinoma therapy.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Idoso , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Perfilação da Expressão Gênica , Células Hep G2 , Humanos , Imuno-Histoquímica , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Pessoa de Meia-Idade , Regulação para Cima
4.
Tumour Biol ; 36(3): 2163-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25398693

RESUMO

Partner of sld five 1 (PSF1) is a member of the heterotetrameric complex termed GINS. Previous studies have shown that PSF1 is unregulated in several cancer and associated with tumor malignant characters. However, the effects of PSF1 in lung cancer are still unclear. The goal of this study was to investigate the effects of PSF1 on the proliferation capacities of lung cancer. To start with, expression of PSF1 in 22 human lung cancer samples and adjacent non-tumor samples were detected by real-time RT-PCR and Western blotting. Our results showed that PSF1 was overexpressed in lung cancer samples compared to adjacent non-tumor samples. To achieve better insights of PSF1 functions in lung cancer cells, we used PSF1-specific small interfering RNA (siRNA) successfully inhibit the expression of PSF1 in messenger RNA (mRNA) and protein levels. In addition, we used lung cancer cell lines with different p53 gene background (p53 null and p53 wild-type). The results showed that knockdown of PSF1 inhibited cell proliferation and caused cell cycle arrest of lung cancer cells in a p53-independent manner. Our data indicated that PSF1 is functionally involved in lung cancer cell proliferation and is a potential target for lung cancer therapy.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Humanos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteína Supressora de Tumor p53/genética
5.
J Surg Res ; 199(2): 664-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26182997

RESUMO

BACKGROUND: With the development of thoracic surgeries, one-lung ventilation (OLV) has been routinely used to facilitate surgical exposure. However, OLV can cause lung injury during the surgical process and becomes an important factor affecting the outcomes. To date, effective treatments for the prevention of lung injury caused by OLV are lacking. Hydrogen has been demonstrated to have effective protection against tissue injuries caused by oxidative stress, inflammation, and apoptosis. This study investigated the efficacy of hydrogen water consumption on the prevention of lung injury induced by OLV in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 32, 240-260 g) were divided randomly into the following four groups: sham group, sham + H2 group, OLV group, OLV + H2 group. The rats drank hydrogen water or degassed hydrogen water for 4 wk before the operation and received OLV for 60 min and two-lung ventilation for 60 min. Lung tissues were assayed for wet-to-dry ratio, oxidative stress variables, proinflammatory cytokines, and hematoxylin-eosin staining. RESULTS: Hydrogen water consumption reduced wet-to-dry weight ratio, malondialdehyde and myeloperoxidase activity and decreased the concentration of TNF-α, IL-1ß, and IL-6 in the lung tissues compared with sham group and sham + H2 group. Hydrogen water consumption further attenuated NF-κB activation and caused histopathologic alterations. CONCLUSIONS: Our data demonstrated that hydrogen water consumption ameliorated OLV-induced lung injury, and it may exert its protective role by its anti-inflammation, antioxidation and reducing NF-κB activity in the lung tissues.


Assuntos
Hidrogênio/administração & dosagem , Lesão Pulmonar/prevenção & controle , Ventilação Monopulmonar/efeitos adversos , Animais , Avaliação Pré-Clínica de Medicamentos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Peroxidase/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
6.
Acta Pharmacol Sin ; 36(2): 241-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25557114

RESUMO

AIM: Forkhead box M1 (FoxM1) is a transcription factor that plays important roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). The aim of this study was to examine the involvement of FoxM1 in the anti-cancer action of sorafenib, a multikinase inhibitor, in human HCC cells. METHODS: HCC cell lines HepG2 and HuH-7 were tested. Cell viability was examined using MTT assay and cell invasion was determined with Transwell migration assay. The relevant mRNA expression was determined with RT-PCR, and the proteins were detected using Western blotting and immunofluorescence assays. RNA interference was used to modify the expression of p53 and FoxM1. HuH-7 cell line xenograft mice were used for in vivo study, which were treated with sorafenib (40 mg/kg, po) daily for 3 weeks. RESULTS: Sorafenib (2-20 µmol/L) inhibited the proliferation of the cells in dose- and time-dependent manners with an IC50 value of nearly 6 µmol/L at 48 h. Sorafenib (6 µmol/L) markedly suppressed the cell invasion. Furthermore, sorafenib (2-6 µmol/L) dose-dependently decreased the expression of FoxM1, MMP-2, and Ki-67, and up-regulated that of p53 in the cells. Silencing p53 abolished the decrease of FoxM1 and increase of p53 in sorafenib-treated cells. Silencing FoxM1 significantly reduced the expression of MMP-2 and Ki-67, and enhanced the anti-proliferation action of sorafenib in the cells, whereas overexpression of FoxM1 increased the expression of MMP-2 and Ki-67, and abrogated the anti-proliferation action of sorafenib. In the xenograft mice, sorafenib administration decreased the tumor growth by 40%, and markedly increased the expression of p53, and decreased the expression of FoxM1, MMP-2, and Ki-67 in tumor tissues. CONCLUSION: Sorafenib inhibits HCC proliferation and invasion by inhibiting MMP-2 and Ki-67 expression due to up-regulation of P53 and suppressing FoxM1.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proteína Forkhead Box M1 , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Camundongos Nus , Invasividade Neoplásica/patologia , Niacinamida/farmacologia , Sorafenibe
7.
Mol Immunol ; 170: 46-56, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615627

RESUMO

Peritoneal B cells can be divided into B1 cells (CD11b+CD19+) and B2 cells (CD11b-CD19+) based on CD11b expression. B1 cells play a crucial role in the innate immune response by producing natural antibodies and cytokines. B2 cells share similar traits with B1 cells, influenced by the peritoneal environment. However, the response of both B1 and B2 cells to the same stimuli in the peritoneum remains uncertain. We isolated peritoneal B1 and B2 cells from mice and assessed differences in Interleukin-10(IL-10) secretion, apoptosis, and surface molecule expression following exposure to LPS and Interleukin-21(IL-21). Our findings indicate that B1 cells are potent IL-10 producers, possessing surface molecules with an IgMhiCD43+CD21low profile, and exhibit a propensity for apoptosis in vitro. Conversely, B2 cells exhibit lower IL-10 production and surface markers characterized as IgMlowCD43-CD21hi, indicative of some resistance to apoptosis. LPS stimulates MAPK phosphorylation in B1 and B2 cells, causing IL-10 production. Furthermore, LPS inhibits peritoneal B2 cell apoptosis by enhancing Bcl-xL expression. Conversely, IL-21 has no impact on IL-10 production in these cells. Nevertheless, impeding STAT3 phosphorylation permits IL-21 to increase IL-10 production in peritoneal B cells. Moreover, IL-21 significantly raises apoptosis levels in these cells, a process independent of STAT3 phosphorylation and possibly linked to reduced Bcl-xL expression. This study elucidates the distinct functional and response profiles of B1 and B2 cells in the peritoneum to stimuli like LPS and IL-21, highlighting their differential roles in immunological responses and B cell diversity.


Assuntos
Apoptose , Subpopulações de Linfócitos B , Interleucina-10 , Interleucinas , Lipopolissacarídeos , Peritônio , Animais , Camundongos , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Proteína bcl-X/metabolismo , Proteína bcl-X/imunologia , Antígeno CD11b/metabolismo , Antígeno CD11b/imunologia , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucinas/imunologia , Interleucinas/farmacologia , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/imunologia , Camundongos Endogâmicos C57BL , Peritônio/imunologia , Peritônio/citologia , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/imunologia
8.
Oncol Res ; 20(8): 341-50, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23924854

RESUMO

Considerable effort has been made in elucidating the appropriate biomarkers and the mechanism and functional significance of these biomarkers in hepatocellular carcinoma (HCC). Glycoprotein nonmetastatic B (GPNMB) overexpression occurs in cutaneous melanomas and breast cancer, and it is an attractive candidate for cancer therapy. However, little is known about the expression and regulation of GPNMB in HCC. In this study, we investigated the expression of GPNMB in HCC histochemically and tested the regulation effects of the epithelial cell adhesion molecule (EpCAM) and colony-stimulating factor (CSF-1) on the expression of GPNMB in HCC cells. Our results demonstrated that GPNMB levels were significantly enhanced in HCC compared with adjacent normal liver tissues. In HCC cells, GPNMB expression was regulated by EpCAM and CSF-1 partly through their common downstream product c-myc. Taken together, these results suggest that GPNMB, the expression of which was regulated in HCC cells by the highly coordinated function of various proteins, may be a potential target for HCC therapy.


Assuntos
Antígenos de Neoplasias/fisiologia , Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/fisiologia , Neoplasias Hepáticas/metabolismo , Fator Estimulador de Colônias de Macrófagos/fisiologia , Glicoproteínas de Membrana/fisiologia , Carcinoma Hepatocelular/terapia , Molécula de Adesão da Célula Epitelial , Células Hep G2 , Humanos , Neoplasias Hepáticas/terapia , Glicoproteínas de Membrana/análise , Proteínas Proto-Oncogênicas c-myc/fisiologia , Regulação para Cima
9.
Poult Sci ; 102(8): 102814, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37327748

RESUMO

This study aimed to determine the mechanisms of heat-induced oxidative stress in the thymus and spleen of broilers. After 28 d, 30 broilers were randomly divided into the control (25°C ± 2°C; 24 h/d) and heat-stressed (36°C ± 2°C; 8 h/d) groups; the experiment lasted for 1 wk. The broilers in each group were euthanized, and some samples were collected and analyzed at 35 d. The results showed that the birds subjected to heat stress reduced the weight (P < 0.01) and the indices of thymus (P < 0.01), the activities of T-AOC (P < 0.01) and SOD (P < 0.05) of spleen, and levels of IL-10 (P < 0.05) and the GSH-PX (P < 0.05) in thymus and spleen, and increased the IL-6 content of thymus (P < 0.05), the MDA content (P < 0.01), and the reactive oxygen species (ROS) levels (P < 0.01) in thymus and spleen. Moreover, the expression of the IgG gene in the thymus and spleen of heat-stressed broilers was increased (P < 0.05); however, the expression of the IgM gene in the spleen was increased (P < 0.05), with no difference (P > 0.05) in the thymus of heat-stressed broilers compared with the control. Furthermore, the relative expression of adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) in the thymus and spleen both increased (P < 0.05). The sodium-dependent vitamin C transporter-2 (SVCT-2) (P < 0.01) and mitochondrial calcium uniporter (MCU) (P < 0.01) mRNA levels in the thymus of heat-stressed broilers increased, and the expression of ABCG2 (P < 0.05), SVCT-2 (P < 0.01), and MCU (P < 0.01) proteins in the thymus and spleen of heat-stressed broilers increased compared with the control group. This study confirmed that heat stress-induced oxidative stress in the immune organs of broilers, further reducing immune function.


Assuntos
Galinhas , Suplementos Nutricionais , Animais , Galinhas/metabolismo , Transportadores de Sódio Acoplados à Vitamina C/metabolismo , Estresse Oxidativo , Resposta ao Choque Térmico , Ração Animal/análise , Dieta/veterinária
10.
Org Lett ; 25(21): 3967-3971, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37200161

RESUMO

Substrates containing disulfide bonds, which are more stable and less smelling, could be used as thiophenol precursors in organic synthesis. Herein, an N-heterocyclic carbene (NHC)-catalyzed reaction between α-bromoenals and 2,2'-dithiodibenzaldehydes was developed. Through the sustained release strategy, the side reaction can be effectively inhibited, and the chiral thiochromene derivatives can be obtained with good yields and high optical purities. Application studies showed encouraging results when the desired products were explored for antimicrobial utilities in pesticide development.

11.
Clin Cardiol ; 46(1): 5-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36168782

RESUMO

BACKGROUND: The association between frailty and older patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is unclear. Therefore, we conducted a systematic review and meta-analysis to investigate the prevalence of frailty in older patients with AMI following PCI, and determine the relationship between frailty and adverse outcomes in these patients. HYPOTHESIS: Older patients with AMI have a higher prevalence of frailty after PCI, and the frailty in these patients increases the risk of adverse outcomes. METHODS: A comprehensive search of the PubMed, Cochrane, Ovid (Medline), Ovid (Embase), and Web of Science databases was performed for articles published until October 2021. A meta-analysis was performed using stata12.0 software. A random-effects model was used when I2 was greater than 50%; otherwise, a fixed-effects model was used. RESULTS: There were a total of 274,976 older patients in the included studies. Nine studies investigated the prevalence of frailty in older patients with AMI after PCI, with an overall prevalence of 39% (95% confidence interval [CI]: 18%-60%, p < .001). Six studies included adverse outcomes of frailty in older patients with AMI after PCI, including all-cause mortality (hazard ratio [HR] = 2.29, 95% CI: 1.65-3.16, p = .285), rehospitalization (HR = 2.53, 95% CI: 1.38-4.63), and in-hospital major bleeding (HR = 1.93, 95% CI: 1.29-2.90, p = .825). CONCLUSION: The frailty prevalence is increased in older patients with AMI after PCI, especially in ST-segment elevation myocardial infarction (STEMI). AMI with frailty after PCI is more likely to be associated with worse clinical outcomes, such as death, bleeding, and rehospitalization.


Assuntos
Fragilidade , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Prevalência , Resultado do Tratamento , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
12.
Thorac Cancer ; 14(32): 3240-3244, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37779217

RESUMO

Pulmonary polymorphic carcinoma (PPC) is a rare and poorly differentiated form of non-small cell lung cancer (NSCLC), accounting for just approximately 0.1% to 0.4% of all NSCLC cases. Historically, the conventional treatments for PPC have been linked to a grim prognosis. However, with the advent of immune checkpoint inhibitors (ICIs), including PD-1 inhibitors, for the management of NSCLC, our center has witnessed encouraging outcomes in two PPC patients who underwent PD-1 inhibitor therapy. The first patient was a 70-year-old male who initially came to our attention after the discovery of a lung mass during a routine physical examination. A lung biopsy confirmed the diagnosis of PPC, and further complications included brain metastasis. Surgical intervention was conducted for the brain metastases, while PD-1 inhibitor therapy was employed for the lung tumors. The second patient was a 60-year-old male who was admitted with a history of persistent coughing and hemoptysis, which led to the diagnosis of a left lung tumor. Subsequent postoperative pathology revealed pulmonary adenocarcinoma coexisting with PPC. However, 2 months later, distant metastases were detected during a follow-up examination. The patient encountered difficulty in tolerating the adverse effects of chemotherapy, prompting the initiation of PD-1 inhibitor treatment. Notably, both patients underwent one cycle of PD-1 inhibitor therapy without encountering significant adverse reactions, and their responses proved to be promising during re-examinations. These findings suggest that surgery combined with immunotherapy PD-1 inhibitor therapy may represent an effective approach for the treatment of PPC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Pulmão/patologia , Antígeno B7-H1/metabolismo
13.
Thorac Cancer ; 14(20): 1932-1940, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37246469

RESUMO

BACKGROUND: The aim of the study was to investigate differences in HLA-I alleles between lung adenocarcinoma patients and healthy controls and determine their association with PD-L1 expression and tumor mutational burden (TMB) to understand the mechanism underlying lung adenocarcinoma susceptibility. METHODS: Differences in HLA allele frequencies between the two groups were analyzed in a case-control study. PD-L1 expression and TMB in lung adenocarcinoma patients were determined and their relationships with HLA-I were analyzed. RESULTS: The lung adenocarcinoma group showed significantly higher HLA-A*30:01 (p = 0.0067, odds ratio [OR], 1.834; 95% confidence interval [CI]: 1.176-2.860), B*13:02 (p = 0.0050, OR, 1.855; 95% CI: 1.217-2.829), and C*06:02 (p = 0.0260, OR, 1.478; 95% CI: 1.060-2.060) and significantly lower B*51:01 (p = 0.0290, OR, 0.6019; 95% CI: 0.3827-0.9467), and C*14:02 (p = 0.0255, OR, 0.5089; 95% CI: 0.2781-0.9312) than the control group. Haplotype analysis results showed that HLA-A*30:01-B*13:02 (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085), A*11:01-C*01:02 (p = 0.0056, OR, 1.909; 95% CI: 1.182-3.085), A*30:01-C*06:02 (p = 0.0111, OR, 1.846; 95% CI: 1.147-2.969), and B*13:02-C*06:02 (p = 0.0067, OR, 1.846; 95% CI: 1.147-2.969) frequencies significantly increased and B*51:01-C*14:02 (p = 0.0219, OR, 0.490; 95% CI: 0.263-0.914) frequency significantly decreased in lung adenocarcinoma patients. Three-locus haplotype analysis showed that HLA-A*30:01-B*13:02-C*06:02 frequency (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085) significantly increased in patients. CONCLUSION: HLA-A*30:01, B*13:02, and C*06:02 may be the susceptibility genes and HLA-B*51:01 and C*14:01 act as the resistance genes of lung adenocarcinoma. The changes in HLA-I allele frequencies had no association with PD-L1 expression and TMB among these patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Antígenos HLA-A , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Alelos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Antígenos HLA-A/genética , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Mutação
14.
Small Methods ; 7(5): e2201086, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36446639

RESUMO

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with >30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ferritinas/uso terapêutico , Morte Celular Imunogênica , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Imunoterapia
15.
J Cardiothorac Surg ; 17(1): 329, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36539826

RESUMO

BACKGROUND: Surgical resection is the most effective curative management of benign rib tumors and carries an excellent prognosis. Due to complex anatomy and narrow field, higher rib resection is technically demanding and requires extensive dissection. CASE PRESENTATION: We report a case of second rib tumor resection performed transthoracic under Da Vinci robot assistance. A 32-year-old male complained about increasing pain in the left anterior chest wall. After 3D reconstruction of CT, it showed a well-circumscribed fusiform lesion with a multi-component structure. Measured 17 × 6 × 4 cm and extended into the chest cavity to the depth below the pectoralis minor muscle. The patient underwent robotic-assisted trans-thoracic second rib resection. At four weeks of outpatient follow-up, the patient reported no pain and uncomplicated wound healing. CONCLUSION: This minimally invasive approach offers optimal visualization and tissue manipulation while dramatically decreasing the possibility of collateral damage, hence ensuring fast function recovery. To the best of our knowledge, these kinds of procedures are rarely reported in detail.


Assuntos
Neoplasias , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Torácicos , Masculino , Humanos , Adulto , Procedimentos Cirúrgicos Robóticos/métodos , Prognóstico , Costelas/cirurgia
16.
Tissue Cell ; 76: 101750, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35182988

RESUMO

Kinesin family member 26B (KIF26B) is reported differently expressed in multiple neoplasms and exerts a pivotal role in carcinogenesis. To date, the relationship between KIF26B and non-small cell lung cancer (NSCLC) is unaddressed. This study explored the possible roles and mechanisms of KIF26B in NSCLC. We observed high levels of KIF26B in NSCLC, and demonstrated that high KIF26B levels predicted an overall shorter duration of survival. Functional experiments demonstrated that restraint of KIF26B by gene knockdown exhibited remarkable tumor-suppressive effects in NSCLC in vitro, including repression of cell proliferation, induction of G0/G1 cell cycle arrest, suppression of cell invasion and epithelial-mesenchymal transition, and enhancement of chemotherapeutic sensitivity. The study further revealed that inhibition of KIF26B was able to affect the activation of ß-catenin via regulation of the AKT/GSK-3ß axis. Moreover, forced expression of ß-catenin could reverse KIF26B-silencing-evoked tumor-suppressive effects. Importantly, NSCLC cells with KIF26B silencing exhibited decreased growth potential in nude mice in vivo. Collectively, our data indicate that restraint of KIF26B has a tumor-suppressive role in NSCLC by affecting the AKT/GSK-3ß/ß-catenin pathway. This work unveils a pivotal role of KIF26B in NSCLC and suggests it as a viable target for anti-NSCLC therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares/genética , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
17.
J Cardiothorac Surg ; 17(1): 281, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333814

RESUMO

BACKGROUND: Thoracoscopic segmentectomy is a common surgical procedure in thoracic surgery today. However, identifying the intersegmental plane is difficult in the surgical process. Therefore, we evaluated the feasibility of the arterial ligation method for determining the intersegmental plane and compared the demarcation status with the intravenous indocyanine green (ICG). METHODS: We retrospectively reviewed the records of 35 patients with peripheral small lung nodules who underwent thoracoscopic segmentectomy between May and December 2020. First, the preoperative three-dimensional reconstruction was performed to distinguish the location of lung nodules and the anatomical structures of targeted segmental arteries, veins, and bronchi. Second, the targeted segmental arteries were ligated, and the intersegmental plane was determined by the inflation-deflation technique. The waiting time for the appearance of the inflation-deflation line was recorded. Thirdly, the intersegmental plane was identified again using the ICG fluorescence method. Finally, the consistency of the two intersegmental planes was evaluated. RESULTS: The intersegmental planes were successfully observed in all patients using the arterial ligation method. Thirty-four patients underwent segmentectomy as planned, and one patient finally underwent lobectomy due to insufficient surgical margin. The waiting time for the appearance of the intersegmental plane by arterial ligation method was 13.7 ± 3.2 min (6-19 min). The intersegmental planes determined by the arterial ligation method and the ICG fluorescence method were comparable, with a maximum distance of no more than 5 mm between the two planes. The mean operative duration was 119.1 ± 34.9 min, and the mean blood loss was 76.9 ± 70.3 ml. No evident air leakage was found during the operation. Only one patient experienced a prolonged air leak (≥ 5 days) during the postoperative recovery. No atelectasis occurred in all cases. The chest tube duration was 3.1 ± 0.9 days. CONCLUSION: The arterial ligation method can efficiently and accurately identify the intersegmental plane, comparable to the ICG fluorescence method.


Assuntos
Neoplasias Pulmonares , Pneumonectomia , Humanos , Pneumonectomia/métodos , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Verde de Indocianina , Tubos Torácicos
18.
Acta Pharmacol Sin ; 32(4): 528-36, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21468086

RESUMO

AIM: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). METHODS: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. RESULTS: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. CONCLUSION: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.


Assuntos
Neoplasias Esofágicas/genética , Inativação Gênica , Proteínas de Homeodomínio/genética , Espécies Reativas de Oxigênio/metabolismo , Animais , Sequência de Bases , Primers do DNA , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Radiação Ionizante
19.
J Int Med Res ; 49(12): 3000605211061045, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34871528

RESUMO

OBJECTIVE: To investigate the relationship between glutathione S-transferase enzyme (GSTM1, T1, and P1) genetic variants and semen quality in men with idiopathic infertility. METHODS: Sperm characteristics were measured using computer-assisted sperm analysis. The malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC) activities were detected by spectroscopic analysis, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was detected by enzyme-linked immunosorbent assay. RESULTS: This study included 246 idiopathic infertile men and 117 controls. The GSTM1(-), T1(-), and M1/T1(-/-) genotype frequencies significantly differed between the groups. The GSTM1(-) and T1(-) genotypes in idiopathic infertile men negatively correlated with sperm concentration, motility, mitochondrial membrane potential, and other parameters. However, these genotypes positively correlated with the amplitude of the lateral head displacement and NO and 8-OHdG levels. The GSTT1(-) genotype positively correlated with mean angular displacement and MDA activity. GSTM1(-) and T1(-) had a synergistic effect on semen quality. Sperm motility, normal morphology, straightness, and TAC were lower and amplitude of lateral head displacement and MDA were higher in the GSTP1(A/G + G/G) group than in the GSTP1(A/A) group among men with idiopathic infertility. CONCLUSIONS: GSTM1, T1, and P1 genetic variants may be risk factors for infertility by affecting the semen quality men with idiopathic oligoasthenospermia.


Assuntos
Infertilidade Masculina , Análise do Sêmen , Estudos de Casos e Controles , Glutationa S-Transferase pi , Glutationa Transferase/genética , Humanos , Infertilidade Masculina/genética , Masculino , Polimorfismo Genético , Motilidade dos Espermatozoides/genética
20.
Acta Pharmacol Sin ; 31(3): 361-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20154714

RESUMO

AIM: To investigate the effects of small interfering RNA (siRNA) knockdown of forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human hepatocellular carcinoma MHCC-97H cells in vitro. METHODS: The expression levels of FoxM1 in human hepatocellular carcinoma samples, adjacent non-hepatocellular carcinoma liver samples and MHCC-97 cell lines were detected by RT-PCR and Western blotting. FoxM1 siRNA was transfected into MHCC-97H cells with Lipofectamine 2000. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle analysis was performed by flow cytometry. Protein expression levels were evaluated by Western blotting. Anchorage-independent growth and the invasive potency of MHCC-97H cells were measured by soft agar colony formation and a transwell cell invasion assay, respectively. RESULTS: FoxM1 was over-expressed in hepatocellular carcinoma samples compared to adjacent non-hepatocellular carcinoma liver samples. FoxM1 siRNA was successfully transfected into MHCC-97H cells, resulting in the significant inhibition of FoxM1 mRNA and protein expression. Down-regulation of FoxM1 inhibited cell proliferation, caused cell cycle arrest, and decreased invasion of MHCC-97H cells. Compared with control and mock groups, the FoxM1 siRNA transfected cells showed decreased protein expressions of cyclin B1 and cyclin D1, whereas p27 protein expression was increased. Down-regulation of FoxM1 reduced the expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA). CONCLUSION: FoxM1 is functionally involved in hepatocellular carcinoma cell proliferation and invasion and is a potential target for hepatocellular carcinoma therapy.


Assuntos
Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Proliferação de Células , Fatores de Transcrição Forkhead/genética , Neoplasias Hepáticas/metabolismo , RNA Interferente Pequeno/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/genética
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