Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Cancer Res Ther ; 20(2): 695-705, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687942

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) are intimately involved in cancer radiochemotherapy resistance. However, the mechanism by which macrophages affect radiosensitivity through autophagy remains unclear. The purpose of our study was to investigate how activating autophagy in type-II macrophages (M2) by using rapamycin (RAP) would affect the radiosensitivity of colorectal cancer (CRC) xenografts. MATERIALS AND METHODS: A nude mouse CRC model was established by injecting LoVo CRC cells. After tumor formation, supernatant from M2 cells (autophagy-unactivated), autophagy-activated M2 cells, or autophagy-downregulated M2 cells was injected peritumorally. All tumor-bearing mice were irradiated with 8-Gy X-rays twice, and the radiosensitivity of CRC xenografts was analyzed in each group. RESULTS: The mass, volume, and microvessel density (MVD) of tumors in the autophagy-unactivated M2 group significantly increased; however, supernatant from M2 cells that were autophagy-activated by rapamycin significantly decreased tumor weight, volume, and MVD compared with negative control. Combining bafilomycin A1 (BAF-A1) with RAP treatment restored the ability of the M2 supernatant to increase tumor mass, volume, and MVD. Immunohistochemical and Western blot results showed that compared with the negative control group, supernatant from M2 cells that were not activated by autophagy downregulated the expression of Livin and Survivin in tumor tissues; activation of M2 autophagy further downregulated the protein levels. CONCLUSIONS: Therefore, autophagy-activated M2 supernatant can downregulate the expression of the antiapoptotic genes Livin and Survivin in CRC xenografts, improving the radiosensitivity of CRC by inducing apoptosis in combination with radiotherapy and inhibiting the growth of transplanted tumors.


Assuntos
Autofagia , Neoplasias Colorretais , Camundongos Nus , Tolerância a Radiação , Sirolimo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/metabolismo , Camundongos , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Humanos , Tolerância a Radiação/efeitos dos fármacos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos da radiação , Survivina/metabolismo , Survivina/genética , Camundongos Endogâmicos BALB C , Masculino
2.
Cancer Sci ; 115(4): 1141-1153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287724

RESUMO

The indigenous microbial milieu within tumorous tissues exerts a pivotal influence on the genesis and advancement of gastric cancer (GC). This investigation scrutinizes the functions and molecular mechanisms attributed to Prevotella intermedia in the malignant evolution of GC. Isolation of P. intermedia from paired GC tissues was undertaken. Quantification of P. intermedia abundance in 102 tissues was accomplished using quantitative real-time PCR (qRT-PCR). Assessment of the biological effects of P. intermedia on GC cells was observed using culture medium supernatant. Furthermore, the protein profile of GC cells treated with tumor-derived P. intermedia was examined through label-free protein analysis. The functionality of perilipin 3 (PLIN3) was subsequently confirmed using shRNA. Our investigation revealed that the relative abundance of P. intermedia in tumor tissues significantly surpassed that of corresponding healthy tissues. The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042). The supernatant derived from tumor-associated P. intermedia bolstered the proliferation, clone formation, migration, and invasion of GC cells. After indirect co-cultivation with tumor-derived P. intermedia, dysregulation of 34 proteins, including PLIN3, was discerned in GC cells. Knockdown of PLIN3 mitigated the malignancy instigated by P. intermedia in GC cells. Our findings posit that P. intermedia from the tumor microenvironment plays a substantial role in the malignant progression of GC via the modulation of PLIN3 expression. Moreover, the relative abundance of P. intermedia might serve as a potential biomarker for the diagnosis and prognosis of GC.


Assuntos
Neoplasias Gástricas , Humanos , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Perilipina-3 , Prevotella intermedia , Prognóstico , Neoplasias Gástricas/patologia , Microambiente Tumoral
3.
Heliyon ; 9(10): e20649, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37829805

RESUMO

There is no precise diagnosis or prognosis for liver cancer (LC) using a single biomarker. Circular RNAs (circRNAs) contribute to the pathogenesis of different cancers, but their role in LC is not entirely understood. In this study, circUSP10, an aberrantly expressed circRNA in LC, was screened using the Gene Expression Omnibus database, and its tissue-specific expression was verified using qRT-PCR. In vitro, functional assays and nude mouse tumorigenesis models were used to investigate circUSP10 role in LC. RNA immunoprecipitation and dual-luciferase reporter assays were performed to study the mechanistic relationship between circUSP10, miR-211-5p, and transcription factor 12 (TCF12). We found that circUSP10 expression was upregulated in LC tissues and cells. CircUSP10 expression was linked to tumor size and tumor node metastasis stage and negatively correlated with LC prognosis. In vitro assays confirmed circUSP10-mediated proliferation, migration, and invasion of LC cells and their association with the epithelial-mesenchymal transition (EMT) pathway. Mechanistically, circUSP10 adsorbed miR-211-5p, which regulated TCF12 and promoted tumorigenesis via the EMT signaling pathway. Therefore, our results suggest that circUSP10 may promote LC progression by modulating the miR-211-5p/TCF12/EMT signaling cascade and may serve as a potential biomarker for LC diagnosis and prognosis.

4.
Theranostics ; 13(13): 4574-4600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37649598

RESUMO

Background: Studies have shown that the expression of histone deacetylases (HDACs) is significantly related to the tumor microenvironment (TME) in gastric cancer. However, the expression of a single molecule or several molecules does not accurately reflect the TME characteristics or guide immunotherapy in gastric cancer. Methods: We constructed an HDAC score (HDS) based on the expression level of HDACs. The single-cell transcriptome was used to analyze the underlying factors contributing to differences in immune infiltration between patients with a high and low HDS. In vitro and in vivo experiments validated the strategy of transforming cold tumors into hot tumors to guide immunotherapy. Results: According to the expression characteristics of HDACs, we constructed an HDS model to characterize the TME. We found that patients with a high HDS had stronger immunogenicity and could benefit more from immunotherapy than those with a low score. The AUC value of the HDS combined with the combined positive score (CPS)for predicting the efficacy of immunotherapy was as high as 0.96. By single-cell and paired bulk transcriptome sequencing analysis, we found that the infiltration levels of CD4+ T cells, CD8+ T cells and NK cells were significantly decreased in the low HDS group, which may be induced by MYH11+ fibroblasts, CD234+ endothelial cells and CCL17+ pDCs via the MIF signaling pathway. Inhibition of the MIF signaling pathway was confirmed to potentially enhance immune infiltration. In addition, our analysis revealed that GPX4 inhibitors might be effective for patients with a low HDS. GPX4 knockout significantly inhibited PD-L1 expression and promoted the infiltration and activation of CD8+ T cells. Conclusion: We constructed an HDS model based on the HDAC expression characteristics of gastric cancer. This model was used to evaluate TME characteristics and predict immunotherapy efficacy. Inhibition of the MIF signaling pathway in the TME and GPX4 expression in tumor cells may be an important strategy for cold tumor synergistic immunotherapy for gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Linfócitos T CD8-Positivos , Células Endoteliais , Microambiente Tumoral , Histona Desacetilases , Imunoterapia
5.
Discov Oncol ; 14(1): 126, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432583

RESUMO

BACKGROUND: Human health and life are threatened by cancer with high morbidity and mortality worldwide. In many experiments, CDKN1B level is associated with cancer risk, Nevertheless, no pan-cancer analysis has been conducted on CDKN1B in human cancers. METHODS: With the help of bioinformatics, a pan-cancer analysis was conducted on the expression levels of CDKN1B in cancer tissues and adjacent tissues from the TCGA, CPTAC and GEO databases. The CDKN1B expression levels in tumor patients was further validated using immunohistochemistry (IHC) and quantitative real-time PCR. RESULTS: In the study, we first investigated the cancer-related roles of CDKN1B's in 40 tumors with malignancy. The CDKN1B gene encodes the p27Kip1 protein, which can block the production cyclin-dependent kinase (CDK), which is obviously related to the function and survival of cancer cells and alters the prognosis of cancer patients. Furthermore, CDKN1B function requires both protein processing and RNA metabolism. Additionally, the elevated expression of the CDKN1B gene and protein was validated in several cancer tissues from the patients. CONCLUSIONS: These results showed that the levels of CDKN1B were considerably different in a number of cancer tissues, offering a potential future target for cancer therapy.

7.
Br J Cancer ; 129(1): 24-37, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37117649

RESUMO

In recent years, the tumour microenvironment (TME) of solid tumours has attracted more and more attention from researchers, especially those non-tumour components such as immune cells. Infiltration of various immune cells causes tumour immune microenvironment (TIME) heterogeneity, and results in different therapeutic effects. Accumulating evidence showed that DNA methylation plays a crucial role in remodelling TIME and is associated with the response towards immune checkpoint inhibitors (ICIs). During carcinogenesis, DNA methylation profoundly changes, specifically, there is a global loss of DNA methylation and increased DNA methylation at the promoters of suppressor genes. Immune cell differentiation is disturbed, and exclusion of immune cells from the TME occurs at least in part due to DNA methylation reprogramming. Therefore, pharmaceutical interventions targeting DNA methylation are promising. DNA methyltransferase inhibitors (DNMTis) enhance antitumor immunity by inducing transcription of transposable elements and consequent viral mimicry. DNMTis upregulate the expression of tumour antigens, mediate immune cells recruitment and reactivate exhausted immune cells. In preclinical studies, DNMTis have shown synergistic effect when combined with immunotherapies, suggesting new strategies to treat refractory solid tumours.


Assuntos
Metilação de DNA , Neoplasias , Humanos , Microambiente Tumoral/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Imunoterapia/métodos , Antígenos de Neoplasias
8.
Cancers (Basel) ; 14(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36230535

RESUMO

Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer.

9.
BMC Surg ; 22(1): 214, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658940

RESUMO

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is defined as acute intestinal ischemia because of decreased blood flow in mesenteric vessels. Only a few cases of NOMI that occur secondary to aortic dissection (AD) have been reported, resulting in the lack of sufficient knowledge of diagnosis and treatment. CASE PRESENTATION: We aimed to report a case of NOMI caused by type B Aortic Dissection. A 26-year-old male patient was transferred to our hospital with the diagnose of NOMI and aortic dissection in April 2018. The abdominal computed tomography (CT) assists the diagnosis of paralytic intestinal obstruction, intestinal wall pneumatosis, and perforation. Emergency laparotomy revealed that the bowel wall supplied by the superior mesenteric artery (SMA) was pale with the palpable but weak pulsation of the parietal artery. The small intestine was extremely dilated with a paper-thin, fragile wall that was ruptured easily and could not be sutured. In this case, extensive resection and segmental drainage were done. Postoperatively, the digestive tract was reconstructed. However, the patient suffered from iron deficiency anemia and short bowel syndrome eight months later, and unfortunately died from long-term complications. CONCLUSION: Aortic dissection leads to continuous decrease in blood pressure and blood flow to the SMA, considering as a predisposing factor for NOMI. During the treatment, extensive resection and segmental drainage are the optimal surgical strategy, which can make benefit in emergencies especially.


Assuntos
Dissecção Aórtica , Isquemia Mesentérica , Adulto , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/diagnóstico por imagem , Humanos , Intestino Delgado/cirurgia , Intestinos , Isquemia/etiologia , Isquemia/cirurgia , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/cirurgia , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/etiologia
10.
Front Microbiol ; 13: 817494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464966

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKP) is an evolving infectious pathogen associated with high mortality. The convergence of hypervirulence and multidrug resistance further challenges the clinical treatment options for K. pneumoniae infections. The QseBC two-component system (TCS) is a component of quorum-sensing regulatory cascade and functions as a global regulator of biofilm growth, bacterial motility, and virulence in Escherichia coli. However, the functional mechanisms of QseBC in hvKP have not been reported, and we aim to examine the role of QseBC in regulating virulence in hvKP strain ATCC43816. The CRISPR-Cas9 system was used to construct qseB, qseC, and qseBC knockout in ATCC43816. No significant alterations in the growth and antibiotic susceptibility were detected between wild-type and mutants. The deletion of qseC led to an increase of biofilm formation, resistance to serum killing, and high mortality in the G. mellonella model. RNAseq differential gene expression analysis exhibited that gene-associated biofilm formation (glgC, glgP, glgA, gcvA, bcsA, ydaM, paaF, ptsG), bacterial type VI secretion system (virB4, virB6, virB10, vgrG, hcp), and biosynthesis of siderophore (entC, entD, entE) were significantly upregulated in comparison with the wild-type control. In addition, qseB, ygiW (encode OB-family protein), and AraC family transcriptional regulator IT767_23090 genes showed highest expressions in the absence of QseC, which might be related to increased virulence. The study provided new insights into the functional importance of QseBC in regulating the virulence of hvKP.

11.
Cancer Lett ; 527: 115-126, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-34952144

RESUMO

Standard treatment of colorectal cancer (CRC) improves the prognosis of CRC patients, but it is still intractable to control the progression of metastatic CRC. Immune microenvironment and immunotherapies of CRC have received extensive attention in recent years, but present immunotherapies of CRC have mainly focused on T cells and therapeutic response is only observed in a small proportion of patients. Innate immune cells are the first-line of defense in the development of malignancies. Natural killer (NK) cells, NKT cells and γδT cells are three types of innate cells of lymphoid origin and show cytotoxicity against various tumor cells including CRC. Besides, in the development of CRC, they can also be inhibited or express regulatory type, promoting tumor progression. Researches about anti-tumorigenic and pro-tumorigenic mechanisms of these cells are ongoing and regulation of these cells is also being unearthed. Meanwhile, immunotherapies using these cells more or less have shown efficacy in animal models and some of them are under exploration in clinical trials. This review provides an overview of intrinsic properties of NK cell, NKT cell and γδT cell, and summarizes current related promising treatment strategies.


Assuntos
Neoplasias Colorretais/imunologia , Imunidade Inata/imunologia , Células Matadoras Naturais/imunologia , Humanos
12.
Radiol Case Rep ; 16(8): 2103-2107, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34158903

RESUMO

Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.

13.
J BUON ; 26(1): 109-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33721440

RESUMO

PURPOSE: Cell-free DNA (cfDNA) in plasma is a useful resource for liquid biopsy. The concentration and integrity of cfDNA may be clinical informative for detecting and predicting cancer progression. METHODS: Plasma from 40 healthy controls and 90 colorectal cancer patients was assessed. qPCR targeting the arithmetic-logic unit (Alu) repeats were performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated by the ratio of the long to the short fragments of amplified Alu repeats. RESULTS: cfDNA concentration was significantly higher in the patients than that in healthy controls. Patients with stage III colorectal cancer showed no significant difference in their cfDNA levels as compared with the healthy controls. In colorectal cancer, cfDNA level of stage IV patients was higher than that of stage 0-III (p=0.049). The DNA integrity was significantly lower in patients with stage I and II cancer than that in normal controls (p=0.007, 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with colorectal cancer from normal controls had an area under the curve of 0.672 (95%CI, 0.572 to 0.772) and cfDNA concentration increased within 21 days following surgery and dropped by 3 months after surgery. CONCLUSION: Concentration of cfDNA is a promising molecular marker for assessing colorectal cancer progression. Both the cfDNA concentration and its integrity are highly variable. Some cancer stage dependent changes were observed, which warrants further investigation with more patients included.


Assuntos
Ácidos Nucleicos Livres/metabolismo , Neoplasias Colorretais/genética , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias
14.
Oncol Res ; 27(7): 779-788, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30841957

RESUMO

The aim of this study was to investigate the underlying mechanisms that transforming growth factor-ß (TGF-ß)-mediated epithelial-to-mesenchymal transition (EMT) in tumor cells contributes to 5-FU resistance. A series of experiments involving cell viability and caspase activity analyses, siRNA transfection, RNA isolation, and quantitative-PCR (qPCR) assay, cell migration analysis, Western blotting analysis of total protein and membrane protein were performed in this study. Mouse xenograft model was used to determine the effect of the PAR2 inhibitor in vivo. In this study, we found that protease-activated receptor 2 (PAR2) induction in 5-FU therapy is correlated with TGF-ß-mediated EMT and apoptosis resistance. PAR2 and TGF-ß were both activated in response to 5-FU treatment in vivo and in vitro, and whereas TGF-ß inhibition sensitized CRC cells to 5-FU and suppressed cell migration, PAR2 activation eliminated the effect of TGF-ß inhibition. Conversely, siRNA-mediated PAR2 depletion or PAR2 inhibition with a specific inhibitor produced a similar phenotype as TGF-ß signal inhibition: 5-FU sensitization and cell migration suppression. Moreover, the results of xenograft experiments indicated that the PAR2 inhibitor can enhance cell killing by 5-FU in vivo and suppress EMT signaling. Our results reveal that the TGF-ß effects require the coordinating action of PAR2, suggesting that PAR2 inhibition could be a new therapeutic strategy to combat 5-FU resistance in CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/farmacologia , Receptor PAR-2/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Fluoruracila/administração & dosagem , Células HCT116 , Células HT29 , Humanos , Camundongos , Piperazinas/administração & dosagem , Piperazinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transfecção , Fator de Crescimento Transformador beta/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Am J Transl Res ; 10(8): 2706-2711, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210707

RESUMO

AIM: The contribution of long non-coding RNAs (lncRNAs) to gastric cancer associated with Helicobacter pylori (H. pylori) infection remains largely unknown. Therefore, the present study aimed to investigate the expression of a lncRNA NR_026827 in gastric epithelial cells infected with H. pylori, and demonstrate its expression characteristic in gastric cancer. MATERIALS AND METHODS: Gastric epithelial cell line cells, GES-1, were cultured and infected with H. pylori. A microarray was used to analyze the lncRNA profile of gastric epithelial cells. Eighty fresh gastric cancer tissues and the paired adjacent non-cancerous tissue samples were randomly selected from patients. The expression of the lncRNA NR_026827 was investigated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The expression of several lncRNAs was significantly altered in GES-1 cells following infection with H. pylori. Of these lncRNAs, NR_026827 was dramatically down-regulated in GES-1 cells infected with H. pylori. In addition, the expression of NR_026827 was decreased in gastric cancer tissues in comparison to the corresponding adjacent non-cancerous tissues. Moreover, the expression of NR_026827 did not change significantly in different gastric cancer stages. CONCLUSION: The lncRNA, NR_026827, is down-regulated in all stages of gastric cancer associated with H. pylori infection and could represent a potential biomarker for the diagnosis of gastric cancer.

16.
PLoS One ; 12(5): e0176501, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28467448

RESUMO

Polydatin (PD), a component isolated from Polygonum cuspidatum, has a number of biological functions. However, the antitumor activity of PD has been poorly investigated. In this study, the effect of PD on cell proliferation was evaluated by thiazolyl blue tetrazolium bromide assay. Cell cycle distribution and apoptosis were investigated by flow cytometry. The phosphorylation levels of panel of phosphor-kinases were detected by human phospho-kinase arrays. The expression of several proteins associated with cell cycle and apoptosis were analyzed by Western blot analysis. Results showed that PD effectively inhibited the growth of MDA-MB-231 and MCF-7 breast cancer cell lines. Cell cycle analysis demonstrated that PD induced S-phase cell cycle arrest. Human phosphor-kinase arrays showed that the phosphorylation level of cAMP response element-bingding proteins(Creb) was down-regulated, and the results were further confirmed by Western blot analysis. Western blot analysis showed that the expression of protein of cyclin D1 decreased in a time- and dose- dependent manner. Results suggest that PD is a potential therapeutic natural compound.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glucosídeos/farmacologia , Estilbenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Fosforilação , Fase S/efeitos dos fármacos
17.
Oncotarget ; 8(17): 29370-29382, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28030850

RESUMO

Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.


Assuntos
Enterovirus Humano A/patogenicidade , Doença de Mão, Pé e Boca/genética , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/metabolismo , Humanos , Masculino , Interleucina 22
18.
BMC Cancer ; 16(1): 943, 2016 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-27938352

RESUMO

BACKGROUND: Circulating cell-free DNA (ccf-DNA) in plasma may contain both specific and non-specific of tumor markers. The concentration and integrity of ccf-DNA may be clinical useful for detecting and predicting cancer progression. METHODS: Plasma samples from 40 healthy controls and 73 patients with gastric cancers (two stage 0, 17 stage I, 11 stage II, 33 stage III, and 10 stage IV according to American Joint Committee on Cancer stage) were assessed respectively. qPCR targeting the Alu repeats was performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated as a ratio of the long to the short fragments of Alu repeats. RESULTS: Plasma DNA concentration was significantly higher in patients with stage III and IV gastric cancers than in healthy controls (p = 0.028 and 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage III and IV gastric cancers from healthy controls had an area under the curve (AUC) of 0.744 (95% CI, 0.64 to 0.85). Circulating cell-free DNA concentration increased within 21 days following surgery and dropped by 3 months after surgery. CONCLUSIONS: Concentration of ccf-DNA is a promising molecular marker for assessing gastric cancer progression. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-DDT-12002848 , 8 October 2012.


Assuntos
DNA/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Adulto , Idoso , Estudos de Casos e Controles , DNA/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/cirurgia , Reação em Cadeia da Polimerase , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
19.
Oncol Rep ; 34(5): 2365-74, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26352729

RESUMO

Interleukin-17A-producing T cells (IL-17A+ T) (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ γδT17 cells) and associated cytokines (IL-17A, IL-23 and IL-1ß) play crucial roles in inflammation-associated diseases, such as infection, autoimmunity and tumors. Th17 cells promote human gastric cancer (GC), although the source of intracellular IL­17A and the roles of Tc17 and γδT17 cells remain poorly understood. In this study, the frequencies of circulating Th17 and γδT17 cells in patients with GC were found to be significantly increased compared to those in healthy donors; however, Tc17 cells were decreased in these patients, and a negative relationship was found between the frequencies of Th17 and Tc17 cells. Moreover, the cytokine IL­17A was found to be produced mainly by Th17 cells in human peripheral blood. Similarly, serum cytokine levels and relative mRNA expression levels of IL­17A, IL­23 and IL­1ß were significantly increased in patients with GC, and the frequency of Th17 cells was closely associated with serum IL­17A concentrations in patients with GC. Additionally, Th17 cells and associated cytokines were present at significantly different levels during the progression and metastasis of GC, as were Tc17 and γδT17 cells. Taken together, these findings suggest that IL-17A+ T cells and associated cytokines might play crucial roles in human GC progression and metastasis and thus represent potential targets for treatment.


Assuntos
Neoplasias Gástricas/sangue , Células Th17/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Interleucina-17/sangue , Interleucina-17/metabolismo , Interleucina-18/sangue , Subunidade p19 da Interleucina-23/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
20.
Saudi Med J ; 36(2): 159-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25719578

RESUMO

OBJECTIVES: To compare laparoscopic extraperitoneal colostomy with transperitoneal colostomy for construction of a permanent stoma by measuring the incidence of parastomal hernia, and other postoperative complications related to colostomy. METHODS: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China in 2014. A literature search of Medline, EMBASE, Cochrane database, and the Chinese Biomedical Literature Database (CBM) from the years 1990 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text words: extraperitoneal colostomy, transperitoneal colostomy, laparoscopic extraperitoneal colostomy, rectal cancer,  laparoscopic abdominoperineal resection, parastomal hernia, permanent stoma, and colostomy-related complications. Two different reviewers carried out the search and evaluated studies independently. RESULTS: One randomized controlled trial and 6 retrospective studies were included. A total of 378 patients (209 extraperitoneal colostomy and 169 transperitoneal colostomy) were identified. Our analysis showed that there was a significantly lower rate of parastomal hernia (odds ratio 0.10; 95% confidence interval 0.03-0.29, p<0.0001) in the extraperitoneal colostomy group. However, the other stoma-related complications were not significantly different between the 2 groups. CONCLUSION: Colostomy construction via the extraperitoneal route using a laparoscopic approach can largely reduce the incidence of parastomal hernia. Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route should be the first choice after laparoscopic abdominoperineal resection. 


Assuntos
Colo Sigmoide/cirurgia , Laparoscopia/métodos , Peritônio/cirurgia , Estomas Cirúrgicos , Humanos , Laparoscopia/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...