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Math Biosci Eng ; 16(6): 7375-7383, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31698617


The heparan sulfate proteoglycan agrin is known to accumulate in the context of hepatocellular carcinoma (HCC). Agrin is important for neoangiogenesis in HCC tissues, and is incorporated into newly formed vasculature, but exactly how agrin contributes to the pathology of HCC remains to be fully defined. We therefore examined the clinical relevance of agrin as it pertains to HCC progression and prognosis using tissue sections from a total of 313 HCC patients. We found that agrin expression was detectable in more HCC samples (25.4% vs. 77.1%; P < 0.05) compared to normal tissue controls. Agrin expression was notably linked to tumor size (P = 0.041) and metastasis (P = 0.034). The recurrence free survival rate of agrin-positive HCC patients was considerably lower than that of agrin-negative patients (P = 0.001). We further confirmed HCC survival to be independently correlated with tumor size, metastasis, microvascular invasion and edmondson Grade via a Cox regression analysis. Upregulation of Agrin may play a crucial role in HCC progression. Together our results suggest that Agrin has the potential to be used as a prognostic indicator in predicting HCC patient outcomes.

Oncol Lett ; 14(5): 5652-5656, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29142609


Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2'-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively. The expression of drug resistance-associated proteins, including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), and autophagy-associated proteins, including beclin 1, nucleoporin 62 (p62) and autophagy protein 5 (ATG5) were detected with western blotting. Treatment with 5-Aza-CdR significantly promoted the MMC chemosensitivity of T24 cells. The proliferation of T24 cells was significantly inhibited with increasing 5-Aza-CdR concentration, whereas apoptosis was significantly increased. This was associated with the decreased expression of P-gp, MRP1, beclin 1, p62 and ATG5. In conclusion, 5-Aza-CdR enhanced MMC chemosensitivity in bladder cancer T24 cells, which may be caused by the suppression of drug resistance- and autophagy-associated proteins.

J Nanobiotechnology ; 13: 67, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26452535


BACKGROUND: Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability. RESULTS: This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing. CONCLUSION: GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.

Receptor de Asialoglicoproteína/metabolismo , Carcinoma Hepatocelular/radioterapia , Galactose/uso terapêutico , Ouro/uso terapêutico , Neoplasias Hepáticas/radioterapia , Nanopartículas Metálicas/uso terapêutico , Polietilenoglicóis/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Sistemas de Liberação de Medicamentos , Galactose/metabolismo , Ouro/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos da radiação , Tamanho da Partícula , Polietilenoglicóis/metabolismo
Tumour Biol ; 36(2): 877-83, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25304156


The aims of this study are to analyze the association of microRNA-141 (miR-141) with the clinicopathological parameters of bladder cancer and evaluate the value of miR-141 in predicting the prognosis of bladder cancer. In this study, 114 patients with bladder cancer were enrolled in the study, and tissue specimens were obtained from the tumor zone and from adjacent normal area. miR-141 expression was determined using SYRB Green quantitative real-time polymerase chain reaction assay and was further correlated with patients' clinicopathological parameters and the follow-up data. The results indicated that miR-141 was upregulated in malignant bladder specimens compared with normal ones (P < 0.001). miR-141 expression was significantly associated with tumor stage (P < 0.001), tumor grade (P < 0.001), and muscle invasion status (P < 0.001). Log-rank test showed that the higher miR-141 expression was associated with longer disease-specific survival of the patients with bladder cancer (P < 0.001), which was also proven by univariate and multivariate Cox regression analysis (P < 0.001 and P = 0.039, respectively). Focusing on patients with non-muscle invasive bladder cancer, univariate analysis using log-rank test and Cox regression analysis found that patients with high miR-141 expression experienced longer disease-free survival (P = 0.031 and P = 0.040, respectively) and disease-specific survival (P = 0.028 and P = 0.038, respectively), which was confirmed by multivariate Cox regression analysis (P = 0.036 and P = 0.042, respectively). In conclusion, this study showed that miR-141 may contribute to the progression of bladder cancer and its upregulation may be independently associated with favorable prognosis of bladder cancer, suggesting that miR-141 might serve as a promising biological marker for further risk stratification in the management of bladder cancer.

Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Prognóstico , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
Asian Pac J Cancer Prev ; 15(7): 3045-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24815445


Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.

Carcinoma de Células Renais/genética , Fatores de Crescimento Endotelial/genética , Neoplasias Renais/genética , Neovascularização Patológica/genética , RNA Interferente Pequeno/administração & dosagem , Inibidores da Angiogênese/genética , Animais , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Fatores de Crescimento Endotelial/biossíntese , Receptores ErbB/antagonistas & inibidores , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Gefitinibe , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto