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1.
Cancer Sci ; 110(1): 458-467, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30407690

RESUMO

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteína NEDD8/genética , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína NEDD8/metabolismo , Invasividade Neoplásica , Prognóstico , Interferência de RNA , Terapêutica com RNAi/métodos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
World J Urol ; 37(9): 1889-1897, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30535713

RESUMO

BACKGROUND: Bladder cancer is the most common malignancy of urinary system with high morbidity and mortality. In general, the development and progression of bladder cancer are complicated pathological processes, and the treatment methods mainly include surgical resection, radiotherapy, chemotherapy, and combined therapy. In recent years, targeted therapy has made progress in the treatment of bladder cancer. Therefore, to improve survival rates of patients with advanced bladder cancer, novel therapeutic targets are still urgently needed. METHODS AND RESULTS: In this study, we found that RAB38 expressed in tumor tissues of patients with bladder cancer was linked to clinical features including pTNM stage and tumor recurrence, and positively correlated with the poor prognosis of bladder cancer. Notably, further results indicated that depletion of RAB38 could significantly inhibit the proliferation and motility of two types of human bladder cancer cells, T24 and 5637 cells. In addition, RAB38 ablation obviously blocked tumor growth and development in mice compared with control. CONCLUSION: In conclusion, this study provides significant evidence that RAB38 promotes the development of bladder cancer and provides a novel therapeutic target of bladder cancer.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias da Bexiga Urinária/patologia , Proteínas rab de Ligação ao GTP/fisiologia , Animais , Humanos , Camundongos , Células Tumorais Cultivadas
3.
Biomaterials ; 281: 121362, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34998170

RESUMO

Surgery is one of the main effective strategies for the treatment of solid tumors, but high postoperative recurrence is also the main cause of death in current cancer therapy. The prevention of postoperative hepatocellular carcinoma (HCC) recurrence is a clinical problem that needs to be solved urgently. At present, there are still some problems to be solved, such as, how to achieve free drugs to target the site of surgical resection; develop a strategy for the simultaneous administration of multiple drugs to inhibit postoperative recurrence; and provide the appropriate animal model that mimics the process of postoperative HCC recurrence. In this study, we used a facile and reproducible method to successfully prepare amphiphilic Janus nanoparticles (JNPs). In order to improve targeting of the JNPs to residual HCC cells after surgery, we modified the side of gold nanorods (GNRs) with lactobionic acid (LA), thus creating LA-JNPs. This provided an active and targeted co-delivery system for hydrophilic and hydrophobic drugs in separate rooms, thus avoiding mutual effects. Next, we established two models to simulate postoperative HCC recurrence: a subcutaneous postoperative recurrence model based on patient-derived tumor xenograft (PDX) tissues and a postoperative recurrence model of orthotopic HCC. By applying these models, the enhanced permeability and retention effect (EPR) based tumor targeting and LA based active targeting can jointly promote the enrichment and uptake of JNPs at tumor site. LA-JNPs represented an efficient targeting system for the co-delivery of Sorafenib/Doxorubicin with an optimized anti-recurrence effect and significantly improved the survival of mice during treatment for postoperative recurrence.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas Multifuncionais , Nanopartículas , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Camundongos , Nanopartículas/química
4.
Dis Markers ; 2019: 4824902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354888

RESUMO

BACKGROUND: Bladder cancer is a common malignancy with uncontrolled and rapid growth. Although lots of the important regulatory networks in bladder cancer have been found, the cancer-relevant genes remain to be further identified. METHODS: We examined the KIF5A expression levels in bladder cancer and normal bladder tissue samples via immunohistochemistry and observed the effect of KIF5A on bladder tumor cell proliferation in vitro and in vivo. Additionally, a coexpression between KIF5A and KIF20B in tumor tissues was explored. RESULTS: KIF5A expression level was higher in the bladder cancer tissues than in the adjacent nontumor tissues. Patients with higher KIF5A expression displayed advanced clinical features and shorter survival time than those with lower KIF5A expression. Moreover, KIF5A knockdown inhibited bladder cancer cell proliferation, migration, and invasion demonstrated in vivo and in vitro. In addition, coexpression was found between KIF5A and KIF20B in tumor tissues. CONCLUSION: The results demonstrated that KIF5A is a critical regulator in bladder cancer development and progression, as well as a potential target in the treatment of bladder cancer.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/metabolismo , Cinesinas/genética , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Cinesinas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
5.
Onco Targets Ther ; 9: 1175-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27022277

RESUMO

OBJECTIVE: The objective of this article was to summarize the relationship between some components of metabolic syndrome (MetS) and the histopathologic findings in bladder cancer in a Chinese population. METHODS: We retrospectively analyzed data of 323 patients from the Department of Urology, Second Hospital of Tianjin Medical University between January 2012 and January 2014. All the patients were diagnosed with bladder cancer for the first time. Age, height, weight, histologic stage, grade, the presence of hypertension, diabetes mellitus, and body mass index were evaluated. The 2009 American Joint Committee on Cancer TNM staging system was used, with Ta and T1 tumors accepted as lower stage and T2, T3, and T4 tumors as higher stage bladder cancers. Also, pathologists assigned tumor grade according to the 1973 World Health Organization grading system. Noninvasive papillary urothelial neoplasms of low malignant potential were regarded as low grade. Analyses were completed using chi-square tests and logistic regression analysis. RESULTS: Of the 323 patients, 164 had hypertension, 151 had diabetes mellitus, and 213 had a body mass index ≥25 kg/m(2). MetS was significantly associated with histologic grade (P<0.001) and stage (P=0.006) of bladder cancer. Adjusted for age in binary logistic regression analysis, the presence of MetS predicts the risk of higher T stage (odds ratio =4.029, P<0.001) and grade (odds ratio =3.870, P<0.001) of bladder cancer. CONCLUSION: The patients with MetS in the People's Republic of China were found to have statistically significant higher T stage and grade of bladder cancer.

6.
Zhongguo Zhen Jiu ; 29(3): 173-6, 2009 Mar.
Artigo em Zh | MEDLINE | ID: mdl-19358495

RESUMO

OBJECTIVE: To explore the main factors influencing the therapeutic effect of acupuncture on neck pain caused by cervical spondylosis, so as to provide references for further increasing the therapeutic effect of acupuncture. METHODS: One hundred and six cases were randomly divided into an observation group and a control group, 53 cases in each group. The observation group was treated with routine acupuncture at Dazhui (GV 14), Jingbailao (Ex-HN 15) and Jianzhongshu (SI 15); and the control group was treated with sham acupuncture at 1 cm lateral to Bailao (Ex-HN 15) and Jianzhongshu (SI 15). The needles were retained for 20 min in the two groups and infrared radiation was used for adjuvant treatment in this period. Northwick Park Neck Pain Questionnaire (NPQ) was used to assess the patients' quality of life before and after the treatment. The potential influential factors were analyzed by Logistic regression. RESULTS: The effective rate was 75.5% in the observation group and 52.8% in the control group with a significant difference between the two groups (P<0.05). The Logistic regression analysis indicated that the therapeutic effect in the observation group was superior to the control group (OR = 2.670), and both the attack frequency and duration of the neck pain will influence the therapeutic effect (OR = 1.055 and OR = 2.446). CONCLUSION: Acupuncture has a better therapeutic effect on neck pain caused by cervical spondylosis, and patient's clinical history about attack frequency and duration of neck pain are factors influencing clinical therapeutic effect.


Assuntos
Terapia por Acupuntura/estatística & dados numéricos , Cervicalgia/terapia , Espondilose/complicações , Pontos de Acupuntura , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cervicalgia/etiologia , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
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