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1.
Oncol Lett ; 20(6): 337, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33123248

RESUMO

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

2.
Prostate ; 80(12): 977-985, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542727

RESUMO

BACKGROUND: Recently, resveratrol (Res) has been suggested to suppress the migration and invasion of prostate cancer (PCa). In the present study, we aimed to investigate the effects of Res on genomic DNA methylation, as well as the migration and invasion of PCa cells. METHODS: The suppression by Res of the growth of PCa cells was verified through a cytotoxicity assay. In addition, the effects of Res on 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation 1 (TET1) levels were assessed, and the cell migration and invasion were also determined. The expressions of TET1, tissue inhibitor of metalloproteinases (TIMP) 2, TIMP3, MMP2, and MMP9 were detected through Western blot analysis. Afterward, TET1 was silenced using lentiviral short hairpin RNA to examine the effect of TET1 on the Res-triggered inhibition of migration and invasion of PCa cells. RESULTS: Our results showed that Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level. Moreover, Res also inhibited the migration and invasion of PCa cells, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9. The silencing of TET1 in the presence of Res showed that Res could exert its effect through TET1. CONCLUSIONS: Our findings indicated that Res inhibited the migration and invasion of PCa cells via the TET1/TIMP2/TIMP3 pathway, which might potentially serve as a target for the treatment of PCa.


Assuntos
Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Resveratrol/farmacologia , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Oxigenases de Função Mista/biossíntese , Oxigenases de Função Mista/genética , Invasividade Neoplásica , Células PC-3 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Resveratrol/farmacocinética , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-3/biossíntese , Inibidor Tecidual de Metaloproteinase-3/genética , Regulação para Cima
3.
Biomed Pharmacother ; 126: 110059, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32208321

RESUMO

Bladder cancer (BC) ranks as the ninth common human tumor in the world with an increasing incidence. Circular RNAs (circRNAs) have been revealed to exhibit promotive or suppressive impacts on tumor progression of various human cancers, including BC. However, due to the variety of circRNAs, the whole circRNAs network in BC remains unclear. In our study, differentially expressed circRNAs between BC and normal samples in GSE92675 dataset was analyzed by microarray. Circ_102336 was identified to be sharply increased in both BC tissue samples and cell lines, and increased circ_102336 is correlated with a worse overall survival rate of BC patients. Overexpression of circ_102336 dramatically increased the cell proliferation viability of T24 and 5637 cells, while knockdown of circ_102336 exhibited opposite effects. Moreover, circ_102336 knockdown could increase the sensitivity of T24 and 5637 cells to CDDP. In mechanism, circ_102336 was demonstrated to directly bind to and negatively regulate miR-515-5p. Inhibition of miR-515-5p reversed the repressive effects of si-circ_102336 on BC cell proliferation viability. KEGG analysis showed that ATP-binding cassette (ABC) transporters and apoptosis were the major two pathways associated with circ_102336/miR-515-5p axis. therefore, we suggested that circ_102336 indirectly regulate apoptosis and ABC transport pathways through miR-515-5p to finally modulate BC cell proliferation and chemo-resistance.

4.
Cancer Manag Res ; 11: 5365-5374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354345

RESUMO

Background: In recent years, inflammation has become widely recognized as a crucial component in tumor development and progression. Neutrophils are one of the most common inflammatory markers during hematological examinations. The prognostic value of neutrophils in metastatic renal cell carcinoma (mRCC) remains inconsistent. The aim of this meta-analysis is to evaluate the prognostic value of pretreatment neutrophil count in patients with mRCC. Methods: PubMed, Web of Science and Embase were searched for data on the association between pretreatment neutrophil count and mRCC prognosis up to October 7, 2017. We sorted out relevant studies and extracted the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS). Results: A total of 13 studies containing 3,021 patients with mRCC were summarized in the present meta-analysis. An elevated pretreatment neutrophil count yielded a worse OS (HR=2.17, 95% CI=1.68-2.79, P<0.001) and PFS (HR=1.78, 95% CI=0.91-3.49, P<0.001). Furthermore, we performed a subgroup analysis based on cut-off value, ethnicity, treatment method and analysis type. As a result, the association between pretreatment neutrophil count and survival was statistically significant in the subgroups of cut-off value, ethnicity, treatment method and analysis type. Conclusion: Our results show that the pretreatment neutrophil count is associated with mRCC outcomes and can be used as a valuable inflammatory marker for prognosis monitoring.

5.
Cancer Med ; 8(10): 4836-4844, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31274247

RESUMO

High-throughput sequencing methods have facilitated the identification of novel selenoproteins, which exert a vital role in the development and progression of tumor diseases. Recently, Selenoprotein M (SELM) is upregulated in several types of cancer. However, the biological roles of SELM in renal cell carcinoma (RCC) remain unclear. In this paper, quantitative reverse transcription PCR (qRT-PCR) and Western blot were used to measure relative levels of SELM in a cohort of RCC tissues with matched normal tissues as well as human RCC cell lines. SELM expression was found to be upregulated in RCC. High level of SELM was related to poor prognosis of RCC. Furthermore, silence of SELM could inhibit the in vitro proliferative, migratory, and invasive capacities of RCC. In addition, downregulated SELM could impede in vivo tumorigenesis of RCC. SELM could activate the PI3K/Akt/mTOR pathway and mediate expressions of matrix metallopeptidase 2 and 9 (MMP2, MMP9). In conclusion, our study reveals the oncogenic function of SELM in RCC, and SELM may be a therapeutic and prognostic target for RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Selenoproteínas/genética , Selenoproteínas/metabolismo , Transdução de Sinais , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima
6.
Onco Targets Ther ; 12: 3595-3607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190862

RESUMO

Background: miR-106b has been reported to play a vital role in pathogenesis of some types of cancer, whilst the role of miR-106b in renal carcinoma cancer (RCC) remains unknown. Purpose: The objective of this study was to identify the mechanism of miR-106b regulating the progression of renal carcinoma. Method: The expression of miR-106b was analyzed in RCC cell lines, RCC and adjacent normal renal tissues through qRT-PCR assays. Target mRNA of miR-106b was predicted with databases and verified by luciferase reporter assays. And the effects of miR-106b or targeted mRNA on cell proliferation, invasion, the process of epithelial-mesenchymal transitions (EMTs) were assessed in vitrothrough CCK-8, transwell cell invasion assays, qRT-PCR and Western blotting assays respectively. In addition, the effects of miR-106b on the growth of xenografts mice were analyzedin vivo. Results: The results demonstrated that miR-106b was significantly increased both in RCC tissues and cell lines. Luciferase reporter assays revealed that miR-106b inhibited Capicua expression by targeting its 3'-UTR sequence. And miR-106b promoted cell proliferation, invasion, EMT progression in RCC cellin vitro, as well as promoted the tumor growth of 786-O cells derived xenografts mice. Additionally, loss of Capicua promoted the activation of MAPK signaling pathway. Conclusion: The study suggested that miR-106b regulated RCC progression through MAPK signaling pathway partly by targeting Capicua, which might provide valuable evidence for therapeutic target development of RCC.

7.
Cancer Manag Res ; 11: 909-919, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30697081

RESUMO

Purpose: In the present study, we aimed to evaluate the prognostic significance of the systemic inflammation response index (SIRI), which was defined based on peripheral blood counts of neutrophils, lymphocytes, and monocytes, in patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC). Patients and methods: The prognostic value of SIRI was evaluated in a primary cohort consisting of 414 patients with localized or locally advanced CCRCC and then further validated in an independent cohort composed of 168 patients. Results: Kaplan-Meier survival analyses of both cohorts revealed that CCRCC patients with high SIRI levels exhibited poorer overall survival (OS) and cancer-specific survival (CSS) compared with those with low SIRI levels. Furthermore, univariate and multivariate analyses identified SIRI as a significant independent predictor for both OS (HR: 4.853; 95% CI: 2.362-9.972; P<0.001) and CSS (HR: 5.913; 95% CI: 2.681-13.040; P<0.001). Following propensity score matching analysis, SIRI remained an excellent predictor for both OS and CSS. The area under the curve for SIRI was larger than that of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score in both cohorts. Conclusion: SIRI might be a better prognostic predictor than PLR, NLR, MLR, and MSKCC score in patients with localized or locally advanced CCRCC. Institutional review board approval number: (2010) Scientific Research Project No. 39.

8.
Onco Targets Ther ; 12: 119-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30588036

RESUMO

Background: This meta-analysis evaluated the clinicopathologic and prognostic significance of RASSF1A promoter methylation in renal cell carcinoma (RCC). Materials and methods: The ORs or HRs and their 95% CIs were calculated. Trial sequential analysis was conducted. Results: Twenty-two articles that included 1,421 patients with RCC and 724 controls were identified. RASSF1A promoter methylation correlated with RCC in tissue, blood, and urine samples. On multivariate analysis, RASSF1A promoter methylation was associated with tumor grade (grade 3-4 vs 1-2: OR=3.59), clinical stage (stage 3-4 vs 1-2: OR=2.15), T classification (pT2-4 vs pT1: OR=2.66), histologic subtypes (papillary vs clear cell: OR=2.91), and cancer-specific survival (HR=1.78), but it was not linked to age, gender, lymph node status, distant metastasis, or overall survival. The Cancer Genome Atlas data also showed that RASSF1A methylation was significantly more likely to be seen in papillary vs clear-cell RCC (OR=23.19). Conclusion: RASSF1A promoter methylation may be associated with the development and progression of RCC, as well as poor cancer-specific survival. Methylation was more frequent in papillary vs clear-cell RCC. More studies are needed to confirm these findings in blood or urine samples.

9.
Cancer Biomark ; 23(4): 515-525, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30452399

RESUMO

OBJECTIVE: Renal cancer accounts for about 3% of human cancer, and clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Recently, microRNAs (miRNAs) are found to be the biomarkers for cancer diagnosis, prognosis and the targets for tumor management. This study aimed to examine the expression of miR-337-3p in ccRCC and to elucidate the molecular mechanisms underlying miR-337-3p-mediated ccRCC progression. METHODS: The miRNA and mRNA expression levels in ccRCC cells and tissues were measured by qRT-PCR. Cell proliferation, cell adhesion, colony growth and cell invasion were examined by CCK-8 assay, cell adhesion assay, colony formation assay and Transwell invasion assay, respectively. The protein levels were detected by western blot assay. The effects of miR-337-3p on tumor growth in vivo was assessed in a nude mice xenograft model. RESULTS: MiR-337-3p was down-regulated in ccRCC cell lines, and miR-337-3p overexpression suppressed cell proliferation, colony growth and invasion, but enhanced cell adhesion in ccRCC; while knockdown of miR-337-3p exerted the opposite effects on ccRCC. Bioinformatics analysis and luciferase reporter assay showed that Calpain small subunit 1 (Capn4) was negatively regulated by miR-337-3p, and overexpression of miR-337-3p attenuated the miR-337-3p-mediated effects on ccRCC cellular functions. In addition, miR-337-3p also suppressed epithelial-mesenchymal transition in ccRCC. The in vivo tumor growth was markedly suppressed after miR-337-3p overexpression. Data from clinical data showed that down-regulation of miR-337-3p and up-regulation of Capn4 mRNA and protein were identified in the ccRCC tissues, and miR-337-3p expression level was inversely correlated with Capn4 mRNA expression level in ccRCC tissues. CONCLUSIONS: Collectively, these data suggested the tumor suppressive role of miR-337-3p in ccRCC. MiR-337-3p suppressed cell proliferation and metastasis in ccRCC partially via targeting Capn4.


Assuntos
Biomarcadores Tumorais/genética , Calpaína/genética , Carcinoma de Células Renais/genética , MicroRNAs/genética , Animais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Metástase Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Cell Int ; 18: 108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087582

RESUMO

Background: The prognostic significance of galectin-1 (Gal-1) expression in cancerous patients has been assessed for several years while the results remain controversial. Thus, we performed the first comprehensive meta-analysis to evaluate the prognostic value of Gal-1 expression in cancerous patients. Methods: We searched Pubmed, Embase and Web of Science to recruit studies on the prognostic impact of Gal-1 expression in cancerous patients. Eighteen studies containing 2674 patients were involved in this meta-analysis until March 30, 2018. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. Results: The pooled results revealed that high Gal-1 expression in cancer tissue associated with a poor OS (HR = 1.79, 95% CI 1.54-2.08, P < 0.001). In the subgroup of tumor type, it's observed that high Gal-1 expression was significant correlated with poor OS in digestive cancers without heterogeneity (HR = 1.94, 95% CI 1.64-2.30, P < 0.001; fixed-effects model; I2 = 20.1%, P = 0.276). Conclusions: Our present meta-analysis indicates that high Gal-1 expression might be a predictive factor of poor prognosis in cancers, particularly in digestive cancers.

11.
Onco Targets Ther ; 11: 3847-3852, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013365

RESUMO

The growing number of findings demonstrate that nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax domain-containing 3 (NSD3) is amplified and overexpressed in multiple cancer types. Nevertheless, the biological roles of NSD3 in carcinogenesis have not been well understood. In this review, we summarize the current knowledge on the mechanisms underlying NSD3 regulation in different cancers. In addition, NSD3 may serve as a potential druggable target for selective cancer therapy in the future.

12.
Medicine (Baltimore) ; 97(29): e11176, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30024501

RESUMO

BACKGROUND: To compare the transperitoneal approach with extraperitoneal approach in laparoscopic radical prostatectomy (LRP) (including pure and robotic-assisted LRP) using meta-analytic techniques. METHODS: Medline (PubMed), Embase, Ovid, CMB, and Cochrane databases were searched for studies that compared the transperitoneal and extraperitoneal approaches in LRP from January 2000 to January 2017. Outcomes included were operative time, operative bloods joss (milliliters), rate of transfusion, rate of open conversion, rate of intraoperative complications, rate of postoperative complications, and time of postoperative catheterization. RESULTS: Thirteen studies including 1674 patients were selected for the meta-analysis. 850 (50.8%) cases had undergone transperitoneal LRP (TLRP) and 824 (49.2%) cases had undergone the extraperitoneal LRP (ELRP). Comparison of operative time between the TLRP group and the ELRP group showed no significant differences (weighted mean difference [WMD] = 21.21,95%CI = -1.16-43.57, P = .06). No significant differences were observed in blood loss (WMD = -6.04, 95%CI = -43.38-31.29, P = .75) and the rate of transfusion (odds ratio [OR] = 1.03, 95%CI = 0.55-1.96, P = .92) between the 2 groups. No significant differences were observed for the rate of intraoperative complications (OR = 1.25, 95%CI = 0.57-2.21, P = .75) and the rate of open conversion (OR = 1.12, 95%CI = 0.32-4.97, P = .75). Significant differences were observed in the TLRP group compared with the ELRP group (OR = 1.69, 95%CI: 1.23-2.32, P = .001) regarding the rate of postoperative complications. CONCLUSIONS: Our meta-analysis findings revealed that the TLRP group showed no significant differences in most important indicators compared with ELRP. Moreover, TLRP showed higher rate of postoperative complications compared with ELRP.


Assuntos
Laparoscopia/métodos , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Transfusão de Sangue/estatística & dados numéricos , Cateterismo , Humanos , Laparoscopia/efeitos adversos , Masculino , Duração da Cirurgia , Peritônio/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Próstata/patologia , Prostatectomia/efeitos adversos , Reoperação/estatística & dados numéricos
13.
Medicine (Baltimore) ; 97(24): e11023, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29901594

RESUMO

RATIONALE: Renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions is a rare subtype of renal cell carcinoma. This predominantly occurs in juveniles, but rarely seen in adults with lymph node or organic metastasis and a worsened prognosis. PATIENTS CONCERNS: Herein, we presented 3 adult cases of Xp11-RCC. Two patients were in early stage and good condition, and the third patient had lymph node metastasis but showed no recurrence after a 3-month follow-up. DIAGNOSES: Case 1: A 50-year-old female without any lumbago and gross hematuria was incidentally detected by left renal mass by ultrasonography. Case 2: A 31-year-old female with 2-year hemodialysis was detected with right renal carcinoma during preoperative examination of renal transplant. Case 3: A 45-year-old male with right lumbago for 1 month was detected with a mass in the lower pole of right kidney by ultrasonography. INTERVENTION: The characteristics of these 3 images are not consistent with each other, and showed some differences with the previous ones. OUTCOMES: All these 3 patients underwent laparoscopic radical nephrectomy, and case 1 patient underwent renal hilar lymphnode dissection at the same time. Immunohistochemistry was performed on all the 3 tumors, revealing that the tumor cells were positive for TFE3 and Melan-A. Case 1 showed lymph node metastasis, and received mTOR inhibitors. The 3 patients had no recurrent and new metastasis in other organs after follow-up for 3 months, 2 months, and 11 months, respectively. LESSONS: Whether the adult-onset Xp-RCC has an aggressive clinical course still remains controversial. Characteristics of the images of the 3 adult cases showed some uniformity but still have some differences. Immunohistochemistry results revealed tumor cell positive for TFE3, but have no consistency in carbonic anhydrase IX, CD117, Ki67, CK8/18 AE1/AE3 and so on. Therefore, the uniform and definitive diagnostic standards of the tumors are uncertain. Hence, more cases and findings are required to elaborate the standards of all the tumor subtypes. Vascular endothelial growth factor-targeted therapy showed some efficacious results in patients with metastasis, but more useful treatments are warranted.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/cirurgia , Feminino , Fusão Gênica , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Tomografia Computadorizada por Raios X , Translocação Genética , Ultrassonografia
14.
Acta Biochim Biophys Sin (Shanghai) ; 50(5): 465-472, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29648579

RESUMO

Calpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of clear cell renal cell carcinoma (ccRCC). This study aimed to further elucidate the molecular mechanisms underlying Capn4-mediated ccRCC progression. The mRNA expression levels in ccRCC cells were measured by quantitative real-time PCR. The effects of Capn4 on cell adhesion, invasion, and migration were examined by cell adhesion assay, cell invasion assay, and wound-healing assay, respectively. The protein levels were detected by western blot analysis. The effect of Capn4 on cancer metastasis in vivo was assessed in a nude mice xenograft model. It was found that Capn4 was up-regulated in the ccRCC cells, and Capn4 overexpression suppressed cell adhesion activity and increased cell invasion and migration in 786-O cells, while Capn4 silencing increased cell adhesion activity and impaired the invasion and migration ability of Caki-1 cells. Capn4 overexpression also increased the protein level of cleaved talin in 786-O cells, while Capn4 silencing decreased the protein level of cleaved talin in Caki-1 cells. The focal adhesion kinase (FAK)/AKT/MAPK signaling was activated by Capn4 overexpression in 786-O cells, and was inhibited by Capn4 down-regulation in Caki-1 cells. Capn4 overexpression increased the protein levels of matrix metalloproteinase 2 (MMP-2), vimentin, N-cadherin, and down-regulated E-cadherin in 786-O cells, while Capn4 silencing decreased the protein levels of MMP-2, vimentin, N-cadherin, and up-regulated E-cadherin in Caki-1 cells. Capn4 also promoted cancer metastasis in the in vivo nude mice xenograft model. Our results implicate the functional role of Capn4 in ccRCC invasion and migration, which may contribute to cancer metastasis in ccRCC.


Assuntos
Calpaína/genética , Carcinoma de Células Renais/genética , Proteína-Tirosina Quinases de Adesão Focal/genética , Neoplasias Renais/genética , Transdução de Sinais/genética , Talina/genética , Animais , Calpaína/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Talina/metabolismo , Transplante Heterólogo
15.
Oncotarget ; 8(29): 48291-48302, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28187463

RESUMO

In this retrospective analysis, we evaluated associations between albumin to globulin ratio (AGR), clinicopathological characteristics, and survival in 592 patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC) prior to nephrectomy. We found that low AGR was associated with more aggressive tumor behavior; patients with low AGR had poorer overall survival (OS) and cancer-specific survival (CSS) in Kaplan-Meier survival analyses both before and after propensity score matching, which was used to compensate for differences in baseline clinicopathological characteristics. AGR was an independent prognostic factor for both OS (HR: 6.799; 95% CI: 3.215-14.377; P < 0.001) and CSS (HR: 8.806; 95% CI: 3.891-19.928; P < 0.001), and its prognostic value was higher than that of other established inflammation-based prognostic scores. When AGR was incorporated into a prognostic model that included T stage, neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR), the resulting nomogram predicted 3- and 5-year OS in the patients more accurately than when AGR was not included. In conclusion, AGR may be particularly useful for improving clinical outcome predictions for patients with localized or locally advanced CCRCC.


Assuntos
Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , Albumina Sérica , Soroglobulinas , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Reprodutibilidade dos Testes
16.
Int J Clin Exp Pathol ; 10(10): 10618-10626, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966404

RESUMO

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which involved in the degradation of extracellular matrix (ECM) and basement membrane (BM), and associated with tumor invasion and metastasis. Membrane type-2 MMP (MT2-MMP) is a member of MT-MMPs subgroup, and is supposed to be an important step for cancer invasion and metastasis. However, the roles of MT2-MMP in human renal cell carcinoma (RCC) remain unknown. In present study, we identified the roles of MT2-MMP in renal cancer progression by MT2-MMP suppression and overexpression in ACHN cells, which expressed highest level of MT2-MMP and lowest level of MT1-MMP in three kinds of renal cancer cells (786-0, ACHN, OS-RC-2). We found that the expression of MMP-2 could be regulated by MT2-MMP suppression or overexpression in ACHN cells, and both adhesion and invasive activities of ACHN cells were suppressed with MT2-MMP siRNA transfection. In addition, we found that MT2-MMP could increase ACHN cell proliferation, and inhibit cell apoptosis. In vitro tumor growth experiment showed that MT2-MMP could increase clone formation of ACHN cells. The results indicated that MT2-MMP could promoter renal cancer cell invasion and adhesion by activating the expression of MMP2, and stimulate tumor growth of renal cancer.

17.
Int J Clin Exp Pathol ; 10(7): 7466-7474, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966590

RESUMO

Previous study found that higher Capn4 mRNA level is observed in patients with more advanced pathological stage of ccRCC and is also associated with decreased overall survival of patients with ccRCC. However, the mechanism by which Capn4 promotes progression of RCC is not understood. In the present study, we found that over-expression of Capn4 in RCC cells enhances tumor cell growth and down-regulation of Capn4 in RCC cells decreases tumor cell growth in vitro. Interestingly, Capn4 was found to increase phosphorylation of specific tyrosine residues of FAK and subsequent activate NF-κB p65 phosphorylation. Furthermore, Capn4-mediated cell proliferation of RCC cells required up-regulation of NF-κB p65 phosphorylation through activation of FAK signaling pathway. Taken together, our data showed that Capn4 can contribute to RCC growth via activation of the FAK and the downstream signaling pathways leading to the activation of NF-κB.

18.
PLoS One ; 11(11): e0166482, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27861542

RESUMO

BACKGROUND: Recently, many studies have shown that the serum lactate dehydrogenase (LDH) level is related to the prognosis of renal cell carcinoma (RCC). We launched this meta-analysis to assess the prognostic value of serum LDH in patients with RCC. METHODS: We searched PubMed, Embase and Web of Science for information on serum LDH and the outcome of RCC through June 14, 2016. The hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) were extracted and integrated from the matching studies. RESULTS: A total of 29 studies including 6629 patients with RCC were incorporated in this meta-analysis. Patients whose serum LDH levels were elevated had a lower OS (HR = 2.13, 95% CI = 1.69-2.69, P < 0.001). Meanwhile, the pooled data showed that a higher serum LDH level was a negative prognostic factor for PFS (HR = 1.74, 95% CI = 1.48-2.04, P < 0.001). Furthermore, subgroup analyses indicated elevated serum LDH was associated with poor survival in different tumor types. Elevated serum LDH was significantly associated with worse prognosis for patients with all stages of RCC (OS, HR = 2.41, 95% CI = 1.09-5.33), metastatic RCC (OS, HR = 2.62, 95% CI 1.57-2.59; CSS, HR = 1.79, 95% CI 1.49-2.15), and non-metastatic RCC (OS, HR = 3.67, CI = 1.33-10.13). Besides, elevated serum LDH also indicated a worse prognosis in subgroups of cut-off values, analysis types and ethnicity. CONCLUSIONS: Our results show that serum LDH levels are associated with the outcomes of RCC and can be used as a valuable biomarker for monitoring prognoses.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , L-Lactato Desidrogenase/sangue , Carcinoma de Células Renais/diagnóstico , Humanos , Neoplasias Renais/diagnóstico , Modelos de Riscos Proporcionais , Viés de Publicação , Curva ROC
19.
Biomed Pharmacother ; 80: 268-275, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27133066

RESUMO

Bladder cancer is the 7th most common cancer type in the world, and microRNAs (miRNAs) play important roles in cancer progression. In the present study, we investigated the roles and molecular mechanisms of miR-194 in bladder cancer. The results demonstrated that the expression level of miR-194 is significantly down-regulated in bladder cancer cell lines and clinical tissues. Overexpression of miR-194 inhibited cell proliferation and invasion in J82 and T24 cells. Further mechanistic study showed that overexpression of miR1-94 induced G0/G1 phase arrest as well as apoptosis in J82 and T24 cells. In addition, by using bioinformatics tool (Targetscan), RAP2B is found to be a target of miR-194, and miR-194 down-regulates the expression level of RAP2B via directly targeting its 3'UTR. Knockdown of RAP2B also inhibited cell proliferation and invasion in J28 cells. More importantly, restoration of RAP2B activity rescued the inhibitory effects of miR-194 on cell proliferation and invasion in J82 cells. Further analysis of bladder cancer clinical samples showed that miR-194 is inversely correlated with RAP2B. Collectively, our study may implicate that miR-194 plays an important role in the regulation of bladder cancer progression. In summary, our study may implicate that miR-194 acts as a tumor suppressor and plays an important role in the regulation of bladder cancer progression.


Assuntos
MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proteínas rap de Ligação ao GTP/genética , Apoptose/genética , Sequência de Bases , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Proteínas rap de Ligação ao GTP/metabolismo
20.
Int J Clin Exp Med ; 8(8): 12182-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550128

RESUMO

In this study, we report an active targeting liposomal formulation directed by a novel peptide (RGD) that specifically binds to the integrins receptors overexpressed on prostatic cancer cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of RGD modified liposomes on PC-3 cells and DU145 cells. The uptake efficiency of RGD-LP was 5.2 times higher than that of LP on PC-3 cells. The uptake efficiency of RGD-LP was 3.2 times higher than that of LP on DU145 cells. The anti-proliferative activity of RGD-LP-PTX against PC-3 cells and DU145 cells were much stronger compared to that of LP-PTX and free PTX, respectively. The tumor spheroids experiment revealed that RGD-LP-PTX was more efficaciously internalized into tumor spheroids than LP in both PC-3 cells and DU145 cells. Compared to LP-PTX and free PTX, RGD-LP-PTX showed the greatest tumor growth inhibitory effect in vivo. In brief, the RGD-LP may be an efficient targeting drug delivery system for prostatic cancer.

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