Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cancer Med ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943867

RESUMO

Cancer susceptibility candidate 9 (CASC9) is a recently identified lncRNA that acted as a tumor promotor in diversified cancer types. However, its role in papillary thyroid cancer (PTC) remains unknown. The expression of CASC9 was measured in 52 human PTC tissues and PTC cell lines as well as their controls. The proliferation, migration, and invasion of PTC cells were determined after knockdown or overexpression of CASC9 to evaluate the effect of CASC9 on PTC cells. Also, the role of PTC tumorigenesis was confirmed in mice xenograft models. Additionally, the underlying mechanisms of CASC9 were further researched. We found that CASC9 expression was augmented in human PTC tissues and cells. Higher CASC9 expression was associated with large tumor size, advanced stage, or lymph node metastasis. Downregulation of CASC9 significantly attenuated the proliferative, migrative, and invasive abilities of PTC cells, and suppressed tumorigenesis in vivo. While overexpression of CASC9 elevated the proliferation, migration, and invasion of PTC cells. miR-488-3p expression was decreased, and ADAM9 level was increased in PTC tissues and cells. CASC9 expression was negatively related to miR-488-3p, but positively associated with ADAM9 expression in PTC tissues. Molecular mechanism analysis revealed that CASC9 functioned via sponging miR-488-3p to regulate ADAM9 expression, followed by activation of EGFR-Akt signaling. In conclusion, lncRNA CASC9 promoted the malignant phenotypes of PTC via modulating miR-488-3p/ADAM9 pathway. This study may provide a novel therapeutic target for the treatment of PTC.

2.
Toxicol Lett ; 319: 187-196, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756459

RESUMO

The clinical drug-drug interactions mediated by heterotropic activation on cytochrome P450 (CYP450) kinetics, especially CYP3A4, have received wide concern in recent years. Flavonoids, a group of important natural substances with various pharmacological activities, distribute widely among vegetables, fruits and herbs. The frequent and numerous uses of flavonoids may increase the risk of food/herb-drug interactions. However, little is known about activation effects of flavonoids on CYP3A4. The aim of this study was to investigate activation of CYP3A4 by flavonoids, explore the molecular mechanism, and assess the biological effects on dronedarone (DND) induced toxicity. The results showed that flavone, tangeretin, sinensetin and 6-hydroxyflavone increased the cell viability by decreasing DND-induced cytotoxicity. These four flavonoids could activate the metabolism of DND in hamster pharmacokinetics study. Furthermore, both molecular docking and circular dichroism analysis partially illustrated the molecular mechanism of heterotropic activation. Finally, the pharmacophore model suggested B aromatic ring, hydrophobic groups at 7-position and hydrogen bond acceptors at 4-position may play a vital role in activation of flavonoids on CYP3A4. Taken together, our findings would provide useful information for predicting the potential risks of flavonoid-containing food/herb-drug interactions in humans.


Assuntos
Antiarrítmicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Dronedarona/toxicidade , Ativadores de Enzimas/farmacologia , Flavonoides/farmacologia , Animais , Antiarrítmicos/farmacocinética , Dicroísmo Circular , Cricetinae , Dronedarona/farmacocinética , Ativação Enzimática , Interações Ervas-Drogas , Ligações de Hidrogênio , Masculino , Mesocricetus , Modelos Moleculares , Simulação de Acoplamento Molecular
3.
Int J Clin Oncol ; 25(2): 338-346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31720994

RESUMO

OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.

4.
J Clin Lab Anal ; 34(1): e23017, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31441128

RESUMO

BACKGROUND: Thromboelastography (TEG) has been established as a sensitive method to assess the whole coagulation process. The aim of the study was to evaluate the diagnosis significance of TEG on hypercoagulability in patients suffering renal mass. METHODS: A total of 478 patients were diagnosed with renal tumor by histolopathologic examination and were assigned to three groups. Group A: 79 patients with benign renal tumor; Group B: 317 patients with renal cell carcinoma (RCC, Fuhrman grades I and II); Group C: 82 patients with high-risk RCC (Fuhrman grades III and IV). Subgroup analysis was performed in malignant renal tumor patients according to the TMN classification. The clinical data, whole blood TEG, and conventional coagulation tests were reviewed. RESULTS: There was no statistically significant difference between subgroups in respect to conventional coagulation tests. Hypercoagulablity was marked in Group C according to the TEG parameters. The elevated platelets and fibrinogen is linked with hypercoagulability in renal tumor. The positive correlation was between fibrinogen and MA value (r = .663, P < .05). The pathologic tumor stages were also associated with the TEG parameters. CONCLUSION: Patients suffering advanced RCC are hypercoagulable which can be identified by TEG. MA value could be potential diagnosis indicators for detecting high-grade RCC.

5.
Mol Cell Endocrinol ; 500: 110634, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678422

RESUMO

BACKGROUND: Thyroid cancer is the most common malignant tumor with relatively high incidence and mortality in endocrine system. Research about thyroid cancer-related targets is the basis for the diagnosis of thyroid cancer and the development of new drugs. However, the predictive value of long non-coding RNA (lncRNA) for the diagnosis and prognosis of thyroid cancer is still in the preliminary stage of exploration. Thus, we for the first time investigated the effects and associated regulatory mechanism of lncRNA Forkhead box D3 antisense RNA 1 (FOXD3-AS1) in thyroid cancer in vitro and in vivo. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA FOXD3-AS1 and miR-296-5p. Cell proliferation was detected through colony formation assay. Cell cycle was analyzed through flow cytometry. Cell mobility was valued through transwell invasion assay and wound healing assay. Western blotting was used to examine the expression of proteins related to cell proliferation and cell migration and TGF-ß1/Smads signaling pathway. Luciferase reporter assay was used to verify the targeting relationship between FOXD3-AS1 and miR-296-5p. Tumor xenograft model was established and immunohistochemistry (IHC) was used to examine the expression of Ki67 and VEGF. RESULTS: We found that the expression of lncRNA FOXD3-AS1was upregulated and it had negative correlation with the level of miR-296-5p in thyroid cancer tissues and cells. LncRNA FOXD3-AS1 knockdown effectively suppressed cell proliferation and cell invasion in vitro. Further study revealed that miR-296-5p was a target of lncRNA FOXD3-AS1 and FOXD3-AS1 exerted anti-tumor effect through up-regulating miR-296-5p. Moreover, we found that FOXD3-AS1 knockdown suppressed the aggressive biological behaviors of thyroid cancer through inactivating the TGF-ß1/Smads signaling pathway. Subsequently, the in vivo experiments further verified that the FOXD3-AS1/miR-296-5p axis exerted obvious anti-tumor effect through inhibiting tumor growth and metastasis and the TGF-ß1/Smads signaling pathway was also inactivated in vivo by the inhibition of FOXD3-AS1. CONCLUSION: Inhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-ß1/Smads signaling pathway.

6.
BMC Oral Health ; 19(1): 266, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791302

RESUMO

BACKGROUND: The aim of the study was to compare the efficacy of the autogenous tooth bone and xenogenic bone grafted in immediate implant placement with bone defect. METHODS: Thirty patients whose compromised anterior teeth need immediate implant placement were enrolled. Autogenous tooth bone made from the extracted teeth by chair-side or the xenogenic bone were used to repaired bone defect. Clinical examination, radiographic assessment about the horizontal bone change in the level of 0 mm, 3 mm and 6 mm below the implant neck and the marginal bone loss were made immediately, 6 and 12 months after implant placement. Questionnaire of the feelings about the surgery were made at the time of removing the sutures. RESULTS: All implants achieved the success criteria without any complications at the follow-up period. The percent of the horizontal bone change and the marginal bone loss at 6 and 12 months were almost the same between two groups (P > .05). The horizontal bone loss at the first or the latter 6 months was almost the same (P > .05). But the horizontal bone loss at the 6 mm level was less than the 0 mm and 3 mm levels at 6 and 12 months (P < .05). Meanwhile patients seem more satisfied with the autogenous tooth bone derived from the questionnaire. CONCLUSION: The bone volume change in the facial part of the implant after immediate placement is almost the same between two groups. Providing clinical evidence that the autogenous tooth bone made from compromised tooth can be an acceptable bone graft material.

7.
Nanotechnology ; 31(6): 065102, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645027

RESUMO

Melittin (MEL), the primary active component of bee venom, has recently emerged as a promising cancer chemotherapeutic agent. However, the instability and rapid degradation of MEL is a significant challenge in practical therapeutic applications. In the present study, graphene oxide (GO)-based magnetic nanocomposites (PEG-GO-Fe3O4) were prepared and adopted as the drug delivery vehicles of MEL, and the anticancer effects of PEG-GO-Fe3O4/MEL complexes on human cervical cancer HeLa cells were studied. PEG-GO-Fe3O4 exhibited a series of unique physical and chemical properties resulting in multiple interactions with MEL, and ultimately the release of MEL. In vitro experiments showed that PEG-GO-Fe3O4/MEL not only distinctly enhanced the inhibition effect on HeLa cells, but also induced pore formation in the cell membrane that ultimately led to cell lysis. In this newly developed drug delivery system, PEGylated GO plays the role of a MEL protector while Fe3O4 nanoparticles act as magnetic responders; therefore active MEL can be released over a long period of time (up to 72 h) and maintain its inhibition effect on HeLa cells.

9.
J Exp Clin Cancer Res ; 38(1): 233, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159832

RESUMO

BACKGROUND: Previous study demonstrated that extracellular ATP could promote cell migration and invasion in multiple human cancers. Till now, the pro-invasive mechanisms of ATP and P2RX6, a preferred receptor for ATP, are still poorly studied in RCC. METHODS: Bioinformatics analysis was performed to identify the differentially expressed genes during RCC different stages. Tissue microarray, IHC staining and survival analysis was respectively used to evaluate potential clinical function. In vitro and in vivo assays were performed to explore the P2RX6 biological effects in RCC progression. RESULTS: We found that ATP might increase RCC cells migration and invasion through P2RX6. Mechanism dissection revealed that ATP-P2RX6 might modulate the Ca2+-mediated p-ERK1/2/MMP9 signaling to increase the RCC cells migration and invasion. Furthermore, METTL14 implicated m6A modification in RCC and down-regulated P2RX6 protein translation. In addition, human clinical survey also indicated the positive correlation of this newly identified signaling in RCC progression and prognosis. CONCLUSIONS: Our findings revealed that the newly identified ATP-P2RX6-Ca2+-p-ERK1/2-MMP9 signaling facilitates RCC cell invasion and metastasis. Targeting this novel signaling pathway with small molecules might help us to develop a new approach to better suppress RCC progression.


Assuntos
Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Metilação de DNA , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores Purinérgicos P2/genética , Animais , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Biologia Computacional/métodos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Neoplasias Renais/metabolismo , Camundongos , Modelos Biológicos , Metástase Neoplásica , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Transdução de Sinais
10.
Mol Cancer ; 18(1): 81, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953521

RESUMO

BACKGROUND: The aberrant expression of long noncoding RNAs (lncRNAs) has recently emerged as key molecules in human cancers; however, whether lncRNAs are implicated in the progression of clear cell renal cell carcinoma (ccRCC) remains unclear. METHODS: Candidate lncRNAs were selected using microarray analysis and quantitative real-time PCR (qRT-PCR) was performed to detect lncRNAs expression in human ccRCC tissues. Overexpression and knocking down experiments in vivo and in vitro were performed to uncover the biological roles of lncRNA-URRCC on ccRCC cell proliferation and invasion. Microarray, chromatin immunoprecipitation, Luciferase reporter assay and western blot were constructed to investigate the molecular mechanisms underlying the functions of lncRNA-URRCC. RESULTS: The microarray analysis and qRT-PCR identified a new lncRNA, URRCC, whose expression is upregulated in RCC samples and associated with poor prognosis, leading to promote ccRCC cell proliferation and invasion. Mechanistically, URRCC enhances the expression of EGFL7 via mediating histone H3 acetylation of EGFL7 promoter, activation of P-AKT signaling, and suppressing P-AKT downstream gene, FOXO3. In return, FOXO3 could inhibit the transcription of URRCC via binding to the special region on the promoter of URRCC. CONCLUSIONS: Our data suggests that targeting this newly identified feed-back loop between LncRNA-URRCC and EGFL7/P-AKT/FOXO3 signaling may enhance the efficacy of existing therapy and potentially imparts a new avenue to develop more potent therapeutic approaches to suppress RCC progression.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fatores de Crescimento Endotelial/metabolismo , Proteína Forkhead Box O3/metabolismo , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima
11.
J Org Chem ; 84(9): 5141-5149, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-30986065

RESUMO

An efficient one-pot synthesis of O-heterocycles or aryl ketones has been achieved using Et3SiH in the presence of InCl3 via a sequential ionic hydrogenation reaction by switching the solvent. This methodology can be used to construct C-O bonds and to prepare conjugate reduction products, including chromans, tetrahydrofurans, tetrahydropyrans, dihydroisobenzofurans, dihydrochalcones, and 1,4-diones in a facile manner. In addition, a novel plausible mechanism involving a conjugate reduction and a tandem reductive cyclization was verified by experimental investigations.

12.
J Chem Inf Model ; 59(4): 1624-1633, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-30856323

RESUMO

Sphingosine-1-phosphate receptor 1 (S1P1R), a member of the G protein-coupled receptor (GPCR) family, is an attractive protein target for the treatment of autoimmune diseases, and a diverse array of S1P1R agonists have been developed. Rational drug design based on S1P1R remains challenging due to the limited information available on the binding mode between S1P1R and its agonists. In this work, the active-like state of S1P1R was modeled via Gaussian accelerated molecular dynamics (GaMD) based on its inactive form, which was further validated by docking studies with two representative S1P1R agonists. Moreover, with the usage of the induced active-like state, the binding mode between S1P1R and its agonists was studied through molecular dynamics simulations and MM-GBSA calculations. The results of those studies indicated that four groups of binding site residues were the major contributors to the ligand and receptor interactions. In addition, this model was verified by five chemically similar compounds synthesized in-house and 1145 known S1P1R agonists collected from the BindingDB database. The elucidation of the key binding characteristics will further complete the cognition of S1P1R, which can guide the rational design of novel S1P1R agonists.

13.
Toxicol Appl Pharmacol ; 369: 49-59, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30790579

RESUMO

Flavonoids are a class of polyphenol antioxygen, despite various known biological activities and therapeutic potential, scattered but not much is known about their interactions with drug transporters. P-glycoprotein (P-gp) as a cellular defense mechanism by effluxing its substrates has been widely investigated. The aim of this study was to investigate the inhibitory effects of 75 flavonoids on P-gp in vitro and in vivo and to illuminate the structure-activity relationships of flavonoids with P-gp. Five flavonoids, including tangeretin, sinensetin, isosinensetin, sciadopitysin and oroxylin A exhibited significant inhibition on P-gp in MDR1-MDCKIIcells, which reduced the P-gp-mediated efflux of paraquat and taxol and consequently increased their cell toxicity. In addition, co-administration of digoxin with five flavonoids increased the AUC0-t of digoxin in different extents in rats, from 19.84% to 81.51%. Molecular docking assays elucidated the inhibitory effect of flavonoids might be related to Pi interactions, but not hydrogen bonds. The pharmacophore model suggested the hydrophobic groups in B benzene ring may play a vital role in the potency of flavonoids inhibition on P-gp. Taken together, our findings would provide the basis for a reliable assessment of the potential risks of flavonoid-containing food/herb-drug interactions in humans.

14.
Bioorg Chem ; 82: 41-57, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30268973

RESUMO

Agonism of S1P1 receptor has been proven to be responsible for peripheral blood lymphopenia and elicts the identification of various S1P1 modulators. In this paper we described a series of oxadiazole-based S1P1 direct-acting agonists disubstituted on terminal benzene ring, with high potency for S1P1 receptor and favorable selectivity against S1P3 receptor. In addition, two representative agents named 16-3b and 16-3g demonstrated impressive efficacy in lymphocyte reduction along with reduced effect on heart rate when orally administered. Furthermore, these compounds have been shown to possess desired pharmacokinetic (PK) and physicochemical profiles. The binding mode between 16-3b and the activated S1P1 model was also studied.


Assuntos
Oxidiazóis/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Animais , Células CHO , Cricetulus , Desenho de Drogas , Humanos , Linfócitos/efeitos dos fármacos , Linfopenia/induzido quimicamente , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Oxidiazóis/farmacocinética , Ratos Sprague-Dawley , Relação Estrutura-Atividade
15.
Mol Cancer ; 17(1): 157, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30419914

RESUMO

PURPOSE: Although microRNAs (miRNAs) were revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment was limited. Here we sought to identify human miRNAs that acted as key regulators in renal cancer metastasis and Sunitinib treatment. EXPERIMENTAL DESIGN: We focused on 2 published microarray data to select out our anchored miRNA and then explored the roles of miR-452-5p both in vitro and in vivo, which was downregulated after Sunitinib treatment while upregulated in metastasis renal cell carcinoma (RCC) tissues. RESULTS: Here, we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cancer cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream gene SMAD7. CONCLUSION: Our study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7 signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , MicroRNAs/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Smad4/metabolismo , Proteína Smad7/metabolismo , Sunitinibe/farmacologia , Regiões 3' não Traduzidas , Animais , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Camundongos , Modelos Biológicos , Metástase Neoplásica , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Ligação Proteica , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Urol Int ; 101(4): 391-399, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30184524

RESUMO

OBJECTIVES: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. METHODS: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. RESULTS: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. CONCLUSIONS: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia Neoadjuvante , Sorafenibe/uso terapêutico , Sunitinibe/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombose/complicações , Trombose/tratamento farmacológico , Resultado do Tratamento
17.
Br J Cancer ; 119(5): 591-604, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30082686

RESUMO

BACKGROUND: Despite the fact that miRNAs play pivotal roles in various human malignancies, their molecular mechanisms influencing RCC are poorly understood. METHODS: The expression of miRNAs from RCC and paired normal renal specimens was analysed by a combined computational and experimental approach using two published datasets and qRT-PCR assays. The functional role of these miRNAs was further identified by overexpression and inhibition assays in vivo and in vitro. Western blots, luciferase assays, and chromatin immunoprecipitation were performed to investigate the potential mechanisms of these miRNAs. RESULTS: Bioinformatics analysis and qRT-PCR revealed that miR-532-5p was one of the most heavily downregulated miRNAs. Overexpression of miR-532-5p inhibited RCC cell proliferation, while knockdown of miR-532-5p promoted cell proliferation. Mechanistic analyses indicated that miR-532-5p directly targets KRAS and NAP1L1. Interestingly, ETS1 suppressed the transcription of miR-532-5p by directly binding a special region of its promoter. Moreover, high levels of ETS1, as an oncogene in RCC, were significantly associated with poor survival in a large cohort of RCC specimens. CONCLUSIONS: Our work presents a road map for the prediction and validation of a miR-532-5p/KRAS-NAP1L1/P-ERK/ETS1 axis feedback loop regulating cell proliferation, which could potentially provide better therapeutic avenues for treating RCC.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , MicroRNAs/metabolismo , Proteína 1 de Modelagem do Nucleossomo/genética , Proteína Proto-Oncogênica c-ets-1/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Células A549 , Animais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Transplante de Neoplasias , Proteína 1 de Modelagem do Nucleossomo/metabolismo , Fosforilação , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Análise de Sobrevida
18.
Eur Radiol ; 28(12): 5035-5043, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29948077

RESUMO

OBJECTIVES: To assess the ability of renal blood oxygen level dependent (BOLD) MRI metrics to predict post-operative renal function. METHODS: We studied 152 patients who underwent laparoscopic partial nephrectomy (LPN) and renal MRI examination including BOLD. Short-term and long-term renal function was evaluated using the glomerular filtration rate (GFR) derived from renal scintigraphy. Renal function decline was assessed as the absolute decline (AD), percentage decline (PD) and optimal renal function preservation (OP). T2* values were analysed in the renal cortex and medulla ipsilateral and contralateral to the tumour. Clinical characteristics and imaging metrics were evaluated using univariate and multivariate linear regression analyses. Risk factors obtained using BOLD metrics (determined by multivariate regression) were then combined and compared with RENAL scores to predict OP. RESULTS: Increasing warm ischaemia time (WIT), resected and ischaemic volume (RAIV), larger tumour size, higher RENAL score and lower preoperative GFR were short-term risk factors for AD, while increasing WIT and lower preoperative GFR were significant for long-term outcomes. Increasing WIT, RAIV, lower T2* value in the cortex and higher T2* value in the medulla on the ipsilateral side were short-term risk factors for PD, while all of the above factors (except WIT and RAIV) were significant for long-term outcomes. The performance of the combination of T2* values in the cortex and medulla on the ipsilateral side to tumour in predicting OP was better than RENAL score (AUC 0.762 vs 0.634, p = 0.013). CONCLUSIONS: Renal BOLD-MRI metrics could provide useful information to the clinician in predicting post-operative renal function outcomes. KEY POINTS: • Renal fMRI metrics may be useful for prediction of renal functional outcomes and merit further study. • Renal fMRI metrics may reflect degree of baseline disease and ability to tolerate warm ischaemia. • Combination of T2* values was better than RENAL score for predicting OP.


Assuntos
Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Imagem por Ressonância Magnética/métodos , Nefrectomia/métodos , Oxigênio/sangue , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Recuperação de Função Fisiológica/fisiologia , Análise de Regressão , Fatores de Risco , Isquemia Quente
19.
BMC Med Genet ; 19(1): 83, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29788924

RESUMO

BACKGROUND: Several association analyses and linkage researches indicated that inherited genetic variations effectively influence differentiated thyroid carcinogenesis. METHODS: The results from 15 published studies on differentiated thyroid carcinoma (DTC) were combined. The genetic model included rs965513, rs944289 and rs1867277. Meta-analyses were performed and cochran's χ2 based Q-statistic and I2 test were performed to assess heterogeneity using STATA software. RESULTS: Significant results were noticed for rs965513(Odds Ratio(OR) = 1.162(1.117, 1.208)), rs944289(OR = 1.082(1.035, 1.131)) and rs1867277(OR = 1.415(1.324, 1.512)). In the subgroup analysis by ethnicity, rs965513 polymorphism conferred that risk of Caucasians (OR = 1.168(1.122, 1.215)) was more than that of East Asians of 1.35 (OR = 0.897(0.680, 1.193)). CONCLUSION: This meta-analysis revealed that common variations of FOXE1 (rs965513, rs944289 and rs1867277) were risk factors associated with increased DTC susceptibility.


Assuntos
Fatores de Transcrição Forkhead/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Glândula Tireoide/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Neoplasias da Glândula Tireoide/etnologia
20.
Urol Oncol ; 36(6): 307.e15-307.e21, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29599070

RESUMO

PURPOSE: We examined the incidence of pulmonary thromboembolism (PE) and deep venous thromboembolism (DVT) in patients who underwent urologic tumor surgery. The aim of this study was to investigate the postoperative D-dimer for prediction of venous thromboembolism events (VTE), as well as to identify other risk factors associated with the occurrence of thromboembolisms. PATIENTS AND METHODS: This was a prospective observational cohort study, which included 1,269 patients who underwent major urologic tumor surgery, from August 2015 to February 2017, at our center. Data comprising age, sex, body mass index, Charlson comorbidity index, type of surgery, Caprini score, postoperative D-dimer levels, and other laboratory tests were collected for analyses. Lower limb venous ultrasound was performed before surgery and the day before hospital discharge to measure DVT. Computerized tomography or ventilation/perfusion lung scan was applied to detect PE. RESULTS: The overall incidence of VTE was 2.4% (31 cases) in 1,269 patients, consisting of 23 PE events and 9 DVT events. Patients undergoing radical cystectomy were most likely to suffer VTE (4.3%). The optimal cutoff value for postoperative D-dimer was 0.98µg/ml, according to the receiver operating characteristic curve analysis, with a sensitivity of 83.9%, and a specificity of 80.0%. On multivariate analysis, hypertension (odds ratio, OR = 2.5, 95% CI: 1.1-5.7; P = 0.026), Charlson comorbidity index ≥ 2 (OR = 5.6, 95% CI: 2.2-14.6; P<0.001), and D-dimer lever ≥ 1µg/ml on postoperative day 1 (OR = 12.52, 95% CI: 4.6-35.2; P<0.001) were independently associated with VTE after urologic tumor surgery. CONCLUSIONS: The overall incidence of urologic-tumor-surgery-associated VTE in an Asian population is similar to those reported in European and North American series. Elevated D-dimer early after operation is an independent predictor of VTE in patients undergoing urologic tumor surgery. In addition, hypertension and the Charlson comorbidity index are both important clinical risk factors. The Caprini score recommended by the guideline is inadequate in this study population. The postoperative D-dimer plasma level is a more reliable marker for identifying patients at high-risk of developing venous thromboembolisms.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Complicações Pós-Operatórias/diagnóstico , Neoplasias Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Tromboembolia Venosa/diagnóstico , Idoso , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA