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1.
Medicine (Baltimore) ; 103(14): e37646, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579099

RESUMO

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse prognosis in several malignancies. For renal cell carcinoma (RCC), the effect of PBT is still debated. OBJECTIVE: To evaluate the impact of PBT on prognosis after nephrectomy in patients with RCC. METHODS: This study is A systematic review and meta-analysis of published article data (PRISMA protocol) for literature related to PBT and RCC through extensive search of EMBASE, Medline via PubMed, Web of Science and Cochrane Library, language limited to English, with no time constraint until May 20, 2022. We pooled the results of multivariable cox regression analyses from each study, with subgroup analyses by dose and timing of transfusion. All analyses were done using Stata14. RESULTS: A total of 12 studies involving 27,683 participants were included. Our meta-analysis pooled the results of multivariable cox regression analysis in each study, showing that PBT is associated with higher overall Mortality (OM; hazard ratio [HR] = 1.34, 1.23-1.44), cancer-specific mortality (CSM; HR = 1.35, 1.20-1.51), and disease recurrence (HR = 1.54, 1.18-1.89). when only patients with nonmetastatic RCC were included, PBT was still associated with higher OM (HR = 1.29, 1.11-1.47) and disease recurrence (HR = 1.58, 1.18-1.98), but the association with CSM (HR = 1.26, 0.99-1.52) was not statistically significant. In subgroup analysis by transfusion dose, small (1-2) units of PBT were not associated with CSM (HR = 1.84, 0.95-2.73), but large (≥3) units were associated with higher CSM (HR = 2.98, 1.74-4.22) and disease recurrence (HR = 1.99, 1.31-2.67). Each additional unit of PBT resulted in a higher CSM (HR = 1.07, 1.04-1.10). In subgroup analysis by transfusion timing, intraoperative transfusion was associated with higher CSM and disease recurrence, but postoperative transfusion was not. CONCLUSIONS: PBT is associated with higher OM, CSM and disease recurrence. This adverse effect seems to be particularly significant in high-dose intraoperative transfusion. It is necessary to limit the overuse of PBT, especially high-dose intraoperative transfusion, in order to improve the prognosis of patients undergoing nephrectomy for RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Transfusão de Sangue/métodos , Nefrectomia/métodos , Neoplasias Renais/patologia
2.
Acta Biomater ; 178: 296-306, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38417646

RESUMO

Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. STATEMENT OF SIGNIFICANCE: The CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells' ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , DNA , Ribonucleoproteínas/genética , Lactatos , Glucose , Neoplasias/genética , Neoplasias/terapia
3.
Comput Biol Med ; 167: 107671, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37948967

RESUMO

The design of orthodontic arch wires is a prerequisite for orthodontic treatment that determines the subsequent orthodontic effects. Current methods for designing orthodontic arch wires are often based on traditional manual techniques, which suffer from problems such as low accuracy and efficiency. To address these issues, a digital orthodontic arch wire design system has been developed using Unity 3D and C#. This system allows for the interactive adjustment and intelligent optimization of the shape of digital orthodontic arch wires. The developed system includes modules for curve design, contour construction, and collision detection of orthodontic arch wires, which can be customized interactively to meet the personalized needs of patients. In addition, an energy-constrained method is employed to optimize the shape of certain regions of the arch wire, which helps overcome distortion and interference issues caused by unreasonable interaction. The effectiveness of the developed system has been evaluated through experiments on digital design and optimization of orthodontic arch wires. Results demonstrate that the system can achieve accurate and efficient digital design of orthodontic arch wires, effectively reduce distortion, and is expected to improve the orthodontic effect.


Assuntos
Fios Ortodônticos , Humanos , Desenho de Equipamento
4.
Sex Med ; 11(2): qfac018, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36910702

RESUMO

Background: Previous studies have shown that Helicobacter pylori (Hp) infection is associated with erectile dysfunction (ED), but the mechanism is unclear. Aim: To assess the relationship between ED and Hp, folic acid (FA), vitamin B12 (B12), and homocysteine (HCY). Methods: This study included 84 patients with ED and 42 healthy men. We adopted an IIEF-5 score <21 (5-item International Index of Erectile Function) as the diagnostic criterion for ED, and the RigiScan monitoring device was used to preliminarily screen for and rule out psychogenic ED. Outcomes: Levels of Hp immunoglobulin G (Hp-IgG) titer, FA, B12, and HCY were compared between the ED group and the non-ED group, and the correlation between the indicators was evaluated. Results: The median Hp-IgG titer was higher in the ED group than the control group (32.34 vs 20.88, P < .001). The ED group had lower median levels of B12 (195 vs 338, P < .001) and FA (4.66 vs 10.31, P < .001) and a higher median level of HCY (12.7 vs 8.1, P < .001). Multivariate logistic regression analysis showed that the level of FA (odds ratio, 0.111; 95% CI, 0.031-0.399; P < .001) was an independent risk factor for ED. Specifically, FA level was significantly higher in the moderate ED group than the severe ED group, which had a higher median Hp-IgG titer and lower level of B12; although not significant, this was still a clinical trend. Hp-IgG titer was negatively correlated with levels of FA (r = -0.601, P < .001) and B12 (r = -0.434, P < .001) and with the IIEF-5 score (r = -0.382, P < .001) and positively correlated with HCY (r = 0.69, P < .001). Clinical Implications: The ED group had higher levels of Hp-IgG titer and HCY and lower levels of B12 and FA. Strengths and Limitations: This study is the first to link Hp infection, FA, B12, and HCY and further explain the relationship between these indicators and the underlying pathologic mechanisms that jointly cause ED. The limitation is that our study was based on Hp-IgG titers, which do not necessarily represent the full extent of Hp infection, despite the avoidance of invasive testing. Conclusion: Hp infection might lead to decreased FA and B12 and then increased HCY, which might be a mechanism leading to ED. Hp eradication or FA and B12 supplementation might have certain clinical value in the treatment of vascular ED.

5.
Clin Transl Oncol ; 25(8): 2587-2606, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37000291

RESUMO

BACKGROUND: Bladder cancer (BLCA) is defined as a type of urinary cancer with high incidence and lack of specific biomarkers and drug targets. Immunogenic cell death (ICD) has been classified as a regulated type of cell death. Growing evidence suggested that ICD can reshape the tumor immune microenvironment, which may contribute to the development of immunotherapy strategies. The aim of this study was to reveal the specific mechanism of ICD in bladder cancer and to further predict the prognostic immunotherapy outcomes. METHODS: By consensus clustering analysis, bladder cancer patients in TCGA database were divided into different ICD subtypes. Additionally, we developed an ICD-scoring system and constructed the ICD score-based risk signature and nomogram to better characterize patients. Furthermore, we carried out a series of experiments to verify the relevant findings. RESULTS: Based on the transcriptome expression levels of ICD-related genes, a total of 403 BLCA patients in the TCGA database were divided into two subgroups with different ICD molecular patterns by consensus cluster analysis. These subgroups showed different clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related scores, and treatment response. Moreover, the established prediction model and ICD score can effectively distinguish high risk/score patients from low risk/score patients, which has excellent predictive value. Finally, we found that the key gene HSP90AA1 was highly expressed in the high-ICD score group and in bladder cancer tissues, and was confirmed to be associated with the proliferation of bladder cancer cells. CONCLUSION: To sum up, we established a new classification system for BLCA based on ICD-related genes. This stratification has significant predictive power for clinical outcomes and can effectively evaluate the prognosis and immunotherapy of BLCA patients. Finally, it was proved that HSP90AA1 was highly expressed in BLCA and would be a promising therapeutic target for BLCA.


Assuntos
Morte Celular Imunogênica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária , Imunoterapia , Morte Celular , Microambiente Tumoral , Prognóstico , Proteínas de Choque Térmico HSP90/genética
6.
Small ; 19(16): e2207194, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36634971

RESUMO

Cancer metastasis is the major cause of cancer-related death. Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors, creating confined spaces for tumor cell migration and metastasis. Confined migration is involved in all metastasis steps. However, confined and unconfined migration inhibitors are different and drugs available to inhibit confined migration are rare. The main challenges are the modeling of confined migration, the suffering of low throughput, and others. Microfluidic device has the advantage to reduce reagent consumption and enhance throughput. Here, a microfluidic chip that can achieve multi-function drug screening against the collective migration of cancer cells under confined environment is designed. This device is applied to screen out effective drugs on confined migration among a novel mechanoreceptors compound library (166 compounds) in hepatocellular carcinoma, non-small lung cancer, breast cancer, and pancreatic ductal adenocarcinoma cells. Three compounds that can significantly inhibit confined migration in pan-cancer: mitochonic acid 5 (MA-5), SB-705498, and diphenyleneiodonium chloride are found. Finally, it is elucidated that these drugs targeted mitochondria, actin polymerization, and cell viability, respectively. In sum, a high-throughput microfluidic platform for screening drugs targeting confined migration is established and three novel inhibitors of confined migration in multiple cancer types are identified.


Assuntos
Neoplasias Pulmonares , Técnicas Analíticas Microfluídicas , Humanos , Avaliação Pré-Clínica de Medicamentos , Movimento Celular , Microfluídica , Dispositivos Lab-On-A-Chip
7.
Oncol Lett ; 24(5): 389, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36276486

RESUMO

[This retracts the article DOI: 10.3892/ol.2013.1123.].

8.
Biosens Bioelectron ; 217: 114692, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150325

RESUMO

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment. We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells.


Assuntos
Técnicas Biossensoriais , Células Neoplásicas Circulantes , Anticorpos/química , Linhagem Celular Tumoral , Humanos , Ácido N-Acetilneuramínico , Células Neoplásicas Circulantes/patologia , Polímeros , Microambiente Tumoral
9.
Oncogene ; 41(5): 732-744, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34845378

RESUMO

Hyperactivation of RAS/MAPK signaling is commonly observed in hepatocellular carcinoma (HCC). Gain-of-function mutations of canonical RAS genes, however, are rarely detected and it remains unclear how the activity of this pathway is turned on during hepatocarcinogenesis. We performed a comprehensive analysis of RAS superfamily genetic alterations across ten subfamilies, 152 members in 377 HCC patients from the Cancer Genome Atlas database. RIT1 (Ras-like without CAAX 1) was the most frequently altered RAS member amplified in 13% of the HCC cohort. Both genomic amplification and CREB-mediated transcriptional activation contributed to the elevated RIT1 expression, and its overexpression correlated with RAS/MAPK activation and poor prognosis. Then, we found that RIT1-induced angiogenesis via the MEK/ERK/EIF4E/HIF1-α/VEGFA axis. MAP3K11 and MAP3K12, in addition to CRAF, could mediate this process by binding to RIT1. Moreover, RIT1 increased the phosphorylation of p38 MAPK and AKT to promote cell survival under reactive oxygen species stress. Based on this mechanistic understanding, we treated RIT1-overexpressing HCC with combined regimen sorafenib plus AKT inhibitor, and achieved enhanced antitumor effects in vivo. Our study reveals RAS "orphan" member RIT1 as the most common genetic alteration of RAS family in HCC and combination of sorafenib with AKT inhibitor might be a promising treatment strategy for RIT1-overexpressing HCC.


Assuntos
Carcinoma Hepatocelular , Humanos
10.
J Xray Sci Technol ; 26(5): 853-864, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30124464

RESUMO

Development of spectral X-ray computer tomography (CT) equipped with photon counting detector has been recently attracting great research interest. This work aims to improve the quality of spectral X-ray CT image. Maximum a posteriori (MAP) expectation-maximization (EM) algorithm is applied for reconstructing image-based weighting spectral X-ray CT images. A spectral X-ray CT system based on the cadmium zinc telluride photon counting detector and a fat cylinder phantom were simulated. Comparing with the commonly used filtered back projection (FBP) method, the proposed method reduced noise in the final weighting images at 2, 4, 6 and 9 energy bins up to 85.2%, 87.5%, 86.7% and 85%, respectively. CNR improvement ranged from 6.53 to 7.77. Compared with the prior image constrained compressed sensing (PICCS) method, the proposed method could reduce noise in the final weighting images by 36.5%, 44.6%, 27.3% and 18% at 2, 4, 6 and 9 energy bins, respectively, and improve the contrast-to-noise ratio (CNR) by 1.17 to 1.81. The simulation study also showed that comparing with the FBP and PICCS algorithms, image-based weighting imaging using MAP-EM statistical algorithm yielded significant improvement of the CNR and reduced the noise of the final weighting image.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Imagens de Fantasmas , Fótons
11.
Australas Phys Eng Sci Med ; 41(2): 371-377, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29637425

RESUMO

Contrast-enhanced subtracted breast computer tomography (CESBCT) images acquired using energy-resolved photon counting detector can be helpful to enhance the visibility of breast tumors. In such technology, one challenge is the limited number of photons in each energy bin, thereby possibly leading to high noise in separate images from each energy bin, the projection-based weighted image, and the subtracted image. In conventional low-dose CT imaging, iterative image reconstruction provides a superior signal-to-noise compared with the filtered back projection (FBP) algorithm. In this paper, maximum a posteriori expectation maximization (MAP-EM) based on projection-based weighting imaging for reconstruction of CESBCT images acquired using an energy-resolving photon counting detector is proposed, and its performance was investigated in terms of contrast-to-noise ratio (CNR). The simulation study shows that MAP-EM based on projection-based weighting imaging can improve the CNR in CESBCT images by 117.7%-121.2% compared with FBP based on projection-based weighting imaging method. When compared with the energy-integrating imaging that uses the MAP-EM algorithm, projection-based weighting imaging that uses the MAP-EM algorithm can improve the CNR of CESBCT images by 10.5%-13.3%. In conclusion, MAP-EM based on projection-based weighting imaging shows significant improvement the CNR of the CESBCT image compared with FBP based on projection-based weighting imaging, and MAP-EM based on projection-based weighting imaging outperforms MAP-EM based on energy-integrating imaging for CESBCT imaging.


Assuntos
Algoritmos , Mama/diagnóstico por imagem , Meios de Contraste/química , Aumento da Imagem , Tomografia Computadorizada por Raios X , Feminino , Humanos , Imagens de Fantasmas
12.
Chemosphere ; 188: 265-273, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28886561

RESUMO

The widespread environmental toxin cadmium (Cd) is associated with numerous human diseases. The essential trace element zinc (Zn) strongly counteracts Cd-induced toxicity; however, the mechanism is incompletely understood. Here, we conducted RNA sequencing and bioinformatics analyses to determine the global gene expression profiles of yeast cells exposed to Cd or Cd plus Zn. We identified 912 Cd-induced and 627 Cd plus Zn-induced differentially expressed genes (DEGs). Adding Zn during Cd exposure efficiently reversed the expression of 92.1% of Cd-induced DEGs; that of 48.7% was entirely reversed. Gene Ontology, Cluster of Orthologous Group and KEGG Ontology analyses revealed that the response of yeasts to Cd or Cd plus Zn was mainly involved in metal-specific oxidative stress; energy production and conversion; ion homeostasis and ribosome biogenesis and translation. Exposure of yeasts to Cd plus Zn protected them from oxidative stress by efficiently inhibiting the expression of genes associated with Cd-triggered oxidative stress and preventing the disruption of Fe- and Zn-ion homeostasis and reduced glutathione and partially restored mitochondrial membrane potential. Moreover, Zn reduced the intracellular level of Cd to prevent the replacement by Cd of elements required for antioxidant enzyme activity and to protect protein sulphydryl groups against oxidation by free radicals. Further, Zn inhibited the synthesis alterations of Cd-induced ribosomal proteins, S-containing amino acids, S-rich proteins and antioxidant enzymes. Conversely, the investigation results of our study on the yeast model revealed that the Cd-treated protective effects of Zn on Cd-induced toxicity might be partially protective.


Assuntos
Cádmio/toxicidade , Homeostase/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Transcriptoma/efeitos dos fármacos , Zinco/farmacologia , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Humanos , Íons/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Leveduras/efeitos dos fármacos , Leveduras/genética
13.
Phys Med ; 32(10): 1339-1343, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27623696

RESUMO

To effectively calculate an overlap volume histogram (OVH) descriptor and improve intensity modulated radiation treatment (IMRT) planning by basing it on previous plans with similar features, a method based on morphology for OVH calculation was proposed and a novel similarity measurement was employed for retrieval of a suitable IMRT plan. First, the minimum and maximum distances between the tumor and organs at risk (OARs) were calculated as the start and end points for contraction or expansion, and a suitable step size for contraction or expansion was determined according to these distances. Then, a dilation or erosion morphology operator was employed to compute the OVH descriptor. Finally, the performance of IMRT plan retrieval was evaluated, where the area between OVH descriptors was taken as the similarity measurement, and a 3D reconstruction for each case was also performed for visual comparison. Twenty-eight nasopharyngeal carcinoma (NPC) cases were evaluated. The results show that OVH descriptors can be calculated effectively with the proposed method, and match well to the 3D geometrical features of the tumor and OARs. Further, the IMRT plan retrieval results match well based on a visual inspection of their 3D geometrical features, and an increase of the area between OVH descriptors leads to a decrease of visual similarity. Therefore, the proposed method can be used effectively for the calculation of an OVH descriptor as well as the retrieval of similar IMRT cases.


Assuntos
Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Radioterapia de Intensidade Modulada/estatística & dados numéricos , Fenômenos Biofísicos , Carcinoma , Estudos de Viabilidade , Humanos , Imageamento Tridimensional/estatística & dados numéricos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco
14.
Biomed Mater Eng ; 24(6): 3479-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25227060

RESUMO

Intensity-Modulated Radiation Therapy (IMRT) mathematically forms a large-scale optimization problem. The development of an IMRT plan is computationally expensive resulting in time-consuming, inefficient, and difficult to develop high-quality IMRT plans. By combining prior knowledge with proposed novel measures derived from both Overlap Volume Histogram (OVH) descriptors and Dose Volume Histograms (DVHs), a novel quality control method for IMRT planning is proposed to assure the high quality of IMRT plan. Clinical approved nasopharyngeal IMRT plans were employed for the experiments, where the reference plan is firstly retrieved from IMRT plan database for each query case by using measures derived from both OVH descriptors and DVHs. Then the DVHs of the reference plan are served as additional goals for the IMRT plan re-optimization. The experimental results show that the proposed method can effectively pick out those IMRT plans, whose quality could be improved substantially (i.e. the doses of their Clinical Targets Volume (CTV) could be effectively increased) and the dose of their Organs at Risk (OARs) could be reduced after the IMRT plan has being re-optimized. In conclusion, the proposed methods can effectively guarantee the high quality of the IMRT planning.


Assuntos
Interpretação Estatística de Dados , Neoplasias Nasofaríngeas/radioterapia , Garantia da Qualidade dos Cuidados de Saúde/normas , Controle de Qualidade , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia Conformacional/normas , Carcinoma , China , Humanos , Carcinoma Nasofaríngeo , Garantia da Qualidade dos Cuidados de Saúde/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
15.
PLoS One ; 8(5): e62734, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23667514

RESUMO

Regulator of Cullins-1 (ROC1) is a key subunit in the Cullin-RING ligase (CRL) protein complex. Overexpression of ROC1 protein is associated with tumor progression and poor prognosis of non-muscle invasive bladder transitional cell carcinoma (NMIBC). This study was designed to assess the effects of ROC1 knockdown in bladder cancer cells and to determine the potential mechanisms involved. A total of 112 bladder cancer tissue specimens were recruited for immunohistochemical analyses of ROC1 overexpression. Bladder cancer cell lines were used to knockdown ROC1 expression using ROC1 siRNA. Our data showed that ROC1 knockdown remarkably inhibited bladder cancer cell growth, arrested cells at the G2 phase of the cell cycle, and induced the p53-dependent cell senescence. Molecularly, G2 arrest was associated with upregulation of p21, p27, cyclin B1, and Cdc2 proteins. ROC1 knockdown induced-senescence functioned through p53/p21 pathway. Knockdown of p21 expression partially rescued ROC1 knockdown-induced growth inhibition in cancer cells. Furthermore, nude mouse xenograft analyses confirmed these in vitro data. In conclusion, data from the current study indicate that ROC1 plays an essential role in bladder cancer progression and could serve as a novel anticancer target for bladder transitional cell carcinoma (BTCC).


Assuntos
Carcinoma de Células de Transição/metabolismo , Proteínas de Transporte/metabolismo , Senescência Celular/fisiologia , Pontos de Checagem da Fase G2 do Ciclo Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias da Bexiga Urinária/metabolismo , Análise de Variância , Animais , Western Blotting , Proteínas de Transporte/genética , Linhagem Celular Tumoral , China , Ensaio de Unidades Formadoras de Colônias , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Primers do DNA/genética , Feminino , Imunofluorescência , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Masculino , Camundongos , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , beta-Galactosidase
16.
Oncol Lett ; 5(3): 829-834, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23425975

RESUMO

The expression of microRNA-125b (miR-125b) has been investigated in many human cancers. It has been demonstrated to be downregulated in certain types of cancer, such as bladder cancer, thyroid anaplastic carcinomas, squamous cell carcinoma of the tongue, hepatocellular carcinoma, ovarian and breast cancer. In the present study, we examined the effects of miR-125b on bladder cancer cell migration and invasion. Following transfection of miR-125b, the expression of miR-125b was analyzed in T24 and EJ bladder cancer cells. Additionally, cell migration, cell invasion and luciferase assays, as well as western blot analysis were conducted in the bladder cancer cells. In this study, we demonstrated that miR-125b inhibited cell migration and invasion in T24 and EJ cells. We also provided the first evidence that miR-125b may directly target matrix metalloproteinase 13 (MMP13) in bladder cancer. Our study provided evidence that miR-125b suppresses cell migration and invasion by targeting MMP13 in bladder cancer cell lines. These results suggested that miR-125b could be used for the development of new molecular markers and therapeutic approaches to inhibit bladder cancer metastasis.

17.
Scand J Urol ; 47(5): 423-32, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23206218

RESUMO

OBJECTIVE: MicroRNA-133a (miR-133a) and microRNA-133b (miR-133b) are located on chromosome 18 in the same bicistronic unit. Recently, they have been commonly identified as being down-regulated in various human malignancies, such as bladder cancer, pancreatic ductal adenocarcinoma, oesophageal squamous cell carcinoma of the tongue, and hepatocellular and lung carcinomas. The present study examined the effects of miR-133a and miR-133b in bladder cancer T24 and EJ cells. MATERIAL AND METHODS: After transfection of miR-133a and miR-133b, the expression of miR-133a/b was assessed, and a cell viability assay, cell migration assay, cell invasion assay, luciferase assay and Western blot were conducted in bladder cancer T24 and EJ cells. RESULTS: Both miR-133a and miR-133b were found to inhibit cell proliferation, migration and invasion in T24 and EJ cells. The first evidence was provided that miR-133a and miR-133b may directly target the epidermal growth factor receptor in bladder cancer. CONCLUSIONS: This study provided the first glimpse of the functional role of miR-133 in bladder cancer T24 and EJ cells. The results may increase our knowledge on the molecular basis of progression and provide potential therapy for bladder cancer.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células , Receptores ErbB/fisiologia , MicroRNAs/fisiologia , Invasividade Neoplásica/fisiopatologia , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Metaloproteinase 2 da Matriz/fisiologia , MicroRNAs/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/fisiologia , Transfecção , Neoplasias da Bexiga Urinária/fisiopatologia
18.
Zhonghua Yi Xue Za Zhi ; 90(44): 3099-102, 2010 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-21211336

RESUMO

OBJECTIVE: To evaluate the urodynamics and functions of upper urinary tract in a substitute of orthotopic T pouch ileal bladder. METHODS: From June 2004 through September 2009, 90 patients underwent the construction of an orthotopic T pouch ileal neobladder after radical cystectomy for muscle-invasive bladder cancer. The radiographic or ultrasound evaluation of upper urinary tract, determination of renal functions and urodynamic evaluation of T pouch ileal neobladder were performed by data analysis. RESULTS: Renal function as determined by serum creatinine remained in a normal range in all patients. Temporary dilation of renal pelvic and ureter was observed in 18 patients (20.0%) at Day 45 post-operation and then disappeared spontaneously in the late follow-up. A slight dilation of collecting system was found in other 4 patients (4.4%), but there was no negative impact on renal function. Reflux into afferent limb of neobladder was observed in 4 patients (4.4%) by cystography. Excellent daytime and nighttime continence was reported in 100% and 82.2% of evaluated patients respectively. The urodynamic assessment showed a mean capacity of (316 ± 96) ml with a mean intra-bladder pressure of (16 ± 10) cm H2O. These evaluated patients voided with a mean maximum intra-bladder pressure of (87 ± 25) cm H2O, a mean maximum flow rate of (17 ± 10) ml/s and a mean residual urine of (33 ± 29) ml. CONCLUSION: With an intermediate follow-up, the functional results of T pouch ileal neobladder are encouraging with an excellent capacity and compliance, successful daytime and nighttime continence and anti-reflux mechanism.


Assuntos
Cistectomia/reabilitação , Íleo/transplante , Neoplasias da Bexiga Urinária/reabilitação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia , Coletores de Urina , Urodinâmica
19.
Comput Med Imaging Graph ; 31(6): 401-7, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17574815

RESUMO

This work deals with the treatment planning optimization for intravascular brachytherapy (IVB) in peripheral arteries. The objective is both to quantitatively study the validity of different hypotheses required for a reliable application of the treatment with current techniques, and to contribute to the definition and the specification of a new optimized procedure taking into account the actual patient's vessel geometry. The detection of vascular luminal surface was performed by an image analysis process, i.e., virtual active navigation, applied to standard CT data. Dose distribution was calculated according to the formalism proposed and recommended by the AAPM in TG43 and TG60. A method combining simulated annealing and BFGS algorithms was applied to optimize the parameters associated with the dwell points such as their number, positions, and dwell times. Dose-surface histogram (DSH) was used to evaluate the dose distribution results. Four levels of accuracy in target surface description were tested. The application of this optimization method to four different CT data sets including patient data, phantom and animal models showed that the treatment plan can be improved when the actual vessel geometry has been taken into account.


Assuntos
Angiografia/métodos , Artérias/efeitos da radiação , Braquiterapia/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/radioterapia , Simulação por Computador , Análise de Elementos Finitos , Humanos , Modelos Biológicos , Radiometria/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa
20.
Zhongguo Yi Liao Qi Xie Za Zhi ; 31(6): 391-4, 444, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18269033

RESUMO

The optimization methods in radiation treatment planning are reviewed in this paper, including the physical and biological optimization models, the optimization for Gamma knife treatment planning, the optimization for intensity modulated radiation treatment planning and the optimization for intravascular brachytherapy treatment planning. The development trend of radiation treatment planning is also introduced in the paper.


Assuntos
Planejamento da Radioterapia Assistida por Computador/métodos , Protocolos Antineoplásicos , Humanos , Modelos Biológicos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/tendências
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