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Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.
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Tomografia Computadorizada de Feixe Cônico , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Processo Alveolar/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Inteligência Artificial , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Dente/diagnóstico por imagemRESUMO
Saliva blood mixed liquid (SBML) appears in oral surgery, such as scaling and root planning, and it affects surgical vision and causes discomfort to the patient. However, removing SBML, i.e. frequent aspiration of the mixed liquid, is a routine task involving heavy workload and interruption of oral surgery. Therefore, it is valuable to alternate the manual mode by autonomous robotic technique. The robotic system is designed consisting of an RGB-D camera, a manipulator, a disposable oral aspirator. An algorithm is developed for detection of SBML. Path planning method is also addressed for the distal end of the aspirator. A workflow for removing SBML is presented. 95% of the area of the SBML in the oral cavity was removed after liquid aspiration among a group of ten SBML aspiration experiments. This study provides the first result of the autonomous aspirating robot (AAR) for removing SBML in oral surgery, demonstrating that SBML can be removed by the autonomous robot, freeing stomatology surgeon from tedious work.
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Procedimentos Cirúrgicos Bucais , Robótica , Humanos , SalivaRESUMO
OBJECTIVE: One of the major difficulties in spinal surgery is the injury of important tissues caused by tissue misclassification, which is the source of surgical complications. Accurate recognization of the tissues is the key to increase safety and effect as well as to reduce the complications of spinal surgery. The study aimed at tissue recognition in the spinal operation area based on electrical impedance and the boundaries of electrical impedance between cortical bone, cancellous bone, spinal cord, muscle, and nucleus pulposus. METHODS: Two female white swines with body weight of 40 kg were used to expose cortical bone, cancellous bone, spinal cord, muscle, and nucleus pulposus under general anesthesia and aseptic conditions. The electrical impedance of these tissues at 12 frequencies (in the range of 10-100 kHz) was measured by electrochemical analyzer with a specially designed probe, at 22.0-25.0°C and 50%-60% humidity. Two types of tissue recognition models - one combines principal component analysis (PCA) and support vector machine (SVM) and the other combines combines SVM and ensemble learning - were constructed, and the boundaries of electrical impedance of the five tissues at 12 frequencies of current were figured out. Linear correlation, two-way ANOVA, and paired T-test were conducted to analyze the relationship between the electrical impedance of different tissues at different frequencies. RESULTS: The results suggest that the differences of electrical impedance mainly came from tissue type (p < 0.0001), the electrical impedance of five kinds of tissue was statistically different from each other (p < 0.0001). The tissue recognition accuracy of the algorithm based on principal component analysis and support vector machine ranged from 83%-100%, and the overall accuracy was 95.83%. The classification accuracy of the algorithm based on support vector machine and ensemble learning was 100%, and the boundaries of electrical impedance of five tissues at various frequencies were calculated. CONCLUSION: The electrical impedance of cortical bone, cancellous bone, spinal cord, muscle, and nucleus pulposus had significant differences in 10-100 kHz frequency. The application of support vector machine realized the accurate tissue recognition in the spinal operation area based on electrical impedance, which is expected to be translated and applied to tissue recognition during spinal surgery.
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Algoritmos , Máquina de Vetores de Suporte , Animais , Impedância Elétrica , Feminino , SuínosRESUMO
A burn mark is a sort of serious surface defect on injection-molded parts. In some cases, it can be difficult to reduce the burn marks by traditional methods. In this study, external gas-assisted injection molding (EGAIM) was introduced to reduce the burn marks, as EGAIM has been reported to reduce the holding pressure. The parts with different severities of burn marks were produced by EGAIM and conventional injection molding (CIM) with the same molding parameters but different gas parameters. The burn marks were quantified by an image processing method and the quantitative method was introduced to discuss the influence of the gas parameters on burn marks. The results show that the burn marks can be eliminated by EGAIM without changing the structure of the part or the mold, and the severity of the burn marks changed from 4.98% with CIM to 0% with EGAIM. Additionally, the gas delay time is the most important gas parameter affecting the burn marks.
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OBJECTIVE: Biopsies are the gold standard for clinical diagnosis. However, a discrepancy between the biopsy sample and target tissue because of misplacement of the biopsy spoon can lead to errors in the diagnosis and subsequent treatment. Thus, correctly determining whether the needle tip is in the tumor is crucial for accurate biopsy results. METHODS: A biopsy needle system was designed with a steerable, flexible, and superelastic concentric tube; electrodes to monitor the electrical resistivity; and load cells to monitor the insertion force. The degrees of freedom were analyzed for two working modes: straight-line and deflection. RESULTS: Experimental results showed that the system could perceive the tissue type in online based on the electrical resistivity. In addition, changes in the insertion force indicated transitions between the interfaces of adjacent tissue layers. CONCLUSION: The two monitoring methods guarantee that the biopsy spoon is at the desired position inside the tumor during an operation. SIGNIFICANCE: The proposed biopsy needle system can be integrated into an autonomous robotic biopsy system.
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Agulhas , Biópsia , Biópsia por Agulha , Desenho de EquipamentoRESUMO
BACKGROUND: Robot-assisted pedicle screw insertion has gained popularity in the spinal surgery field. Due to high cost, these spinal robots are not extensively applied in clinical surgeries. Developing an effective robot system with low cost and high clinical acceptability is one of the future trends. METHODS: We developed a novel fluoroscopy-based robot system for pedicle screw insertion. Four live pigs were conducted with percutaneous pedicle screw insertion. Robot-assisted surgery was performed on the left side of pedicle, while the right opposite side is placed by freehand. The respect accuracy, surgical time and fluoroscopy time were recorded. RESULTS: Robot-assisted group achieved 100% (23/23) accuracy. The average times (6.4 ± 1.7) for intraoperative fluoroscopy usage per procedure were lesser than freehand group (12.5 ± 3.6), and the surgical time (6.8 ± 2.1 min) per screw was reduced compared with freehand group (12.1 ± 4.8 min). CONCLUSIONS: Our robot system is cost-effective and feasible for pedicle screw placement. Low economic cost makes it easier for extensive application in primary hospitals.
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Parafusos Pediculares , Robótica , Fusão Vertebral , Cirurgia Assistida por Computador , Animais , Fluoroscopia , Vértebras Lombares , SuínosRESUMO
In this chapter, we present a multi-object model-based multi-atlas segmentation constrained grid cut method for automatic segmentation of lumbar vertebrae from a given lumbar spinal CT image. More specifically, our automatic lumbar vertebrae segmentation method consists of two steps: affine atlas-target registration-based label fusion and bone-sheetness assisted multi-label grid cut which has the inherent advantage of automatic separation of the five lumbar vertebrae from each other. We evaluate our method on 21 clinical lumbar spinal CT images with the associated manual segmentation and conduct a leave-one-out study. Our method achieved an average Dice coefficient of 93.9 ± 1.0% and an average symmetric surface distance of 0.41 ± 0.08 mm.
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Processamento de Imagem Assistida por Computador , Vértebras Lombares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Algoritmos , HumanosRESUMO
Angiosarcoma is a malignant tumor of endothelial origin. Epithelioid angiosarcoma is a subtype of angiosarcoma, in which the malignant endothelial cells have a predominantly epithelioid appearance. So far, few cases of primary hepatic epithelioid andiosarcoma (PHEA) have been described. In this case report, we describe two rare cases of PHEA. Microscopically, the tumors were consistently composed of atypical epithelioid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm. One patient had metastatic disease and underwent palliative hepatic surgery following radiotherapy and chemotherapy, and had a postoperative survival time of 12 months, while the other patient is still alive after tumor resection. PHEA is an aggressive malignant tumor with a high rate of metastasis.
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BACKGROUND: Sacroiliac (SI) screw fixation is a demanding technique, with a high rate of screw malposition due to the complex pelvic anatomy. TiRobot™ is an orthopedic surgery robot which can be used for SI screw fixation. This study aimed to evaluate the accuracy of robot-assisted placement of SI screws compared with a freehand technique. METHODS: Thirty patients requiring posterior pelvic ring stabilization were randomized to receive freehand or robot-assisted SI screw fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty-five screws were placed at levels S1 and S2. In both methods, the primary end point screw position was assessed and classified using postoperative computed tomography. Fisher's exact probability test was used to analyze the screws' positions. Secondary end points, such as duration of trajectory planning, surgical time after reduction of the pelvis, insertion time for guide wire, number of guide wire attempts, and radiation exposure without pelvic reduction, were also assessed. RESULTS: Twenty-three screws were placed in the robot-assisted group and 22 screws in the freehand group; no postoperative complications or revisions were reported. The excellent and good rate of screw placement was 100% in the robot-assisted group and 95% in the freehand group. The P value (0.009) showed the same superiority in screw distribution. The fluoroscopy time after pelvic reduction in the robot-assisted group was significantly shorter than that in the freehand group (median [Q1, Q3]: 6.0 [6.0, 9.0] s vs. median [Q1, Q3]: 36.0 [21.5, 48.0] s; χ2 = 13.590, respectively, P < 0.001); no difference in operation time after reduction of the pelvis was noted (χ2 = 1.990, P = 0.158). Time for guide wire insertion was significantly shorter for the robot-assisted group than that for the freehand group (median [Q1, Q3]: 2.0 [2.0, 2.7] min vs. median [Q1, Q3]: 19.0 [15.5, 45.0] min; χ2 = 20.952, respectively, P < 0.001). The number of guide wire attempts in the robot-assisted group was significantly less than that in the freehand group (median [Q1, Q3]: 1.0 [1.0,1.0] time vs. median [Q1, Q3]: 7.0 [1.0, 9.0] times; χ2 = 15.771, respectively, P < 0.001). The instrumented SI levels did not differ between both groups (from S1 to S2, χ2 = 4.760, P = 0.093). CONCLUSIONS: Accuracy of the robot-assisted technique was superior to that of the freehand technique. Robot-assisted navigation is safe for unstable posterior pelvic ring stabilization, especially in S1, but also in S2. SI screw insertion with robot-assisted navigation is clinically feasible.
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Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Ossos Pélvicos/cirurgia , Robótica/métodos , Sacro/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: The hand-eye calibration is used to determine the transformation between the end-effector and the camera marker of the robot. But the robot movement in traditional method would be time-consuming, inaccurate and even unavailable in some conditions. The method presented in this article can complete the calibration without any movement and is more suitable in clinical applications. METHODS: Instead of solving the classic non-linear equation AX = XB, we collected the points on X and Y axes of the tool coordinate system (TCS) with the visual probe and fitted them using the singular value decomposition algorithm (SVD). Then, the transformation was obtained with the data of the tool center point (TCP). A comparison test was conducted to verify the performance of the method. RESULTS: The average translation error and orientation error of the new method are 0.12 ± 0.122 mm and 0.18 ± 0.112° respectively, while they are 0.357 ± 0.347 mm and 0.416 ± 0.234° correspondingly in the traditional method. CONCLUSIONS: The high accuracy of the method indicates that it is a good candidate for medical robots, which usually need to work in a sterile environment.
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Algoritmos , Fixação de Fratura/instrumentação , Robótica/métodos , Cirurgia Assistida por Computador/métodos , Calibragem , Olho , Fixação de Fratura/métodos , Mãos , Humanos , ManequinsRESUMO
BACKGROUND: Spatial positioning is the key function of a surgical navigation robot system, and accuracy is the most important performance index of such a system. METHODS: The kinematic parameters of a six degrees of freedom (DOF) robot arm were used to form the transformation from intraoperative fluoroscopy images to a robot's coordinate system without C-arm calibration and to solve the redundant DOF problem. The influences of three typical error sources and their combination on the final navigation error were investigated through Monte Carlo simulation. RESULTS: The navigation error of the proposed method is less than 0.6 mm, and the feasibility was verified through cadaver experiments. Error analysis suggests that the robot kinematic error has a linear relationship with final navigation error, while the image error and gauge error have nonlinear influences. CONCLUSIONS: This kinematic parameters based method can provide accurate and convenient navigation for orthopedic surgeries. The result of error analysis will help error design and assignment for surgical robots.
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Procedimentos Ortopédicos/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Algoritmos , Fenômenos Biomecânicos , Cadáver , Desenho de Equipamento , Fluoroscopia , Humanos , Modelos Anatômicos , Monitorização Intraoperatória/instrumentação , Monitorização Intraoperatória/métodos , Monitorização Intraoperatória/estatística & dados numéricos , Método de Monte Carlo , Movimento (Física) , Procedimentos Ortopédicos/instrumentação , Procedimentos Ortopédicos/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/estatística & dados numéricosRESUMO
We here evaluated the potential anti-colorectal cancer activity by erastin, a voltage-dependent anion channel (VDAC)-binding compound. Our in vitro studies showed that erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells, which was evidenced by VDAC-1 and cyclophilin-D (Cyp-D) association, mitochondrial depolarization, and cytochrome C release. Caspase inhibitors, the ROS scavenger MnTBAP, and mPTP blockers (sanglifehrin A, cyclosporin A and bongkrekic acid), as well as shRNA-mediated knockdown of VDAC-1, all significantly attenuated erastin-induced cytotoxicity and apoptosis in colorectal cancer cells. On the other hand, over-expression of VDAC-1 augmented erastin-induced ROS production, mPTP opening, and colorectal cancer cell apoptosis. In vivo studies showed that intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Together, these results demonstrate that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. Erastin may be further investigated as a novel anti-colorectal cancer agent.
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Apoptose/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Piperazinas/farmacologia , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HT29 , Humanos , Camundongos SCID , Poro de Transição de Permeabilidade Mitocondrial , Piperazinas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Computer-assisted navigation technology has been widely used during spine surgery; however, the desired accuracy cannot be easily obtained and sustained. Our goal was to determine whether and how clinical factors affect the accuracy of a CT-based active infrared navigation system. METHODS: Using the Sawbone model, we recorded the clinical accuracy of the navigation system, based on several clinical statuses. RESULTS: Clinical accuracy may change when the height or angle of the bed is changed. Within the visible area of the camera, the nearer the distance between the camera and the model, the better the clinical accuracy. The clinical accuracy of the CT-based active infrared navigation system may decrease due to exposure to shadowless lamps. CONCLUSIONS: The clinical accuracy of the CT-based active infrared navigation system may be influenced by the clinical status of shadowless lamps, different distances between the camera and model and different postures of the surgical bed. Copyright © 2015 John Wiley & Sons, Ltd.
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Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Raios InfravermelhosRESUMO
OBJECTIVE: To investigate the role of transmembrane protein (TMP) 21 in human thyroid cancer. METHODS: The recombinant expression vector pcDNA3.1 (+)-TMP21 and specific small interfering RNAs (siRNA) against TMP21 were transfected into a papillary thyroid cancer cell line (TPC1). After transfection, the expression of TMP21 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, cell viability and apoptosis rate were respectively determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry (FCM). Additionally, Western blotting was performed to analyze the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways associated protein (P-AMPKα(Thr172), P-mTOR(Ser2448), light chain (LC)-II/LC3-I, and P-S6K(Thr389)) after pre-treatment with AMPK inhibitor, compound C (Com C) and siTMP21. RESULTS: The TMP21 protein level and cell viability were significantly higher, but apoptotic rate was significantly lower by transfection with pcDNA3.1-TMP21 than those in control group (P < 0.05), and reverse results were obtained by transfection with siTMP21. However, qRT-PCR showed different results due to the feedback inhibition of mRNA. Besides, silencing of TMP21 significantly reduced the levels of P-mTOR(Ser2448) and P-S6K(Thr389) (P < 0.05), but significantly increased the levels of P-AMPKα(Thr172) and LC3-II/LC3-I compared with the control group (P < 0.01). Whereas, the levels of P-AMPKα(Thr172) and LC3-II/LC3-I were significantly decreased by Com C compared with the control group (P < 0.05). CONCLUSION: TMP21 modulates cell growth in TPC1 cells by inducing autophagy, which may be associated with activation of AMPK/mTOR pathway.
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Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Carcinoma/enzimologia , Proliferação de Células , Proteínas de Membrana/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Glândula Tireoide/enzimologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Apoptose , Autofagia/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Carcinoma Papilar , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Proteínas de Transporte Nucleocitoplasmático , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Transdução de Sinais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , TransfecçãoRESUMO
The objectives of this study were to evaluate the in vitro anti-tumor (human thyroid cancer cell lines) potential of curcumin and to elucidate its molecular mechanisms. Here, we investigated the effects of curcumin on the cell viability, apoptosis, migration and invasion of human thyroid cancer cell lines FTC133. We also investigated the effects of curcumin on PI3K, p-Akt, MMP1/7, and COX-2 protein expressions using Western blot. Results showed that curcumin inhibited growth, cell migration and invasion in FTC133, and promoted its apoptosis. Western blot assay data demonstrated that curcumin inhibited phosphorylation of PI3K and Akt signaling pathways and subsequently attenuated MMP1/7 and COX-2 protein expressions in FTC133. In conclusion, curcumin suppresses FTC133 cell invasion and migration by inhibiting PI3K and Akt signaling pathways. Therefore, curcumin produces anti-metastatic activity in FTC133 cells.
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Antineoplásicos/farmacologia , Curcumina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Neoplasias da Glândula Tireoide/enzimologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/biossíntese , Humanos , Metaloproteinase 1 da Matriz/biossíntese , Metaloproteinase 7 da Matriz/biossíntese , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/patologiaRESUMO
Colorectal cancer is a major contributor of cancer-related mortality. The mammalian target or rapamycin (mTOR) signaling is frequently hyper-activated in colorectal cancers, promoting cancer progression and chemo-resistance. In the current study, we investigated the anti-colorectal cancer effect of a novel mTOR complex 1 (mTORC1) and mTORC2 dual inhibitor: AZD-2014. In cultured colorectal cancer cell lines, AZD-2014 significantly inhibited cancer cell growth without inducing significant cell apoptosis. AZD-2014 blocked activation of both mTORC1 (S6K and S6 phosphorylation) and mTORC2 (Akt Ser 473 phosphorylation), and activated autophagy in colorectal cancer cells. Meanwhile, autophagy inhibition by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the apoptosis inhibitor had no rescue effect. In vivo, AZD-2014 oral administration significantly inhibited the growth of HT-29 cell xenograft in SCID mice, and the mice survival was dramatically improved. At the same time, in xenografted tumors administrated with AZD-2014, the activation of mTORC1 and mTORC2 were largely inhibited, and autophagic markers were significantly increased. Thus, AZD-2014 inhibits colorectal cancer cell growth both in vivo and in vitro. Our results suggest that AZD-2014 may be further investigated for colorectal cancer therapy in clinical trials.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Camundongos SCID , Resultado do TratamentoRESUMO
Colorectal cancer is the second leading cause of cancer-related deaths. Drug resistance and/or off-target toxicity against normal cells limit the effectiveness of current chemotherapies for the treatment of colorectal cancer. In the current study, we studied the potential cytotoxic effects of short-chain and cell-permeable C6 ceramide in cultured colorectal cancer HT-29 cells and focused on the underlying mechanisms. We observed that C6 ceramide-induced HT-29 cell death and growth inhibition in a dose- and time-dependent manner. However, no significant apoptosis was observed in C6 ceramide-treated HT-29 cells. Our data support that autophagy contributed to C6 ceramide-induced cytotoxic effects, as autophagy inhibitors, 3-methyladenine (3-MA) and hydroxychloroquine, inhibited C6 ceramide's effect; however, autophagy activators, everolimus (RAD001) and temsirolimus, mimicked C6 ceramide effects and induced HT-29 cell death. Further, we indentified that AMP-activated protein kinase (AMPK)/Ulk1 signaling was required for autophagy induction by C6 ceramide, and AMPK silencing by a specific short hairpin RNA suppressed C6 ceramide-induced autophagy and cytotoxic effects. Reversely, forced activation of AMPK by its activator AICAR or by genetic manipulation caused autophagic death in HT-29 cells, which was inhibited by 3-MA. Our results suggest that autophagy, but not apoptosis, is a major contributor for C6 ceramide-induced cytotoxic effects in HT-29 cells, and activation of AMPK/Ulk1 is required for the process.
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Proteínas Quinases Ativadas por AMP/fisiologia , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Ceramidas/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Apoptose , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais , Ativação Enzimática/efeitos dos fármacos , Everolimo , Células HCT116 , Células HT29 , Humanos , Ribonucleotídeos/farmacologia , Transdução de Sinais , Sirolimo/análogos & derivados , Sirolimo/farmacologiaRESUMO
BACKGROUND: Image guided navigation systems (IGNS) have been implemented successfully in orthopaedic trauma surgery procedures because of their ability to help surgeons position and orient hand-held drills at optimal entry points. However, current IGNS cannot prevent drilling tools or instruments from slipping or deviating from the planned trajectory during the drilling process. A method is therefore needed to overcome such problems. METHODS: A novel passive/active hybrid robot (the HybriDot) for positioning and supporting surgical tools and instruments while drilling and/or cutting in orthopaedic trauma surgery is presented in this paper. This new robot, consisting of a circular prismatic joint and five passive/active back-drivable joints, is designed to fulfill clinical needs. In this paper, a system configuration and three operational modes are introduced and analyzed. Workspace and layout in the operating theatre (OT) are also analyzed in order to validate the structure design. Finally, experiments to evaluate the feasibility of the robot system are described. RESULTS: Analysis, simulation, and experimental results show that the novel structure of the robot can provide an appropriate workspace without risk of collision within OT environments during operation. The back-drivable joint mechanism can provide surgeons with more safety and flexibility in operational modes. The mean square value of the positional accuracy of this robot is 0.811 mm, with a standard deviation (SD) of 0.361 mm; the orientation is accurate to within 2.186º, with a SD of 0.932º. Trials on actual patients undergoing surgery for distal locking of intramedullary nails were successfully conducted in one pass using the robot. CONCLUSION: This robot has the advantages of having an appropriate workspace, being well designed for human-robot cooperation, and having high accuracy, sufficient rigidity, and easy deployability within the OT for use in common orthopaedic trauma surgery tasks such as screw fixation and drilling assistance.
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Procedimentos Ortopédicos/instrumentação , Robótica/instrumentação , Cirurgia Assistida por Computador/instrumentação , Ferimentos e Lesões/cirurgia , Fenômenos Biomecânicos , Desenho de Equipamento , Humanos , Salas Cirúrgicas , Interface Usuário-ComputadorRESUMO
The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA (mtDNA) replication and transcription. Disruption of TFAM results in heart failure and premature aging in mice. But very little is known about the role of TFAM in cancer development. Here, we report the identification of frequent frameshift mutations in the coding mononucleotide repeat of TFAM in sporadic colorectal cancer (CRC) cell lines and in primary tumors with microsatellite instability (MSI), but not in microsatellite stable (MSS) CRC cell lines and tumors. The presence of the TFAM truncating mutation, in CRC cells with MSI, reduced the TFAM protein level in vivo and in vitro and correlated with mtDNA depletion. Furthermore, forced overexpression of wild-type TFAM in RKO cells carrying a TFAM truncating mutation suppressed cell proliferation and inhibited RKO cell-induced xenograft tumor growth. Moreover, these cells showed more susceptibility to cisplatin-induced apoptosis due to an increase of cytochrome b (Cyt b) expression and its release from mitochondria. An interaction assay between TFAM and the heavy-strand promoter (HSP) of mitochondria revealed that mutant TFAM exhibited reduced binding to HSP, leading to reduction in Cyt b transcription. Collectively, these data provide evidence that a high incidence of TFAM truncating mutations leads to mitochondrial copy number reduction and mitochondrial instability, distinguishing most CRC with MSI from MSS CRC. These mutations may play an important role in tumorigenesis and cisplatin-induced apoptotic resistance of most microsatellite-unstable CRCs.
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Apoptose/genética , Neoplasias Colorretais/genética , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/genética , Mutação da Fase de Leitura , Instabilidade de Microssatélites , Proteínas Mitocondriais/genética , Fatores de Transcrição/genética , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sequência de Bases , Linhagem Celular Tumoral , Cisplatino/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Citocromos b/genética , Citocromos b/metabolismo , Regulação para Baixo , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Transcrição Gênica , Transplante HeterólogoRESUMO
A pH-sensitive gold nanoparticle-cysteamine/carboxymethyl cellulose (Au-CA/CMC) dispersion system was prepared by a simple approach. Gold nanoparticles (AuNPs) were first synthesized by directly reducing chloroauric acid (HAuCl(4)) with sodium carboxymethyl cellulose (CMC). Then the AuNPs were decorated by an electrostatic compound of cysteamine hydrochloride (CA) and sodium carboxymethyl cellulose (CMC) through ligand exchange to get the assembly of Au-CA/CMC. The Au-CA/CMC dispersion system exhibits strongly reversible pH-responsive behavior with the aggregation of AuNPs caused by the combined action of the chain conformation change of CMC and electrostatic interactions between CA and CMC at different pH values. Finally, the reversible aggregation mechanism of AuNPs in the Au-CA/CMC dispersion system has been investigated by transmission electron microscopy (TEM) and ultraviolet-visible spectroscopy (UV-vis spectroscopy). This study provides a new method to fabricate a stimuli-responsive system free from complicated organic synthesis without using a toxic reducing agent.