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INTRODUCTION: The postoperative survival of oral squamous cell carcinoma (SCC) relies on precise detection and complete resection of original tumors. The mucosal extension of the tumor is evaluated visually during surgery, but small and flat foci are difficult to detect. Real-time fluorescence imaging may improve detection of tumor margins. MATERIALS AND METHODS: In the current study, a peptide-based near-infrared (NIR) fluorescence dye, c-MET-binding peptide-indocyanine green (cMBP-ICG), which specifically targets tumor via c-MET binding, was synthetized. A prospective pilot clinical trial then was conducted with oral SCC patients and intraoperatively to assess the feasibility of cMBP-ICG used to detect tumors margins. Fluorescence was histologically correlated to determine sensitivity and specificity. RESULTS: The immunohistochemistry (IHC) results demonstrated increased c-Met expression in oral SCC compared with normal mucosa. Tumor-to-background ratios ranged from 2.71 ± 0.7 to 3.11 ± 1.2 in different concentration groups. From 10 patients with oral SCC, 60 specimens were collected from tumor margins. The sensitivity and specificity of discriminative value derived from cMBP-ICG application in humans were respectively 100% and 75%. CONCLUSIONS: Topical application of cMBP-ICG is feasible and safe for optimizing intraoperative visualization and tumor margin detection in oral SCC patients, which could clinically increase the probability of complete resections and improve oncologic outcomes.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Verde de Indocianina , Corantes Fluorescentes , Estudos Prospectivos , PeptídeosRESUMO
A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.
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Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Quinolizinas/farmacologia , Sophora/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Quinolizinas/química , Quinolizinas/isolamento & purificação , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Solubilidade , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Água/química , MatrinasRESUMO
Long noncoding RNA (lncRNA) DUXAP10 has been shown to act as an oncogene in various tumors; however, its roles in glioma progression have never been established. Here, we show that DUXAP10 is overexpressed in glioma tissues and cells. Loss of function experiments reveal that DUXAP10 knockdown has little effects on glioma cell viability, but significantly reduces the stemness of glioma cells, which is characterized as the decrease of stemness marker expression, tumor sphere-forming ability, and ALDH activity. RNA immunoprecipitation and immunofluorescence assays indicate that DUXAP10 can directly interact with HuR protein and suppress the cytoplasm-nuclear translocation of HuR, which subsequently enhances Sox12 mRNA stability in cytoplasm and thus increases Sox12 expression. Further rescuing experiments show that the HuR/Sox12 axis is responsible for DUXAP10-mediated effects on glioma cell stemness.
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Glioma , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Estabilidade de RNA , RNA Longo não Codificante/genética , Fatores de Transcrição SOXCRESUMO
Brainstem hemorrhage is presumed to be invariably associated with a poor prognosis in people with spontaneous hypertensive cerebral hemorrhage. The optimal timing of tracheostomy placement in brainstem hemorrhage patients, who generally require endotracheal intubation for airway protection, remains uncertain. Our research aim was to analyze the impact of early tracheostomy versus late tracheostomy on brainstem hemorrhage patients related outcomes and prognostic factors at 30 days. We identified early tracheostomy and how it could benefit the patients with brainstem hemorrhage and ameliorate the predictors of functional recovery at 30 days. Data on 136 patients with brainstem hemorrhage and Glasgow Coma Scale score ≤ 8, were retrospectively collected from 2012 to 2019. Patients were divided into the early tracheostomy group and the late tracheostomy group. Patients in the early tracheostomy group had a significantly lower neurosurgical intensive care unit stay (both overall and survival) compared with the late tracheostomy group (15.6 days vs. 19.0 days, P = 0.041, overall and 14.5 vs. 19.5 days, P = 0.023, survival). Also, the good outcomes (modified Rankin Score ≤ 3) were higher in the early tracheostomy group (P = 0.036). Multivariate analysis demonstrated that less hemorrhagic volume, high Glasgow Coma Scale score on admission, young age, and early tracheostomy were significantly associated with a better 30-day functional outcome. In conclusion, an early tracheostomy in patients with brainstem hemorrhage can reduce neurosurgical intensive care unit stay, and in addition to improvements in prognosis at 30 days.
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Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/patologia , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/cirurgia , Traqueostomia , Feminino , Humanos , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores de Interleucina-1 , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
How to select and combine good traits of rice to get high-production individuals is one of the key points in developing crop ideotype cultivation technologies. Existing cultivation methods for producing ideal plants, such as field trials and crop modeling, have some limits. In this paper, we propose a method based on a genetic algorithm (GA) and a functional-structural plant model (FSPM) to optimize plant types of virtual rice by dynamically adjusting phenotypical traits. In this algorithm, phenotypical traits such as leaf angles, plant heights, the maximum number of tiller, and the angle of tiller are considered as input parameters of our virtual rice model. We evaluate the photosynthetic output as a function of these parameters, and optimized them using a GA. This method has been implemented on GroIMP using the modeling language XL (eXtended L-System) and RGG (Relational Growth Grammar). A double haploid population of rice is adopted as test material in a case study. Our experimental results show that our method can not only optimize the parameters of rice plant type and increase the amount of light absorption, but can also significantly increase crop yield.
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Algoritmos , Oryza/genética , Característica Quantitativa Herdável , Absorção de Radiação , Simulação por Computador , Aptidão Genética , Luz , Tamanho do Órgão , Oryza/anatomia & histologia , Oryza/efeitos da radiação , Fenótipo , Reprodutibilidade dos TestesRESUMO
A method to compute the similarity between different plants is proposed, using features of a plant׳s topological structure and peripheral contour, as well as its geometry. The topological structures are described using tree graphs, and their similarity can be calculated based on the edit distance of these graphs. The peripheral contour of a plant is abstracted by its three-dimensional convex hull, which is projected in several directions. The similarity of the different projections is calculated by an algorithm to compute the similarity of two-dimensional shapes. The similarity of the geometrical detail is computed by considering the geometrical properties of different level branches. Finally the overall similarity between different plants is calculated by combining these different similarity measures. The validity of proposed method is evaluated by detailed experiments.
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Imageamento Tridimensional/métodos , Plantas/anatomia & histologia , Algoritmos , Simulação por Computador , Especificidade da Espécie , Árvores/anatomia & histologiaRESUMO
Background: Posterior fossa craniotomy is commonly performed for various pathologies. However, intra-cranial infection following craniotomy causes morbidity. Pseudomeningocele is one of the main complications following posterior fossa operation. This study aimed to test the hypothesis that the risk of intra-cranial infection is increased in patients who undergo posterior fossa craniotomy with pseudomeningocele compared with those without pseudomeningocele. Methods: We retrospectively analyzed the data of patients undergoing posterior fossa craniotomy for the management of neurological pathologies at our institute from 2011 to 2020. A total of 308 craniotomies were included, and the primary outcome of interest was the occurrence of intra-cranial infection. Standard statistical methods were used to explore associations between several parameters, including pseudomeningocele, intra-cranial infection, and wound leak. Results: Of the 308 craniotomies, 41 (13.3%) developed intra-cranial infection and 59 (19.2%) involved pseudomeningocele. Of cases involving pseudomeningocele, 27 (45.8%) developed an intra-cranial infection compared with only 14 of 249 without pseudomeningocele (5.6%; p < 0.001). In the multi-variable analysis, pseudomeningocele was associated with intra-cranial infection (odds ratio [OR] 8.56; 95% confidence interval [CI] 3.145-23.299; p < 0.001) and wound leak (OR 91.339; 95% CI 10.437-799.364; p < 0.001). Conclusion: The findings indicate that patients undergoing posterior fossa craniotomy are at a greater risk of intra-cranial infection if there is pseudomeningocele after the operation.
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Introduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy. Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO). Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells. Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.
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Meios de Contraste , Compostos de Manganês , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Óxidos , Imageamento por Ressonância Magnética , Microambiente TumoralRESUMO
Glioblastoma (GBM), one of the most malignant brain tumors in the world, has limited treatment options and a dismal survival rate. Effective and safe disease-modifying drugs for glioblastoma are urgently needed. Here, we identified a small molecule, Molephantin (EM-5), effectively penetrated the blood-brain barrier (BBB) and demonstrated notable antitumor effects against GBM with good safety profiles both in vitro and in vivo. Mechanistically, EM-5 not only inhibits the proliferation and invasion of GBM cells but also induces cell apoptosis through the reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Furthermore, EM-5 causes mitochondrial dysfunction and blocks mitophagy flux by impeding the fusion of mitophagosomes with lysosomes. It is noteworthy that EM-5 does not interfere with the initiation of autophagosome formation or lysosomal function. Additionally, the mitophagy flux blockage caused by EM-5 was driven by the accumulation of intracellular ROS. In vivo, EM-5 exhibited significant efficacy in suppressing tumor growth in a xenograft model. Collectively, our findings not only identified EM-5 as a promising, effective, and safe lead compound for treating GBM but also uncovered its underlying mechanisms from the perspective of apoptosis and mitophagy.
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Apoptose , Neoplasias Encefálicas , Proliferação de Células , Glioblastoma , Mitofagia , Espécies Reativas de Oxigênio , Ensaios Antitumorais Modelo de Xenoenxerto , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Mitofagia/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Camundongos , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos Nus , Serina-Treonina Quinases TOR/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Glioblastoma is the most common glioma with high mortality and poor prognosis. Radiation resistance is one of the large challenges in the treatment of glioma. The study aimed to identify whether DNA polymerase ζ affects glioma cell radiosensitivity. The mRNA and protein levels of REV3L and REV7 were examined using quantitative real-time PCR and western blot. After REV3L and REV7 knockdown in a GBM cell line (A172), we assessed cell viability, colonies, apoptosis, and immune escape. The underlying mechanisms were evaluated using western blot and were confirmed using rescue experiments. The results showed that REV3L and REV7 levels were increased in glioma and related to poor survival. γ-ray treatment inhibited cell viability, survival fraction, and immune escape, and induced apoptosis of glioma cells from a GBM cell line, whereas knockdown of REV3L or REV7 enhanced these effects. Mechanically, silencing of REV3L or REV7 inactivated the PI3K/AKT/mTOR pathway. IGF-1 treatment abrogated the effects on cell viability, colonies, and apoptosis induced by REV3L or REV7 knocking down. Taken together, silencing of REV3L and REV7 inhibited radiation resistance via inactivating the PI3K/AKT/mTOR pathway, suggesting that targeting DNA polymerase ζ may be a new strategy to reduce the radiotherapy resistance of glioma.
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Glioma , Proteínas Proto-Oncogênicas c-akt , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Glioma/genética , Glioma/radioterapia , Serina-Treonina Quinases TOR/metabolismo , Tolerância a Radiação/genética , Linhagem Celular Tumoral , Apoptose/genética , Proliferação de Células , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/farmacologia , Proteínas de Ligação a DNARESUMO
BACKGROUND: Calponin 3 (CNN3) is involved in the proliferation and invasion of cervical cancer and osteosarcoma cells. However, the role of CNN3 in glioma tumorigenesis remains to be elucidated. METHODS: CNN3 mRNA expression in normal brain tissue and gliomas, including glioblastoma multiforme and lower-grade glioma, was analyzed using GEPIA 2 and Oncomine. CNN3 levels in glioma tissues were identified using immunohistochemical data provided by the Human Protein Atlas website. The relationship between CNN3 mRNA expression and clinical characteristics of patients with glioma was analyzed using the Oncomine database and The Cancer Genome Atlas. The diagnostic value of CNN3 expression in glioma was analyzed using receiver operating characteristic analysis according to The Cancer Genome Atlas and Genotype-Tissue Expression data. The relationship between CNN3 and prognosis was analyzed using GEPIA 2. The function of CNN3 knockdown in glioma cell lines was analyzed using cell proliferation, Transwell, and Western blot assays. RESULTS: Both mRNA and protein levels of CNN3 were distinctly higher in lower-grade glioma and glioblastoma multiforme tissues than those in normal brain tissues, particularly glioblastoma. A higher CNN3 mRNA level had significant relationship with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, and 1p/19q noncodeletion. CNN3 mRNA expression is a highly accurate marker for the diagnosis of glioma. Patients with glioma in the high-CNN3 group had significantly lower disease-free survival and survival rates. In addition, CNN3 silencing significantly inhibited cell proliferation, migration, invasion, and the phosphorylation of P65 NF-κB. CONCLUSIONS: CNN3 expression is increased in glioma, particularly glioblastoma. Silencing CNN3 expression inhibited the proliferation, migration, and invasion of glioma cell lines.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , Humanos , Isocitrato Desidrogenase/genética , Proteínas dos Microfilamentos , NF-kappa B/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , CalponinasRESUMO
Spinal epidural hematomas are rare, with trauma being the most common cause. Spinal epidural hematomas caused by coagulation dysfunction are even rarer; however, long-term warfarin therapy increases the risk. The clinical manifestations of spinal epidural hematoma are neurological deficits below the corresponding spinal cord segment level. Magnetic resonance imaging (MRI) is the preferred method for diagnosis, and the main treatment for epidural hematoma with typical symptoms is urgent decompression of the lumbar spine. We describe an almost 80-year-old female patient who received long-term oral warfarin therapy for atrial fibrillation. She developed sudden onset waist pain, and 2 days later, she developed pain and weakness in both lower limbs. Computed tomography (CT) of the thoracolumbar spine showed no obvious hematoma. Eight days after admission, contrast-enhanced CT of the thoracolumbar spine showed intraspinal hematomas at T5-T8 and T12-L2 levels. We performed T3-T7 laminectomy, T5-T8 hematoma removal, and spinal dural repair. The clinical symptoms did not improve significantly, postoperatively. The low incidence of spinal epidural hematoma after anticoagulation treatment means this condition is not recognized timely, and it is misdiagnosed easily. Clinicians should consider this condition when patients treated with anticoagulants have neurological deficits below a spinal segmental plane.
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Hematoma Epidural Espinal , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Hematoma Epidural Espinal/induzido quimicamente , Hematoma Epidural Espinal/diagnóstico por imagem , Hematoma Epidural Espinal/cirurgia , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Varfarina/efeitos adversosRESUMO
Previously, convolutional neural networks mostly used deep semantic feature information obtained from several convolutions for image classification. Such deep semantic features have a larger receptive field, and the features extracted are more effective as the number of convolutions increases, which helps in the classification of targets. However, this method tends to lose the shallow local features, such as the spatial connectivity and correlation of tumor region texture and edge contours in breast histopathology images, which leads to its recognition accuracy not being high enough. To address this problem, we propose a multi-level feature fusion method for breast histopathology image classification. First, we fuse shallow features and deep semantic features by attention mechanism and convolutions. Then, a new weighted cross entropy loss function is used to deal with the misjudgment of false negative and false positive. And finally, the correlation of spatial information is used to correct the misjudgment of some patches. We have conducted experiments on our own datasets and compared with the base network Inception-ResNet-v2, which has a high accuracy. The proposed method achieves an accuracy of 99.0% and an AUC of 99.9%.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Mama/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: We conducted this study to assess the value of clinically relevant data for predicting the failure of removing urinary catheters among patients with intracerebral hemorrhage postoperatively. MATERIALS AND METHODS: We retrospectively analyzed the medical records of all patients with intracerebral hemorrhage who underwent surgery for removal of intracerebral hematoma between January 2014 and December 2019, all of whom retained their urinary catheter. The patients were classified into 2 groups. Group A included patients who underwent successful removal of the catheter while group B included patients who underwent a failed removal. Univariate analysis was performed to determine the relationship between the failure of catheter removal and the patients' preoperative clinical characteristics. Independent prognostic predictors were identified using multivariate analyses. RESULTS: The site of intracerebral hematoma ( P =0.004), volume of hematoma ( P <0.001), intraventricular hemorrhage ( P <0.001), admitted Glasgow Coma Scale (GCS) ( P <0.001), GCS before urinary catheter removal ( P <0.001), smoking ( P =0.011), herniation ( P <0.001), urine protein ( P =0.013), creatinine ( P =0.037), and timing of urinary catheter removal ( P <0.001) were significantly different among the 2 groups. Multiple logistical regression analysis indicated that GCS before urinary catheter removal (odds ratio=1.171; 95% confidence interval=1.050-1.306; P =0.005) and timing for urinary catheter removal (odds ratio=0.962; 95% confidence interval=0.944-0.981; P <0.001) were associated with failure of urinary catheter removal. CONCLUSIONS: This study demonstrated that GCS before urinary catheter removal and the timing of urinary catheter removal are independent factors associated with failure of urinary catheter removal among patients with intracerebral hemorrhage.
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Hemorragia Cerebral , Cateteres Urinários , Humanos , Estudos Retrospectivos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/cirurgia , Hematoma/cirurgia , Hematoma/complicações , Escala de Coma de GlasgowRESUMO
Excessive iron ions in cancer cells can catalyze H2O2 into highly toxic â¢OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of the ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinic. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG-modified gadolinium engineering magnetic iron oxide-loaded Dox (ipGdIO-Dox). The introduction of the gadolinium compound disturbed the structure of ipGdIO-Dox, making the magnetic nanocatalyst be more sensitive to weak acid. When ipGdIO-Dox entered into cancer cells, abundant Fe(II) ions were released and then catalyzed H2O2 into highly toxic OHâ¢, which would elevate cellular oxidative stress to damage mitochondria and cell membranes and induce cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto the nanoplatform was also broken by high expression of GSH, and then, the Dox was released. This process not only effectively inhibited DNA replication but also further activated cellular ROS, making the nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery of ipGdIO-Dox significantly enhanced the T1- and T2-weighted MRI signal of the tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, ipGdIO-Dox might be a promising candidate for developing an MRI-guided chemo- and ferroptosis synergistic theranostic system.
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Antibióticos Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Imageamento por Ressonância Magnética , Nanopartículas/química , Antibióticos Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Neoplasias da Mama/patologia , Catálise , Linhagem Celular Tumoral , Doxorrubicina/química , Ferroptose/efeitos dos fármacos , Gadolínio/química , Humanos , Teste de Materiais , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Aim: This retrospective study investigated bevacizumab in treating refractory brain edema in patients with brain-metastatic tumors from different sources.Methods: From January 2013 to December 2019, 83 patients with brain metastases and refractory brain edema were treated with bevacizumab. They were divided into lung cancer group and breast cancer group. The clinical data, the efficacy, and the side effects of bevacizumab were recorded. Magnetic resonance imaging was performed before and after bevacizumab treatment. The volume of tumor and brain edema were measured respectively.Results: After treatment with bevacizumab, 72 cases of refractory brain edema were significantly relieved. The edema control rate was 93.75% in the lung cancer group and 77.14% in the breast cancer group (P < .05). The brain edema volume was significantly reduced after bevacizumab treatment from 198,286.84 ± 60,564.40 to 114,677.71 ± 42,337.38mm3 (P < .01), and the edema index was reduced from 26.14 ± 7.24 to 17.18 ± 5.14 (P < .01). Hypertension was observed in 14 cases.Conclusion: Bevacizumab could significantly reduce refractory brain edema with a control rate of 86.75%. The efficacy of bevacizumab in the treatment of refractory brain edema caused by lung cancer is better than that of breast cancer.
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Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Edema Encefálico/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Adulto , Edema Encefálico/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Previous reports suggest that DNA polymerase ζ is highly expressed in glioma tissues. The present study aimed to investigate the roles of the REV7 subunit of DNA polymerase ζ in glioma cell chemoresistance and its underlying mechanisms. The bioinformatics method was used to compare the expression of REV7 in glioma and normal tissues. The expression of REV7 in glioma tumor samples and the adjacent tissue was examined by reverse transcription polymerase chain reaction. Moreover, an in vitro analysis using glioma cells was used to test the effects of REV7 siRNA on the proliferation and apoptosis of glioma cell line U251 cells, and the effect of REV7 siRNA on the sensitivity of the U251 cells to cisplatin was also explored. The expression of REV7 in glioma tumors was significantly increased. Moreover, the knockdown of REV7 in glioma cells decreased the proliferation and increased the apoptosis of U251 cells; moreover, REV7 siRNA also increased the sensitivity of U251 cells to cisplatin. Finally, REV7 may regulate the proliferation, apoptosis, and chemosensitivity of U251 cells by affecting phosphoinositide 3-kinase signaling. Our data suggest that REV7 is involved in the chemosensitivity of glioma cells and provides a theoretical basis for targeting DNA polymerase ζ to improve the sensitivity of glioma cells to chemotherapy.
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Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos/genética , Glioma , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Circular RNA circSKA3 plays an oncogenic role in breast cancer, while its role in glioblastoma (GBM) is unknown. This study aimed to explore the role of circSKA3 in GBM. METHODS: Differential expression of circSKA3 and miR-1 in GBM and adjacent non-cancer tissue samples were analyzed by RT-qPCR. GBM cells were transfected with circSKA3 expression vector or miR-1 mimic, followed by RT-qPCR to explore the potential crosstalk between them. Methylation-specific PCR (MSP) was carried out to assess the role of circSKA3 in regulating the methylation of miR-1 gene. The role of circSKA3 and miR-1 in regulating GBM cell proliferation was analyzed by CCK-8 assay. RESULTS: We found that circSKA3 was upregulated in GBM and inversely correlated with miR-1 across GBM tissues. High expression levels of circSKA3 and low expression levels of miR-1 were significantly correlated with the poor survival of GBM patients. In GBM cells, overexpression of circSKA3 increased the methylation of miR-1 gene and decreased the expression of miR-1. CCK-8 assay showed that overexpression of circSKA3 reduced the inhibitory effects of miR-1 on cell proliferation. CONCLUSION: Therefore, circSKA3 may downregulate miR-1 through methylation in GBM to promote cancer cell proliferation.
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The conventional treatment for the resection of cervical spinal tumors comprises anterior, posterior, and combined surgical approaches. However, these approaches have certain limitations when tumors invade the vertebrae, vertebral artery, or spinal nerves. Herein, we report an interesting case where a 45-year-old patient was admitted for neck pain. An invasive cervical spinal tumor was discovered and approached in two stages: stage 1 was open biopsy with posterior instrumentation, which was followed by stage 2 with an anterolateral approach for definitive surgical resection. A series of preoperative tests including angiography as well as a balloon occlusion test of the vertebral artery facilitated stage 2 surgical planning for gross total resection of the tumor while minimizing surgical complications.
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Four new alkaloids (1-4) belonging to rare examples of bis-amide matrine-type were isolated from the seeds of sophora alopecuroides. Their structures including absolute configuration were determined by extensive spectroscopic analysis, electronic circular dichroism (ECD) interpretation, and X-ray diffraction crystallography. Chemically, bis-amide matrine-type alkaloids can provide new molecular template for structural modification. Compounds 3-4 displayed obvious anti-inflammatory effects based on the inhibition of two key pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in a dose-dependent manner, with IC50 values from 35.6 to 45.8 µm.