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Graphene oxide-quenching-based fluorescence in situ hybridization (G-FISH) to detect RNA in tissue: Simple and fast tissue RNA diagnostics
摘要： FISH-based RNA detection in paraffin-embedded tissue can be challenging, with complicated procedures producing uncertain results and poor image quality. Here, we developed a robust RNA detection method based on graphene oxide (GO) quenching and recovery of fluorescence in situ hybridization (G-FISH) in formalin-fixed paraffin-embedded (FFPE) tissues. Using a fluorophore-labeled peptide nucleic acid (PNA) attached to GO, the endogenous long noncoding RNA BC1, the constitutive protein β-actin mRNA, and miR-124a and miR-21 could be detected in the cytoplasm of a normal mouse brain, primary cultured hippocampal neurons, an Alzheimer’s disease model mouse brain, and glioblastoma multiforme tumor tissues, respectively. Coding and non-coding RNAs, either long or short, could be detected in deparaffinized FFPE or frozen tissues, as well as in clear lipid-exchanged anatomically rigid imaging/immunostaining-compatible tissue hydrogel (CLARITY)-transparent brain tissues. The fluorescence recovered by G-FISH correlated highly with the amount of miR-21, as measured by quantitative real time RT-PCR. We propose G-FISH as a simple, fast, inexpensive, and sensitive method for RNA detection, with a very low background, which could be applied to a variety of research or diagnostic purposes.
关键词： glioblastoma multiforme tumor,tissue RNA diagnostics,Graphene oxide-quenching-based fluorescence in situ hybridization (G-FISH),Alzheimer’s disease,formalin-fixed paraffin-embedded (FFPE) tissue
更新于2025-09-23 15:23:52
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Combined Fluorescence Using 5-Aminolevulinic Acid and Fluorescein Sodium at Glioblastoma Border: Intraoperative Findings and Histopathologic Data About 3 Newly Diagnosed Consecutive Cases
摘要： Fluorescence-guided glioblastoma surgery is an intraoperative technique developed in recent years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and fluorescein sodium (Fl-Na). Despite a large amount of literature on both techniques, few data are available on the use of both compounds in the same patient. Three consecutive patients affected by a newly diagnosed glioblastoma underwent surgical resection using both 5-ALA and Fl-Na. 5-ALA was orally administered 3 hours before induction of anesthesia at a dosage of 20 mg/kg, whereas fluorescein was intravenously administered at induction of anesthesia at a dosage of 4 mg/kg. Tumor resection was carried out combining these fluorophores. At tumor borders, multiple samples were collected, and fluorescent pattern of each sample was registered. Samples were then analyzed by a neuropathologist blinded for intraoperative fluorescence findings. Eighteen samples were analyzed. At tumor margin, bright pink fluorescence was highly indicative of residual tumor (positive predictive value [PPV], 94%), and it was superior to faint pink and fluorescein (PPVs, 89% and 87%, respectively). The gradual reduction of pink fluorescence warned of the risk of gradually entering healthy tissue (specificity of 67% compared with 33% with fluorescein). Using 5-ALA, detecting no fluorescence was highly suggestive of healthy tissue (negative predictive value of 100% compared with 50% with fluorescence). In our experience with 3 patients, the 2 techniques presented different advantages and limitations in specific steps of tumor resection, showing complementary properties. Larger studies are mandatory to investigate the synergistic use of both techniques.
关键词： Tumor border,5-ALA,Fluorescein,Glioblastoma
更新于2025-09-23 15:21:21
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[IEEE 2019 IEEE International Symposium on Antennas and Propagation and USNC-URSI Radio Science Meeting - Atlanta, GA, USA (2019.7.7-2019.7.12)] 2019 IEEE International Symposium on Antennas and Propagation and USNC-URSI Radio Science Meeting - An Aperture-Coupled Dual-Polarized Stacked Patch Antenna for Multi-Layer Organic Package Integration
摘要： Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults because of its highly invasive behavior. The existing treatment for GBM, which involves a combination of resection, chemotherapy, and radiotherapy, has a very limited success rate with a median survival rate of <1 year. This is mainly because of the failure of early detection and effective treatment. We designed a novel 3-D GBM cell culture model based on microwells that could mimic in vitro environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive polyethylene glycol material for the control of in vitro 3-D culture. We applied the 3-D micropatterning system to GBM (U-87) cells using the photolithography technique to control the cell spheroids’ shape, size, and thickness. Our preliminary results suggested that uniform GBM spheroids can be formed in 3-D, and the size of these GBM spheroids depends on the size of microwells. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. We believe that in vitro 3-D cell culture model could help to reduce the time of the preclinical brain tumor growth studies. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses.
关键词： Glioblastoma,microwells,PEG hydrogel,in vitro
更新于2025-09-23 15:21:01
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Prediction of recurrent glioblastoma after laser interstitial thermal therapy: The role of diffusion imaging
摘要： Background. Evaluate the utility of diffusion-weighted imaging (DWI) for the assessment of local recurrence of glioblastoma (GBM) on imaging performed 24?h following MRI-guided laser interstitial thermal therapy (LITT). We hypothesize that microscopic peritumoral infiltration correlates with early subtle variations on DWI images and apparent diffusion coefficient (ADC) maps. Methods. Of 64 patients with GBM treated with LITT, 39 had MRI scans within 24?h after undergoing LITT. Patterns on DWI images and ADC maps 24?h following LITT were correlated with areas of future GBM recurrence identified through coregistration of subsequent MRI examinations. In the areas of suspected recurrence within the periphery of post-LITT lesions, signal intensity values on ADC maps were recorded and compared with the remaining peritumoral ring. Results. Thirty-nine patients with GBM met the inclusion criteria. For predicting recurrent GBM, areas of decreased DWI signal and increased signal on ADC maps within the expected peritumoral ring of restricted diffusion identified 24? h following LITT showed 86.1% sensitivity, 75.2% specificity, and high correlation (r? =? 0.53) with future areas of GBM recurrence (P < .01). Areas of future recurrence demonstrated a 37% increase in the ADC value (P < .001), compared with findings in the surrounding treated peritumoral region. A?significantly greater area under the receiver operating characteristics curve was determined for ADC values (P < .01). Conclusions. DWI obtained 24?h following LITT can help predict the location of GBM recurrence months before the development of abnormal enhancement. This may alter future treatment planning, perhaps suggesting areas that may be targeted for additional therapy.
关键词： apparent diffusion coefficient,MRI-guided laser interstitial thermal therapy,laser interstitial thermal therapy,diffusion-weighted image,glioblastoma
更新于2025-09-23 15:19:57
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The invasive proteome of glioblastoma revealed by laser-capture microdissection
摘要： Background: Glioblastomas are heterogeneous tumors composed of a necrotic and tumor core and an invasive periphery. Methods: Here, we performed a proteomics analysis of laser-capture micro-dissected glioblastoma core and invasive areas of patient-derived xenografts. Results: Bioinformatics analysis identified enriched proteins in central and invasive tumor areas. Novel markers of invasion were identified, the genes proteolipid protein 1 (PLP1) and Dynamin-1 (DNM1), which were subsequently validated in tumors and by functional assays. Conclusion: In summary, our results identify new networks and molecules that may play an important role in glioblastoma development and may constitute potential novel therapeutic targets.
关键词： Proteomics analysis,patient-derived xenograft,intra-tumor heterogeneity,invasion,glioblastoma
更新于2025-09-23 15:19:57
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Lessons Learned in Using Laser Interstitial Thermal Therapy for Treatment of Brain Tumors: A Case Series of 238 Patients from a Single Institution
摘要： Background: Laser interstitial thermal therapy (LITT) is a novel, minimally invasive alternative to craniotomy, and as with any new technology, comes with a learning curve. Objective: We present our experience detailing the evolution of this technology in our practice in one of the largest patient cohorts to date regarding LITT in neuro-oncology. Methods: We reviewed 238 consecutive brain tumor patients treated with LITT at our institution. Data on patient, surgery and tumor characteristics, and follow-up were collected. Patients were categorized into two cohorts: Early (<2014, 100 patients) and Recent (>2015, 138 patients). Median follow up for the entire cohort was 8.4 months. Results: The indications for LITT included gliomas (70.2%), radiation necrosis (21.0%), and metastasis (8.8%). Patient demographics stayed consistent between the two cohorts, with the exception of age (Early: 54.3, Recent: 58.4, p=0.04). Operative time (6.6 versus 3.5, p<0.001) and number of trajectories (53.1% versus 77.9% with 1 trajectory, p<0.001) also decreased in the Recent cohort. There was a significant decrease in permanent motor deficits over time (15.5 versus 4.4%, p=0.005) and 30-day mortality (4.1% versus 1.5%) also decreased (not statistically significant) in Recent cohort. In terms of clinical outcomes, poor preoperative KPS (≤70) were significantly correlated with increased permanent deficits (p=0.001) and decreased overall survival (p<0.001 for all time points). Conclusions: We observed improvement in operative efficiency and permanent deficits over time and also patients with poor preoperative KPS achieved suboptimal outcomes with LITT. As many other treatment modalities, patient selection is very important in this procedure.
关键词： Stereotactic Laser Ablation,Radiation Necrosis,Tumor,Glioblastoma,Glioma,Minimally-Invasive
更新于2025-09-23 15:19:57
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Combining multimodal imaging and treatment features improves machine learning-based prognostic assessment in patients with glioblastoma multiforme
摘要： Background: For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients’ overall survival (OS) and progression‐free survival (PFS) on the basis of clinical, pathological, semantic MRI‐based, and FET‐PET/CT‐derived information. Finally, the value of adding treatment features was evaluated. Methods: One hundred and eighty‐nine patients were retrospectively analyzed. We assessed clinical, pathological, and treatment information. The VASARI set of semantic imaging features was determined on MRIs. Metabolic information was retained from preoperative FET‐PET/CT images. We generated multiple random survival forest prediction models on a patient training set and performed internal validation. Single feature class models were created including "clinical," "pathological," "MRI‐based," and "FET‐PET/CT‐based" models, as well as combinations. Treatment features were combined with all other features. Results: Of all single feature class models, the MRI‐based model had the highest prediction performance on the validation set for OS (C‐index: 0.61 [95% confidence interval: 0.51‐0.72]) and PFS (C‐index: 0.61 [0.50‐0.72]). The combination of all features did increase performance above all single feature class models up to C‐indices of 0.70 (0.59‐0.84) and 0.68 (0.57‐0.78) for OS and PFS, respectively. Adding treatment information further increased prognostic performance up to C‐indices of 0.73 (0.62‐0.84) and 0.71 (0.60‐0.81) on the validation set for OS and PFS, respectively, allowing significant stratification of patient groups for OS. Conclusions: MRI‐based features were the most relevant feature class for prognostic assessment. Combining clinical, pathological, and imaging information increased predictive power for OS and PFS. A further increase was achieved by adding treatment features.
关键词： prognostic model,machine learning,VASARI,glioblastoma,FET‐PET,biomarker,MRI
更新于2025-09-23 15:19:57
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Reconfigurable Three-Mode Converter Based On Cascaded Electro-Optic Long-Period Gratings
摘要： Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults because of its highly invasive behavior. The existing treatment for GBM, which involves a combination of resection, chemotherapy, and radiotherapy, has a very limited success rate with a median survival rate of <1 year. This is mainly because of the failure of early detection and effective treatment. We designed a novel 3-D GBM cell culture model based on microwells that could mimic in vitro environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive polyethylene glycol material for the control of in vitro 3-D culture. We applied the 3-D micropatterning system to GBM (U-87) cells using the photolithography technique to control the cell spheroids’ shape, size, and thickness. Our preliminary results suggested that uniform GBM spheroids can be formed in 3-D, and the size of these GBM spheroids depends on the size of microwells. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. We believe that in vitro 3-D cell culture model could help to reduce the time of the preclinical brain tumor growth studies. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses.
关键词： in vitro,PEG hydrogel,microwells,Glioblastoma
更新于2025-09-19 17:13:59
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[IEEE 2019 IEEE/CIC International Conference on Communications in China (ICCC) - Changchun, China (2019.8.11-2019.8.13)] 2019 IEEE/CIC International Conference on Communications in China (ICCC) - Pulse-laser Based Long-range NLOS Ultraviolet Communication: Pulse Response Position Estimation and Frame Synchronization optimization
摘要： Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults because of its highly invasive behavior. The existing treatment for GBM, which involves a combination of resection, chemotherapy, and radiotherapy, has a very limited success rate with a median survival rate of <1 year. This is mainly because of the failure of early detection and effective treatment. We designed a novel 3-D GBM cell culture model based on microwells that could mimic in vitro environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive polyethylene glycol material for the control of in vitro 3-D culture. We applied the 3-D micropatterning system to GBM (U-87) cells using the photolithography technique to control the cell spheroids’ shape, size, and thickness. Our preliminary results suggested that uniform GBM spheroids can be formed in 3-D, and the size of these GBM spheroids depends on the size of microwells. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. We believe that in vitro 3-D cell culture model could help to reduce the time of the preclinical brain tumor growth studies. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses.
关键词： Glioblastoma,microwells,PEG hydrogel,in vitro
更新于2025-09-16 10:30:52
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Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory
摘要： Brain tumors present unique therapeutic challenges and they include glioblastoma (GBM) and metastases from cancers of other organs. Current treatment options are limited and include surgical resection, radiation therapy, laser interstitial thermal therapy and chemotherapy. Although much research has been done on the development of immune-based treatment platforms, only limited success has been demonstrated. Herein, we demonstrate a novel treatment of GBM through the use of plasmonic gold nanostars (GNS) as photothermal inducers for synergistic immuno photothermal nanotherapy (SYMPHONY), which combines treatments using gold nanostar and laser-induced photothermal therapy with checkpoint blockade immunotherapy. In the treatment of a murine flank tumor model with the CT-2A glioma cell line, SYMPHONY demonstrated the capability of producing long-term survivors that rejects rechallenge with cancer cells, heralding the successful emergence of immunologic memory. This study is the first to investigate the use of this novel therapy for the treatment of GBM in a murine model.
关键词： gold nanostars,cancer immunology,immunotherapy,cancer vaccines,photothermal therapy,glioblastoma
更新于2025-09-12 10:27:22