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Mechanism for enhanced 5-aminolevulinic acid fluorescence in isocitrate dehydrogenase 1 mutant malignant gliomas
摘要： Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has become the main treatment modality in malignant gliomas. However unlike glioblastomas, there are inconsistent result about fluorescence status in WHO grade III gliomas. Here, we show that mutational status of IDH1 is linked to 5-ALA fluorescence. Using genetically engineered malignant glioma cells harboring wild type (U87MG-IDH1WT) or mutant (U87MG-IDH1R132H) IDH1, we demonstrated a lag in 5-ALA metabolism and accumulation of protoporphyrin IX (PpIX) in U87MG-IDH1R132H cells. Next, we used liquid chromatography–mass spectrometry (LC-MS) to screen for tricarboxylic acid (TCA) cycle-related metabolite changes caused by 5-ALA exposure. We observed low baseline levels of NADPH, an essential cofactor for the rate-limiting step of heme degradation, in U87MG-IDH1R132H cells. High levels of NADPH are required to metabolize excessive 5-ALA, giving a plausible reason for the temporarily enhanced 5-ALA fluorescence in mutant IDH1 cells. This hypothesis was supported by the results of metabolic screening in human malignant glioma samples. In conclusion, we have discovered a relationship between enhanced 5-ALA fluorescence and IDH1 mutations in WHO grade III gliomas. Low levels of NADPH in tumors with mutated IDH1 is responsible for the enhanced fluorescence.
关键词： 5-ALA,glioma,oncology,fluorescence,brain tumors,IDH1,NADPH
更新于2025-09-23 15:22:29
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Enhanced X-ray absorption by using gold nanoparticles in a biological tissue
摘要： In recent years, application of nanoparticles (NPs) in diagnosis and treatment of cancer has been the issue of extensive research. In this study, we investigated the effect of gold nanoparticles (GNPs) in a tumor during X-ray therapy. Our simulation, based on the Monte Carlo method, shows that the GNPs injected into a tumor considerably enhanced the absorbed dose during X-ray therapy, especially in the energy range between 10 keV and 150 keV. This increase in the absorbed dose is due to a combination of increased photoelectric interaction and Auger electron generation from the gold atoms. Furthermore, the absorbed dose in a biological cell is strongly influenced by the size of the GNPs; our results show that the ideal diameter of GNPs should be around 50 nm, and this result was confirmed by several authors.
关键词： human organ,X-ray,radiation dose,tumors
更新于2025-09-23 15:21:01
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Subretinal Fluid Optical Density and Spectral-Domain Optical Coherence Tomography Characteristics for the Diagnosis of Circumscribed Choroidal Hemangioma
摘要： Purpose: To investigate spectral domain-optical coherence tomography (SD-OCT) features of untreated circumscribed choroidal hemangioma (CCH), and the optical density (OD) of the associated subretinal fluid (SRF). Procedures: This international retrospective multicenter study conducted at 5 tertiary retina referral centers included 34 patients with symptomatic CCH imaged on SD-OCT. CCH surface, size, and overlying retinal changes and OD ratio (ODR) were evaluated. Results: The mean ODR of the SRF was 0.808 ± 0.287. Tumor base measured on ultrasound correlated significantly with the ODR (p = 0.012). ODR values in cases of CCH were similar to those of choroidal metastasis, but significantly lower than those of choroidal melanoma (p = 0.006). Thirty-two out of 34 cases (94%) presented with a regular smooth choroidal surface. OCT demonstrated SRF overlying the CCH in 29 eyes (85%). The presence of SRF correlated significantly with a larger basal tumor diameter (p = 0.035). OCT displayed sub- and intraretinal hyperreflective foci, correlating with both larger maximal retinal thickness overlying the tumor (p = 0.031) and the amount of SRF (p = 0.016) in 29 eyes (85%). Conclusion: CCH displays typical findings on SD-OCT. ODR is a new important tool in the differential diagnosis of choroidal tumors and should be considered for enhancing the accuracy of diagnosing CCH. This benefit is especially relevant for cases in which the presentation of CCH is atypical.
关键词： Optical density,Optical coherence tomography,Ocular tumors,Circumscribed choroidal hemangioma
更新于2025-09-23 15:21:01
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Computing uveal melanoma basal diameters: a comparative analysis of several novel techniques with improved accuracy
摘要： Background: We sought to compare the accuracy of standard and novel echographic methods for computing intraocular tumor largest basal diameter (LBD). Design: Multicenter, retrospective cohort study. Subjects: All patients presenting with new diagnosis of uveal melanoma (UM). Methods: Ultrasounds were obtained for all patients, and axial length (AL) was measured for a subset of patients. LBD was calculated as: (1) a single chord measured on B scan ultrasound (one-chord method [1CM]), or (2) by subdividing the basal diameter into two chords, which were summated (two-chord method [2CM]), or (3) by a mathematically-derived formula (MF) based on geometric relationships. The accuracy of each method was then compared, and sensitivity of each technique to factors such as tumor size and AL were analyzed. Main outcome measures: Accuracy, robustness, correctness of predicted plaque size. Results: 116 UMs were analyzed; 1CM-calculated LBD underestimated 2CM-calculated LBD by 7.5% and underestimated LBD by MF by 7.8%; 2CM and MF were tightly correlated (average LBD difference 0.038%). At larger LBDs, 1CM underestimated 2CM and MF by a much greater percentage (p < 0.001). By linear regression, 1CM underestimated LBD compared to 2CM by 0.8% and underestimated LBD compared to MF by 1.2% for every 1-mm LBD increase (p < 0.001 for each). Increasing the number of ultrasound chords beyond two did not significantly impact LBD calculations. For eyes with AL within two standard deviations of the mean, AL did not impact plaque selection using MF. 1CM would have led to selection of an undersized plaque in 41% of cases compared to 2CM and would have misclassified half of all eyes that actually required enucleation. For tumors with LBD < 12 mm, 1CM does not significantly underestimate LBD. Conclusions: Tumor LBD by 1CM is an inaccurate means of determining actual LBD, especially for larger tumors. Using either 2CM or MF is much more accurate, especially for tumors > 12 mm, where a single chord on ultrasound is more likely to lead to incorrect, undersized plaque selection. Our MF can be applied with great accuracy even in cases where the AL of the eye is not measured, using the population average AL (23.7 mm), and the formula LBD = 23.7 sin?1(chord length/23.7).
关键词： Ultrasonography,Plaque brachytherapy,Uveal melanoma,Ocular tumors
更新于2025-09-19 17:15:36
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Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue
摘要： Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.
关键词： brain tumors,diagnosis,meta-analysis,Raman spectroscopy
更新于2025-09-19 17:15:36
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Statement of the BVA, the DOG, and the RG on treatment of choroidal neovascularization in diseases other than neovascular age-related macular degeneration; Stellungnahme des BVA, der DOG und der RG zur Therapie chorioidaler Neovaskularisationen bei anderen Erkrankungen als der neovaskul?ren altersabh?ngigen Makuladegeneration (Englische Version);
摘要： Choroidal neovascularizations (CNV) occur not only in age-related macular degeneration (AMD), but also in numerous other macular and retinal disorders of varying etiology and, if left untreated, can cause irreversible visual loss. The diagnosis of CNV as well as the indication for treatment should be made in the same way as in neovascular AMD: On initial diagnosis: best-corrected visual acuity, fundus examination, optical coherence tomography (OCT), and fluorescein angiography. At follow-up: best-correct visual acuity, fundus examination, OCT, and, depending on findings, fluorescein angiography. Active CNV should be treated with intravitreal operative medication (IVOM) using vascular endothelial growth factor (VEGF) inhibitors if patients have visual acuity of at least 0.05 or if there is sufficient reason to assume that visual acuity could increase to over 0.05 under treatment. Underlying disorders can include, e.g., high myopia, angioid streaks, central serous chorioretinopathy, active and inactive uveitis of varying etiology, including retinochoroiditis, chorioretinitis, and choroiditis, eye injuries, retinal dystrophies, e.g., best disease and pattern dystrophies, idiopathic CNV, subretinal masses (osteomas, hamartomas, nevi). If CNV is not present as a complication in the above-mentioned disorders, IVOM with VEGF inhibitors should not be performed. Ranibizumab and aflibercept are approved in Germany for the treatment of CNV secondary to pathologic myopia. Ranibizumab has been approved in Germany since 12/2016 for the treatment of CNV in disorders other than neovascular AMD and pathologic myopia irrespective of the underlying disease. The other VEGF inhibitors, aflibercept and bevacizumab, can be used off-label. Due to its overall significantly poorer treatment results, photodynamic therapy (PDT) should only be used in exceptional cases and extrafoveal localization. After one initial intravitreal administration of VEGF inhibitors, further CNV activity should be monitored monthly for the first 6 months (see point 2). In the case of persisting or recurrent activity, repeated IVOM should be performed. Depending on disease course, the follow-up interval might be extended 6 months after the last IVOM. In individual justified cases (e.g., patients requiring frequent re-injections), a different treatment regimen (e.g., treat and extend) can be considered in the further course. If visual acuity drops below 0.05 on anti-VEGF treatment, or no further positive treatment outcome is expected (e.g., in the presence of atrophy and/or fibrosis), treatment should be discontinued, unless there is a clear possibility that visual acuity could increase again to over 0.05 under treatment. If no improvement is seen under therapy with a certain VEGF inhibitor, or if deterioration occurs, one can consider switching to an alternative VEGF inhibitor.
关键词： Choroidal neovascularization,Myopia,Retinal dystrophies,Ranibizumab,VEGF inhibitors,Uveitis,Idiopathic CNV,Central serous chorioretinopathy,Angioid streaks,Photodynamic therapy,Subretinal tumors,Aflibercept,Bevacizumab,Eye injuries
更新于2025-09-19 17:15:36
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Biomineralization-inspired nanozyme for single-wavelength laser activated photothermal-photodynamic synergistic treatment against hypoxic tumors
摘要： Hypoxia, one of the features of most solid tumors, can severely impede the efficiency of oxygen-dependent treatments such as chemotherapy, radiotherapy and type-II photodynamic therapy. Herein, a catalase-like nanozyme RuO2@BSA (RB) was first prepared through a biomineralization strategy, and a high efficiency near-infrared photosensitizer (IR-808-Br2) was further loaded into the protein shell to generate the safe and versatile RuO2@BSA@IR-808-Br2 (RBIR) for the imaging-guided enhanced phototherapy against hypoxic tumors. RB not only acts like a catalase, but also serves as a photothermal agent that speeds up the oxygen supply under near-infrared irradiation (808 nm). The loaded NIR photosensitizer could immediately convert molecular oxygen (O2) to cytotoxic singlet oxygen (1O2) upon the same laser irradiation. Results indicated that RBIR achieved enhanced therapeutic outcomes with negligible side effects. Features such as a simple synthetic route and imaging-guided and single-wavelength-excited phototherapy make the nanozyme a promising agent for clinical applications.
关键词： biomineralization,solid tumors,photodynamic therapy,IR-808-Br2,photothermal therapy,nanozyme,RuO2@BSA,hypoxia
更新于2025-09-19 17:13:59
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[IEEE 2019 IEEE 4th International Conference on Integrated Circuits and Microsystems (ICICM) - Beijing, China (2019.10.25-2019.10.27)] 2019 IEEE 4th International Conference on Integrated Circuits and Microsystems (ICICM) - A Laser Modulation Driver in 130-nm CMOS Technology for Quantum Key Distribution System
摘要： The imaging of dysregulated cell-surface receptors (or biomarkers) is a potential means of identifying the presence of cancer with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Recently, surface-enhanced Raman-scattering (SERS) nanoparticles (NPs) have attracted wide interest due to their potential for sensitive and multiplexed biomarker detection. In this review, we focus on the most recent advances in tumor imaging using SERS-coded NPs. A brief introduction of the structure and optical properties of SERS NPs is provided, followed by a detailed discussion of key imaging issues such as the administration of NPs in tissue (topical versus systemic), the optical configuration and imaging approach of Raman imaging systems, spectral demultiplexing methods for quantifying NP concentrations, and the disambiguation of specific versus nonspecific sources of contrast through ratiometric imaging of targeted and untargeted (control) NP pairs. Finally, future challenges and directions are briefly outlined.
关键词： molecular imaging,fiberoptic probes,Biomarkers,cancer detection,nanomedicine,tumors,Raman spectroscopy,biomedical optical imaging
更新于2025-09-19 17:13:59
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Laser interstitial thermal therapy (LITT) of the brain – Experiences and new indications
摘要： The glioma is the most common type of primary brain tumor; more than 40% of gliomas are malignant. For decades, open microsurgical resection and postoperative radiochemotherapy have been the international standard methods of treatment. During the last few years, the importance of the (sub-)total tumor resection has been recognized, especially in respect of the patient’s progression-free survival time. Different modalities of neuronavigation, intraoperative imaging (“open MR” system) and intraoperative fluoroscopy with 5-ALA have proved to be important technical achievements to support this aim. However, the overall survival time of patients with anaplastic gliomas is poor. Successful curative treatments are statistically insignificant. As a result, it was and still is important to find new adjuvant methods to treat (recurrent) brain tumors. One of the most promising minimally invasive procedures is the laser interstitial thermal therapy (LITT), performed under stereotactic or “open” magnetic resonance imaging (MRI) guidance.
关键词： brain tumors,minimally invasive,Laser interstitial thermal therapy,gliomas,LITT
更新于2025-09-16 10:30:52
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Gutartige Lidtumoren: CO2-Laser statt Skalpell
摘要： Gutartige Tumoren am Augenlid werden zumeist chirurgisch entfernt. Dies erfolgt so wenig invasisv und so kosmetisch wie m?glich; dennoch gibt es Patienten, denen man z. B. aufgrund ihrer allgemeinen Verfassung oder ihrer Vorbehalte eine Alternative anbieten m?chte. Dies kann z. B. eine Laserbehandlung sein: Eine retrospektive klinische Studie analysierte die Ergebnisse einer Tumorexzision mit dem ultragepulsten CO2-Laser.
关键词： surgical alternative,laser therapy,benign eyelid tumors,CO2-Laser
更新于2025-09-16 10:30:52