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Targeting fluorescent nanodiamonds to vascular endothelial growth factor receptors in tumor
摘要： The increased expression of vascular endothelial growth factor (VEGF) and its receptors is associated with angiogenesis in a growing tumor, presenting potential targets for tumor-selective imaging by way of targeted tracers. Though fluorescent tracers are used for targeted in vivo imaging, the lack of photostability and biocompatibility of many current fluorophores hinder their use in several applications involving long-term, continuous imaging. To address these problems, fluorescent nanodiamonds (FNDs), which exhibit infinite photostability and excellent biocompatibility, were explored as fluorophores in tracers for targeting VEGF receptors in growing tumors. To explore FND utility for imaging tumor VEGF receptors, we used click-chemistry to conjugate multiple copies of an engineered single-chain version of VEGF site-specifically derivatized with trans-cyclooctene (scVEGF-TCO) to 140 nm FND. The resulting targeting conjugates, FND-scVEGF, were then tested for functional activity of the scVEGF moieties through biochemical and tissue culture experiments and for selective tumor uptake in Balb/c mice with induced 4T1 carcinoma. We found that FND-scVEGF conjugates retain high affinity to VEGF receptors in cell culture experiments and observed preferential accumulation of FND-scVEGF in tumors relative to untargeted FND. Microspectroscopy provided unambiguous determination of FND within tissue by way of the unique spectral shape of nitrogen-vacancy induced fluorescence. These results validate and invite the use of targeted FND for diagnostic imaging and encourage further optimization of FND for fluorescence brightness.
关键词： Vascular Endothelial Growth Factor,Oncology,Targeted Fluorescence Imaging,Nanodiamond,Angiogenesis
更新于2025-11-21 11:24:58
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Photodegradable MEH-PPV in a natural rubber matrix: Toward a biocompatible colorimetric film for real-time light dosimetry
摘要： This paper reports an interesting strategy of incorporating a photodegradable polymeric luminophore, the poly [2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] - OC10C6-PPV (MEH-PPV), in an inert natural rubber (Hevea brasiliensisis) - C5H8 (NR) matrix for monitoring and recording the radiation dose administered to patients under phototherapy, particularly in the treatment for jaundice newborns. A time-trend spectro?uorimetric study has been carried out to characterize the luminescent changes of the MEH-PPV/NR luminophore system upon photodegradation by realistic conditions of phototherapy treatment, and the dependence between color and dose was used to determine the dose-response relationships of this color ?lm dosimeter. Cytotoxicity tests (CHO-K1 cell line) have also been conducted on extracts of the OC10C6-PPV/C5H8 before and after photolysis. The experimental results reported here highlight the potential application of photodegradable polymer/natural rubber as a biocompatible skin-mountable patch to monitor light exposure to improve patient care in phototherapy, photodynamic, lasers and radiation therapies.
关键词： Medical-devices,Dosimeter,Printable device,Photooxidation,Organic device,Semiconducting polymer,Radiation oncology
更新于2025-11-14 15:18:02
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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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Interventional Oncology (Principles and Practice of Image-Guided Cancer Therapy) || Imaging in interventional oncology: Role of image guidance
摘要： Advances in medical imaging have created the opportunity for minimally invasive, image-guided oncologic care by allowing: (1) procedure planning; (2) device delivery; (3) intraprocedure monitoring; and (4) therapy assessment. Although most current image-guided therapy still utilizes standard diagnostic imaging equipment, interventional use of imaging equipment has in fact different priorities compared with diagnostic uses of such equipment. Therefore, interventional procedures prioritize imaging equipment that: (1) provides real-time imaging; (2) lowers radiation dose; and (3) provides greater physician access to the patient. In contrast to diagnostic imaging, lower image quality is an acceptable compromise for real-time imaging for interventional procedures. Patients have already undergone high-quality diagnostic imaging when they are referred to interventional therapies. Moreover, high-quality diagnostic imaging may require more time and more radiation dose than fast imaging of a restricted region of interest as performed for image guidance of interventions.
关键词： image-guided therapy,real-time imaging,physician access,medical imaging,radiation dose,interventional oncology
更新于2025-09-23 15:21:01
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The radiation oncology ontology (ROO): Publishing linked data in radiation oncology using semantic web and ontology techniques
摘要： Purpose: Personalized medicine is expected to yield improved health outcomes. Data mining over massive volumes of patients’ clinical data is an appealing, low-cost and noninvasive approach toward personalization. Machine learning algorithms could be trained over clinical “big data” to build prediction models for personalized therapy. To reach this goal, a scalable “big data” architecture for the medical domain becomes essential, based on data standardization to transform clinical data into FAIR (Findable, Accessible, Interoperable and Reusable) data. Using Ontologies and Semantic Web technologies, we attempt to reach mentioned goal. Methods: We developed an ontology to be used in the field of radiation oncology to map clinical data from relational databases. We combined ontology with semantic Web techniques to publish mapped data and easily query them using SPARQL. Results: The Radiation Oncology Ontology (ROO) contains 1,183 classes and 211 properties between classes to represent clinical data (and their relationships) in the radiation oncology domain following FAIR principles. We combined the ontology with Semantic Web technologies showing how to efficiently and easily integrate and query data from different (relational database) sources without a priori knowledge of their structures. Discussion: When clinical FAIR data sources are combined (linked data) using mentioned technologies, new relationships between entities are created and discovered, representing a dynamic body of knowledge that is continuously accessible and increasing.
关键词： ontologies,radiation oncology,semantic web
更新于2025-09-19 17:15:36
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Study of the IR Spectra of the Saliva of Cancer Patients
摘要： Feasibility has been demonstrated in principle for the diagnosis of lung and breast cancer by subjecting saliva to Fourier transform IR spectroscopy. Statistically significant differences in the saliva of lung cancer patients are seen at 1070–1240 cm–1, while significant differences are seen throughout the entire range for breast cancer patients. The I1398/1454 and I1240/1310 ratios were determined and found to be statistically reliable for detecting cancer pathology. Correlations were found for the intensities of the absorption bands in these IR spectra with nonspecific biochemical saliva parameters, which generally characterize greater intoxication as well as suppression of the systems for antioxidant protection and the immune response. A promising research trend involves the use of the IR spectroscopy of saliva for monitoring treatment and cancer recurrence.
关键词： Fourier transform IR spectroscopy,saliva,diagnostics,oncology
更新于2025-09-19 17:15:36
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Point-of-care cervical cancer screening using deep learning-based microholography
摘要： Most deaths (80%) from cervical cancer occur in regions lacking adequate screening infrastructures or ready access to them. In contrast, most developed countries now embrace human papillomavirus (HPV) analyses as standalone screening; this transition threatens to further widen the resource gap. Methods: We describe the development of a DNA-focused digital microholography platform for point-of-care HPV screening, with automated readouts driven by customized deep-learning algorithms. In the presence of high-risk HPV 16 or 18 DNA, microbeads were designed to bind the DNA targets and form microbead dimers. The resulting holographic signature of the microbeads was recorded and analyzed. Results: The HPV DNA assay showed excellent sensitivity (down to a single cell) and specificity (100% concordance) in detecting HPV 16 and 18 DNA from cell lines. Our deep learning approach was 120-folder faster than the traditional reconstruction method and completed the analysis in < 2 min using a single CPU. In a blinded clinical study using patient cervical brushings, we successfully benchmarked our platform’s performance to an FDA-approved HPV assay. Conclusions: Reliable and decentralized HPV testing will facilitate cataloguing the high-risk HPV landscape in underserved populations, revealing HPV coverage gaps in existing vaccination strategies and informing future iterations.
关键词： microholography,Cervical cancer,point-of-care screening,deep learning,global oncology
更新于2025-09-16 10:30:52
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Radical Laser Interstitial Thermal Therapy Ablation Volumes Increase Progression-Free Survival in Biopsy-Proven Radiation Necrosis
摘要： Radical Laser Interstitial Thermal Therapy Ablation Volumes Increase Progression-Free Survival in Biopsy-Proven Radiation Necrosis
关键词： oncology,brain tumor,radiation necrosis,brain metastasis,progression free survival,Laser interstitial thermal therapy,post-radiation treatment effects
更新于2025-09-16 10:30:52
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A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination
摘要： Background: Blue light photodynamic therapy (PDT) is effective for actinic keratosis (AK), but many patients experience stinging pain during illumination. Objective: Compare a conventional regimen (1 h ALA preincubation, followed by blue light), to a new modified regimen in which blue light is started immediately after ALA application. Methods: A clinical trial with a bilaterally controlled, intrapatient study design was conducted in 23 patients. Topical 20% ALA was applied to the entire face and/or scalp. On one side of the body, blue light was started immediately and continued for either 30, 45, or 60 min (“simultaneous PDT”). On the contralateral side, blue light began 1 h after ALA application and lasted 1000 sec (“conventional PDT”). Pain was evaluated on a 0-10 scale. AK lesion counts were determined by clinical exam and photography. Results: All patients experienced significantly less pain during simultaneous illumination than during the conventional regimen. At 3 months post-treatment, lesion clearance was nearly identical on the two sides, as determined by statistical testing of non-inferiority ± 15% margin. Limitations: Although bilaterally controlled, the study was relatively small. Additional studies are recommended. Conclusion: The modified PDT regimen is essentially painless, yet provides treatment efficacy similar to a conventional regimen.
关键词： skin cancer,phototherapy,therapeutics,oncology,clinical research
更新于2025-09-12 10:27:22
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Fluorescein Application in Cranial and Spinal Tumors Enhancing at Preoperative MRI and Operated With a Dedicated Filter on the Surgical Microscope: Preliminary Results in 279 Patients Enrolled in the FLUOCERTUM Prospective Study
摘要： Objective: Sodium fluorescein, a green, water soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier (BBB) disruption. The authors report the preliminary results of a prospective observational study regarding the use of fluorescein-guided technique for the resection of suspected malignant neoplasms of the central nervous system (CNS), contrast enhancing at preoperative magnetic resonance imaging (MRI), using a dedicated filter on the surgical microscope. Methods: In March 2016 the authors started a prospective, observational trial to evaluate intraoperative fluorescence’s characteristics of CNS tumors, the percentage of extent of resection thanks to fluorescein aid and side effects related to fluorescein administration. This report is based on a preliminary analysis of the results of first 279 enrolled patients. Fluorescein was intravenously injected after intubation or immediately at the entrance in the operating room for awake procedures; the tumor was removed using a dedicated filter on the surgical microscope in an inside-out fashion until all fluorescent tissue was removed, as considered feasible by the surgeon. Results: The 279 patients finally enrolled in the trial, both firstly diagnosed and recurrent, were categorized according to WHO pathological classification and there were 212 neuroepithelial tumors, 25 brain metastases, 10 cerebral lymphomas, 7 hemangioblastomas, or hemangioendotheliomas and 25 other tumors and conditions. No adverse reaction related to the administration of fluorescein or to the combined use of fluorescein with other fluorophores was registered. Fluorescein accumulated in cerebral regions where the BBB was damaged, representing a significant surgical aid in most of the CNS tumors with contrast enhancement. In cases of complete removal of all fluorescent tissue, as intraoperatively judged by the surgeon, postoperative MRI revealed a gross total resection in 181/198 patients (91.4%). Conclusions: Based on these preliminary results, fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration.
关键词： neuro-oncology,fluorescein,spinal tumors,central nervous system,brain tumors,biopsy,YELLOW 560
更新于2025-09-12 10:27:22