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Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
摘要： Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour–immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered the validation of clinically relevant immunotherapies and therapeutic vaccines to date. To address this need, we stably integrated the near-infrared phytochrome iRFP720 at the ROSA26 genomic locus of ID8 mouse OC cells. Intrabursal ovarian implantation into C57BL/6 mice, followed by regular, non-invasive fluorescence imaging, permitted the direct visualization of tumour mass and distribution over the course of progression. Four distinct phases of tumour growth and dissemination were detectable over time that closely mimicked clinical OC progression. Progression-related changes in immune cells also paralleled typical immune profiles observed in human OCs. Specifically, we observed changes in both the CD8+ T cell effector (Teff):regulatory (Treg) ratio, as well as the dendritic cell (DC)-to-myeloid derived suppressor cell (MDSC) ratio over time across multiple immune cell compartments and in peritoneal ascites. Importantly, iRFP720 expression had no detectible influence over immune profiles. This new model permits non-invasive, longitudinal tumour monitoring whilst preserving host–tumour immune interactions, and allows for the pre-clinical assessment of immune profiles throughout disease progression as well as the direct visualization of therapeutic responses. This simple fluorescence-based approach provides a useful new tool for the validation of novel immuno-therapeutics against OC.
关键词： iRFP720,syngeneic,ovarian cancer,iRFP,tumour,T cell,immune,ID8
更新于2025-09-23 15:22:29
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Polarizing Graphene Quantum Dots towards Long-acting Intracellular Reactive Oxygen Species Evaluation and Tumour Detection
摘要： The evaluation of intracellular reactive oxygen species (ROS) would greatly deepen the understanding of cell metabolism/proliferation and tumour detection. However, current long-acting level tracking techniques for intracellular ROS remain unsuited to practical application. To solve this problem, we synthesized cyclotriphosphazene doped graphene quantum dots (C-GQDs) whose quantum yield is highly sensitive to ROS (increased by 400% from 0.12 to 0.63). Electron cloud polarisation of oxidized cyclotriphosphazene rings in C-GQDs is confirmed to account for this novel optical property by density functional theory calculation and experimental results. In combination with excellent biological stability, C-GQDs achieve a long-acting evaluation of intracellular ROS level (more than 72 h) with an accuracy of 98.3%. In addition, recognition rates exceeding 90% are demonstrated to be feasible for eight kinds of tumour cell lines cultured with C-GQDs, which can also be expanded to in vivo detection. C-GQDs also show a high recognition rate (82.33%) and sensitivity (79.65%) for tumour cells in blood samples.
关键词： CTC,tumour detection,intracellular reactive oxygen species,photoluminescence,graphene quantum dots
更新于2025-09-23 15:19:57
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Developing infrared spectroscopic detection for stratifying brain tumour patients: glioblastoma multiforme <i>vs.</i> lymphoma
摘要： Over a third of brain tumour patients visit their general practitioner more than five times prior to diagnosis in the UK, leading to 62% of patients being diagnosed as emergency presentations. Unfortunately, symptoms are non-specific to brain tumours, and the majority of these patients complain of headaches on multiple occasions before being referred to a neurologist. As there are currently no methods in place for the early detection of brain cancer, the affected patients’ average life expectancy is reduced by 20 years. These statistics indicate that the current pathway is ineffective, and there is a vast need for a rapid diagnostic test. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is sensitive to the hallmarks of cancer, as it analyses the full range of macromolecular classes. The combination of serum spectroscopy and advanced data analysis has previously been shown to rapidly and objectively distinguish brain tumour severity. Recently, a novel high-throughput ATR accessory has been developed, which could be cost-effective to the National Health Service in the UK, and valuable for clinical translation. In this study, 765 blood serum samples have been collected from healthy controls and patients diagnosed with various types of brain cancer, contributing to one of the largest spectroscopic studies to date. Three robust machine learning techniques – random forest, partial least squares-discriminant analysis and support vector machine – have all provided promising results. The novel high-throughput technology has been validated by separating brain cancer and non-cancer with balanced accuracies of 90% which is comparable to the traditional fixed diamond crystal methodology. Furthermore, the differentiation of brain tumour type could be useful for neurologists, as some are difficult to distinguish through medical imaging alone. For example, the highly aggressive glioblastoma multiforme and primary cerebral lymphoma can appear similar on magnetic resonance imaging (MRI) scans, thus are often misdiagnosed. Here, we report the ability of infrared spectroscopy to distinguish between glioblastoma and lymphoma patients, at a sensitivity and specificity of 90.1% and 86.3%, respectively. A reliable serum diagnostic test could avoid the need for surgery and speed up time to definitive chemotherapy and radiotherapy.
关键词： glioblastoma multiforme,brain tumour,infrared spectroscopic detection,lymphoma,machine learning,ATR-FTIR spectroscopy
更新于2025-09-12 10:27:22
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Serum TGF-?2 and TNF-?± During Psoriasis Therapy with Narrowband Ultraviolet B
摘要： Although it is now an accepted concept that narrow-band UVB therapy is an efficacious therapy for psoriasis, the relationship between the response rate and the potential effects on serum cytokines is less well-established. The purpose of this study was to investigate the correlation between the response rate and the changes of serum TGF-β and TNF-α necessary for understanding the underlying mechanisms of narrow-band UVB phototherapy. NB-UVB is effective against psoriasis without any obvious side effects and can significantly decrease serum TNF-α and promote TGF-β level of psoriasis patients. Additionally, measurement of TGF-β and TNF-α in serum could be considered as biomarkers of psoriasis activity during NB-UVB therapy.
关键词： Serum Transforming Growth Factor-β (TGF-β),Narrow-Band Ultraviolet B (NB-UVB),Psoriasis,Tumour Necrosis Factor-α(TNF-α)
更新于2025-09-10 09:29:36
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An Optically Induced Dielectrophoresis (ODEP)-Based Microfluidic System for the Isolation of High-Purity CD45neg/EpCAMneg Cells from the Blood Samples of Cancer Patients—Demonstration and Initial Exploration of the Clinical Significance of These Cells
摘要： Circulating tumour cells (CTCs) in blood circulation play an important role in cancer metastasis. CTCs are generally de?ned as the cells in circulating blood expressing the surface antigen EpCAM (epithelial cell adhesion molecule). Nevertheless, CTCs with a highly metastatic nature might undergo an epithelial-to-mesenchymal transition (EMT), after which their EpCAM expression is downregulated. In current CTC-related studies, however, these clinically important CTCs with high relevance to cancer metastasis could be missed due to the use of the conventional CTC isolation methodologies. To precisely explore the clinical signi?cance of these cells (i.e., CD45neg/EpCAMneg cells), the high-purity isolation of these cells from blood samples is required. To achieve this isolation, the integration of ?uorescence microscopic imaging and optically induced dielectrophoresis (ODEP)-based cell manipulation in a micro?uidic system was proposed. In this study, an ODEP micro?uidic system was developed. The optimal ODEP operating conditions and the performance of live CD45neg/EpCAMneg cell isolation were evaluated. The results demonstrated that the proposed system was capable of isolating live CD45neg/EpCAMneg cells with a purity as high as 100%, which is greater than the purity attainable using the existing techniques for similar tasks. As a demonstration case, the cancer-related gene expression of CD45neg/EpCAMneg cells isolated from the blood samples of healthy donors and cancer patients was successfully compared. The initial results indicate that the CD45neg/EpCAMneg nucleated cell population in the blood samples of cancer patients might contain cancer-related cells, particularly EMT-transformed CTCs, as suggested by the high detection rate of vimentin gene expression. Overall, this study presents an ODEP micro?uidic system capable of simply and effectively isolating a speci?c, rare cell species from a cell mixture.
关键词： optically induced dielectrophoresis (ODEP),cancer metastasis,cell isolation,micro?uidic systems,circulating tumour cells (CTCs)
更新于2025-09-10 09:29:36
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Unveiling Ga(III) phthalocyanine-a different photosensitizer in neuroblastoma cellular model
摘要： Phthalocyanines (Pc) and their metallated derivatives are strongly considered for photodynamic therapy (PDT) possessing unique properties as possible new photosensitizers (PS). We have used toxicological assessments, real‐time monitoring of cellular impedance, and imagistic measurements for assessing the in vitro dark toxicity and PDT efficacy of Ga(III)‐Pc in SHSy5Y neuroblastoma cells. We have established the non‐toxic concentration range of Ga(III)‐Pc, a compound which shows a high intracellular accumulation, with perinuclear distribution in confocal microscopy. By choosing Ga(III)Pc non‐toxic dose, we performed in vitro experimental PDT hampering cellular proliferation. Our proposed Ga(III)‐Pc could complete a future PS panel for neuroblastoma alternate therapy.
关键词： toxicity,gallium(III),photosensitizer,proliferation,tumour,photodynamic therapy,neuroblastoma,viability
更新于2025-09-10 09:29:36
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Modulating the cellular uptake of fluorescently tagged substrates of prostate-specific antigen before and after enzymatic activation
摘要： A series of peptides based on the prostate-specific antigen (PSA) specific sequence histidine-serine-serine-lysine-leucine-glutamine were functionalised with an anthraquinone fluorophore at the C-terminal residue side chain using the copper(I) catalyzed azide-alkyne cycloaddition reaction. The effect of incorporating a negatively charged N-terminal tetra-glutamic acid group to the substrate and the effect of masking the negatively charged C-terminal carboxylic acid functionality of the substrate was investigated using confocal fluorescence microscopy in two cell lines (DLD-1 and LnCaP). The addition of a tetra-glutamic acid group to the N-terminus of the intact sequence was shown to reduce cellular uptake of the intact substrate prior to activation by PSA. In contrast, masking the C-terminal carboxylic acid group of the substrate as a methyl ester was shown to improve cellular uptake of the peptide fragment after activation by PSA. The synthesized C-terminal methyl ester substrates with the anthraquinone attached to the side chain were confirmed to be cleaved by PSA in LC-MS analysis, and the cytotoxicity of the substrates was shown to increase in the presence of PSA, consistent with cleavage and uptake of the C-terminal fragment. The results indicate that C- and N- terminal functionalisation of peptide substrates targeting PSA can be used to modulate the cellular uptake of peptides before and after enzymatic activation, and may thus be an important consideration in the design of tumour activated prodrugs.
关键词： peptide substrates,cellular uptake,tumour activated prodrugs,prostate-specific antigen,anthraquinone fluorophore
更新于2025-09-04 15:30:14