Tool For Early Cancer Diagnosis Research Articles

Development of a microcantilever-based biosensor for detecting Program Death Ligand 1

The ongoing global concern of cancer worldwide necessitates the development of advanced diagnostic and therapeutic strategies. The majority of recent detection strategies involve the employment of biomarkers. A critical biomarker for cancer immunotherapy efficacy and patient prognosis is Programmed Death Ligand 1 (PD-L1), which is a key immune checkpoint protein. PD-L1 can be particularly linked to cancer progression and therapy response. Current detection methods, such as enzyme-linked immunosorbent assay (ELISA), face limitations like high cost, time consumption, and complexity. This study introduces a microcantilever-based biosensor designed for the detection of soluble PD-L1 (sPD-L1), which has a specific association with PD-L1. The biosensor utilizes anti-PD-L1 as the sensing layer, capitalizing on the specific binding affinity between anti-PD-L1 and sPD-L1. The presence of the sensing layer was confirmed through Atomic Force Microscopy (AFM) and contact angle measurements. Binding between sPD-L1 and anti-PD-L1 induces a shift in the microcantilever's resonance frequency, which is proportional to the PD-L1 concentration. Notably, the resonance frequency shift demonstrates a robust linear relationship with the increasing biomarker concentration, ranging from 0.05 ng/ml to 500 ng/ml. The detection limit of the biosensor was determined to be approximately 10 pg/ml. The biosensor demonstrates excellent performance in detecting PD-L1 with high specificity even in complex biological matrices. This innovative approach not only provides a promising tool for early cancer diagnosis but also holds potential for monitoring immunotherapy efficacy, paving the way for personalized and effective cancer treatments.

Research progress of exosome biosensors

At present, cancer is still an important cause of high morbidity and mortality worldwide. Early diagnosis has become the key to improving the cure rate and life quality of patients. Exosomes are small extracellular vesicles that play important roles in intercellular communication. Exosomes contain a variety of biomarkers, such as DNA, RNA, proteins, lipids, and metabolites, which reflect the state of the parent cell. Since exosomes affect tumorigenesis and metastasis in cancer patients, they are excellent non-invasive potential indicators for early cancer detection. In addition, the growing understanding of the structure and function of cancer marker exosomes provides new solutions for early cancer detection. Nowadays, the main cancer screening methods (ultrasound, nuclear magnetic resonance, tissue biopsy, etc.) are expensive, time-consuming, and require professionals to operate imaging, etc. Exosome biosensors have become effective tools for early cancer diagnosis due to their advantages of simple operation and cost-effectiveness. Therefore, based on the structure and function of exosomes, this study summarizes the research progress of different types of biosensor detection, discusses the characteristics of current biosensors, and looks forward to future research trends.

A novel feedback catalytic hairpin assembly strategy for sensitive mRNA imaging in living cells

Achieving specific and sensitive imaging of mRNA in living cells plays a key role in cancer diagnosis and treatment. Catalytic hairpin assembly (CHA) has been widely used for mRNA imaging. However, it has been significantly constrained by limited in-depth amplifications. Herein, a novel feedback catalytic hairpin assembly (FCHA) with exponential amplification efficiency was proposed for mRNA imaging in living cells. The FCHA system consisted of with two hairpin DNAs (H1, H2) and a double stranded DNA (H3L). After the probes enter the cell by using β-FeOOH nanoparticles (NPs) as delivery vector, the intracellular target Tk1 mRNA acted as catalyst to trigger the FCHA between H1, H2 and H3L, which achieved the exponential growth of CHA product. This FCHA system has demonstrated improved reaction kinetics and sensitivity compared to traditional CHA, which was 106 times more sensitive than conventional CHA. This strategy can be used for real-time imaging and indication of changes in the mRNA expression. This strategy slao can distinguish the expression difference of mRNA in normal and tumor cells, and can evaluate the anti-tumor drug’s efficacy. Benefiting from these outstanding advantages, we believe that this FCHA will become a powerful tool for early cancer diagnosis.

A novel near-infrared fluorescent probe for specific imaging of telomerase reverse transcriptase in vivo

Identifying the expression levels of human telomerase reverse transcriptase (hTERT) is important for early cancer diagnosis and cancer-related drug screening. However, a small-molecule fluorescent probe has rarely been used for rapidly determining the hTERT level with high sensitivity has been scarce. Herein, we designed and synthesized a novel near-infrared fluorescent probe (NB-BIBRA) by conjugating an inhibitor analog (BIBRA) to the fluorophore Nile blue (NB) for specific imaging of hTERT in living cells and in vivo. In the absence of hTERT, NB-BIBRA mainly exists in aggregates, exhibiting self-quenching photoactivity. However, once NB-BIBRA interacts with hTERT, NB-BIBRA aggregates are disrupted and their fluorescence intensity is drastically enhanced. Notably, the probe exhibited a low detection limit, high selectivity and rapid response to hTERT, allowing rapid imaging of hTERT in living cells and solid tumor tissue in vivo. To the best of our knowledge, NB-BIBRA is the first near-infrared fluorescent probe for the detection and imaging of hTERT in living cells and in vivo, thus providing a powerful tool for early cancer diagnosis and cancer-related drug screening.

Application of Metal-Based Nanomaterials in In Vitro Diagnosis of Tumor Markers: Summary and Prospect.

Cancer, which presents with high incidence and mortality rates, has become a significant health threat worldwide. However, there is currently no effective solution for rapid screening and high-quality treatment of early-stage cancer patients. Metal-based nanoparticles (MNPs), as a new type of compound with stable properties, convenient synthesis, high efficiency, and few adverse reactions, have become highly competitive tools for early cancer diagnosis. Nevertheless, challenges such as the difference between the microenvironment of detected markers and the real-life body fluids remain in achieving widespread clinical application of MNPs. This review provides a comprehensive review of the research progress made in the field of in vitro cancer diagnosis using metal-based nanoparticles. By delving into the characteristics and advantages of these materials, this paper aims to inspire and guide researchers towards fully exploiting the potential of metal-based nanoparticles in the early diagnosis and treatment of cancer.

ОСОБЕННОСТИ ЛОКАЛЬНОГО ИММУННОГО ОТВЕТА И ИММУНОГИСТОХИМИЧЕСКИЕ МАРКЕРЫ ПРОГНОЗА ПРИ РАКЕ ШЕЙКИ МАТКИ

According to modern data, cervical cancer (CC) occupies one of the leading places in the structure of malignant neoplasms in women of the Republic of Belarus and the Russian Federation; it is also the fourth most common cancer among women worldwide and the seventh in the general statistics of the incidence of human malignant tumors. Currently, there is a tendency towards an increase in the incidence of cervical cancer among young women, and therefore the problem of diagnosing and evaluating the prognosis of this tumor pathology is becoming increasingly important. The process of carcinogenesis in the cervix has a complex multifactorial nature and includes many biochemical mechanisms. To evaluate them various immunohistochemical markers are used. In order to determine the biological potential of squamous cell carcinoma of the cervix, the researchers have evaluated the role of the expression of p53, Ki67, cyclin D1 and CD45 proteins; these markers have also been supposed to be used as a tool for early cancer diagnosis. However, the data on the role of local immunity in assessing the invasive and metastatic potential of a malignant neoplasm are still extremely scarce. The article presents current literature data on the prognostic role of the expression of immunohistochemical markers in cervical cancer and the features of local immunity in cervical neoplasia.

Magnetic Nanoparticle-Based Electrochemical Sensing Platform Using Ferrocene-Labelled Peptide Nucleic Acid for the Early Diagnosis of Colorectal Cancer.

Diagnostic biomarkers based on epigenetic changes such as DNA methylation are promising tools for early cancer diagnosis. However, there are significant difficulties in directly and specifically detecting methylated DNA regions. Here, we report an electrochemical sensing system based on magnetic nanoparticles that enable a quantitative and selective analysis of the methylated septin9 (mSEPT9) gene, which is considered a diagnostic marker in early stage colorectal cancer (CRC). Methylation levels of SEPT9 in CRC samples were successfully followed by the selective recognition ability of a related peptide nucleic acid (PNA) after hybridization with DNA fragments in human patients’ serums and plasma (n = 10). Moreover, this system was also adapted into a point-of-care (POC) device for a one-step detection platform. The detection of mSEPT9 demonstrated a limit of detection (LOD) value of 0.37% and interference-free measurement in the presence of branched-chain amino acid transaminase 1 (BCAT1) and SRY box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1). The currently proposed functional platform has substantial prospects in translational applications of early CRC detection.

The Role of Cancer Stem Cell-Derived Exosomes in Cancer Progression.

Cancer stem cells (CSCs) represent a small portion of tumor cells with self-renewal ability in tumor tissues and are a key factor in tumor resistance, recurrence, and metastasis. CSCs produce a large number of exosomes through various mechanisms, such as paracrine and autocrine signaling. Studies have shown that CSC-derived exosomes (CSC-Exos) carry a variety of gene mutations and specific epigenetic modifications indicative of unique cell phenotypes and metabolic pathways, enabling exchange of information in the tumor microenvironment (TME) to promote tumor invasion and metastasis. In addition, CSC-Exos carry a variety of metabolites, especially proteins and miRNAs, which can activate signaling pathways to further promote tumor development. CSC-Exos have dual effects on cancer development. Due to advances in liquid biopsy technology for early cancer detection, CSCs-Exos may become an important tool for early cancer diagnosis and therapeutic drug delivery. In this article, we will review how CSC-Exos exert the above effects based on the above two aspects and explore their mechanism of action.

A high-performance enzyme-activated near-infrared probe for the sensing and tracking of tumor-related NQO1 in cells and in vivo

High-performance near-infrared (NIR) probes can achieve rapid and effective imaging and tracking of tumor biomarkers, which have attracted extensive attention in tumor visualization and early diagnosis. Fast response speed and high contrast fluorogenic enhancement are important criteria for high-performance imaging probes. Here, by introducing two hydrophilic sulfonates into the probe structure, we designed and optimized a new NAD(P)H:quinone oxidoreductase-1 (NQO1) activated NIR fluorogenic probe (S-QCy7-NQO1) for sensitive detection and evaluation of NQO1 activity in cell and tumor xenografts mice. The catalytic reduction activity of NQO1 quickly eliminated the highly selective quinone trigger, and then the probe S-QCy7-NQO1 was converted into S-QCy7 with an extended conjugated system, resulting in a 245-fold increase in NIR fluorescence, 4.9 times higher than that of QCy7-NQO1 without sulfonates. The introduction of two hydrophilic sulfonates also endows S-QCy7-NQO1 a fast response to NQO1, which is 2 times faster than QCy7-NQO1. The probe S-QCy7-NQO1 showed remarkable responsiveness, sensitivity and optical performance to NQO1 under physiological conditions, allowing the detection of endogenous NQO1 activity in living cells with an ultra-high positive-to-negative ratio (108-fold). Notably, with the improved responsiveness and optical properties, it was further applied to high-contrast imaging of tumor-bearing mice, achieving the maximum fluorescence response within 10 min. On this basis, S-QCy7-NQO1 can be a potentially practical tool for early cancer diagnosis characterized by elevated NOQ1 levels.

Octahedral silver oxide nanoparticles enabling remarkable SERS activity for detecting circulating tumor cells.

The detection of circulating tumor cells (CTCs) is a crucial tool for early cancer diagnosis, prognosis, and postoperative evaluation. However, detection sensitivity remains a major challenge because CTCs are extremely rare in peripheral blood. To effectively detect CTCs, octahedral Ag2O nanoparticles (NPs) with high dispersibility, good biocompatibility, remarkable surface-enhanced Raman scattering (SERS) enhancement, and obvious enhancement selectivity are designed as an SERS platform. Ag2O NPs with many oxygen vacancy defects are successfully synthesized, which exhibit an ultra-high SERS enhancement factor (1.98×106) for 4-mercaptopyridine molecules. The remarkable SERS activity of octahedral Ag2O NPs is derived from the synergistic effect of the surface defect-promoted photo-induced charge transfer (PICT) process and strong vibration coupling resonance in the Ag2O-molecule SERS complex, greatly amplifying the molecular Raman scattering cross-section. The promoted PICT process is confirmed using ultraviolet-visible (UV-Vis) absorption spectroscopy, demonstrating that obvious PICT resonance occurs in Ag2O SERS system under visible light. An additional growth step of SERS bioprobe is proposed by modifying the Raman signal molecules and functional biological molecules on Ag2O NPs for CTC detection. The Ag2O-based SERS bioprobe exhibits excellent detection specificity for different cancer cells in rabbit blood. Importantly, the high-sensitivity Ag2O-based SERS bioprobe satisfies the requirement for rare CTC detection in the peripheral blood of cancer patients, and the detection limit can reach 1 cell per mL. To our knowledge, this study is the first time that a semiconductor SERS substrate has been successfully utilized in CTC detection. This work provides new insights into CTC detection and the development of novel semiconductor-based SERS platforms for cancer diagnosis.

Withdrawal Notice: Electrophoresis as a Tool for Early Cancer Diagnosis

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Design and Synthesis of a Novel NIR Celecoxib-Based Fluorescent Probe for Cyclooxygenase-2 Targeted Bioimaging in Tumor Cells.

Cyclooxygenase-2 (COX-2) imaging agents are potent tools for early cancer diagnosis. Almost all of the COX2 imaging agents using celecoxib as backbone were chemically modified in the position of N-atom in the sulfonamide group. Herein, a novel COX-2 probe (CCY-5) with high targeting ability and a near-infrared wavelength (achieved by attaching a CY-5 dye on the pyrazole ring of celecoxib using a migration strategy) was evaluated for its ability to probe COX-2 in human cancer cells. CCY-5 is expected to have high binding affinity for COX-2 based on molecular docking and enzyme inhibition assay. Meanwhile, CCY-5 caused stronger fluorescence imaging of COX-2 overexpressing cancer cells (Hela and SCC-9 cells) than that of normal cell lines (RAW 264.7 cells). Lipopolysaccharide (LPS) treated RAW264.7 cells revealed an enhanced fluorescence as LPS was known to induce COX-2 in these cells. In inhibitory studies, a markedly reduced fluorescence intensity was observed in cancer cells, when they were co-treated with a COX-2 inhibitor celecoxib. Therefore, CCY-5 may be a selective bioimaging agent for cancer cells overexpressing COX-2 and could be useful as a good monitoring candidate for effective diagnosis and therapy in cancer treatment.

A MEMS lens scanner based on serpentine electrothermal bimorph actuators for large axial tuning.

Confocal microscopes and two-photon microscopes are powerful tools for early cancer diagnosis because of their high-resolution 3D imaging capability, but applying them for clinical use in internal organs is hindered by the lack of axially tunable lens modules with small size, high image quality and large tuning range. This paper reports a compact MEMS lens scanner that has the potential to overcome this limitation. The MEMS lens scanner consists of a MEMS microstage and a microlens. The MEMS microstage is based on a unique serpentine inverted-series-connected (ISC) electrothermal bimorph actuator design. The microlens is an aspheric glass lens to ensure optical quality. The MEMS microstage has been fabricated and the lens scanner has been successfully assembled. The entire lens scanner is circular with an outer diameter of 4.4 mm and a clear optical aperture of 1.8 mm. Experiments show that the tunable range reaches over 200 µm at only 10.5 V and the stiffness of the microstage is 6.2 N/m. Depth scan imaging by the MEMS lens scanner has also been demonstrated with a 2.2 µm resolution, only limited by the available resolution target.

Proteome Analysis of Colorectal Cancer Cell Line SW480 Released Extracellular Vesicles

The detection and profiling of disease-specific extracellular vesicles (EVs) from body fluids has been challenging research area during recent years. However, the question – can EVs surface proteins be exploited as a credible tool for early cancer diagnosis – is still not answered. Objective of the current study was to find out whether hypoxia induces differences in protein profiles of EVs released from hypoxic human colorectal cancer cells SW480 (EVHyp) and EVs released from these cells grown in normoxic conditions – EVNorm. Obtained results show differences in EVs surface protein samples. Some protein fragments were found only or mostly in EVHyp surface protein samples. Finding of one or two such EVHyp protein fragments allows us to suggest that deciphered EVHyp surface proteins might be indices of hypoxia-induced proteome changes and might serve as a hint to find a cancer specific protein.

Narrow Band Imaging in Pituitary Adenomas Surgery

Objective: Narrow band imaging (NBI) has demonstrated to be a useful tool for early cancer diagnosis, from lung and esophageal cancer. NBI enhances micro-vessel vision to detect early vascular anomalies leading to discriminate healthy and pathologic tissues. NBI endoscopy has been proposed as diagnostic tool and as a surgical aid for endoscopic procedures in various specialties. In neurosurgical field the only application of NBI is in ventricular lesions biopsies. We present the application of NBI imaging to pituitary adenoma trans-sphenoidal resection.

Mid infra-red hyper-spectral imaging with bright super continuum source and fast acousto-optic tuneable filter for cytological applications.

Mid-IR imaging spectroscopy has the potential to offer an effective tool for early cancer diagnosis. Current development of bright super-continuum sources, narrow band acousto-optic tunable filters and fast cameras have made feasible a system that can be used for fast diagnosis of cancer in vivo at point of care. The performance of a proto system that has been developed under the Minerva project is described.

Ultrasensitive self-powered cytosensors based on exogenous redox-free enzyme biofuel cells as point-of-care tools for early cancer diagnosis.

An exogenous redox-free, membrane-less enzyme biofuel cell-based ultrasensitive self-powered cytosensing platform was fabricated. With the ultrahigh sensitivity and the merits of not requiring external power sources or exogenous reagents, the device has great potential as a point-of-care tool for early diagnosis of cancer in vivo.

Investigation of urinary pteridine levels as potential biomarkers for noninvasive diagnosis of cancer

Background Biomarkers are good potential tools for early cancer diagnosis. Here we have analyzed eight different pteridines in the urine samples of cancer patients and compared them with samples from healthy subjects. Pteridines are important cofactors in the process of cell metabolism, and they have recently become a focal point of cancer screening research because certain pteridine levels have been shown to reflect the presence of cancers. Methods We analyzed 8 pteridines; 6,7-dimethylpterin, 6-biopterin, d-(+)-neopterin, 6-hydroxymethylpterin, pterin, isoxanthopterin, xanthopterin and pterin-6-carboxylic acid using a house-built high-performance capillary electrophoresis with laser-induced fluorescence detection (HPCE-LIF). The levels of pteridines were reported as a ratio of pteridine to creatinine. Statistical hypothesis testing was conducted and P values were calculated to analyze the data. Results Among the eight pteridines studied, 6-biopterin, 6-hydroxymethylpterin, pterin, xanthopterin, and isoxanthopterin levels were significantly higher in samples from cancer patients than in those from healthy subjects. Further, xanthopterin and isoxanthopterin levels were compared in breast cancer and lung cancer patients, but no significant difference was observed. Conclusion Some pteridine levels can be used as biomarkers for noninvasive diagnosis of cancer; however, more data is needed to support this hypothesis.

Molecular diagnosis in oncology

Recent advances of molecular genetics have made a noticeable impact in some areas of clinical medicine. Almost comprehensive understanding of the nature of hereditary tumors is frequently heralded as the most substantial practical achievement of molecular oncology. Proper diagnostic algorithms have already been developed for the vast majority of known familial cancer syndromes. Interestingly, an unexpectedly strong "founder" effect has been documented at least for some hereditary cancers occurring in Russia, that significantly simplifies the detection of the corresponding disease-associated gene variants. The number of tests aimed to customize cancer treatment continues to grow every year. EGFR mutation test appears to be the most impressive, as it allows to predict lung cancer response or non-response to gefitinib or erlotinib with indeed unique level of accuracy. The approaches helping to determine individual efficacy and safety profiles for fluoropyrimidines, platinum compounds, irinotecan etc. are currently under development Methods aiming to detect residual amounts of disseminated cancer cells represent another popular avenue of the research. It is expected that these technologies will improve the quality of prediction of local and distant metastases, facilitate monitoring of the minimal residual disease and, in the long perspective, provide the tool for early cancer diagnosis. One has to remember that the molecular detection of disseminated tumor cells is currently used mainly in research settings and is not yet incorporated into routine clinical practice.

Laser-induced autofluorescence microscopy of normal and tumor human colonic tissue

Laser-induced autofluorescence (LIAF) spectroscopy has been found to be a promising tool for early cancer diagnosis in various organs, but the reasons responsible for the spectral differences between normal and diseased tissue are still not well understood. In this study, a microspectrophotometer (MSP) system was used to identify the microscopic origins of tissue autofluorescence in the colon under the excitation of a helium-cadmium laser at 442 nm. Colonic tissue samples (normal: n=8, adenocarcinoma: n=10) were obtained from 12 patients with known or suspected malignancies of the colon. The intrinsic fluorescence spectra and images of fresh tissue sections prepared from normal and tumor colonic tissue were measured by the MSP system. Three distinct tissue layers of the colon were found for fluorescence, the mucosa, the submucosa and the muscularis propria, with submucosa being the most fluorescent. Differences in the spectral shape and intensity of the intrinsic fluorescence originating from different colonic layers indicate that fundamentally different fluorophores may be present in the respective tissue layers. There was no significant difference in the intrinsic fluorescence features of the submucosa between normal and tumor colonic tissue, but the fluorescence intensity of the submucosa in tumor tissue was significantly reduced due to the infiltration of tumor cells into the submucosa. The intrinsic fluorescence spectrum peaking at about 520 nm for tumor stroma appeared more evident than that of normal lamina propria. Limited areas of the lamina propria layer in some adenocarcinoma colon exhibited an emission band at about 635 nm, which was attributed to endogenous porphyrins in tumor. Autofluorescence microscopy revealed that differences in the clinically measured autofluorescence spectra between normal and tumor tissue were mainly due to thickening of the tumor mucosa resulting in a reduced submucosa fluorescence contribution, as well as the increased hemoglobin absorption in tumor tissue. Therefore, investigation of the microscopic origins of tissue autofluorescence and images can provide new insights into morphological structures and biochemical components of tissues, which are vital to improve the implementation of the LIAF technique for non-invasive in vivo tissue diagnostics.