Diagnosis Of Cancer In Clinical Practice Research Articles

Innovative Colorimetric NQO1 Detection Strategy via Substrate Competitive and Biomimetic Cascade Reactions with a Highly Active NADH Oxidase Mimic.

NAD(P)H: quinone oxidoreductase-1 (NQO1) plays critical roles in antioxidation and abnormally overexpresses in tumors. Developing a fast and sensitive method of monitoring NQO1 will greatly promote cancer diagnosis in clinical practice. This study introduces a transformative colorimetric detection strategy for NQO1, harnessing an innovative competitive substrate mechanism between NQO1 and a new NADH oxidase (NOX) mimic, cobalt-nitrogen-doped carbon nanozyme (CoNC). This method ingeniously exploits the differential consumption of NADH in the presence of NQO1 to modulate the generation of H2O2 from CoNC catalysis, which is then quantified through a secondary, peroxidase-mimetic cascade reaction involving Prussian blue (PB) nanoparticles. This dual-stage reaction framework not only enhances the sensitivity of NQO1 detection, achieving a limit of detection as low as 0.67 μg mL-1, but also enables the differentiation between cancerous and noncancerous cells by their enzymatic activity profiles. Moreover, CoNC exhibits exceptional catalytic efficiency, with a specific activity reaching 5.2 U mg-1, significantly outperforming existing NOX mimics. Beyond mere detection, CoNC serves a dual role, acting as both a robust mimic of cytochrome c reductase (Cyt c) and a cornerstone for enzymatic regeneration, thereby broadening the scope of its biological applications. This study not only marks a significant step forward in the bioanalytical application of nanozymes but also sets the stage for their expanded use in clinical diagnostics and therapeutic monitoring.

Next-generation sequencing using tissue specimen collected with a 1.1 mm-diameter cryoprobe in patients with lung cancer.

Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis. Patients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively. A total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection. TBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing.

Clinical Role of Upfront F-18 FDG PET/CT in Determining Biopsy Sites for Lung Cancer Diagnosis.

This study aimed to investigate the impact of FDG PET/CT timing for biopsy site selection in patients with stage IV lung cancer regarding complications and diagnostic yield. This retrospective analysis was performed on 1297 patients (924 men and 373 women with a mean age of 71.4 ± 10.2 years) who underwent percutaneous needle biopsy (PNB) for stage IV lung cancer diagnosis in two hospitals. Data collected included the patient's characteristics, order date of the biopsy and PET/CT exams, biopsy target site (lung or non-lung), guidance modality, complications, sample adequacy, and diagnostic success. Based on the order date of the PNB and PET/CT exams, patients were categorized into upfront and delayed PET/CT groups. PNB for non-lung targets resulted in significantly lower rates of minor (8.1% vs. 16.2%), major (0.2% vs. 3.4%), and overall complications (8.3% vs. 19.6%) compared to PNB for lung targets (p < 0.001 for all types of complications). Compared to the delayed PET/CT group, the upfront PET/CT group exhibited a lower probability of lung target selection of PNB (53.9% vs. 67.1%, p < 0.001), including a reduced incidence of major complications (1.0% vs. 2.9%, p = 0.031). Moreover, there was no significant difference in the occurrence of minor and total complications between the two groups. Upfront PET/CT and delayed PET/CT groups showed no significant difference regarding sample adequacy and diagnostic success. Upfront PET/CT may have an impact on the selection of the biopsy site for patients with advanced lung cancer, which could result in a lower rate of major complications with no change in the diagnostic yield. Upfront PET/CT demonstrates potential clinical implications for enhancing the safety of lung cancer diagnosis in clinical practice.

Sensitive detection of stage I lung adenocarcinoma using plasma cell-free DNA breakpoint motif profiling.

SummaryBackgroundEarly diagnosis benefits lung cancer patients with higher survival, but most patients are diagnosed after metastasis. Although cell-free DNA (cfDNA) analysis holds promise, its sensitivity for detecting early-stage lung cancer is unsatisfying. We leveraged cfDNA fragmentomics to develop a predictive model for invasive stage I lung adenocarcinoma (LUAD).Methods292 stage I LUAD patients from three medical centers were included together with 230 healthy controls whose plasma cfDNA samples were profiled by whole-genome sequencing (WGS). Multiple cfDNA fragmentomic motif features and machine learning models were compared in the training cohort to select the best model. Model performance was assessed in the internal and external validation cohorts and an additional dataset.FindingsA logistic regression model using the 6bp-breakpoint-motif feature was selected. It yielded 98·0% sensitivity and 94·7% specificity in the internal validation cohort [Area Under the Curve (AUC): 0·985], while 92·5% sensitivity and 90·0% specificity were achieved in the external validation cohort (AUC: 0·954). It is sensitive for early-stage (100% sensitivity for minimally invasive adenocarcinoma, MIA) and <1 cm (92·9%–97·7% sensitivity) tumors. The predictive power remained high when reducing sequencing depth to 0·5× (AUC: 0·977 and 0·931 for internal and external cohorts).InterpretationHere we have established a cfDNA breakpoint motif-based model for detecting early-stage LUAD, including MIA and very small-size tumors, shedding light on early cancer diagnosis in clinical practice.FundingNational Key R&D Program of China; National Natural Science Foundation of China; CAMS Initiative for Innovative Medicine; Special Research Fund for Central Universities, Peking Union Medical College; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences; Beijing Hope Run Special Fund of Cancer Foundation of China.

Dual Rolling Circle Amplification-Assisted Single-Particle Fluorescence Profiling of Exosome Heterogeneity for Discriminating Lung Adenocarcinoma from Pulmonary Nodules

Dual Rolling Circle Amplification-Assisted Single-Particle Fluorescence Profiling of Exosome Heterogeneity for Discriminating Lung Adenocarcinoma from Pulmonary Nodules

Discovery of Turn-On Fluorescent Probes for Detecting Bcl-2 Protein.

B-cell-lymphoma-2-gene (Bcl-2) family proteins play a central role in regulating programmed cell death. In cancer, antiapoptotic Bcl-2 proteins, such as Bcl-2 and Mcl-1, are overexpressed. However, there are few developed labeling techniques for tracing the dynamic processes of Bcl-2. To study the physiological process of Bcl-2 protein, a novel series of small-molecule fluorescent probes (1-3) were designed and evaluated for their labeling properties. Our probes can be applied to the identification of tumor-tissue slices and the differentiation of tumor and normal tissues effectively, a feature that renders these probes compatible with future cancer diagnosis in clinical practice.

Design and synthesis of NQO1 responsive fluorescence probe and its application in bio-imaging for cancer diagnosis

As an over-expressed flavoprotein in several kinds of tumor cells, NAD(P)H: quinone oxidoreductase-1 (NQO1) is considered as a potent biomarker in early-stage cancer diagnosis. Developing a fast, selective and sensitive method of monitoring NQO1 on cellular level will greatly promote cancer diagnosis in clinical practice. In this paper, a fast NQO1 responsive fluorescence probe SYZ-30 containing quinone acid and 7-nitro-2,1,3-benzoxadiazole (NBD) fluorophore is constructed. The probe could selectively respond to NQO1 and rapidly emit strong fluorescence in vitro within only 5 min. Notably, the peak fluorescent intensities at 550 nm showed a linear relationship with NQO1 concentrations in the range of 3–30 ng/ml and limit of detection (LOD) was 0.0667 ng/ml. Furthermore, it was validated that the probe has good biocompatibility and could be applied for bio-imaging in NQO1 over-expressed cancer cells, together with its mitochondria targeting ability. Importantly, confocal fluorescence imaging confirmed the NQO1 detection ability on cellular level, which can be used for real-time detection of several cancer subtypes like adenocarcinoma. To conclude, the probe is rapidly responsive, highly sensitive and selective which will potentially become a practical tool for early cancer detection and diagnosis.

MP53-11 A PRE-BIOPSY NOMOGRAM FOR PREDICTION OF THE RISK OF GLEASON SCORE = 7 PROSTATE CANCER ON COMBINED MRI-US FUSION TARGETED AND SYSTEMATIC PROSTATE BIOPSY AMONG MEN WITH NO PREVIOUS BIOPSY

INTRODUCTION AND OBJECTIVES: MRI-targeted prostate biopsy (PB) is increasingly being utilized to aid cancer diagnosis in clinical practice. Our objective was to develop a nomogram to predict the probability of Gleason score 7 prostate cancer (CaP) on MRI targeted and systematic prostate biopsy in men with no previous biopsy. METHODS: From June 2012 to June 2015, MR-US fusion targeted prostate biopsy was performed on approximately 1,140 men with suspicious regions identified on pre-biopsy 3T multiparametric-MRI along with systematic 12 core biopsy, utilizing the ProFuse|Artemis system. Logistic regression modeling was used to evaluate predictors of Gleason score 7 CaP, and corresponding nomograms were generated. Models were created with a randomly selected training sample (n1⁄4232), tested (n1⁄459), and then validated (n1⁄498). Bias-corrected using bootstrap resampling, and Akaike information criterion was used to select best-fit models. RESULTS: A total of 389 men with no previous biopsy and complete records were included for analysis (median age 66 years, PSA 4.8 ng/ml, prostate volume 46 cc, PSA density 0.09 ng/ml-cc). Statistically significant independent positive predictors of CaP on targeted and systematic PB were found to be PSA density, age, and MRI suspicion score (MRIss). A CaP probability nomogram (Figure 1) was generated using the predictors and model performance characteristics bias-corrected areas under the receiver-operating characteristic curves (AUC) were validated (Figure 2). CONCLUSIONS: PSA density, age, and MRI suspicion score predict CaP on MRI-targeted and systematic biopsy. Our CaP probability nomogram may allow further individualization of the decision to perform PB in men with clinical suspicion of prostate cancer and no previous biopsy. Source of Funding: None