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"Online Monitoring and Isotope Tracing of Tumor-Associated Volatiles in vivo"

This study explores real-time monitoring and stable isotope tracing of tumor-associated volatile compounds in a murine model. By capturing metabolic changes in vivo, it provides insights into cancer-related biomarkers, offering a non-invasive approach for early detection and disease progression tracking. The findings enhance our understanding of tumor metabolism and potential diagnostic applications.


Introduction

Cancer cells exhibit altered metabolism, leading to distinct biochemical byproducts, including volatile organic compounds (VOCs), which can be exhaled or emitted from biological tissues. These tumor-associated volatiles serve as potential biomarkers for cancer detection and disease progression monitoring. This study focuses on real-time (online) monitoring and stable isotope tracing of these volatile compounds in a murine model to identify and track tumor-associated metabolic changes in vivo.

Objectives

  1. Real-Time Detection: Develop and apply advanced analytical techniques to continuously monitor tumor-related VOCs in a living system.
  2. Stable Isotope Tracing: Use isotope-labeled metabolic precursors to trace the origins of tumor-associated volatiles and understand their biochemical pathways.
  3. Non-Invasive Cancer Monitoring: Establish VOC-based biomarkers that can serve as non-invasive tools for early cancer detection and treatment response assessment.

Methods

  • Animal Model: A murine model with induced tumors is used to study the emission of volatile biomarkers.
  • Online Monitoring Techniques: Advanced mass spectrometry (e.g., proton transfer reaction mass spectrometry [PTR-MS] or selected ion flow tube mass spectrometry [SIFT-MS]) is employed for real-time tracking of VOCs.
  • Stable Isotope Labeling: Specific metabolic substrates (e.g., labeled glucose, amino acids, or lipids) are introduced to the system to trace the metabolic pathways leading to VOC formation.
  • Data Analysis: VOC profiles from tumor-bearing mice are compared with those from healthy controls to identify cancer-specific signatures.

Key Findings

  • Certain VOCs are significantly elevated in tumor-bearing mice compared to healthy controls.
  • Isotope tracing reveals that specific metabolic pathways (e.g., altered glucose and lipid metabolism) contribute to the production of these tumor-associated volatiles.
  • Real-time analysis enables dynamic observation of metabolic shifts in response to tumor progression or treatment interventions.

Implications

  • Early Cancer Detection: The ability to detect tumor-related volatiles in real-time opens avenues for non-invasive breath-based diagnostics.
  • Metabolic Insights: Understanding VOC biosynthesis in tumors provides deeper knowledge of cancer metabolism, aiding in biomarker discovery.
  • Therapeutic Monitoring: Tracking VOC changes can help assess the effectiveness of treatments, allowing for personalized therapy adjustments.

Conclusion

This study demonstrates the feasibility of online monitoring and isotope tracing of tumor-associated VOCs in vivo. By combining real-time detection with metabolic pathway analysis, it enhances the potential for VOC-based cancer diagnostics and monitoring strategies. Further research may lead to clinical applications, particularly in breath analysis for non-invasive cancer screening.

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