Cancer detection by circulating tumor cell capturing combined with molecular marker verification and synergistic anti-cancer effects of proanthocyanidins from the plant urceola huaitingii with chemotherapeutics

Abstract

The development of cancer diagnosis and treatment is directly associated with the welfare of patients. Early detection of cancer significantly increases the patients’ long-term survival rates and effective treatment ensures good living conditions. Circulating tumor cell (CTC) detection for clinical diagnostic purposes has become a very popular research topic in the recent twenty years. CTCs are tumor cells that detach from the primary tumor and flow in the blood. They are believed to arise from surgical lesions or tumors that grow into a metastatic stage. CTC counts from patients’ blood samples can also indicate the treatment progress in the patients or metastatic status of the tumor. We developed a technique in which two traditional methods work in a sequential manner to optimize their performances. In this technique, a size-based porous membrane filtration is the first step enriching CTCs within a small area. To identify CTCs from normal blood cells captured on the membrane, immunofluorescence staining tests using molecular markers was then performed.

Five packaging methods were compared for filtration and the slot-blot system was finally selected as the setup for its best performance in filtration and compatibility with imaging and numeration. Filtration parameters including the number of filter papers, filtration area and vacuum pressure, were optimized for laboratory and clinical tests. The finalized device had a cancer cell capture rate of over 80% using cell culture suspension and a sensitivity of 91% and a specificity of 98% were obtained in clinical tests on 44 gastric cancer patients and 43 healthy controls. This is the first time that these molecular markers were used for CTC detection and the first technique that demonstrated consistent CTC detection from patients without clinically detectable metastasis. The future work will be on expanding the sample population of the clinical tests and comparative studies with existing technologies.

Extraction and testing of effective compounds from Chinese herbs has been widely conducted in the studies of the mechanisms of Traditional Chinese Medicine (TCM) as well as drug discovery. Many compounds from TCM demonstrate a broad spectrum of effects including anti-cancer activities. Nine prothancyanidins (compound 1-9) extracted from the plant Urceola huaitingii by our collaborators were investigated for anti-cancer activities alone and in combination with Doxorubicin or Cisplatin. Some compounds, especially compound 7, exhibited synergistic effects in combination with doxorubicin or Cisplatin, indicating potential combinatory treatment formulas with lower concentrations of chemotherapeutics to lower the side effects on the patients. Further verification on the synergism and investigation on the potential exploitations will be carried out in collaboration with researchers working in medicinal chemistry.

Date of Award	2018
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology