Analyze the growth and behavior of longitudinally established CTCs. It is documented that virulence of the CTCs reflects the malignant potential of the disease (64-67). Behavior of ex vivo expanded CTCs, therefore, may serve as a measure of tumor status in situ in the patient. The modeling will be complemented by additionally analyzing longitudinally cultured CTCs from blood samples of 4 returning patients from the on-going clinical trial. They will be sampled every 3 months for at least 3 consecutive time points. Behavior of the CTCs will be correlated to status of patient disease progression including the extent of metastasis and responsiveness to therapy. These CTCs will be invaluable for elucidating the relationship of genomics, epigenetics, and gene expression with the mechanisms of cancer metastasis and therapeutic resistance
Genomic characterization and expressional profiling. For a mechanistic understanding of PDAC metastasis and therapeutic resistance, 3 CTC representative cultures for each of the 4 disease groups and a total of 12 CTC-PDX models will be analyzed. Together with matched pairs of normal and cancerous tumor specimens, this analysis ...
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...ith our newly developed anti-tumor NIR dye-gemcitabine conjugates and CSMC-357. Two therapeutic schemes will be followed to fully assess the clinical usefulness of the agents. In the first scheme, mice subjected to s.c. CTC inoculation will be treated at the time of inoculation with either NIR dye-gemcitabine conjugates or CSMC-357 (50 mg/kg, i.p, daily, 21 days) to evaluate the preventive efficacy of these agents. In the second scheme, CTC inoculated mice will be maintained till tumor size reaches 300 mm3 in volume, and then treated with the above agents to assess whether the treatment can eradicate previously formed PDAC tumors in mice. NIR dye and gemcitabine will be used separately as a control treatment for NIR dye-gemcitabine conjugates, while SAHA and tideglusib will be used separately as a control for CSMC-357 to determine the added efficacy of the conjugate.
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