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The Clinical Implication Of Circulating Tumor Cells In Pancreatic Cancer And The Preliminary Study Of The Relationship Between Circulating Tumor Cells And Cancer Stem Cells

Posted on:2011-06-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W ZhangFull Text:PDF
GTID:1114360305467961Subject:Oncology
Abstract/Summary:PDF Full Text Request
Pancreatic cancer is a devastating malignancy and a leading trouble to the clinical doctor. The most important reason of death is metastasis and recurrence. Although the prognosis of not only advanced and metastatic pancreatic cancer but also even that of resectable pancreatic cancer is poor, its 5 years survival less than 20%. A better understanding of tumor progression and recurrence has led to the hypothesis that distant metastasis steered by a specific subset of 'tumor-driving cells', generically named circulating tumor cells (CTCs). Circulating tumor cells are rare malignant cells found in the peripheral blood that originate from the primary tumor or metastatic sites. CTCs in the circulating system stimulate immune response, and most of tumor cells had been killed. However a small part of tumor cells escaped and gathered into a cell cluster. These part of tumor cells contribute to the metastasis. Therefore CTCs had been the basis of tumor metastasis. New techniques have been developed to isolate and characterize those cells. CTCs enumeration has been incorporated into different fields of oncology as a prognostic marker, a tool to monitor therapy response, and a method to understand basic tumor characteristics. The study on CTCs of pancreatic cancer has important clinical significance.Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis. Those cells are thought to be highly resistant to standard treatment modalities. Recent progress in stem cell biology and technologies has successfully achieved the identification of CSCs in a variety of cancers, such as breast cancer, colorectal cancer and many malignant tumors. The cancer stem cells have self-renewal and multipotent capacity to generate progeny of various differentiation states that constitute the bulk of the tumor. Although not all types of cancers follow the CSC theory, it provides a possible cellular mechanism to account for the metastasis and recurrence of the tumor The expression of cell-surface markers can be used to identify and isolate cancer stem cells. These markers can serve as either positive or negative criteria for a stem cell phenotype. Pancreatic cancer stem cells'phenotype have been identified as CD44+CD24+ESA+. CD133 and AFP also had been reported as CSCs markers and more markers will be found in new researches.83 patients diagnosed as pancreatic cancer had been researched for CTCs by immunomagetic negative enrichment together with immunofluorescence. Leukocytes were removed by immunomagnetic beads coupled with CD45 antibody. The identification of CTCs can be made only both cytokeratin 8,18,19-phycoerythrin staining and DAPI staining positive.1807 (0-208) circulating tumor cells were identied from 124 blood sample collected from all patients before and/or after theropy. The relationship of CTCs and CSCs had been studied in cell line, tissue specimen and CTCs with stem cell markers. Most of markers,such as CD24, CD44, ESA and AFP were positive in CTCs, therfore, Cancer stem cell phenotype had been found in CTCs. Next reaserch may be carried out on these results.
Keywords/Search Tags:Pancreatic cancer, Circulating tumor cells, Immunomagnetic bead, Immunomagetic negative enrichment, Diagnosis, Resectability, Pathology, Metastasis, Prognosis, Cancer Stem cell
PDF Full Text Request
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