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Influence Of Pre-operative Chemotherapy With 5-FU On Disseminated Malignant Cells And Chemokines In Blood Of Gastric Cancer Patients

Posted on:2007-12-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H WuFull Text:PDF
GTID:1104360212984431Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective: To investigate the expression of three micrometastases-associated markers: cacinoembryonic antigen (CEA)mRNA, cytokeratin 19(CK19)mRNA, human telome-rase reverse transcriptase(hTERT)mRNA in peripheral blood of patients with gastric cancer and their correlation with staging, chemotherapy and surgery, the expression of vascular endothelial growth factor (VEGF), pulmonary and activation-regulated che-mokine (PARC), monocyte chemoattractant protein-1 (MCP-1) in plasma were also assessed.Methods: 60 patients with pathological proved gastric cancer were randomized into two groups before operation. Patients in group one were given pre-operative chemo-therapy(CF200mg iv gtt d1-3+5-FU500mg iv gtt d1-3)and underwent surgery in d4, while patients in group two received surgery only. CEA mRNA, CK19 mRNA and hTERT mRNA in peripheral blood were detected by Taq Man reverse transciptase -polymerase chain reaction (RT-PCR) before and after chemotherapy and operation. VEGF, PARC and MCP-1 in plasma were detected by enzyme-linked immunosorbentassay(ELISA) meanwhile. Drainage blood from stomach(left gastric vein or right gastroepiploic vein) to portal vein were also examined after laparotomy. Peripheral blood from 20 healthy people was examined as normal control.Results: CEA mRNA, CK19 mRNA and hTERT mRNA were all negative in healthy people. The positive rates of CEA mRNA, CK19 mRNA and hTERT mRNA in peripheral blood were 72.9%, 83.1% and 81.4%, respectively. The levels of CEA mRNA,CK19 mRNA and hTERT mRNA were positively correlated with primary tumor(T),regional lymph nodes(N),distant metastasis(M) and TNM staging and cancer embolus respectively. The levels of hTERT mRNA in peripheral blood decreased after chemotherapy compared with the level before chemotherapy (p=0.055), same was the level of CK19mRNA(p=0.055) though the decrement is not significantly . Change of the level of CEA mRNA, CK19 mRNA and hTERT mRNAin peripheral blood after surgery had no statistical significance. Patients whose level of hTERT mRNA in drainage blood from stomach higher than the level in peripheral blood in chemotherapy group were fewer than that in another group(p=0.004), same was the tendency when measured with CEA mRNA or CK19 mRNA though has no statistical significance(p=0.054; 0.083). The levels of VEGF, MCP-1, PARC in peripheral blood of patients with gastric cancer were significantly higher than that in healthy people, the data were 132.92+10.50 vs 59.02±6.28(pg/ml) p=0.000, 25.05 ±1.22 vs 15.95 + 1.15 (pg/ml) p=0.000, 115.94 + 22.56 vs 42.46+13.97 (pg/ml) p=0.000, respectively. The level of VEGF positively correlated with primary tumor(T),regional lymph nodes(N) and TNM staging; The level of MCP-1 inversely correlated with N staging; The level of PARC inversely correlated with N staging, TNM staging and positively correlated with histological grade. The level of VEGF in stage I patients, the level of MCP-1 in stage IV and the level of PARC in stageIII, IV had no difference with that in healthy people. Chemotherapy had no influence on the level of VEGF, MCP-1 and PARC. The level of MCP-1 increased after operation (p=0.004), while the level of VEGF or PARC was not affected by surgery.Conclusion: CEA mRNA, CK19 mRNA and hTERT mRNA in peripheral blood can be used not only as markers in the detection of tumor micrometastases in gastric cancer, but in evaluating chemotherapy response. The levels of MCP-1 and PARC in plasma of gastric cancer patients reflect tumor progression in different phases compared with VEGF, combination of the three indexes in gastric cancer patients plays an important role in cancer evaluation and prognosis.
Keywords/Search Tags:Gastric Cancer, Chemotherapy, Micrometastases, Cytokine, CEAmRNA, CK19mRNA, hTERTmRNA, VEGF, PARC, MCP-1, Real-time RT-PCR
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