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Correlation between Expression of Inducible Nitric Oxide Synthase, Tumour-associated Macrophages and

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Tutor: GeChunLin
School: China Medical University
Course: General Surgery
Keywords: Pancreatic Cancer,Inducible nitric oxide synthase,Tumor-associated macrophages,L
CLC: R735.9
Type: Master's thesis
Year:  2007
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Preface pancreatic cancer is clinically more common malignancies, early hard-to-find, late often surrounding tissue, blood vessels and nerves of the invasion and lymph node metastasis. , INOS is considered to be one of the most important factors in the proliferation and metastasis of malignant tumor cells. Now the study, iNOS has a role in promoting tumor growth, progression and metastasis through a variety of channels. NO tumor cell signal transduction pathways important messenger molecule, regulation and cell proliferation related gene expression, increased angiogenesis of tumor blood supply, and promote tumor growth, invasion and metastasis. VEGF angiogenic factors involved in the angiogenesis process, the only specific role of the vascular endothelial cell mitogen, plays an important role in all aspects of tumor angiogenesis. VEGF on endothelial cell migration, proliferation and lumen formation in part through its induced signal transduction molecules NO to complete. The study found that there is a close relationship between VEGF and NO. Tumor NO VEGFmRNA level raised VEGF levels positively correlated with the degree of tumor vascularization. , NO synthase may VEGF regulation of angiogenesis downstream channels and media. Recent study found that tumor-associated macrophages (tumour-associated macrophages, TAMs) are closely related with lymph node metastasis. Many tumor tissues, especially epithelial tissues, including lung, breast, stomach, solid tumors, the presence of a large number of TAMs. TAMs mainly derived from the peripheral blood mononuclear cells, are also part of the fixed tissue macrophages. The infiltration site mainly located in the tumor stroma and vascular endothelium. The anti-tumor effect of macrophages, tumor tissue, despite the large number of TAMs infiltration, but it can continue to grow, TAMs may promote tumor growth. TAMs mechanism of action of tumor tissue is not entirely clear. Immunohistochemical staining and microvessel counts related to the formation the TAMs and blood vessels of some tumors. Some studies have shown that the number of esophageal cancer in TAMs and iNOS expression, also confirmed that iNOS and peritumoral lymphatic vessel density and lymph node metastasis. The TAMs and iNOS and lymph node metastasis in pancreatic cancer relationship no report. In this study, using immunohistochemical methods comparison study. Materials and methods collected from 1999 to 2005, China Medical University Affiliated Hospital surgical resection of pancreatic cancer specimens of 35 cases, including 24 males and 11 females, aged 34 to 76 years, with an average of 54.2 years. The Preoperative are without any treatment. All specimens were confirmed by pathology. 19 cases of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma in 9 cases, 7 cases of poorly differentiated adenocarcinoma. TNM staging: Ⅰ 8 cases, Ⅱ 12 cases, Ⅲ of 10 cases, Ⅳ of five cases. 15 cases of lymph node metastasis in 20 cases without lymph node metastasis. Collected six cases of normal pancreatic tissue resected distal bile duct cancer underwent pancreaticoduodenectomy, 4 males and 2 females, aged 39 to 75 years, an average of 58.4 years. Above specimens have been dehydrated, formalin-fixed, paraffin-embedded serial sections (thickness 4 μm). Antigen retrieval, conventional SP method normal pancreas and pancreatic cancer tissue by immunohistochemical staining. The mouse anti-human CD68 monoclonal antibody labeled macrophages, mouse anti-human iNOS monoclonal antibody labeling of iNOS. Set of positive and negative control, and conventional HE staining. To light microscope random three cancer organizations high power field (400-fold) mean of of TAMs cell number of the cases TAMs value. iNOS expression in its score values: cancer tissue staining intensity score (none, 0 points; weak, 1 min;, 2 points;, 3 points) rating and the rate of positive cells (less than 5%, 0 points; 5 ~ 10%, 1 min; 10 ~ 20%, 2 minutes; 20 to 50%, 3 points; greater than 50%, 4 points), and of the illness score value, the rated value is less than or equal to 2 sub-set negative cases, more than 2 points as positive cases. Statistical analysis was performed using SPSS 12.0 statistical software, measurement data, ((?) ± s) said. T (t ') test was used to compare between the two groups, more than three sets or three sets of pairwise comparisons using analysis of variance (Newman-keuls method, q test). Pearson correlation coefficients of the relationship between test the VEGF score and TAMs count, P <0.05 considered statistically significant. Results 1. Immunohistochemical staining results normal macrophages obvious sparsely distributed to yellow or brown granular CD68 expression in the pancreatic cancer group, mainly located in the membrane and cytoplasm of macrophages. Widely distributed in the cancer tissue and cancer organizations. The expression of iNOS yellow or brown particles, mainly located in the cytoplasm of cancer cells, expressed in cancer cells and the cancer surrounding normal tissue less expression. 2. iNOS expression and the clinical indicators of positive iNOS expression in the pancreatic cancer group was 54% (19/35) rated value of 3.17 ± 1.22, significantly higher than the normal group (P <0.01). No significant difference between the pancreatic pathological grade group and clinical stage group (P> 0.05). INOS expression in lymph node metastasis group than the group without lymph node metastasis, and the difference was statistically significant (P <0.05). 3. TAMs count and the clinical indicators of pancreatic cancer TAMs count mean of 112.27 ± 24.57. Differences between pancreatic cancer pathological grade group and clinical stage group were statistically significant (P <0.05). Lymph node metastasis in TAMs count is higher than the group without lymph node metastasis, and the difference was statistically significant (P <0.05). 4. The relationship between pancreatic cancer in the expression of iNOS and TAMs count in pancreatic cancer in the expression of iNOS and macrophage count was a positive linear correlation (γ = 0.551, P <0.05). I.e., with the the macrophage count increases in the tumor tissue, the expression of iNOS is also increased. Discussion Pancreatic cancer is more common malignancies. Angiogenesis is the premise of malignant tumor growth and metastasis. iNOS is the role of a strong pro-angiogenic growth factor one. This study shows that iNOS expression in pancreatic cancer tissue, peritumoral and normal tissue less expression. Pancreatic cancer cells contain a large number of iNOS in order to promote the formation of tumor blood vessels. No significant difference in clinical stage group, the expression of iNOS and pathological grade group, rather than not transfer the transfer group iNOS expression were significantly higher, indicating that iNOS expression with lymph node metastasis, suggesting that iNOS may be some mechanism to promote the growth of lymphatic , leading to lymph node metastasis. Found a large number of macrophage infiltration in many tumor tissues. This study shows that pancreatic tissue infiltration of a large number of tumor-associated macrophages (TAMs), are mainly located in the pancreatic interstitial. TAMs expression were significant differences in the clinical stage and histological grade group, TAMs count mean significantly higher than those without metastasis group and metastasis, differentiation of TAMs with pancreatic metastasis of. TAMs may also secrete promote tumor growth and metastasis of factors involved in tumor growth and metastasis. TAMs count is higher, the pancreatic differentiation may lower, the more prone to metastasis. The study also found that pancreatic expression of iNOS and TAMs count was close positive correlation between prompt the secretion of iNOS TAMs infiltration is closely related to, and with pancreatic transfer. And research has shown that iNOS is induced chemotactic factor TAMs infiltration. May be cancer cells produce iNOS promote angiogenesis, induction of TAMs infiltration, TAMs also produce iNOS promote tumor growth. But in pancreatic TAMs produce iNOS needs further study. The study also found that the the TAMs expression with pancreatic cancer staging grades iNOS expression and staging of pancreatic cancer grade, iNOS and TAMs expression, is not exactly the same, may, respectively, and the role of other factors , TAMs in pancreatic cancer differentiation and metastasis may be more important. Inhibit infiltration of TAMs may be a meaningful direction in future to explore the treatment of pancreatic cancer. Conclusion iNOS expression and TAMs were associated with pancreatic cancer lymph node metastasis are closely related, and there are close ties between the two. iNOS expression and staging of pancreatic cancer grade, while the the TAMs expression and staging of pancreatic cancer grade, TAMs may be more important in pancreatic cancer differentiation and metastasis.
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