ObjectiveTo investigate the expression of tumor metastasis associated genes-1 (MTA1) and vascular endothelial growth factor-C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) and the relationship between them and lymphangiogenesis. MethodA total of 107 patients who received excision for ESCC in the Cardiothoracic Surgery Department of Suining Central Hospital from March 2013 through January 2014 were enrolled. And the paraffinembedded esophageal tissues in 56 healthy persons were collected. The expression of MTA1 and VEGF-C in ESCC was detected using the immunohistochemical method. And D2-40 was used to label the micro-lymphatic endothelial cells of the tumor tissues while the micro-lymphatic vessel density (LVD) was counted. Meanwhile, a statistical analysis was performed for the relationship between MTA1 with VEGF-C and clinical pathological parameters. ResultsThe expression rates of MTA1 protein and VEGF-C protein in ESCC (50.4% and 58.8%, respectively) were higher than those in normal esophageal tissues with a statistical difference (P<0.05). Besides, their high expression rates in stage T3/T4 ESCC and lymph node metastasis group were significantly higher than those in stage T1/T2 ESCC and metastasisfree group, with statistical differences (P<0.05). The high expression rates of MTA1 and VEGF-C protein in ESCC with different TNM stages were compared using Kruskal-Wallis test with statistical differences (P<0.05). Moreover, a positive correlation existed in the expression level between MTA1 protein and VEGF-C protein of ESCC (Spearman coefficient r=0.512, P=0.000). And LVD of the high expression group for MTA1 protein and VEGF-C protein was statistically different from that of the low expression group (P<0.05). ConclusionThe expression of MTA1 is positively correlated with the expression of VEGF-C in ESCC. And they may co-promote lymphangiogenesis and lymphatic metastasis in ESCC. Therefore, both can be used as the laboratory indicators to determine the prognosis of ESCC.
Objective To investigate the clinical meanings of lymphangiogenesis, lymph vessel invasion (LVI) and lymph node (LN) micrometastasis in gastric cancer. Methods The expression of D2-40 in 68 patients with gastric cancer of primary lesion and the expressions of CK20 and (or) CKpan in 791 lymph nodes from 51 cases which were detected by immunohistochemical staining were analyzed, as well as their clinicopathologic profiles. The relationship of lymph vessel density (LVD), LVI and LN micrometastasis with LN metastasis and other clinicopathologic parameters was analyzed respectively. Results Positive rate of LVI with HE (LVI-HE) and D2-40 (LVI-IM) staining was respectively 66.2%(45/68) and 76.5%(52/68), P=0.118. The positive rate of LVI-IM was related to deeper tumor invasion (P=0.044), later stage of TNM (P=0.003) and LN metastasis (P=0.000). Average LVD of 68 cases was (18.19±7.44)/HP. The increment of LVD was significantly associated with LVI-HE positive status （P=0.040）, LVI-IM positive status （P=0.001）, venous invasion （P=0.037）, later stage of TNM （P=0.020） and LN metastasis （P=0.001）. The survival rate of the group sharing ≥15/HP of LVD was significantly lower than that in the group sharing ≤14/HP of LVD in early period of follow-up （P=0.032）. The incidence of nodal involvement in 51 patients was increased from 74.5%(38/51) by HE staining to 88.2%(45/51) by CK (CK20 or CKpan) immunostaining. The detection rate of metastasized LN was increased from 32.0%（253/791） by HE staining to 41.5%（328/791） by CK immunostaining (Plt;0.001). The significant difference of LN micrometastasis detection rate between CK20 (8.7%) and CKpan (12.3%) was also identified (P=0.003). The increased number of LN micrometastasis was related to larger diameter of tumor (P=0.001), higher LVI-HE positive rate (P=0.040), deeper invasion of tumor (P=0.018) and later stage of TNM (P=0.012). Both LN stage and TNM stage were changed according to the detection of LN micrometastasis: Seven patients of N0 should be recognized as N1 (N0→N1)， 6 as N1→N2, 1 as N2→N3. Four patients of stage Ⅰb should be recognized as stage Ⅱ (Ⅰb→Ⅱ)， 4 as Ⅱ→Ⅲa， 3 as Ⅲa→Ⅲb， 1 as Ⅲb→Ⅳ. Conclusion Detection of D2-40 and CK in diagnosis of LVI and LN micrometastasis is better than HE staining. The combined detection of CK20 and CKpan may be much easier to find out the LN with micrometastasis. Later stage of TNM the tumor is, more frequently the LN micrometastasis happens. The relationships of LVI-IM, LVD and LN micrometastasis with LN metastasis in gastric cancer has been demonstrated. Patients with higher LVD share a lower survival rate in early period of follow-up.
【Abstract】Objective To introduce the current studies of the role of vascular endothelial growth factorC (VEGFC) and VEGFD in lymphangiogenesis and lymph node metastasis of gastrointestinal neoplasma. Methods The related literatures in recent 5 years were reviewed. Results The growth factors VEGFC and VEGFD enhance lymphangiogenic metastasis of gastrointestinal neoplasma with the property of angiogenesis and lymphangiogenesis. In gastric adenocarcinoma, VEGFC mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis, venous invasion and reduced 5year survival rates. The role of VEGFC in esophageal squamous cancer and colorectal cancer and VEGFD in colorectal cancer is not certain, with conflicting reports in the published literatures.Conclusion The VEGFC, VEGFD/VEGFR3 signal pathway may become the ideal target for inhibition of tumor proliferation and metastases, antilymphangiogenesis therapy may be a novel potential strategy in tumor biological therapy.
Objective To study the expression of inducible nitric oxide synthase (iNOS)，endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human gastric cancer and their relationship with tumor angiogenesis and to investigate the interaction of NOS and VEGF in gastric cancer. Methods The expression and distribution of VEGF, iNOS and eNOS in 34 gastric cancer specimens were detected with immunohistochemistry. Microvessel density (MVD) was counted with FⅧRAg immune specific staining. Results The expression rates of iNOS, eNOS and VEGF in 34 gastric cancers were 73.5%, 82.4% and 91.2% respectively. The expression of VEGF had a significant positive relation with iNOS, but not with eNOS. The MVDs of VEGF or iNOS positive gastric cancers were obviously higher than those of VEGF or iNOS negative gastric cancers. There was no significant difference between the MVDs of eNOS positive gastric cancers and eNOS negative ones. Conclusion MVD increases with increase of expression of VEGF and iNOS in gastric cancer. It is indicated that VEGF and iNOS can promote gastric cancer angiogenesis. VEGF and iNOS have a significant positive correlation, which suggests that in human gastric cancer, iNOS plays an important role in the production and action of VEGF.
ObjectiveTo investigate the relationship between vascular endothelial growth factor receptor-3 (VEGFR-3) and clinical pathology of gastric carcinoma(GC).MethodsThe expression of VEGFR-3 in 80 GCs and 20 gastric benign tissues (GBT) was detected by immunohistochemistry(SP), by which the density of lymphatic vessels (DLV) was calculated. ResultsThe DLV in GC was （5.800 0±2.318 9）/×200, in GBT （2.380 0±0.462 9）/×200(P=0.000); in GC with lymph node metastasis （6.948 3±1.583 1）/×200, without lymph node metastasis （2.772 7±0.428 9）/×200 （P=0.000）. In poorly differentiated type group, DLV was （7.681 8±0.982 9）/×200, higher than that in moderately and highly differentiated type group 〔(3.500 0±1.028 2）/×200, P=0.000〕. DLV in pTNM Ⅰ+Ⅱ was （4.291 7±1.688 0）/×200, in Ⅲ+Ⅳ （8.062 5±0.759 4）/×200 （P=0.000）.ConclusionDLV shows positive relations with pTNM stage, differentiation and lymph node metastasis of GC.
ObjectiveTo find the role of oncogene cmet and suppressor gene p53 in the process of tumor angiogenesis and their clinical significance. MethodsBy immunohistochemical method and computer image analysis technique, microvessel count and cmet, p53 protein expression were quantitatively determined in 80 cases of breast carcinoma and 20 cases of breast fibroadenoma. ResultsThe high microvessel count and the positive expression of cmet, p53 were significantly correlated with histologic grade, lymph node metastasis and the stage of the tumor (P＜0.01). The high microvessel count was significantly correlated with the positive expression of cmet and p53 (P＜0.01).ConclusionBoth oncogene cmet and suppressor gene p53 modulate tumor angiogenesis of breast carcinoma.
Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). MethodsThe monoclonal antiVEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling (TUNEL) assay. ResultsIn the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm2 vs (105.77±17.40) mm2 (P＜0.001) and (45.20±23.02) mm2 vs (150.77±77.41) mm2 (P＜0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm2 vs (3 900±328)/mm2(P＜0.001 ) and AI being (15.31% vs 6.83%), P＜0.005. Conclusion The antiVEGF antibody can suppress the xenograft tumour growth of the human SMMC7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.
ObjectiveTo discuss the feasibility of treating noumenon tumor by antiangiogenesis.MethodsRelated literatures of recent 5 years was reviewed.ResultsTumor angiogenesis were related closely with growth, development, metastasis and prognosis of noumenon tumor. It was possible to inhibit the growth and metastasis of noumenon tumor with antiangiogenesis in vitro and vivo.ConclusionAntiangiogenesis will be a new therapy of treating noumenon tumor.
Lymphangiogenesis plays an active role in lung cancer metastasis. Currently, it attracts more and more attention because of its role in tumor metastasis and become a hotspot in the field. Lymph node metastasis of lung cancer is the key factor for the unfavourable prognosis of the patient suffered lung cancer. But the correlation of lymphangiogenesis and lung cancer metastasis is yet unknown. Some development about it is reviewed.
摘要:目的: 探讨选择性内皮素A受体拮抗剂BQ123对人喉癌Hep2细胞裸鼠种植瘤的生长及血管形成的影响。 方法 :将实验动物裸鼠随机分为3组:BQ123［n =8,2mg/(kg·day)］、氟尿嘧啶组［n =8,2mg/(kg·day)］、生理盐水组(n =8),比较各组裸鼠成瘤体积、微血管密度(MVD)。 结果 :BQ123组肿瘤体积为(162±053)cm3,明显小于生理盐水组及氟尿嘧啶组,差异具有统计学意义;BQ123组的肿瘤组织中MVD高倍镜下为232,明显低于生理盐水组(586)及氟尿嘧啶组(395),差异具有统计学意义。 结论 :BQ123对人喉癌Hep2细胞在裸鼠体内有明显抑瘤作用,肿瘤的体积、肿瘤组织MVD显著低于对照组,表明BQ123可通过抑制肿瘤血管生成而显著抑制肿瘤生长。Abstract: Objective: To study the effects of endothelin A receptor blockade BQ123 on the implanted human laryngeal carcinoma angiogenesis of nude mouse. Methods : From March 2008 to July 2009, 24 Balb/c nude mice were randomly divided into three groups: BQ123 group ［〖WTBX〗n =8, BQ123 at 2mg/(kg·day)］, 5Fu group ［〖WTBX〗n =8, fluorouracil at 2mg/(kg·day)］ and the control group (〖WTBX〗n =8, normal saline). The carcinoma volume and microvascular density of each group were compared. Results : The tumor size of BQ123 group, which was (162±053)cm3 in average, was significant smaller than the tumor sizes of the other two group s. The average microvascular density score of the tumors in BQ123 group was 232 per hyper power len (HP), which was also significantly less than the average scores of control groups (586 and 395 respectively). Conclusion : Nude mouse experiments show that the carcinoma volume and microvascular density of BQ123 group are significantly lower than those of the control groups. BQ123 inhibits the growth of carcinoma by its inhibition of carcinoma angiogenesis.