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1.
AIM: To investigate integrin β3 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS: In situ hybridization(ISH) of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS: The positive rate of integrin β3 mRNA in non-tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, X^2 = 10.20, P 〈 0.01). In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type (P 〈 0.01), stage T1-T2 (P 〈 0.01), non-vessel invasion (P 〈 0.01), without lymphatic metastasis (P 〈 0.01), without hepatic and peritoneal metastasis (P 〈 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P 〈 0.01), stage T1-T2 (P 〈 0.01), non-vessel invasion (P 〈 0.01), without lymphatic metastasis (P 〈 0.01), without hepatic and peritoneal metastasis (P 〈 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P 〈 0.01), stage T1-T2 (P 〈 0.01), non-vessel invasion (P 〈 0.01), without lymphatic metastasis (P 〈 0.01), without hepatic and peritoneal metastasis (P 〈 0.01), respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein (P 〈 0.01) and MVD (P 〈 0.05),  相似文献   

2.
AIM: To investigate integrin 133 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS: In situ hybridization(ISH) of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS: The positive rate of integrin 133 mRNA in non- tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, x2 = 10.20, P < 0.01). In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type (P < 0.01), stage T1-T2 (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P < 0.01), stage T1-T2 (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P < 0.01), stage T1-T2 (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein (P < 0.01) and MVD (P < 0.05), meanwhile the positive expression rate of VEGF protein was positively related to NVD (P < 0.05). The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA (P < 0.05) and VEGF (P < 0.01), and MVD < 54.9/mm2 (P < 0.01). Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly lower than those with negative expression of integrin β3 mRNA (P < 0.05), VEGF (P < 0.05), and NVD < 54.9/mm2 (P < 0.01). CONCLUSION: Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.  相似文献   

3.
AIM:To investigate the correlation between expressionof vascular endothelial growth factor (VEGF) and celldifferentiation,invasion,metastasis and Naspin expressionin gastric carcinoma.METHODS:Formalin-fixed paraffin-embedded tissuespecimens from 73 cases of gastric carcinoma were studiedwith SP immunohistochemistry,using anti-VEGF monoclonalantibody,and thirty-nine of them were studied using anti-Maspin monoclonal antibody.VEGF expression was comparedwith the dinical stage,lymph node metastasis,and Borrrnann'sand WHO's classification of gastric carcinoma.RESULTS:The positive rate of VEGF expression wassignificantly higher in adjacent non-carcinoma epithelia(ANCE) than in non-metaplastic,non-carcinoma gastricepithelia (NMNCE),which were at least 4 cm distant fromthe primary tumor (P=0.000,X~2=73.03).The positiverate of VEGF expression was significantly higher in advancedgastric carcinoma (AGC) than in early gastric carcinoma(EGC) (P=0.032,X~2=4.62).The positive rate of VEGFexpression in gastric carcinomas with lymph node metastaseswas significantly higher than that in those without metastasis(P=0.006,X~2=7.47).Maspin was weakly expressed in 16out of 39 cases of NINCE,and the positive immunoreactionwas limited to gland cells of the stomach body.There wasno significant correlation between the expression of VEGFand histological or gross classifications,and correlationbetween the expressions of VEGF and laspin in gastriccarcinoma (P=0.648,X~2=0.21).CONCLUSION:Expression of VEGF is significantly correlatedto the malignant biological behaviors of gastric carcinoma,but there is no significant correlation between the expressionof VEGF and Maspin.  相似文献   

4.
AIM: To investigate the correlation between expression of vascular endothelial growth factor (VEGF) and cell differentiation, invasion, metastasis and Maspin expression in gastric carcinoma.METHODS: Formalin-fixed paraffin-embedded tissue specimens from 73 cases of gastric carcinoma were studied with SP immunohistochemistry, using anti-VEGF monoclonal antibody, and thirty-nine of them were studied using antiMaspin monoclonal antibody. VEGF expression was compared with the clinical stage, lymph node metastasis, and Borrmann‘s and WHO‘s classification of gastric carcinoma.RESULTS: The positive rate of VEGF expression was significantly higher in adjacent non-carcinoma epithelia (ANCE) than in non-metaplastic, non-carcinoma gastric epithelia (NMNCE), which were at least 4 cm distant from the primary tumor (P = 0.000, x^2= 73.03). The positive rate of VEGF expression was significantly higher in advanced gastric carcinoma (AGC) than in early gastric carcinoma (EGC) (P = 0.032, x^2 = 4.62). The positive rate of VEGF expression in gastric carcinomas with lymph node metastases was significantly higher than that in those without metastasis (P = 0.006, x^2 = 7.47). Maspin was weakly expressed in 16 out of 39 cases of NMNCE, and the positive immunoreaction was limited to gland cells of the stomach body. There was no significant correlation between the expression of VEGF and histological or gross classifications, and correlation between the expressions of VEGF and Maspin in gastric carcinoma (P = 0.648, x^2 = 0.21).CONCLUSION: Expression of VEGF is significantly correlated to the malignant biological behaviors of gastric carcinoma,but there is no significant correlation between the expression of VEGF and Maspin.  相似文献   

5.
AIM: The expressive balance between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a critical role in maintaining the degradation and synthesis of extracellular matrix. Loss of such balance is associated with invasion and metastasis of tumors. This study aimed to determine the expression of MMP-9 and TIMP-1 in gastric carcinoma, and the association of the expressive imbalance between MMP9 and TIMP-1 with the invasion and metastasis and prognosis of gastric carcinoma.METHODS: We used immunohistochemistry to determine the expressions of MMP-9, TTMP-1 and proliferating cell nuclear antigen Ki-67 in the gastric specimens taken from 256 patients with primary gastric carcinoma. The patients were followed-up for up to 96 months.RESULTS: No association between the expression of MMP9 and TIMP-1 and patients' sex and age, tumor size and location of gastric carcinoma was observed. The incidence of the positive expression of MMP-9 in cases with tumors invasion to muscularis propria and visceral peritoneum (70.13% and 69.09%, respectively) was significantly higher than that in cases with tumor invasion only to lamina propria or submucosa (42.50 %, P=0.0162). The positive correlation between MMP-9 expression and the depth of tumor invasion was observed (Pearson correlation coefficient=0.2129,P=0.016). Along with the increase of the metastatic station of lymph nodes, the incidence of the MMP-9 expression was increased by degrees; a positive correlation between them was observed (Pearson correlation coefficient=0.2910,P=0.0001). There was also a significant correlation between MMP-9 expression and the TNM stage in gastric carcinoma (Pearson correlation coefficient=0.3027, P<0.0001). The incidence of MMP-9 expression in stage Ⅱ and Ⅲ/Ⅳ (75.00%and 76.15%, respectively) was significantly higher than those in stage Ⅰ (46.15 %, P<0.0001). A negative correlation between TIMP-1 immunoreactivity and the depth of invasion,status of lymph node metastasis and TNM stage was observed (Pearson correlation coefficient =-0.1688, -0.3556and -0.3004, P=0.023, <0.0001 and <0.0001, respectively).Four types of co-expression of MMP-9 and TIMP-1 were observed; i.e. MMP-9 positive but T IMP-1 negative (n=115),both positive (n=52), both negative (n=62) and MMP-9negative but TIMP-1 positive (n=27). The frequency of serosal invasiveness was significant higher in patients with MMP-9 but without TIMP-1 expression than those with other types of the co-expression (P=0.0303). The incidence of lymph node metastasis was highest in patients with MMP-9but without TIMP-1 expression, and lowest in those with TIMP-1 but without MMP-9 expression (P<0.0001). The survival rate in patients with MMP-9 but without TIMP-1expression was lower than that in those with TIMP-1 but without MMP-9 expression (P=0.0014).CONCLUSION: Our results in gastric carcinoma demonstrated a significant positive association of MMP-9 over-expression with proliferation of tumor cells, the depth of invasiveness,lymph node metastasis and TNM stage, suggesting MMP-9can serve as a molecular marker of tumor invasion and metastasis. We also demonstrate a significant negative relationship of TIMP-1 expression with the depth of invasiveness and lymph node metastasis, which provide a new idea in the tumor biological and genetic treatment.The interaction between MMP-9 and TIMP-1 in the processes of tumor invasion and metastasis is that MMP-9 mainly promotes tumor invasion and metastasis and TIMP-1 inhibits functions of MMP-9. The imbalance between MMP-9 and TIMP-1 expression may suggest the occurrence of tumor invasion and metastasis, predict poor prognosis. For patients with imbalanced MMP-9 and TIMP-1 expression, the optimal treatment scheme needs to be selected.  相似文献   

6.
AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD),invasion, metastasis, and prognosis. METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas. RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions, which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2, respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs= 0.211, P= 0.031; rs= 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs= 0.579, P= 0.001; rs = 0.209, P= 0.032), lymph node metastasis (rs= 0.405, P= 0.001; rs= 0.343, P= 0.001) and distant metastasis (rs= 0.474, P= 0.001; rs = 0.468, P = 0.001), but not correlated to tumor type (rs=0.134,P=0.173;rs=0.103,P=0.145) and differentiations (rs=0.096,P= 0.332;rs=0.102,P=0.298). The mean MVD was much higher in the tumors with infiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t=5.961,P=0.001),with non-vessel invasion (t=7.394,P=0.001),non-lymph node metastasis (t = 3.819, P= 0.01) and non-distant metastasis (t = 10.578, P= 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA (t = 3.207, P=0.002; t = 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate were lower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA. CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bFGF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.  相似文献   

7.
AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.  相似文献   

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AIM:To study the expression of vascular endothelial growthfactor C (VEGF-C) and chemokine receptor CCR7 in gastriccarcinoma and to investigate their associations with lymphnode metastasis of gastric carcinoma and their values inpredicting lymph node metastasis.METHODS:The expression of VEGF-C and CCR7 in gastriccarcinoma tissues obtained from 118 patients who underwentcurative gastrectomy was examined by immunohistochemistry.Among these patients,39 patients underwent multi-slicespiral CT (MSCT) examination.RESULTS:VEGF-C and CCR7 were positively expressed in52.5 and 53.4% of patients.VEGF-C expression was morefrequently found in tumors with lymph node metastasis thanthose without it (P<0.001).VEGF-C expression was alsoclosely related to lymphatic invasion (P<0.001),vascularinvasion (P<0.01),and TNM stage (P<0.001).However,there was no significant correlation between VEGF-Cexpression and age at surgery,gender,tumor size,tumorlocation,Lauren classification,and depth of invasion.CCR7expression was significantly higher in patients with lymphnode metastasis compared with those without lymph nodemetastasis (P<0.001) and was also associated with tumorsize (P<0.01),depth of invasion (P<0.001),lymphaticinvasion (P<0.001),and TNM stage (P<0.001).However,the presence of CCR7 had no correlation to age at surgery,gender,tumor location,Lauren classification,and vascularinvasion.Among the 39 patients who underwent MSCTexamination,only CCR7 expression was related to lymphnode metastasis determined by MSCT (P<0.05).In thecurrent retrospective study,the sensitivity,specificity,positivepredictive value (PPV),negative predictive value (NPV),andaccuracy of VEGF-C and CCR7 expression in the diagnosisof lymph node metastasis for patients with gastric carcinomawere 73.8%,70.2%,72.6%,71.4% and 72.0%,and 82.0%,77.2%,79.4%,80.0% and 79.7%,respectively.Aftersubdivision according to the combination of VEGF-C andCCR7 expression,receiver operating characteristic (ROC)analysis showed that the accuracy of the combinedexamination of VEGF-C and CCR7 expression in predicting lymph node metastasis was relatively high (area under ROCcurve [Az]=0.83).CONCLUSION:The expression of VEGF-C and CCR7 isrelated to lymph node metastasis of gastric carcinoma andboth of them may become new targets for the treatment ofgastric carcinoma.Furthermore,the combined examinationof VEGF-C and CCR7 expression in endoscopic biopsyspecimens may be useful in predicting lymph node metastasisof gastric carcinoma and deciding the extent of surgical lymphnode resection.  相似文献   

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血管内皮生长因子和血管生成与大肠癌发展的关系   总被引:7,自引:0,他引:7  
目的:探讨血管内皮细胞生长因子(VEGF)和血管生成与大肠癌发展的关系。方法:应用免疫组化法,检测102例大肠癌组织VEGF蛋白表达和微血管密度(MVD),分析VEGF和MVD及其与大肠癌组织学分级、浸润深度、Dukes分期、淋巴结转移、肝转移和预后的关系。结果:VEGF阳性者MVD值显著高于阴性者(P<0.01),VEGF表达和MVD与大肠癌Dukds分期、淋巴结转移和肝转移密切相关(P均<0.01),VEGF表达阳性或高MVD的大肠癌患者5年生存率较低(P<0.01)。结论:VEGF与大肠癌的血管生成密切相关,对大肠癌的生长和浸润转移有促进作用,VEGF和MVD可作为反映大肠癌生物学行为的客观指标。  相似文献   

13.
AIM: To investigate the role of cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) in the development of gastric carcinoma and correlation between expression of COX-2 and VEGF and clinicopathologic features in tissues from patients with gastric carcinoma. METHODS: 281 patients with gastric carcinoma who underwent surgical resection between 1990 and 1999 at the First Affiliated Hospital, Anhui Medical University, PRC, were followed up. Expression of COX-2 and VEGF was investigated retrospectively in 232 gastric carcinoma tissues and 60 noncancerous specimens by using immunohistochemistry. RESULTS: The 5-year survival rates of early gastric carcinoma (EGC) and advanced gastric carcinoma (AGC) were 93.4 % and 59.0 %, respectively. Survival time was highly correlated with lymph node metastasis, vascular invasion, depth of invasion and treatment with chemotherapy. Compared with paired noncancerous tissues, expression of COX-2 and VEGF and microvessel density (MVD) value in carcinoma tissue were significantly higher. The MVD value was much higher in COX-2-positive group and VEGF-positive group than that in COX-2-negative group and VEGF-negative group. Expression of COX-2 and VEGF, as well as MVD value were highly correlated with lymph node metastasis and vascular invasion. The 5-year survival rate of patients with expression of COX-2 or VEGF was significantly lower than that of patients without COX-2 or VEGF expression. Multivariate analysis revealed that VEGF overexpression, lymph node metastasis, COX-2 overexpression, depth of invasion and vascular invasion were all independent prognostic factors of gastric carcinoma. CONCLUSION: Overexpression of COX-2 and VEGF in patients with gastric carcinoma can enhance the possibility of invasion and metastasis, implicating a poor prognosis. They may serve as the fairly good prognostic factors to indicate biologic behaviors of gastric carcinoma.  相似文献   

14.
目的探讨LKB1和血管内皮生长因子(VEGF)在胃癌中的表达及临床意义。方法采用免疫组织化学(SP)法检测115例胃癌组织和20例胃正常组织中LKB1和VEGF的表达,并探讨其与胃癌分期、淋巴结转移、Lauren's分型及预后的关系。结果 LKB1在胃癌组织中的阳性率为20.9%,低于正常胃组织中的95.0%(P0.01);VEGF在胃癌组织中的阳性率为64.3%,高于正常胃组织中的5.0%(P0.01)。LKB1在胃癌组织中的低表达与胃癌的TNM分期、淋巴结转移、Lauren's分型及预后有关(P0.05);VEGF在胃癌中的表达与淋巴结转移、远处转移、TNM分期及预后相关(P0.05)。结论 LKB1的低表达与胃癌的发生、发展有关,对胃癌恶性生物学行为的评估及预后判断具有重要的指导意义。  相似文献   

15.
BACKGROUND/AIMS: To investigate whether the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) are of prognostic significance in ampullary carcinoma. METHODOLOGY: Twenty-two resected tumor specimens from patients with ampullary carcinoma were immunohistochemically stained for VEGF and CD34 (surrogate for vessels) by streptavidin-peroxidase method. RESULTS: Expression of VEGF in tumor tissue was found in 50% of patients. The mean MVD for entire group was 26.4 +/- 12.8. A significantly higher MVD was observed in the tumors with positive VEGF expression (35.0 +/- 9.6) compared with that of negative VEGF expression (17.7 +/- 9.3) (p<0.01). The expression of VEGF and MVD were closely related lymph node status and tumor TNM stage. The positive expression rate of VEGF and the average MVD in patients with lymph node metastases were 85.7% and 33.1 +/- 10.8 respectively, which were significantly higher than those in patients without lymph node metastases (33.3% and 22.8 +/- 11.8 respectively) (p<0.05). The positive expression rate of VEGF and the average MVD in patients with stage III and were 75% and 36.3 +/- 8.4 respectively, which were significantly higher than those in patients with stage I (25% and 18.4 +/- 10.1 respectively) or stage II (50% and 23.8 +/- 13.4 respectively) (p<0.05). The Kaplan-Meier survival curves showed that the 3-year survival rate for patients with positive VEGF expression or a high MVD (9.1% and 10% respectively) were lower than those in patients with negative VEGF expression or a low MVD (63.64% and 58.33% respectively) (p<0.05). CONCLUSIONS: VEGF is positively correlated with MVD in ampullary carcinoma. VEGF and angiogenesis may play an important role in lymph node metastasis and progression of ampullary carcinoma. VEGF and MVD appear to be important prognostic predictor in patients with ampullary carcinoma.  相似文献   

16.
目的 探讨老年人胃癌术前活检标本血管内皮生长因子 (VEGF)和血小板衍化内皮细胞生长因子 (PD ECGF)的表达及其与老年胃癌患者预后的关系。 方法 采用免疫组化法检测 92例老年胃癌VEGF、PD ECGF表达情况 ,并分析它们与胃癌临床病理特征关系及对预后的影响。 结果 VEGF、PD ECGF在胃癌组织的表达明显高于慢性萎缩性胃炎 ,进展期癌的表达又高于早期癌(P <0 0 1) ,VEGF、PD ECGF表达呈显著正相关 (相关系数R =0 4 0 5 4 )。VEGF、PD ECGF的阳性表达随着肿瘤大小、浸润深度、TNM分期的递增而呈上调表达 ,有淋巴结转移、血管癌栓的患者表达也明显高于无淋巴结转移、血管癌栓者 (P <0 0 1)。VEGF、PD ECGF阳性表达者总体生存率明显低于VEGF、PD ECGF阴性表达者 (P <0 0 1) ,VEGF、PD ECGF共同表达者生存率更低 (P <0 0 1)。多因素分析表明 ,淋巴结转移、TNM分期、VEGF的表达是老年人胃癌独立的预后因素。 结论 VEGF与PD ECGF表达呈正相关 ,均与胃癌生长、浸润转移关系密切 ,可作为估计老年人胃癌预后的重要因素。  相似文献   

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