Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.

EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR IN DIFFERENT SALIVARY ADENOID CYSTIC CARCINOMA CELL LINES

Objective： To investigate the expression of epidermal growth factor receptor, a receptor tyrosine protein kinase, in the subcellular fractions of human salivary adenoid cystic carcinoma cell lines SACC-83 and SACC-LM. Methods： Low metastatic and high metastatic cells of the adenoid cystic carcinoma, SACC-83 and SACC-LM, were cultured. Their subcellular fractions were extracted. The expression of epidermal growth factor receptor was detected with Western blot method, and the results of protein expression were quantitatively analyzed by FluorChem V2.0 software. Results： The results of Western blot analysis indicated that, EGFR expression on the membrane of SACC-83 cells was significantly higher than that of SACC-LM cells, but its expression in cytoplasm was significantly less in the former than the later （P〈0.01）. In SACC-83 cell line, EGFR was over-expressed in membrane （P〈0.01）, but in SACC-LM cell line, EGFR was over-expressed in cytoplasm （P〈0.01）. Conclusion： The results suggest that the obtaining of metastasis ability is related to the high expression of EGFR protein in cytoplasm, so the molecular targeting therapy to EGFR may be an ideal treatment for the invasion and metastasis of salivary adenoid cystic carcinoma.

Effect of Exogenous bFGF on the Proliferation of Human Adenoid Cystic Carcinoma ACC-2 Cells

To observe the effects of basic fibroblast growth factor （bFGF） on human adenoid cystic carcinoma ACC-2 cell line proliferation and ERK, cyclin D1/p21^waf/cip1 signaling pathways, human adenoid cystic carcinoma cells （ACC-2） were cultured and the influence of bFGF of different concentrations on cell proliferation was determined by MTT. Protein was detected by immuno-precipitation and ERK activity by using ERK agent kit. p-ERK1/2 and down-stream cyclin D1, p21^waf/cip1 expression were detected by Western blotting and the interfering role of mitogen protein-activated kinase （MEK） suppressor U0126 in the afore-mentioned indicators was examined. MTT demonstrated ACC-2 cell proliferation was substantially enhanced by bFGF, immuo-precipitation displayed ERK activity was up-regulated by bFGF, and immuno-imprinting also showed p-ERK1/2, cyclin D1 expression was greatly enhanced and p21^waf/cip1 expression was inhibited by bFGE U0126 suppressed the effect of bFGF. It is concluded that bFGF can promote the proliferation of human adenoid cystic carcinoma ACC-2 cells, and its pathways are associated with the up-regulated activity and expression of p-ERK1/2, inhibited p21waf/cip1 expression and enhanced cyclin D1 expression.

Expression of Angiogenic Factors in Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization

In order to investigate the changes of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression in residual hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE), the expression levels of VEGF and bFGF expression in specimens surgically removed from 48 HCC patients were detected by immunohistochemical methods, and staining intensity of VEGF and bFGF was assessed by a computer-assisted image-analyzer Among the 48 patients, 25 underwent partial hepatectomy alone (single operating group), and 23 were subjected to second stage surgical resection after TACE (TACE group) The results showed that the average absorbance value (A) of VEGF was higher in TACE group than that in single operating group (0 152±0 021 vs 0 131±0 012, P< 0 01) The Average A of bFGF in TACE group was 0 127±0 023, higher than in single operating group (0 111±0 016, P <0 05) These results suggested that TACE of HCC can up-regulate the expression of VEGF and bFGF in HCC tissues possibly due to anoxia and ischemia

^(125)I-labeled anti-b FGF monoclonal antibody inhibits growth of hepatocellular carcinoma

AIM: To investigate the inhibitory efficacy of 125I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with 125I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of 125I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), 125I-bFGF mAb, 125I plus bFGF mAb, bFGF mAb, or 125I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction.RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, 125I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the 125I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the 125I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for 125I group) compared with the control group.CONCLUSION: 125I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of 125I-bFGF mAb is more effective than the concomitant use of 125I and bFGF mAb.

贝伐珠单抗与GC化疗方案联合治疗晚期非小细胞肺癌的效果及药物经济学评价

目的 探究贝伐珠单抗联合GC化疗方案(顺铂+吉西他滨)治疗晚期非小细胞肺癌(NSCLC)的效果及药物经济学价值。方法 选取2020年7月—2022年7月收治的86例晚期NSCLC,依据治疗方案分为对照组和观察组,每组43例。对照组给予GC化疗方案,观察组给予贝伐珠单抗联合GC化疗方案。对比2组疗效、毒副反应发生情况以及治疗前后血生化指标,并进行成本-效果分析。结果 观察组客观缓解率58.14%(25/43)、疾病控制率93.02%(40/43)均高于对照组的32.56%(14/43)、72.09%(31/43)(P<0.05)。治疗2、4个疗程,观察组血清癌胚抗原、糖类抗原125、神经元特异性烯醇化酶、血管内皮生长因子、碱性成纤维细胞生长因子均低于对照组(P<0.05)。2组各项毒副反应总发生率比较无显著差异(P>0.05)。观察组总成本高于对照组(P<0.05)。观察组成本-效果比为790.67低于对照组的901.31,且敏感性分析显示,成本-效果分析稳定可靠。结论 贝伐珠单抗联合GC化疗方案治疗晚期NSCLC患者,可下调肿瘤标志物及血管内皮因子水平,提升疗效,且成本-效果优势明显。

NGF在涎腺腺样囊性癌中的表达及与嗜神经侵袭和疼痛的关系

目的 :观察神经生长因子 (nervegrowthfactor,NGF)在涎腺腺样囊性癌 (adenoidcysticcarcinoma,ACC)的表达情况 ,探讨NGF与ACC嗜神经侵袭情况及疼痛症状的关系 .方法 :以 32例ACC标本为研究对象 ,患者按照有无嗜神经侵袭及疼痛症状进行分组 ;以 5例正常腮腺及 3例腺泡细胞癌作为对照 ,采用免疫组化法对NGF进行检测 .结果 :NGF在正常腮腺的导管细胞表达为阳性 ,在腺泡细胞癌为阴性 .在ACC中的阳性率为 96 .9% (31 / 32 ) ,且发现沿神经周围分布的肿瘤细胞染色强度明显高于远离神经者 .NGF表达水平的组间对比 :存在嗜神经现象组明显高于未见嗜神经现象组 (P <0 .0 5 ) ,存在疼痛症状组亦显著高于无疼痛症状组 (P <0 .0 5 ) .结论 :ACC中NGF表达的增高可能是促进其嗜神经侵袭及疼痛症状发生的原因之一 .

神经生长因子、血管内皮生长因子在腺样囊性癌侵袭转移中的作用

目的:观察神经生长因子(nerve growth factor,NGF)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在腺样囊性癌(adenoid cystic carcinoma,ACC)组织中的表达,探讨NGF和VEGF在ACC侵袭转移机制中的作用。方法:采用免疫组化SP法对NGF、VEGF在63例ACC组织中的表达进行检测,并采用Cox比例风险回归模型对影响预后的多项临床因素进行分析。结果:NGF、VEGF在ACC组织中具有较高阳性表达,Cox模型提示NGF、VEGF、神经是否有侵袭、TNM分期、复发等是预后的危险因素,腺样-管状型的预后较实性型好。结论:ACC的预后与多因素相关,其中NGF、VEGF与ACC的侵袭转移有较大关系,可望作为判断预后的参考指标。

CD147和MMP-2、VEGF在腺样囊性癌侵袭转移中的作用

目的:研究CD147和基质金属蛋白酶-2(MMP-2)、血管内皮生长因子(VEGF)在腺样囊性癌(adenoid cystic carcinoma,ACC)组织中的表达和意义。方法:采用免疫组化EnvisionTM法检测72例ACC组织中CD147和MMP-2、VEGF的表达情况,结合临床病理资料进行统计分析。结果:CD147和MMP-2、VEGF在ACC组织中高表达,阳性表达率分别为62.5%、65.3%、73.6%;三者的表达均与肿瘤病理分型和临床分期有关(P<0.05),而与患者的性别、年龄无明显关联(P>0.05);神经侵袭组的CD147和MMP-2表达明显强于无神经侵袭组(P<0.05),VEGF在有无神经侵袭组间的表达无统计学差异(P>0.05);血管侵袭组和肿瘤发生转移组的CD147和MMP-2、VEGF的表达均明显强于对应组(P<0.05);CD147的表达与MMP-2和VEGF的表达具有显著相关性(P<0.001)。结论:CD147和MMP-2、VEGF的表达与ACC的侵袭转移密切相关,检测三者的表达有助于对ACC进行临床病理研究及转移潜势预测。

32例涎腺腺样囊性癌病理学与血管内皮细胞生长因子表达的关系

目的 了解血管内皮细胞生长因子 ( VEGF)在涎腺腺样囊性癌和癌周组织中的表达。探讨VEGF与 ACC病理亚型侵袭和转移的关系 ,为临床提供减少复发和转移提供资料。方法 采用免疫组化 SABC法 ,对 32例 ACC及癌周正常涎腺组织表达进行检测。结果 1 .肿瘤组织中 VEGF表达为80 % ( 2 6/32 ) ,癌周组织表达率 1 8.9% ( 6/32 )。 2 .实性型及复发转移中 VEGF表达大于筛状型。结论 VEGF在 ACC的亚型 ,侵袭及转移中发挥重要作用 ,表达强阳性 ,可以作为临床预防复发。

神经生长因子在腺样囊性癌中的表达

目的:通过检测神经生长因子(NGF)在体外体内腺样囊性癌(ACC)中的表达探讨NGF与ACC神经侵袭的关系。方法:采用Western印迹技术检测体外培养增殖期ACCM中NGF的表达。采用免疫组化的方法检测14dACC眶下神经侵袭的裸鼠模型中ACCM癌组织和眶下神经的NGF表达;比较邻近神经的ACC癌组织与远离神经的癌组织中NGF阳性表达细胞的密度;比较侵袭侧与非侵袭侧眶下神经NGF阳性染色的灰度值。结果:NGF在体内、体外ACC细胞中均有表达。NGF阳性表达细胞的密度在邻近神经的ACC中为30.67±5.91,远离神经的ACC中为9.33±2.81,两者相差显著(P<0.01)。受侵袭侧与非侵袭侧眶下神经NGF阳性染色的灰度值分别为46.79±2.91和47.01±2.56,无显著差异(P=0.299)。结论:NGF参与ACC细胞的增殖,ACC中NGF表达增强与神经侵袭显著相关。

NGF及其受体P75与肝素酶在口腔腺样囊性癌嗜神经侵袭中的表达及相关性分析

目的:探讨腺样囊性癌(adenoid cystic carcinoma,ACC)组织中肝素酶(heparanase,HPA)和神经生长因子(nerve growth factor,NGF)及其受体P75的表达和相互作用,以及与ACC嗜神经侵袭之间的关系。方法:应用免疫组化SP法检测42例ACC组织中HPA、NGF和P75的表达,并对他们在不同病理类型和组织学部位的表达进行统计学分析。结果:NGF和P75在嗜神经(PNI)组和非嗜神经(NPNI)组的表达有统计学差异(P<0.05),两者呈正相关(r=0.429,P<0.05)。嗜神经组HPA和P75的表达正相关(r=0.558,P<0.05)。P75在神经周组织和远离神经部位的表达有显著性差异(P<0.05),NGF在神经组织和远离神经处的表达无明显差异。结论:在ACC的神经浸润中,NGF及其受体P75扮演着重要角色,但并非唯一因素,NGF可以通过和受体p75结合可以提高HPA的表达率和生物活性,进而促进ACC对神经组织的浸润。

bFGF和MMP9在鼻咽癌组织中的表达及其临床意义

目的:探讨碱性成纤维细胞生长因子(bFGF)和基质金属蛋白酶9(MMP9)在鼻咽癌患者中的表达及其临床意义。方法:应用免疫组化方法检测289例鼻咽癌患者活检组织治疗前bFGF和MMP9的表达水平,并分析二者与鼻咽癌患者临床病理特征和预后的关系。结果:289例鼻咽癌组织bFGF和MMP9阳性表达率分别为71.3%和61.6%;bFGF和MMP9的阳性表达与鼻咽癌的N分期和临床分期有显著的相关性(P<0.05),且两者的高表达均与鼻咽癌的不良预后显著相关(P<0.01);在鼻咽癌组织中Spearman相关分析发现,bFGF的表达与MMP9的表达呈明显正相关(r=0.634,P<0.05);亚组分析表明,bFGF和MMP9表达水平均升高的鼻咽癌患者的预后最差。结论:bFGF和MMP9在鼻咽癌组织中的表达升高,且两者与鼻咽癌的不良预后明显相关,联合应用有可能成为鼻咽癌的诊断、治疗及判断预后的生物标志物。

VEGF和bFGF在浅表膀胱移行细胞癌中的表达及意义

背景与目的:血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)和碱性成纤维细胞生长因子(basicfibroblastgrowthfactor,bFGF)都能促进血管内皮细胞分裂和诱导血管形成,是肿瘤的生长、浸润、和转移过程中非常重要的物质。但它们在单发性和多发性浅表膀胱移行细胞癌中表达的差异则未见报道,本研究主要是探讨VEGF和bFGF在浅表膀胱移行细胞癌中的表达及意义。方法:采用免疫组化法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行VEGF和bFGF的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF和bFGF表达的关系。结果:多发性浅表膀胱移行细胞癌的VEGF阳性率为55.6%、bFGF阳性率为50.0%,以及VEGF和bFGF共同表达阳性率为50.0%,均明显高于单发者的水平,而高水平表达的多发性肿瘤患者的术后复发率61.1%也明显高于单发组的复发率(单发组的复发率16.7%)。结论:VEGF和bFGF表达水平的高低与浅表膀胱移行细胞癌的生物学行为有关。

肝细胞癌螺旋CT表现特征与VEGF、bFGF表达和血管生成关系的研究

目的 探讨肝细胞癌 (HCC)螺旋CT表现特征与血管内皮生长因子 (VEGF)、碱性成纤维细胞生长因子 (bFGF)、血管生成及其他因素之间的关系。方法 回顾性分析 5 0例 (5 4个 )经CT双期增强扫描的HCC病灶 ,将CT表现特征与免疫组化、临床病理结果进行对比分析。结果 Logistic回归分析显示 :与动脉期强化类型有关的因素是病灶大小和瘤内坏死 ;与包膜类型有关的因素是FⅧRA表达部位和微血管密度 (MVD) ;与侵袭转移性有关的是VEGF和MVD ;与病灶大小有关的是AFP水平 ;与肝硬化有关的是HBsAg。结论 HCC的CT表现特征受HCC血管生成。

涎腺腺样囊性癌组织中神经生长因子表达及其临床病理特征的Meta分析

目的涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)是常见的涎腺恶性肿瘤,神经生长因子(nervegrowth factor,NGF)在不同临床病理特征的SACC中表达情况不尽相同。系统评价有关SACC组织中NGF表达及其临床病理特征之间的关系。方法计算机检索Cochrane Library、PubMedline、中国生物医学文献数据库(China BioMedical Bibliograph-ic Database,CBMdisc)、中国学术期刊全文数据库(Chinese National Knowledge Infrastructure,CNKI)、中文科技期刊全文数据库(VIP Datebase for Chinese Technical Periodicals,VIP)、万方数据库,并辅以文献追溯的方法,收集公开发表的所有关于SACC组织中NGF表达及其与临床意义关系的病例对照研究。检索年限均从建库至2011年7月1日。按纳入排除标准筛选文献并评价纳入研究的质量后,应用RevMan5.0软件进行Meta分析。结果共纳入6个病例对照研究,其中腺样囊性癌267例,正常涎腺对照44例。Meta分析结果显示,NGF在SACC组与正常涎腺对照组中腺泡细胞的表达差异有统计学意义[OR=46.70,95%CI(3.30,661.71)];NGF在腺样囊性癌腺样/管状型组与实性型组的表达差异有统计学意义[OR=0.41,95%CI(0.20,0.86)];NGF在腺样囊性癌嗜神经侵袭(perineural invasion,PNI)组与非PNI组的表达差异有统计学意义[OR=7.14,95%CI(3.49,14.60)]。结论 NGF高表达与涎腺腺样囊性癌病理分型、PNI等临床病理特征显著相关。但受纳入文献质量的影响,以上结论需要高质量的病例对照研究进一步证实。

碱性成纤维细胞生长因子在肝细胞癌中的表达及意义

目的 探讨bFGF在肝细胞癌中的表达及其临床病理意义。方法 使用免疫组化SABC法检测 41例肝细胞癌手术切除标本及 5例外伤性肝破裂肝切取标本。结果 正常对照组bFGF均为阴性。肝细胞癌组bFGF阳性率为 70 .7% (2 9/4 1)。bFGF表达与患者年龄、性别、AFP是否阳性、HBsAg是否阳性无关 (P >O .0 5 ) ;而与肝癌分化程度、有无癌栓、包膜是否完整有关。在高侵袭转移组与低侵袭转移组间 ,bFGF阳性率分别为 86.4%和 5 2 .6% ,差异具有显著性 (P <0 .0 5 )。结论 bFGF在肝细胞癌中高表达 ,可以作为判断肝癌恶性程度及转移潜能的参考指标。

环氧合酶-2和碱性成纤维细胞生长因子在鼻咽癌组织中的表达及与放疗敏感性的相关性

目的探讨环氧合酶-2(COX-2)和碱性成纤维细胞生长因子(bFGF)在鼻咽癌组织中的表达及其与放疗敏感性的相关性。方法应用免疫组化方法检测97例鼻咽癌患者活检组织放疗前COX-2和bFGF的表达,并分析二者与放疗敏感性的关系。结果97例鼻咽癌组织COX-2和bFGF阳性表达率分别为71.1%(69/97)和64.9%(63/97);COX-2的阳性表达与鼻咽癌的T分期和N分期有显著的相关性(P<0.05),bFGF的阳性表达与鼻咽癌的N分期有显著的相关性(P<0.05)。COX-2在放疗敏感组和放疗不敏感组的阳性表达率分别为62.8%和92.6%,bFGF在放疗敏感组和放疗不敏感组的阳性表达率分别为57.1%和85.2%,在鼻咽癌组织中Spearman相关分析发现,COX-2的表达与bFGF的表达呈明显正相关(相关系数r=0.486,P<0.05);根据COX-2和bFGF表达情况,把患者分为4组:COX-2(-)and bFGF(-),COX-2(-)and bFGF(+),COX-2(+)and bFGF(-),and COX-2(+)and bFGF(+)。联合COX-2表达和bFGF表达分析后,发现不同亚组与鼻咽癌的放疗敏感性明显相关(P<0.05)。结论 COX-2和bFGF在鼻咽癌组织中的表达升高,且两者与肿瘤的放疗敏感性明显相关,可作为预测鼻咽癌放疗敏感性的重要指标。

bFGF对人涎腺腺样囊性癌ACC-2细胞株增殖及MEK/ERK、NF-κB通路的影响

目的:观察碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)对人涎腺腺样囊性癌ACC-2细胞株增殖及MEK/ERK、核转录因子-κB(NF-κB)信号通路的影响。方法:培养人涎腺腺样囊性癌细胞株(ACC-2),MTT比色法测定不同浓度bFGF对细胞增殖的影响;免疫沉淀法纯化蛋白并ERK试剂盒测定ERK活性;Western-blot测定p-ERK及NF-κB抑制物(I-κBα)表达。并观察丝裂原蛋白活化激酶激酶(MEK)抑制剂U0126对上述指标的干预作用。结果:MTT实验显示bFGF明显增强ACC-2细胞增殖,免疫沉淀法显示bFGF上调ERK活性,免疫印记法显示bFGF明显增强p-ERK1/2表达及抑制I-κBα表达。U0126可抑制bFGF的以上效应。结论:bFGF可促进人涎腺腺样囊性癌ACC-2细胞株增殖,其途径与上调ERK活性,激活ERK、NF-κB信号通路有关。

STAT3、VEGF蛋白在涎腺腺样囊性癌中的表达及对血管生成的影响

目的:探讨信号转导和转录活化因子-3(STAT3)及血管内皮生长因子(VEGF)蛋白在涎腺腺样囊性癌(SACC)组织中的表达情况及其与SACC临床病理参数、血管生成的关系。方法:采用免疫组织化学法检测50例SACC(SACC组)与15例正常腮腺组织(对照组)中STAT3、VEGF蛋白表达和微血管密度(MVD)。结果:(1)SACC组的STAT3及VEGF蛋白表达阳性率分别为66%和72%,明显高于正常组的6.7%和20%(P<0.01)。(2)STAT3和VEGF的表达在SACC的不同组织类型、TNM分期、有无淋巴结转移方面差异均有统计学意义(P<0.05),但在不同性别、年龄及肿瘤部位方面差异均无统计学意义(P>0.05)。(3)STAT3与VEGF表达呈正相关(P<0.05);SACC组的STAT3蛋白及VEGF蛋白表达中阳性与阴性者的MVD差异比较均有统计学意义(均P<0.05)。结论:STAT3可能通过上调VEGF表达,促进SACC中新生血管的形成,STAT3可能会成为SACC的抗血管生成的治疗靶点。