Serum vascular endothelial growth factor and serum leptin in patients with cervical cancer

OBJECTIVES: Acridine compounds are believed to exhibit anti-cancer cytotoxic effects because of interactions with both DNA and RNA. Pyrazoloacridine (PZA) (NSC No. 366140) is a 9-methoxyacridine compound that has demonstrated activity in some patients with solid tumors. The Gynecologic Oncology Group (GOG) performed a phase II trial of PZA to determine the response rate of this agent in patients with recurrent platinum-sensitive ovarian cancer. METHODS: Patients with recurrent ovarian cancer who experienced a progression-free interval of greater than 6 months after response to platinum-based chemotherapy are defined as platinum sensitive by the GOG and were eligible for this trial. PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 3 weeks. RESULTS: Among 42 evaluable patients, there was 1 (2.4%) complete response and 9 (21.5%) partial responses, including 1 patient who had a partial response after 10 courses of treatment. The major toxicity was neutropenia; severe thrombocytopenia was infrequent. CONCLUSION: PZA demonstrates moderate activity in this chemotherapy-sensitive population, with manageable hematologic toxicity. Due to its unique mechanism of action and preclinical activity against hypoxic and noncycling cells, PZA should be considered for evaluation in combination with other active agents.     

VEGFR-3在早期宫颈癌进展过程中的作用

目的:探讨VEGFR-3在早期宫颈癌进展过程中的作用。方法:免疫组织化学法检测41例早期子宫颈癌(ⅠA～ⅡA)组织中VEGF-C、VEGF-D、VEGFR-3的表达,同时检测VEGFR-3标记的脉管密度(MVD),分析其与临床病理因素的关系。结果:(1)VEGFR-3除于淋巴管内皮细胞表达外,部分血管内皮细胞也有表达。形态学上VEGFR-3阳性脉管部分为血管,部分为淋巴管,主要分布于肿瘤组织周围间质中。肿瘤细胞中可见VEGF-C、VEGF-D、VEGFR-3蛋白表达,其表达阳性率分别为48.7%(20/41)、58.5%(24/41)、63.4%(26/41);(2)肿瘤细胞中VEGFR-3蛋白表达与宫颈癌患者月经状态、组织学分级、组织学类型无关,与临床分期、淋巴结转移、淋巴管浸润及VEGF-C、D蛋白表达相关;MVD与月经状态、组织学分级、组织学类型、淋巴结转移、淋巴管浸润均无关,与临床分期及VEGF-C、D蛋白表达相关。结论:VEGFR-3可能通过促进肿瘤血管生成和淋巴管生成,参与了早期宫颈癌的恶性进展。     

血管内皮生长因子和微血管密度在宫颈癌中表达的研究

目的探讨血管内皮生长因子(VEGF)和微血管密度(MVD)在宫颈癌血管生成中的作用及其与临床病理因素的关系。方法 应用免疫组化ABC法检测62例宫颈癌和18例正常宫颈组织血管内皮生长因子及Ⅷ因子的蛋白表达。结果 VEGF在宫颈癌中的阳性表达率为56.5％,正常宫颈组织中无VEGF阳性表达。肿瘤内MVD为(25.0±8.5)个/高倍视野,明显高于正常宫颈组织(13.6±5.7)个,高倍视野,VEGF表达阳性肿瘤的MVD明显高于阴性者(P<0.05)。腺癌组织中MVD和VEGF水平明显高于鳞癌组织(P<0.005和P<0.05)。结论 VFGF能促进宫颈癌新生血管形成,可能对腺癌的作用更重要。     

Secretion of vascular endothelial growth factor in ovarian cancer.

Vascular endothelial growth factor (VEGF) is an important regulator of vascular endothelial cell function during vasculogenesis and tumor growth and is believed to play a major role in peritoneal fluid accumulation in ascites tumors. High VEGF production from primary tumors has been reported to correlate with increased metastatic spreading and worse prognosis compared to low VEGF secreting tumors. In addition, VEGF secretion has recently been proposed as one of the major factors responsible for defective immune function in cancer patients. In order to evaluate whether ovarian carcinomas actively secrete VEGF, in this study we have analyzed and quantified VEGF secretion in several fresh and established human ovarian carcinoma cell lines in vitro using a sensitive enzyme-linked immunosorbent assay (ELISA). In addition, VEGF levels were also evaluated in the ascitic fluids and plasma of six ovarian cancer patients. All fresh tumors secreted high levels of VEGF (mean = 5,046, range between 1,760 and 7,780 pg/ml/10(5) cells/48 hr) when compared to established ovarian carcinoma cell lines (mean = 493, range between 160 to 1,120 pg/ml/10(5) cells/48 hr) (p <0.02). Importantly, high grade malignancies were found to secrete larger amounts of VEGF (mean = 6,660 pg/ml) when compared to lower grade tumors (mean = 1,820 pg/ml) (p <0.01). Ascitic fluids from all patients were rich in VEGF (mean = 5,483, range between 1,300 and 11,200 pg/ml) and plasma levels of VEGF in ovarian cancer patients were significantly higher (mean = 408, range between 160 and 810 pg/ml) when compared with healthy individuals (mean = 46, range between 35 and 60 pg/ml) (p <0.01). Taken together, these data demonstrate that ovarian cancers secrete large amounts of VEGF in vitro and in vivo. This findings therefore suggest that this factor may play a crucial role in the genesis of ascitic fluid accumulation, angiogenesis and tumor induced immunosuppression in ovarian cancer patients. The design of anti-angiogenic treatment directed at blocking the action of VEGF may be a reasonable novel therapeutic approach in the treatment of ovarian cancer.     

血清血管内皮细胞生长因子水平评价子宫颈癌预后的价值

目的探讨宫颈癌患者的血清血管内皮生长因子（VEGF）水平与宫颈癌临床病理特征及预后的关系。方法采用酶联免疫吸附法（ELISA）检测100例宫颈癌、50例宫颈上皮内瘤变患者和30例正常健康妇女血清中VEGF水平，并进行对照分析。结果宫颈癌患者的血清VEGF水平明显高于宫颈上皮内瘤变患者和健康妇女（P〈0.001），血清VEGF水平与患者的临床分期、分化程度、淋巴结转移、肿瘤大小及浸润深度显著相关（P〈0．001），而与病理类型无明显的相关（P〉0．05），术后血清VEGF平均含量较术前明显下降，术后复发血清VEGF含量较复发前明显升高，差异有显著性（P〈0．001）。结论检测血清VEGF对判断宫颈癌患者的肿瘤负荷、疗效、复发转移、预后都有重要的参考价值。     

宫颈癌VEGF-C表达和淋巴管、血管生成关系的探讨

目的:检测宫颈癌组织中血管内皮生长因子-C(VEGF-C)、受体VEGFR-3和CD34的表达,探讨VEGF-C与癌周淋巴管、血管生成和肿瘤转移的关系。方法:采用免疫组化法检测55例宫颈癌组织中VEGF-C、VEGFR-3和CD34的表达。结果:55例宫颈癌组织VEGF-C阳性率为69.1%(38/55),VEGFR-3阳性率为61.8%(34/55),二者表达高度一致(P<0.01)。淋巴结转移组中VEGF-C与VEGFR-3阳性表达明显高于无转移组(P<0.05)。低分化组VEGF-C和VEGFR-3的表达明显高于高、中分化组(P<0.05)。随着临床分期增加,VEGFR-3表达的阳性率增高(P<0.01)。淋巴结转移组中淋巴管密度(LMVD)明显高于无转移组(P<0.01)。VEGF-C表达阳性的组织中血管密度(MVD)明显升高(P<0.05)。VEGF-C和VEGFR-3表达阳性的患者生存率有降低的趋势。结论:宫颈癌中VEGF-C通过受体VEGFR-3促进组织生长、抑制分化,促进肿瘤细胞间质淋巴管和血管生成,是促使宫颈癌发生扩散和转移的重要原因。二者阳性表达可预示预后不良。     

宫颈癌中血管内皮生长因子、环氧合酶-2的表达及意义

目的　探讨环氧合酶 - 2 (COX - 2 )在宫颈癌中的表达 ,及其与血管内皮生长因子 (VEGF)表达和肿瘤微血管密度 (MVD)的关系。方法　应用免疫组化法检测 5 4例宫颈癌中COX - 2、VEGF的表达和MVD值 ,并以 1 0例宫颈CIN和 1 0例正常宫颈上皮为对照组。结果　宫颈癌中COX - 2阳性表达率分别为Ⅰ期5 6 7%、Ⅱ期为 6 6 7%、Ⅲ期 77 8%。VEGF在宫颈癌中阳性表达率分别为Ⅰ期 76 7%、Ⅱ期 80 0 % ,Ⅲ期88 9%。COX - 2在宫颈癌Ⅰ、Ⅱ、Ⅲ期间差异无显著性 (P >0 0 5 )。VEGF宫颈癌Ⅰ、Ⅱ期间差异无显著性 (P>0 0 5 ) ,Ⅰ期与Ⅲ期之间差异有显著性 (P <0 0 5 )。COX - 2、VEGF与MVD的表达呈正相关 ,而与不同的病理分级无明显相关性 (P >0 0 5 )。结论　VEGF、COX - 2、MVD在宫颈癌的发生、发展过程中起着重要作用 ,VEGF、COX - 2、MVD值可作为检测指标 ,为宫颈癌的诊断、临床分期及治疗起指导作用     

Co-expression of vascular endothelial growth factor and thymidine phosphorylase in endometrial cancer.

OBJECTIVE: To examine expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) together with microvessel count in endometrial cancer, and to investigate the relationship with clinicopathological and biological factors. METHODS: VEGF expression, TP expression, the microvessel count (factor VIII-related antigen positive cells), bcl-2 expression, proliferating cell nuclear antigen (PCNA) index, and p53 expression were determined in 50 resected endometrial cancer specimens, using immunohistochemistry. The relationship between VEGF and TP expression and correlation between expression and microvessel count were also given attention. These 3 factors were analyzed with regard to clinicopathological factors, bcl-2 expression, PCNA index, and p53 expression. RESULTS: Staining status of VEGF and TP was identical in 37 (74%) of 50 tumors, the correlation being statistically significant (p < 0.01). Combined analysis of VEGF and TP status showed that tumors which were VEGF-positive and/or TP-positive had a significantly higher microvessel count than did tumors which were both VEGF-negative and TP-negative (p < 0.001 and p < 0.05, respectively). TP expression correlated with bcl-2 expression, and VEGF expression inversely correlated with the PCNA index. Although clinical stage (p < 0.01), PCNA index (p < 0.01), and p53 expression (p < 0.01) significantly correlated with disease-free survival, neither VEGF/TP expression nor microvessel count contributed to prognostic estimates. CONCLUSIONS: VEGF and TP may cooperatively promote angiogenesis in endometrial cancer, but these expressions may have limited additional prognostic value.     

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.     

血管内皮生长因子C及其受体3在宫颈癌组织中的表达及意义

目的探讨血管内皮生长因子-C(VEGF-C)及其受体3在宫颈癌中的表达及其与癌周淋巴管生成、淋巴结转移的关系。方法采用免疫组化二步法检测55例宫颈癌组织中VEGF-C、VEGFR-3的表达情况。结果宫颈癌组织VEGF-C、VEGFR-3阳性率分别为69.1%、61.8%。VEGF-C与VEGFR-3阳性率在淋巴结转移、低分化组织中均明显升高(均P<0.05)。淋巴结转移的宫颈癌组织中淋巴管密度(LMVD)明显升高(P<0.01)。VEGF-C、VEGFR-3阳性的患者有明显预后不良的趋势。结论VEGF-C通过受体VEGFR-3在宫颈癌发生盆腔淋巴结转移中发挥重要作用。     

上皮性卵巢癌血管内皮生长因子的表达与肿瘤内微血管密度的相关性研究

目的 :探讨上皮性卵巢癌组织中血管内皮生长因子 (VEGF)是否与肿瘤内微血管密度 (MVD)、淋巴转移等临床病理学因素存在相关性。方法 :以多克隆抗VEGF抗体和单克隆抗CD34抗体分别标记 4 5例FIGOⅠ～Ⅳ期上皮性卵巢癌术后标本的VEGF和MVD。用彩色图像病理分析系统测定VEGF的相对含量 ,MVD采用人工计数。分析VEGF与MVD、肿瘤期别、组织学类型、腹水量以及淋巴转移的关系。结果 :(1)VEGF的平均吸光度为 0 .178± 0 .14 9(中位数 0 .16 7)。MVD值平均为 72 .2 6± 5 8.5 2 /mm2 (中位数 6 8.4 7/mm2 ) ;(2 )VEGF表达水平与MVD之间存在显著相关性 (r =0 .92 6 ,P <0 .0 1) ;(3)盆腔淋巴转移(n =12 )VEGF平均吸光度 (0 .193± 0 .15 3)显著高于无盆腔淋巴转移组 (n =32 )的 0 .138± 0 .0 90 ,(P <0 .0 5 )。不同期别 ,组织学类型和腹水量之间的VEGF表达强度无显著差异(P >0 .0 5 )。结论 :VEGF表达与上皮性卵巢癌血管生成的增强密切相关     

Serum vascular endothelial growth factor in epithelial ovarian neoplasms: correlation with patient survival.

OBJECTIVE: To investigate the relationship between serum vascular endothelial growth factor (VEGF) and clinicopathological factors and to determine whether VEGF is an independent prognostic factor of ovarian cancer patients. METHODS: Fifty-six women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer undergoing surgery were enrolled. Clinical and pathologic items were recorded. Pretreatment VEGF serum samples of the 56 women were measured by an enzyme-linked immunosorbent assay. The results were correlated to clinical data. The histopathologic items and serum VEGF influencing clinical outcome were evaluated comparatively. RESULTS: The median VEGF serum level in ovarian cancer patients was 458.7 pg/mL. The 75% quatile was defined as the cutoff level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with poorer disease-free survival (DFS) (log rank test, P = 0.001) and overall survival (OS) (log rank test, P < 0.001) on all of the 56 patients. Besides, significantly reduced DFS (log rank test, P = 0.001) and OR (log rank test, P = 0.006) were also observed on 40 patients with residual disease less than 2 cm. High histologic grade (RR = 2.24 for DFS; RR = 2.38 for OS) and elevated serum VEGF levels (RR = 3.34 for DFS; RR = 4.47 for OS) are the prognostic factors on the 56 ovarian carcinoma patients by multivariate analyses. The advanced surgical staging (RR = 3.28 for DFS; RR = 3.84 for OS), high histologic grade (RR = 2.55 for DFS; RR = 2.44 for OS), and elevated serum VEGF levels (RR = 5.62 for DFS; RR = 5.37 for OS) are the prognostic factors for 40 ovarian carcinoma patients with residual disease less than 2 cm by multivariate analyses. CONCLUSIONS: Pretreatment VEGF serum levels might be regarded as an additional factor in predicting the outcome of ovarian cancer patients. It also could provide prognostic information in clinically relevant subsets, such as those of residual disease less than 2 cm. Anti-angiogenic therapy, if is available, might be a new treatment modality for ovarian cancer patients with poor prognosis predicted by VEGF and other clinical parameters.     

血管内皮生长因子水平变化与IVF-ET关系的研究

目的 :探讨体外受精 胚胎移植 (IVF ET)治疗周期的不孕症患者在不同阶段血清及卵泡液内血管内皮生长因子 (VEGF)的浓度变化以及它与卵泡生长发育、卵母细胞成熟、受精、卵裂及胚胎质量的关系。方法 :IVF治疗周期妇女 6 0例 ,在应用促性腺激素前、注射绒毛膜促性腺激素日、取卵日分别抽取外周血 ,穿刺取卵时留取卵泡液 ,应用酶联免疫法 (ELISA)检测血清及卵泡液中VEGF的浓度变化 ,并记录相应卵子的成熟度、受精、卵裂情况与胚胎质量。结果 :(1)控制超排卵过程中 ,随着卵泡的生长发育 ,VEGF浓度逐步升高 ,在取卵日达到较高水平 ;(2 )在控制超排卵过程中 ,卵巢反应类型不同 ,其VEGF水平亦不同 ,卵巢高反应组在取卵日血清中VEGF水平差异有显著性 (P <0 .0 5 )。患者卵泡液中VEGF浓度均明显高于外周血浓度 (P <0 .0 0 1) ;(3)成熟卵的卵泡液中VEGF浓度明显高于未成熟卵 ;(4)受精卵卵泡液中VEGF水平高于未受精卵 ,VEGF浓度高的卵母细胞受精后优质胚胎形成率高 (P <0 .0 5 )。结论 :VEGF调节卵母细胞的成熟、受精、卵裂过程 ,并可能影响早期胚胎的质量。     

血管内皮生长因子在卵巢癌细胞浸润转移中的作用

目的 :探讨血管内皮生长因子 (VEGF)在卵巢癌浸润转移中的作用。方法 :阳离子脂质体介导VEGF165质粒转染 2株卵巢癌细胞CaOV 3、COC1,并经逆转录聚合酶链式反应 (RT PCR)、Western免疫印迹检测转染VEGF165质粒前后癌细胞VEGFmRNA及其蛋白表达水平 ;用Boyden小室体外侵袭实验比较VEGF165质粒转染前后以及单克隆抗体作用后 2株癌细胞通过人工重组基底膜的能力强弱变化。结果 :VEGF165质粒转染后 ,2株细胞mRNA和蛋白表达水平均较转染前明显增强 (P <0 .0 5 )。VEGF165质粒转染的癌细胞CaOV 3、COC1穿过人工重组基底膜的相对百分率分别为 4 2 .5± 4 .1、2 6 .8± 2 .4 ,明显高于对照组穿膜细胞相对百分率 (2 4 .7± 1.9、8.6± 1.1) (P <0 .0 5 ) ;而在VEGF单克隆抗体存在时 ,2株癌细胞穿膜细胞相对百分率 (10 .2± 0 .7、5 .4± 0 .3)较处理前均有不同程度的下降 (P <0 .0 5 )。结论 :VEGF参与了卵巢癌转移的侵袭、浸润阶段 ,应用VEGF单克隆抗体可针对性地抑制VEGF介导的卵巢癌侵袭、浸润。     

Interleukin-6 polymorphisms and the risk of cervical cancer

Recent data implicate that cytokine gene polymorphisms are important in pathogenesis of various neoplastic and nonneoplastic human diseases, and it was recently suggested that polymorphisms in interleukin (IL)-6 might increase the risk of gynecological malignancies, including cervical carcinomas. The aim of this case-control study is to compare the IL-6 polymorphisms in cervical cancer patients and healthy controls and to assess whether any of these polymorphisms would increase the risk of developing cervical cancer. The material in this case-control study consists of 56 patients with cervical carcinoma and 253 population-based control subjects, all ethnic Brazilian women. Control subjects were cancer-free women, following a negative cervical cytology and colposcopy. IL-6 genotyping was performed using a polymerase chain reaction-based restriction fragment length polymorphism. Distribution of the GG, GC, and CC genotypes in cases and controls was significantly different (P= 0.033). Compared with the GG genotype as reference, the adjusted odds ratio for the combined GC and CC genotypes in cancer patients was 1.90 (95% confidence interval, 1.1-3.4). These data suggest that women carrying at least one C genotype in their IL-6 promoter region (-174G-->C) are at higher risk of developing cervical cancer.     

上皮性卵巢癌组织中血管内皮生长因子的表达及其临床意义

目的：探讨上皮性卵巢癌组织中血管内皮生长因子（ＶＥＧＦ）的表达及其临床意义。方法：以ＳＡＢＣ免疫组化分析法检测３７例上皮性卵巢癌组织中ＶＥＧＦ的表达。结果：上皮性卵巢癌、交界性卵巢肿瘤及良性肿瘤组织中ＶＥＧＦ阳性表达率分别为７２．９７％、６２．５０％及３８．４６％,恶性肿瘤及交界性肿瘤组织中ＶＥＧＦ表达率较良性肿瘤者明显增高（Ｐ＜０．０５）,且前两者的ＶＥＧＦ强阳性表达率也较良性肿瘤者明显增高（Ｐ＜０．０５）。上皮性卵巢癌中ＶＥＧＦ阳性表达率与有淋巴结转移者密切相关（Ｐ＜０．０５）。ＶＥＧＦ表达率与卵巢癌的临床分期及病理分级未见显著相关性。结论：ＶＥＧＦ在上皮性卵巢癌的生长及转移中可能起着重要作用。     

Cytosol vascular endothelial growth factor in endometrial carcinoma: correlation with disease-free survival

OBJECTIVE: The aim of this study was to evaluate whether vascular endothelial growth factor (VEGF) could be a marker for disease-free survival in endometrial carcinoma patients. METHODS: Fifty-three patients with endometrial carcinoma undergoing surgery were enrolled. Clinical and pathologic items were recorded. Cytosol VEGF was quantified by enzyme immunoassay. The microvessel density (MVD) of the excised tumors was immunohistochemically assessed. The relationship among MVD, cytosol VEGF concentration of the tumor tissues, and clinicopathologic parameters was analyzed. The risk factors influencing clinical outcome were tested. RESULTS: Higher cytosol VEGF concentrations and MVD values were noted in tumors with advanced stage (more than stage I) (917 versus 125 pg/mg, P = 0.03; 94.1 +/- 37.8 versus 60.8 +/- 38.9, P = 0.008), lymphovascular emboli (917 versus 102 pg/mg, P = 0.001; 94.4 +/- 33.2 versus 62.4 +/- 40.7, P = 0.009), and lymph node metastasis (1032 versus 95 pg/mg, P < 0.001; 116.5 +/- 30.8 versus 56.7 +/- 33.3, P < 0.001). The cytosol VEGF and MVD showed a positive linear correlation (VEGF versus MVD, r = 0.41, P = 0.003). Grade 3 tumor and overexpressed cytosol VEGF (> 800 pg/mg) are independent risk factors for recurrence. There was a trend that patients with grade 1 or 2 tumors and normal-expressed VEGF had the highest probability of disease-free survival, and patients with grade 3 tumors and overexpressed cytosol VEGF had the poorest probability of disease-free survival. CONCLUSIONS: Cytosol VEGF had a good correlation with the disease progression and metastasis in endometrial carcinoma, and it might also be an independent prognostic factor for disease-free survival of endometrial carcinoma patients.