Does the direct measurement of oxygen tension in tumors have any adverse effects?

A new polarographic histograph was tested in tumors to assess its potential adverse effects in mice. The tumor cell lines used were: the lewis lung carcinoma (3LL) and two human xenografts (Na11+ and HRT18). The C57BL/6 mice survival and number of pulmonary metastases were not altered after pO2 measurements. Whatever the cell line, tumor doubling times were not changed after pO2 measurements. The new polarographic histograph was found to be reliable.     

重组人血管内皮抑制素联合TACE对兔VX-2肝癌模型微血管密度及Notch通路的影响

目的:探讨重组人血管内皮抑制素（rhES）联合经导管动脉内化疗栓塞术（TACE）对果蝇双翅边缘缺刻同源基因（Notch）通路的调控作用,及对兔VX-2肝癌模型微血管密度（MVD）的影响。方法:取新西兰大白兔60只,随机取50只用肿瘤种植法建立兔VX-2肝癌模型,分为模型组、TACE组、TACE+rhES组（TACE术+rhES溶液0.75 mg/kg）、Notch激活剂jagged1组（TACE术+jagged1溶液13 ng/kg）、TACE+rhES+jagged1组（TACE术+rhES溶液0.75 mg/kg+jagged1溶液13 ng/kg）,每组10只,未造模的10只兔作为正常对照组。治疗2周后,行CT成像,获取兔肿瘤周边血流量（BF）、血容量（BV）、毛细血管表面渗透面积（PS）值;称取兔体重并处死取肝脏,计算肝脏指数、肿瘤体积;免疫组化法检测肝脏MVD;蛋白免疫印迹法（Western blot）检测癌灶周边非坏死肝脏组织Notch、Notch配体（jagged1）、血管内皮生长因子（VEGF）、活化蛋白1（AP-1）蛋白相对表达水平。结果:与正常对照组相比,模型组兔出现饮食、活动减少及精神萎靡现象,肿瘤结节为暗红色且出现坏死、液化及囊性改变等病理损伤,肝脏指数、肿瘤体积、肝组织MVD、Notch、jagged1、VEGF、AP-1蛋白表达升高（P＜0.05）,体质量、BF、BV及PS水平下降（P＜0.05）。与模型组相比,TACE组肿瘤结节为乳白色,肿瘤体积显著下降（P＜0.05）,其余指标差异无统计学意义（P＞0.05）;jagged1组兔精神萎靡及肿瘤组织坏死程度加重,肝脏指数、肿瘤体积、MVD、Notch、jagged1、VEGF、AP-1蛋白表达升高（P＜0.05）,体质量、BF、BV及PS水平下降（P＜0.05）;TACE+rhES组兔饮食、精神等好转,肿瘤组织坏死程度减轻,肝脏指数、肿瘤体积、Notch、jagged1、VEGF、AP-1蛋白表达降低（P＜0.05）,体质量、BF、BV及PS水平升高（P＜0.05）。与TACE+rhES组相比,TACE+rhES+jagged1组上述指标变化趋势相反且有统计学差异（P＜0.05）。结论:TACE+rhES联合治疗可通过抑制Notch/jagged1信号通路激活,抵抗肝癌模型兔肿瘤血管生成。     

兔VX2脑瘤血管生成的灌注CT研究

Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.     

多层螺旋CT灌注成像评价非小细胞肺癌分化程度的价值及其机制

目的 探讨多层螺旋CT(MSCT)灌注成像评价非小细胞肺癌(NSCLC)分化程度的价值及机制.方法 应用MSCT对44例NSCLC行灌注成像,其中22例构建微血管构筑二维表型(2D-TMAP).用Spearman相关分析和趋势检验,探讨不同区域血流量(BF)、血容量(BV)、强化峰值(PEI)、平均通过时间(MTT)、达峰时间(TTP)与NSCLC分化程度、2D-TMAP指标的关系.结果 趋势检验和相关分析结果均显示,总BF、总BV和总PEI随NSCLC分化程度降低而减低,r分别为-0.613(P=0.000)、-0.309(P=0.042)和-0.350(P=0.020).总PEI与总微血管密度(MVD)呈正相关(r=0.441,P=0.046),周围区BF、总BF、总BV、总PEI与未形成完整管腔的MVD、鼠抗人增殖细胞核抗原(PCNA)的表达强度均呈负相关(均P<0.05).NSCLC的分化程度与未形成完整管腔的周围区MVD、PCNA和血管内皮生长因子(VEGF)的表达强度均呈正相关,r分别为0.477(P=0.034)、0.656(P=0.002)和0.430(P=0.048),而与总MVD无关.未形成完整管腔的周围区MVD与VEGF、PCNA、ephrinB2和EphB4表达强度均呈正相关,r分别为0.586(P=0.005)、0.430(P=0.048)、0.634(P=0.002)和0.634(P=0.002).结论 灌注成像能有效评价NSCLC的分化程度,其机制在于通过检测微血管的管腔化程度来评价NSCLC的血流模式.     

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

PURPOSE: To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model. METHODS AND MATERIALS: CC531 tumors were induced in WAG/Rij rats. DCE-MRI was performed before and 5 days after 5 x 5 Gy of RT and parametric maps generated of the endothelial transfer constant (K(trans)) and the fractional interstitial space (Ve) according to the Tofts model. Tissue pO2 mapping was performed in each tumor core and rim before and after RT. Microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and pimonidazole hypoxia staining were compared with a control group of tumor-bearing rats. RESULTS: Mean K(trans) and v(e) were significantly reduced after RT in all tumor regions. Mean pO2 was 6.8 mm Hg before RT vs. 7.7 mm Hg after RT (p < 0.001) in the tumor rim and 3.5 mm Hg before RT vs. 4.4 mm Hg after RT (p < 0.001) in the tumor core. Mean MVD in the tumor rim was 10.4 in the RT treated group vs. 16.9 in the control group (p = 0.061). VEGF expression was significantly higher in RT-treated rats. After RT, no correlation was found between DCE-MRI parameters and histologic parameters. A correlation was seen after RT between pO2 and K(trans) (r = -0.57, p = 0.08) and between pO2 and v(e) (r = -0.65, p = 0.04). CONCLUSIONS: Dynamic contrast-enhanced-MRI with P792 allows quantification of microvascular changes in this colorectal model. RT significantly reduces neovascular leakage and enhances tissue oxygenation and VEGF expression. After RT, DCE-MRI parameters are related to tumor pO2, but not to MVD or VEGF expression.     

Direct demonstration of instabilities in oxygen concentrations within the extravascular compartment of an experimental tumor

To test the hypothesis that temporal variations in microvessel red cell flux cause unstable oxygen levels in tumor interstitium, extravascular oxygenation of R3230Ac mammary tumors grown in skin-fold window chambers was measured using recessed tip polarographic microelectrodes. Red cell fluxes in microvessels surrounding pO2 measurement locations were measured using fluorescently labeled red cells. Temporal pO2 instability was observed in all experiments. Median pO2 was inversely related to radial distance from microvessels. Transient fluctuations above and below 10 mm Hg were consistently seen, except in one experiment near the oxygen diffusion distance limit (140 microm) where pO2 fluctuations were <2 mm Hg and median pO2 was <5 mm Hg. Vascular stasis was not seen in these experiments. These results show that fluctuations in red cell flux, as opposed to vascular stasis, can cause temporal variations in pO2 that extend from perivascular regions to the maximum oxygen diffusion distance.     

Clinical Observation and Therapeutic Evaluation of Rhendostatin Combined with DP Regimen in Treating Patients with Advanced Esophageal Cancer

Objective: To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Methods: Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. Results: the therapeutic effect ofrh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rhendostatin +DP regimen group was obviously lower than single chemotherapy group (P<0.01). The expression of VEGF had positive correlation with BF and BV but negative correlation with MTT. Compared with treatment before for rh-endostatin +DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P<0.05). However, there were no significant differences between treatment before and after treatment in single chemotherapy (P>0.05). Conclusions: Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.     

Estimating hypoxic status in human tumors: a simulation using Eppendorf oxygen probe data in cervical cancer patients

PURPOSE: To define the minimal number of pO(2) measurements, with 90% sensitivity and 90% specificity, needed to categorize cervical tumors as either hypoxic or oxic. METHODS AND MATERIALS: Using Eppendorf oxygen probe data from our ongoing prospective trial, we simulated the measurement of tumor oxygenation with a smaller number of data points in 135 patients with cervical cancer. The hypoxic proportion, defined as the percentage of pO(2) values <5 mm Hg (HP5), was calculated for each tumor. Hypoxic tumors were defined as those with a median HP5 >50%, and tumors with normal oxygen levels as those with a median HP5 < or =50%. A small number of pO(2) measurements were randomly selected from the Eppendorf measurements in each tumor, or per Eppendorf track, and used to define the tumor as hypoxic or oxic. The sensitivity and specificity were calculated, considering the classification as given by the complete set of Eppendorf measurements as the reference standard. RESULTS: The probability of falsely classifying the tumor decreased as the selected number of pO(2) measurements per tumor increased, and at 16 measurements was approximately 10%. Adding additional measurements per tumor beyond 24 improved the ability to classify the tumor accurately only slightly. The probability of falsely classifying the tumor decreased as the pO(2) measurements per track increased. At five measurements per track, the probability of falsely classifying the tumor was approximately 9%. CONCLUSION: Approximately 20 measurements per tumor, or five measurements per track, using the Eppendorf pO(2) histograph, are sufficient to categorize cervical tumors as hypoxic or oxic. The results of this study will serve as a guide for research clinicians in the use of this and other systems in the assessment of tumor oxygenation in humans.     

Changes in oxygenation status and blood flow in a rat tumor model by mild temperature hyperthermia

PURPOSE: Experiments were conducted to elucidate the relationship between the changes in oxygen partial pressure (pO2) and blood flow in heated tumors with an ultimate goal of using mild temperature hyperthermia (MTH) to increase tumor oxygenation. METHODS AND MATERIALS: The blood flow and pO2 in the R3230 adenocarcinoma grown (subcutaneously) in the right hind limbs of Fischer rats were measured immediately or 24 h after heating at 40.5 degrees-43.5 degrees C for 30 or 60 min. The blood flow was measured with the radioactive microsphere method and the tumor pO2 was measured polarographically using an Eppendorf pO2 histograph. RESULTS: The tumor PO2 significantly increased immediately and 24 h after heating for 30 min at 40.5 degrees-43.5 degrees C or for 60 min at 40.5 degrees and 41.5 degrees C. On the other hand, in tumors heated at 42.5 degrees C for 60 min, the tumor pO2 immediately after heating was similar to the control value whereas that 24 h after heating was about threefold greater than the control tumor pO2. Heating at 43.5 degrees C for 60 min resulted in a significant decline in pO2 immediately after and 24 h after heating. The increase in tumor pO2 immediately after heating appeared to be due to an increase in tumor blood flow. However, the changes in tumor pO2 and tumor blood flow 24 h after heating, particularly after high thermal doses (e.g., 60 min heating at 42.5 degrees or 43.5 degrees C), were not correlated. CONCLUSION: Heating at mild temperatures (i.e., 40.5 degrees-42.5 degrees C for 30-60 min), caused thermal dose-dependent increases in pO2 in the R3230 AC tumors of Fischer rats during 0-24 h after heating. Such an increase in tumor oxygenation after MTH appeared to be due to an increase in tumor blood flow.     

多层螺旋CT灌注成像在肾肿瘤中的应用及与分子病理学的相关性

[目的]探讨多层螺旋CT（MSCT）灌注成像在肾肿瘤诊断中的价值。[方法]59例肾肿瘤行MSCT灌注扫描．应用perfusion2软件包计算血流量（BF）、血容量（BV）、表面通透性fPS）及平均通过时间（MTT）．同时检测肾肿瘤及肿瘤旁正常组织中血管内皮生长因子（VEGF）的表达及微血管密度（MVD）,[结果]59例肾肿瘤术后病理证实为。肾癌48例,肾盂癌6例,肾血管平滑肌脂肪瘤5例。在不同级别的肾细胞癌中．其灌注参数BF、BV和PS均明显低于正常肾皮质（P〈0．01）,且高级别的肾癌灌注参数BF、BV和PS均明显高于低级别的肾癌（P〈0．01）。肾血管平滑肌脂肪瘤和肾盂癌的灌注值均明显低于肾癌,有显著性差异（P〈0．01）。肾癌的BF、BV、PS值与肿瘤的VEGF表达呈显著正相关（P〈0．01）,MTT、值与VEGF表达呈显著负相关（P〈0．01）。[结论]MSCT灌注成像能定量评价肿瘤血管生成,血管灌注及血管通透性改变,有助于肾细胞癌的术前分级．并在肾肿瘤的鉴别诊断方面具有一定的临床应用价值。     

卵巢交界性肿瘤血管内皮生长因子表达和微血管密度的研究

背景与目的:血管生成是实体肿瘤生长、侵袭、扩散转移的关键,微血管密度(microvesselofdensity,MVD)可反映肿瘤的血管形成情况。血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)是具有重要意义的促血管生长因子,它与肿瘤的生长密切相关。本研究检测卵巢交界性肿瘤组织中VEGF的表达和MVD,探讨它们与临床病理特征及预后的关系。方法:采用免疫组化SP法和原位杂交技术检测69例卵巢交界性肿瘤、18例卵巢良性肿瘤和27例卵巢恶性肿瘤组织中VEGF蛋白及VEGFmRNA的表达,用FⅧ因子单克隆抗体标记新生血管内皮,计数并计算MVD。结果:VEGF蛋白、VEGFmRNA在卵巢交界性肿瘤组织中的表达均介于卵巢良性肿瘤与卵巢恶性肿瘤之间,其结果差异均有显著性(P<0.05);也与卵巢交界性肿瘤的临床分期、MVD值密切相关(P<0.05);但VEGF与卵巢交界性肿瘤的组织分型、有无腹腔种植无关(P>0.05)。结论:VEGF与卵巢肿瘤的生长、侵袭、转移密切相关;检测VEGF有助于判断卵巢肿瘤的恶性程度,为判断卵巢交界性肿瘤患者的预后提供依据。     

Tumor oxygenation and radiosensitization by pentoxifylline and a perflubron emulsion carbogen breathing

Oxygen tension measurements were made in three tumors: (i) the murine FSaII fibrosarcoma, (ii) the rat 9L gliosarcoma and (iii) the rat 13672 mammary adenocarcinoma using a pO2 histograph. Tumor oxygenation measurements were made while the animals breathed air or breathed carbogen (95% oxygen/5% carbon dioxide). Pentoxifylline or a perflubron emulsion was administered to the animals and tumor oxygen measurements were repeated under both breathing conditions. Both pentoxifylline and the perflubron emulsion improved the oxygenation of the FSaII fibrosarcoma under air breathing conditions but did not alter the oxygen profiles of either rat tumor compared with air breathing alone. Carbogen breathing increased the oxygenation of all tumors. Pentoxifylline administration did not change the oxygen profiles of the tumors under carbogen breathing conditions but administration of the perflubron emulsion increased the oxygenation of all three tumors under carbogen breathing conditions compared with carbogen breathing alone. Co-administration of pentoxifylline and the perflubron emulsion enhanced the radiation response of the Lewis lung tumor to daily fractionated radiation under air breathing conditions with a dose modifying factor of 1.65 and under carbogen breathing conditions with a dose modifying factor of 2.25. Over a range of perflubron emulsion doses, pentoxifylline increased the growth delay of the Lewis lung tumor in a constant manner. These results indicate that pentoxifylline and the perflubron emulsion have the largest impact on the oxygenation of more hypoxic tumors and that administration of the perflubron emulsion/carbogen breathing is the most effective means of increasing tumor oxygenation and radiation response.     

Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors

PURPOSE: To investigate the effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors in Balb/c Rw mice. Texaphyrins are synthetic, porphyrin-like molecules capable of stably coordinating lanthanide and nonlanthanide metals. Metallotexaphyrin compounds containing gadolinium (MGd), lutetium (MLu), europium (Eu-Tex), dysprosium (Dy-Tex), and manganese (Mn-Tex) were evaluated. METHODS: Tumor oxygenation was measured using an Eppendorf pO2 histograph when tumors, implanted intradermally in the rear dorsum, reached 150-200 mm3. Oxygen measurements were also made in the leg muscle of tumor-bearing mice, to determine whether changes in oxygenation occurred in nontumor tissue. RESULTS: Motexafin gadolinium (Xcytrin, MGd) seems to be an effective modulator of tumor oxygen tension. The mean of the median tumor pO2 6 hours after injection of MGd was 8.0 +/- 2.4 mm Hg. The control value was 1.5 +/- 0.4 mm Hg. The oxygen levels within EMT6 tumors were shifted significantly toward higher oxygen tensions 6-8 hours after i.v. injection of 40 micromol/kg MGd, thereby reducing the percentage of severely hypoxic readings (MGd, 6 hours: 44.6 +/- 4.3% <2.5 mm Hg; Control: 69.4 +/- 3.0% <2.5 mm Hg). There was no significant change in the oxygenation of the leg muscle after MGd treatment. Eu-Tex and Mn-Tex increased the tumor oxygenation to a much lesser degree than MGd. MLu, Dy-Tex, and the vehicle (a 5% mannitol solution) did not modulate tumor oxygenation. CONCLUSIONS: MGd is an effective modulator of tumor oxygenation. The central metal composition of texaphyrin compounds is an important determinant of the effect of the texaphyrins on tumor oxygenation.     

The natural progression of microvasculature in primary tumor and lymph node metastases in a breast carcinoma model: relationship between microvessel density, vascular endothelial growth factor expression, and metastatic invasion

The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5-6 tumor doublings. Excised tumors were examined for (i) MVD assessed by immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with increasing tumor weight in both primary and metastatic tumors. The MVD saturation level was significantly greater for primary tumors (MVD = 22) than for ALNs or ILNs (MVD = 14). Maximal VEGF score was not statistically different between the three kinds of tumors, however the rate of rise in VEGF expression was different. Near-maximal VEGF expression occurred early in tumor growth, preceding microvessel development. Both MVD and VEGF expression in lymph nodes were proportional to the pathology score characterizing increasing metastatic invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an ability to survive without significant vasculature. These findings underscore the differences in angiogenesis between primary tumors and LNMs and have implications for therapy of metastatic cancer.     

骨肉瘤CT灌注成像与血管生成的关系*

目的:探讨64排螺旋CT灌注成像（computed tomography perfusion imaging,CTPI）参数与骨肉瘤血管生成之间的关系。方法:选取2007年9 月至2009年6 月南京军区南京总医院26例经病理证实为骨肉瘤的患者,治疗前均行CTPI检查,从而获得骨肉瘤患者肿瘤及正常肌肉组织的血流量（blood flow,BF）、血容量（blood volume,BV）、达峰时间（time to peak ,TTP）、表面通透性（permeability surface,PS）等灌注参数。运用免疫组织化学技术计算治疗前骨肉瘤穿刺标本的微血管密度（microvessel density,MVD）。 对肿瘤组织和肌肉组织灌注参数值进行配对样本t 检验,对灌注参数与MVD运用Pearson相关系数分析,P<0.05为差异有统计学意义。结果:骨肉瘤中的BF、BV、TTP 以及PS值分别为46.6 ± 25.1mL/（100g·min）、61.8 ± 29.5mL/100g、122.9 ± 26.2s 和44.5 ± 14.6mL/（100g·min）。 而正常肌肉组织的BF、BV、TTP 以及PS值分别为5.2 ± 6.6mL/（100g·min）、9.6 ± 7.3mL/100g、115.5 ± 33.1s和17.0 ± 29.3mL/（100g·min）,骨肉瘤组的BF、BV和PS高于肌肉组,差异显著并有统计学意义（P=0.000、P=0.000、P=0.000）,但TTP的差异无统计学意义,骨肉瘤组的BF、BV以及PS值与MVD的r 值分别为0.83、0.87和0.63,P<0.05,呈明显正相关性,而TTP 与MVD的r 值为-0.02,P=0.93,无显著相关性。结论:CTPI能够很好动态地评价骨肉瘤的血流灌注,并可以反映血管生成及MVD的表达。      

卵巢癌组织中VEGF及MVD表达及其临床意义

目的 分析微血管密度(MVD)以及卵巢上皮性肿瘤血管内皮生长因子(VEGF)的表达与卵巢癌临床病理因素的关系及两者的相关性.方法 选取手术切除的卵巢上皮性肿瘤标本88例以及正常卵巢组织标本35例,采用免疫组化染色方法检测所有标本中VEGF及MVD的表达情况,分析两者相关性及与卵巢上皮性肿瘤临床病理因素的关系.结果 VEGF在卵巢癌组织中的表达阳性率为92.0％及MVD平均值为(30.26±8.69),显著高于良性卵巢上皮性肿瘤组织VEGF的阳性表达率[52.6％,(11.52±3.46)] (P ＜0.05);而良性卵巢上皮性肿瘤组织中VEGF阳性表达率及MVD平均值均高于正常对照组(P＜0.05).VEGF阳性表逸的卵巢癌组织中MVD平均值显著高于VEGF阴性表达者,VEGF阳性表达与MVD平均值呈正相关(P＜0.05).卵巢癌组织中VEGF阳性表达与肿瘤临床分期及细胞分化程度存在明显相关性(P＜0.05),而与肿瘤直径、组织学类型以及患者年龄无明显相关性(P＞0.05).MVD与肿瘤临床病理特征无明显相关性(P＞0.05).结论 VEGF及MVD均能反映卵巢上皮性肿瘤的良恶性和恶性进展程度,并可能成为卵巢癌临床生物学治疗的参考指标.     

Peripheral lung carcinoma: correlation of angiogenesis and first-pass perfusion parameters of 64-detector row CT

PURPOSE: To investigate the value of 64-detector row CT first-pass perfusion imaging in the evaluation of tumor perfusion in patients with lung carcinoma, and to assess the correlation between the perfusion parameters and tumor angiogenesis. MATERIALS AND METHODS: Forty-six surgically peripheral lung carcinomas were examined with 64-detector row CT. First-pass CT perfusion study comprised of 12 repeated spiral acquisitions over 60s following a 50-ml intravenous bolus of contrast medium at 6-7 ml/s. Tumor specimens were assessed for microvessel density (MVD). Perfusion, peak enhancement intensity (PEI), time to peak (TTP), and blood volume (BV) and MVD of the tumor were compared by means of one-way ANOVA analysis of variance among histological type, size, metastasis and necrosis. Pearson correlation coefficients were conducted to represent the relationships between the perfusion parameters and MVD of the tumor. RESULTS: Mean values for perfusion, PEI, TTP, and BV of the 46 tumors were 70.3+/-39.4 ml/min/ml, 67.0+/-37.6 HU, 36.9+/-11.2s, and 34.9+/-17.9 ml/100g, respectively. No statistically significant differences in perfusion parameters were found among different histological types (p>0.05). Considerable differences with higher perfusion, PEI and BV were noted in tumor < or = 3.0 cm than in tumor>3.0 cm (p<0.05). No statistically significant differences were found between nodule metastasis positive and negative groups (p>0.05). The necrotic tumors showed significantly lower perfusion, PEI and BV compared with non-necrotic tumors (p<0.05). Perfusion, PEI, and BV of the necrotic part manifested significantly lower, but TTP longer, than those of non-necrotic part of the necrotic tumors (p<0.05). Perfusion, PEI and BV were positively correlated with extent of MVD (r=0.715, 0.681, 0.762, respectively, all p<0.001), whereas no significant correlation was found between TTP and MVD (r=-0.154, p>0.05). CONCLUSION: 64-detector row CT first-pass perfusion imaging is a valuable noninvasive method in evaluating tumor perfusion of peripheral lung carcinoma. CT perfusion parameters can be indicators for evaluating tumor necrosis and angiogenesis.     

Radiobiological Hypoxia in the KHT Sarcoma: Predictions Using the Eppendorf Histograph

Purpose: To investigate whether electrode measurements of tumor oxygenation obtained under a range of different treatment conditions designed to alter the degree of tumor hypoxia could be correlated with estimates of radiobiological hypoxia measured under the same conditions.

Methods and Materials: Experiments were performed in restrained, nonanesthetized, female C3H/He mice, which had 0.5 g KHT sarcomas growing intramuscularly in the hind limbs. The treatments used to modify tumor oxygenation status included breathing gas mixtures of varying oxygen content, altering tumor blood flow, and shifting the hemoglobin oxygen dissociation curve. Radiobiological hypoxic fraction was estimated using the paired survival curve assay, while electrode measurements of tumor oxygenation were obtained with an Eppendorf histograph.

Results: With the selected manipulations it was possible to vary the radiobiological hypoxic fraction in the tumors from 1 to 100% of the total viable cell population. Furthermore, these changes in radiation response were directly reflected in the changes in tumor oxygenation measurements made with the Eppendorf histograph.

Conclusion: These findings suggest that in the KHT tumor model the Eppendorf electrode measurements could predict the response of the tumors to radiation as determined by the proportion of hypoxic cells.     

肝细胞癌p53和VEGF的表达及其与肿瘤血管形成的关系

目的 :研究p5 3和血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的表达和肿瘤微血管密度 (microvesseldensity ,MVD)测定在人肝细胞癌 (HCC)中的意义。方法 :采用免疫组织化学方法 ,检测 5 0例HCC患者手术切除标本p5 3和VEGF的表达 ,并用抗CD3 4 抗体标记癌组织血管内皮细胞 ,计算MVD。结果 :p5 3、VEGF总阳性表达率分别为 5 4 0 % (2 7 5 0 )和 76 0 % (38 5 0 ) ,p5 3、VEGF的表达和MVD均与HCC组织病理分级呈正相关 ,P <0 0 5。p5 3和VEGF的阳性表达符合率为 74 % (37 5 0 ) ,两者的表达呈相关性 ,P <0 0 5。p5 3阳性和VEGF阳性的癌组织MVD分别为 178± 6 2和 175±5 9 ,而相应的阴性组分别为 12 5± 5 1和 131± 6 1,两者差异有显著意义 ,P <0 0 5。p5 3、VEGF表达均为阳性者 ,MVD为 176± 6 3;p5 3、VEGF的表达均为阴性者 ,MVD为 12 3± 5 2 ;两者差异有显著意义 ,P <0 0 5。结论 :1)p5 3、VEGF的表达以及MVD的测定可作为判断HCC恶性潜能的重要生物学指标 ;2 )p5 3、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测p5 3、VEGF的表达对了解肿瘤血管形成的机制有一定意义