Bacterial antigen-induced release of white cell- and platelet-derived bioactive substances in vitro

Summary Objectives. Poor prognosis after resection of primary colorectal cancer may be related to the combination of perioperative blood transfusion and subsequent development of infectious complications. Various white cell- and platelet-derived cancer-growth substances may be involved in this process. Therefore, we studied the in vitro release of substances from white cells and platelets stimulated by bacterial antigens and supernatants from stored red-cell components. Methods. Eight units of whole blood (WB) and 8 U of buffy-coat-depleted red-cell (SAGM) blood were donated by healthy blood donors. Subsequently, one-half of each unit was leucocyte-depleted by filtration, and all 32 half-units were stored under standard conditions for 35 d. Just after storage, and on d 7, 21, and 35 during storage, aliquots of the supernatants were removed from the units and frozen at −80°C. WB from other healthy donors was stimulated for 2 h with sodium chloride (controls), with Escherichia coli (E. coli) lipopolysaccharide (LPS) alone, or with LPS plus supernatants from the WB units (diluted 1:10), or from the SAGM units (diluted 1:20) stored for 0, 7, 21, or 35 d, respectively. Similar assays were performed using Staphylococcus aureus-derived protein A as a stimulatory antigen. The concentration of eosinophil cationic protein (ECP), myeloperoxidase (MPO), histamine (HIS), and plasminogen-activator inhibitor-1 (PAI-1) were determined in supernatants from the stored blood and in assay supernatants by using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) methods. Results. The extracellular concentration of ECP, MPO, and HIS increased significantly in a storage-time-dependent manner in nonfiltered WB and SAGM blood, and the increase was abrogated by prestorage leukofiltration. Similarly, PAI-1 increased significantly in nonfiltered WB, and the increase was abrogated by prestorage leukofiltration. The supernatant concentrations of the four substances were significantly increased in LPS-stimulated (0.5-4 fold) and in protein A-stimulated (0.5-13.5-fold) assays compared with controls. The addition of supernatants from stored nonfiltered WB or SAGM blood significantly increased the assay supernatant of ECP, MPO, HIS, and PAI-1 concentrations storage--time-dependently in LPS-stimulated assays. Prestorage leukofiltration abrogated the additional effect of supernatants from stored blood. Similar results were observed for ECP and HIS through the addition of supernatants from stored blood to protein A-stimulated assays. Protein A stimulation did not lead to increased PAI-1 release in assays diluted by supernatants from stored blood. However, the MPO concentrations were significantly (p=0.004), and independent of storage time and leukofiltration, increased in protein A-stimulated assays diluted by supernatants from stored blood compared with sodium chloride dilution. Conclusion. Extracellular ECP, MPO, HIS, and PAI-1 accumulate during storage of nonfiltered red-cell components, but the accumulation can be prevented by prestorage leukofiltration. In addition, bacterial antigens appear to induce significant release of the substances from white cells and platelets. Addition of supernatants from stored, nonfiltered WB and SAGM blood may increase the substance levels in a storage-time-dependent manner, and prestorage leukofiltration may prevent further increase by supernatants, except for MPO.     

Prestorage and bedside leucofiltration of whole blood modulates storage-time-dependent suppression of in vitro TNFα release

Immunosuppression after transfusion may be related to the content of leucocytes in the transfused blood. Therefore we studied the effects of prestorage and bedside leucodepletion by filtration on the suppression by whole blood of in vitro stimulated tumour necrosis factor alpha (TNFalpha) release. Nine units of whole blood were leucofiltered prestorage and stored for 35 d. 27 units, 3 x 9, were stored and leucofiltered at the bedside after 7, 21 and 35 d. Supernatants were collected from all units during storage and added to a whole blood assay of E. coli-LPS-stimulated TNFalpha release. The effects of storage were assessed and compared with supernatants collected immediately after donation as reference. TNFalpha release was storage time dependently suppressed to: 81%, 74% and 57% by supernatants from non-filtered blood stored for 7, 21 and 35 d, respectively. Prestorage leucofiltration almost eliminated this effect, but we still observed a storage-time-dependent suppression by bedside-leucofiltered blood to 88%, 78% and 65%, respectively. Prestorage leucofiltration appeared to reduce storage-time-dependent suppression of in vitro stimulated TNFalpha release induced by plasma from whole blood compared with non-filtered and bedside-leucofiltered whole blood.     

Role of platelet-derived growth factor and vascular endothelial growth factor in obliterative airway disease

RATIONALE: Platelet-derived growth factor (PDGF) is an important smooth muscle cell mitogen, and vascular endothelial growth factor (VEGF) is a known angiogenic and proinflammatory growth factor. We hypothesized that specific therapy aimed at these growth factors might inhibit the development of experimental obliterative airway disease (OAD). METHODS: In fully mismatched rat tracheal allografts, we used imatinib and PTK/ZK, either alone or in combination, to block PDGF and VEGF receptor protein tyrosine kinase (RTK) action, respectively. Prophylaxis was initiated at the time of transplantation. Early treatment was commenced on Day 7 during the inflammatory phase and late treatment on Day 14 during the fibroproliferative phase of OAD. No immunosuppression was administered. MEASUREMENTS AND MAIN RESULTS: Prophylaxis with either PTK/ZK or imatinib alone significantly reduced OAD, and combined prophylaxis completely prevented its development. Early treatment with PTK/ZK and imatinib also effectively reduced the development of OAD. Late treatment failed to show significant efficacy. Blocking VEGF RTK action with PTK/ZK reduced the activation of allograft blood vessels and the number of lymph vessels in the allograft airway wall, and significantly diminished allograft inflammation, whereas PDGF blockade with imatinib inhibited the growth of smooth muscle cells in the proliferating lesion. CONCLUSIONS: Combined prophylactic PDGF and VEGF RTK blockade completely prevents the development of OAD. Also, when early treatment with PTK/ZK and imatinib is commenced during the inflammatory phase of OAD development, it significantly attenuates the development of tracheal occlusion, suggesting that these drugs could potentially be used to treat bronchiolitis obliterans syndrome in its early phase.     

Leucocyte and platelet-derived bioactive substances in stored blood: effect of prestorage leucocyte filtration

Abstract: Adverse reactions to transfusion of allogeneic blood may depend on content of leucocytes and platelets and on storage-time of the erythrocyte suspensions. Therefore, we studied the efficacy of prestorage leucocyte reduction by filtration on total content and extracellular accumulation of histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in samples obtained from 5 units of SAGM blood, 7 units of plasma-reduced whole-blood and 6 units of whole-blood before and after filtration, respectively. In addition, we analysed supernatants from the same units after storage at +4°C for 0, 21 and 35 d, respectively. The filtration was performed at room temperature within 2–4 h after donation. The substances were analysed by ELISA and RIA methods and we also analysed the donor plasma levels of the same bioactive substances. The total content of histamine, ECP, EPX, and MPO were 10–70-fold higher in all unfiltered erythrocyte products compared to donor plasma concentrations, while PAI-1 content was 15–20-fold higher only in plasma-reduced whole-blood and whole-blood. Prestorage leucocyte filtration significantly reduced the total histamine, ECP, EPX, MPO and PAI-1 content to levels similar to donor plasma levels in plasma-reduced whole-blood and whole-blood, while PAI-1 was still low in filtered SAGM blood. In addition, the levels of extracellular bioactive substances at d 0 after donation and filtration were within the range of concentrations in donor plasma, and there was no time-dependent accumulation during storage for 35 d at +4°C. IL-6 was not detected in either plasma or samples obtained from the blood bags. These results suggest prestorage leucocyte filtration to deplete leucocyte contents to levels, which prevent the previously shown time-dependent accumulation of leucocyte derived bioactive substances in various erythrocyte suspensions. In addition, the PAI-1 results suggest leucocyte filters to reduce the obligatory platelet content in whole-blood products.     

Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells

Objectives: HMG-CoA reductase inhibitors (statins) can modulate the formation of new blood vessels, but the reports on their contribution to angiogenesis are contradictory. Therefore, we investigated whether the effect of statins is dependent either on the concentration of the drug or on the cell type. Methods and results: Under basal conditions human vascular smooth muscle cells (HVSMC) and microvascular endothelial cells (HMEC-1) constitutively generate and release vascular endothelial growth factor (VEGF). In contrast, primary macrovascular endothelial cells (HUVEC) produce minute amounts of VEGF. Different statins (atorvastatin, simvastatin and lovastatin, 1–10 μmol/l) significantly reduced basal and cytokine-, nitric oxide- or lysophosphatidylcholine (LPC)-induced VEGF synthesis in HMEC-1 and HVSMC. Interestingly, at the same concentrations statins upregulated VEGF generation in HUVEC. Furthermore, statins exerted dual, concentration-dependent influence on angiogenic activities of HUVEC as determined by tube formation assay. At low concentrations (0.03–1 μmol/l) the pro-angiogenic activity of statins is prevalent, whereas at higher concentrations statins inhibit angiogenesis, despite increasing VEGF synthesis. Conclusion: Our data show that statins exert concentration- and cell type-dependent effects on angiogenic activity of endothelial cells and on VEGF synthesis. The data are of relevance for elucidating the differential activity of statins on angiogenesis in cardiovascular diseases and cancer.     

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic factors such as hypoxia-inducible factor 1 alpha (HIF-1 alpha and vascular endothelial growth factor (VEGF). METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after the occurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF. RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry. HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis. CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1 alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.     

大肠癌组织中P16蛋白和血管内皮生长因子的表达及其临床意义

目的：探讨大肠癌组织中P16蛋白和血管内皮生长因子（VEGF）表达及其临床意认。方法：用S－P免疫组织化学方法测定66例大肠癌组织和20例正常大肠组织中P16蛋白和VEGF的表达。结果：大肠癌中P16蛋白阳性率为48．5％（32／66）明显低于对照组的70．0％（14／20）（P＜0．01），VEGF阳性率为72．7％（48／66）则明显高于对照组的15．0％（3／20）（P＜0．01）：P16蛋白和VEGF在大肠癌中表达具有明显负相关性；P16蛋白和VEGF表达与大肠癌组织学类型、肿瘤直径、肿瘤部位无关（P＞0．05），而与淋巴结转移、Duke's分期五年生存率有明显的关系（P＜0．01）。结论：大肠癌中存在P16蛋白下调和VEGF上调，P16蛋白和VEGF表达可作为反映大肠癌生物学行为的指标之一。     

Prediction of long-term remission of oligo/polyarticular juvenile idiopathic arthritis with S100A12 and vascular endothelial growth factor

Objectives: This study aimed to evaluate the usefulness of S100A12 and vascular endothelial growth factor (VEGF) for predicting the stability of remission for discontinuing methotrexate (MTX) and/or biological agents in Japanese patients with oligo/polyarticular juvenile idiopathic arthritis (JIA).

Methods: Forty-four patients with oligo/polyarticular JIA who received MTX with or without biological agents were enrolled. Serum concentration of both S100A12 and VEGF were simultaneously evaluated by ELISA in active and in remission phase determined by activity markers including DAS-28.

Results: S100A12 and VEGF were correlated with DAS-28. Of the 22 patients with oligo/polyarticular JIA in clinical remission, 13 patients with low S100A12 and VEGF concentrations could discontinue treatment without relapse over 2 years. However, nine patients without low S100A12 and VEGF concentrations relapsed afterwards, even though they had been in clinical remission. The cut-off levels of S100A12 and VEGF for division into two groups of the maintenance remission and relapse groups were 177 ng/ml and 158 pg/ml, respectively.

Conclusions: S100A12 and VEGF are useful markers for assessing disease activity of oligo/polyarticular JIA in remission phase. These markers should be kept low when clinicians consider tapering or discontinuing treatments in oligo/polyarticular JIA patients.     

Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in patients with soft-tissue sarcoma

Purpose: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been suggested to be important mediators for tumor-induced angiogenesis. We measured serum VEGF and bFGF levels from patients with soft-tissue sarcomas and correlated serum VEGF and bFGF levels with tumor status at surgery and histological grading. Materials and methods: A group of 18 healthy controls and 85 patients with soft-tissue sarcoma were enrolled in this study. The patients were classified according to tumor status at surgery. Serum levels of VEGF and bFGF were also correlated with histological grading. VEGF and bFGF levels were determined by enzyme-linked immunosorbent assay (Quantikine R&D Systems). Results: Serum VEGF and bFGF levels were significantly elevated in the patient group (VEGF: 580pg/ml, bFbF: 21pg/ml, P = 0.0001). The highest concentrations of serum VEGF and bFGF were found in patients with macroscopic tumor lesions or G3 histology. Serum VEGF levels showed a statistically significant correlation with tumor status and grading (P = 0.006 for tumor status, P = 0.0001 for grading). Conclusions: This study reveals that elevated preoperative serum VEGF and bFGF levels can be detected in the majority of patients with soft-tissue sarcoma. The significant correlation with tumor mass and histological grading suggests that a consecutive monitoring of VEGF and bFGF in the serum of patients with soft-tissue sarcoma might be a valuable marker for tumor follow-up. Received: 26 April 1999 / Accepted: 17 May 1999     

20(s)-原人参二醇对肝癌血管内皮生长因子及碱性成纤维细胞生长因子蛋白表达的影响

目的 探讨20(s)-原人参二醇(Ppd)对肝癌血管内皮生长因子(VEGF)及碱性成纤维细胞生长因子(bFGF)表达的影响.方法 建立肝癌动物模型,将实验动物分为五组,每组10只,分对照组、环磷酰胺组(CTX)、20(s)-原人参二醇25mg/kg、50mg/kg、100mg/kg给药组,给药二周后处死动物.称肿瘤重量及肿瘤体积,制成组织切片,以备免疫组化应用.结果 与对照组相比,给药组VEGF、bFGF表达受到抑制,肿瘤的重量及体积明显减轻,组间有显著性差异(P＜0.01).结论 提示Ppd抑制了VEGF、bFGF蛋白的表达,抑制了肿瘤生长.     

Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus

Purpose: Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We aimed at evaluating the gene expression of PD-ECGF and VEGF in hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Patients and methods: Surgical specimens (28 HCC, 28 nontumorous liver tissues and 18 PVTT) were studied by Northern blot analysis. The levels of PD-ECGF mRNA and VEGF mRNA expression were measured by densitometric scanning of the autoradiographs, and they were normalized to the level of expression of an internal control (glyceraldehyde-phosphate dehydrogenase) mRNA. Results: The expression rates of PD-ECGF mRNA in PVTT, HCC and nontumorous liver tissues were 77.8% (14/18), 67.9% (19/28) and 35.7% (10/28), being 88.9% (16/18), 75.0% (21/28) and 17.9% (5/28) respectively for VEGF mRNA. The expressions of PD-ECGF mRNA and VEGF mRNA were higher in HCC with PVTT than when PVTT was absent (P < 0.05). The PVTT was more often seen in patients with positive expression of both PD-ECGF mRNA and VEGF mRNA in HCC than in patients who were positive for only one of these factors or negative for both (P < 0.05). Conclusion: Both PD-ECGF and VEGF correlated well with the formation of PVTT of HCC. Received: 20 June 1999 / Accepted: 20 July 1999     

血管内皮生长因子、血小板源性生长因子-BB与2型糖尿病患者血糖波动及微血管病变的关系

目的观察糖化血红蛋白（HbAlC）〈7．0％的2型糖尿病患者血糖波动与糖尿病微血管病变（视网膜病变、糖尿病肾病）及血清血管内皮生长因子（VEGF）、血小板源性生长因子-BB（PDGF—BB）水平之间的关系,探讨其在HbAlC达标患者中的相互影响机制。方法选取2010年10月至2012年8月在黑龙江省医院内分泌科就诊的2型糖尿病患者100例,其中男52例、女48例,年龄40～66岁。根据是否合并糖尿病微血管病变分为单纯2型糖尿病组[A组,n=30,男14例,女16例,年龄（50±11）岁],糖尿病肾病组[B组,n=38,男20例,女18例,年龄（52±10）岁]和糖尿病视网膜病变组[C组,n=32,男18例,女14例,年龄（53±13）岁]。另以同期于黑龙江省医院进行体检的25名健康者为正常对照组[Con组,n=25,男12例,女13例,年龄（48±9）岁]。人院前糖尿病患者均使用药物治疗。所有参试者均测定空腹血糖浓度（FPG）、总胆固醇（TC）、甘油i酯（TG）、低密度脂蛋白胆同醇（LDL—C）、高密度脂蛋白胆固醇（HDL—C）、餐后2h血糖浓度（2hPG）、24h尿微量白蛋白（24h尿ALB）和HbAlc。应用动态血糖监测系统连续监测血糖3d,计算平均血糖（MBG）、平均血糖标准差（SDBG）、平均血糖波动幅度（MAGE）、日内最大血糖波动幅度（LAGE）、日间血糖平均绝对差（MODD）和曲线下面积（AUC）。采用酶联免疫吸附法分别检测血清中VEGF和PDGF—BB水平。计量资料组间比较采用t检验,多组间比较采用单因素方差分析,糖尿病微血管并发症的影响因素采用logistic回归分析,PDGF．BB、VEGF相关因素采用多元线性回归分析。结果（1）B组PDGF—BB水平高于A组和Con组[分别为（53±12）、（31±6）、（26±4）μg／ml,F=9．56,P〈0．05];C组VEGF水平高于A组和Con组[分别为（217±57）、（105±12）、（74±10）μg／ml,F=8．13,P〈0．05]。（2）动态血糖监测指标B组与A组比较,SDBG、LAGF、MAGE、MODD、AUC明显升高（t=2．57、3．46、5．75、3．59、4．28,均P〈0．05）,C组与A组比较,SDBG、LAGF、MAGE、MODD、AUC明显升高（t=3．29、3．77、5．38、4．54、3．16,均P〈0．05）,而MBG在3组间的差异无统计学意义,均P〉0．05。（3）logistic回归分析显示PDGF-BB、VEGF及血糖波动是糖尿病微血管并发症独立危险因素。分别以PDGF-BB、VEGF为因变量,以血糖波动指标SDBG、LAGF、MAGE、MODD、AUC及2hPG为自变量,采用多元线性回归分析可能影响PDGF-BB、VEGF的相关因素,结果显示,MAGE、SDBG和2hPG对PDGF-BB、VEGF影响最大。结论2型糖尿病患者微血管病变的发生发展与血糖波动具有明显相关性,血糖波动可导致血清血管内皮生长因子和血小板源性生长因子-BB水平增高,从而参与糖尿病视网膜病变、糖尿病肾病等微血管病变的进展。     

非小细胞肺癌中肝素酶基因与血管内皮生长因子表达的研究

目的　探讨肝素酶基因及血管内皮生长因子 (VEGF)在非小细胞肺癌 (NSCLC)中的表达及其临床病理学意义。方法　选取 85例肺部手术标本 ,所有标本分成两份 ,1份用于逆转录PCR检测肝素酶mRNA ,1份用于免疫组化检测VEGF。结果　 (1)肝素酶mRNA及VEGF在NSCLC中表达率均高于良性病变肺组织 (P <0 0 5 )。 (2 )肝素酶mRNA表达率在淋巴结转移组、远处转移组、Ⅲ期 +Ⅳ期组、低分化组、腺癌组、肿瘤最大径≥ 5cm组分别高于无淋巴结转移组、无远处转移组、Ⅰ期 +Ⅱ期组、高中分化组、鳞癌组、最大径 <5cm组 (P <0 0 5 )。 (3)VEGF表达率在淋巴结转移组、远处转移组、Ⅲ期 +Ⅳ期组分别高于无淋巴结转移组、无远处转移组、Ⅰ期 +Ⅱ期组 (P <0 0 5 )。 (4 )NSCLC中肝素酶mRNA与VEGF表达无相关性 (P >0 0 5 )。结论　肝素酶与VEGF参与了NSCLC的侵袭转移过程 ,可作为判断NSCLC转移潜力指标 ;肝素酶与VEGF通过互不依赖的机制促进NSCLC的侵袭与转移 ,二者联合检测将有利于提高判断NSCLC转移潜力的敏感性及特异性。     

血管内皮生长因子和肿瘤特异性生长因子对恶性肿瘤的诊断价值

目的　探讨血管内皮生长因子 (VEGF)和肿瘤特异性生长因子 (TSGF)联合检测对恶性肿瘤诊断的价值。方法　采用酶联免疫吸附试验 (ELISA)和化学法分别检测了 10 4例恶性肿瘤 ,3 0例良性疾病患者和 3 0例正常血清中的VEGF和TSGF的含量。结果　恶性肿瘤患者血清中VEGF和TSGF的含量均明显高于正常对照组及良性疾病组 (P <0 0 1)。恶性肿瘤患者血清VEGF的阳性率为 84 6% ,TSGF的阳性率为 85 6% ,两者总阳性率为 94 2 %。结论　研究资料血清VEGF和TSGF含量异常有助于恶性肿瘤的诊断     

Differential expression of vascular endothelial growth factor isoforms and receptor subtypes in the infarcted heart

Aims

The vascular endothelial growth factor (VEGF) family contains four major isoforms and three receptor subtypes. The expressions of each VEGF isoform and receptor subtype in cardiac repair/remodeling after myocardial infarction (MI) remain uncertain and are investigated in the current study.

Methods and results

Temporal and spatial expressions of VEGF isoforms and VEGFR subtypes were examined in the infarcted rat heart. Sham-operated rats served as controls. We found that the normal myocardium expressed all VEGF isoforms. Following MI, VEGF-A was only increased in the border zone at day 1 and was significantly decreased in the infarcted heart during the 42 day observation period afterwards. VEGF-B was significantly suppressed in the infarcted heart. VEGF-C and VEGF-D were markedly increased in the infarcted heart in both early and late stages of MI. VEGFR-1 and 2 were significantly decreased in the infarcted heart, while VEGFR-3 was significantly increased, which was primarily expressed in blood vessels and myofibroblasts (myoFb).

Conclusions

VEGF isoforms and VEGFR subtypes are differentially expressed in the infarcted heart. Increased VEGF-A in the very early stage of MI suggests the potential role in initiating the cardiac angiogenic response. Suppressed cardiac VEGF-B postMI suggests that it may not be critical to cardiac repair. The presence of enhanced VEGF‐C and VEGF-D along with its receptor, VEGFR-3, in various cell types of the infarcted heart suggest that these isoforms may regulate multiple responses during cardiac repair/remodeling.     

Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor

Purpose: Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. Methods: Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. Results: The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0–6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. Conclusion: The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.     

Expression of vascular endothelial growth factor in human myocardial infarction

Summary To define mechanisms that may influence collateral circulation and angiogenesis, we investigated vascular endothelial growth factor (VEGF) mRNA expression in human hearts. In non-ischemic human hearts, VEGF mRNA was not detected in vessels, but was found in cardiomyocytes. In hearts with myocardial infarction, the intensity of the VEGF signal was much higher in smooth muscle cells of arterioles adjacent to necrosis and in infiltrating macrophages than in myocytes around the site of the necrosis. This study suggests that levels of VEGF expression are high in smooth muscle cells and macrophages around infarcted areas after myocardial infarction and that VEGF may play a role in promoting collateral circulation and angiogenesis in human ischemic hearts.