Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen

Summary.  Previously we demonstrated that domain 5 (D5) of high-molecular-weight kininogen (HK) inhibits neovascularization in the chicken chorioallantoic membrane (CAM) assay and further found that kallikrein cleaved HK (HKa) inhibited FGF2-and VEGF-induced neovascularization, and thus was antiangiogenic. In this study, we sought to demonstrate whether uncleaved HK stimulates neovascularization and thus is proangiogenic. The chick chorioallantoic membrane was used as an in ovo assay of angiogenesis. Low-molecular-weight kininogen stimulates angiogenesis, indicating that D5 is not involved. Bradykinin stimulates neovascularization equally to HK and LK and is likely to be responsible for the effect of HK. A murine monoclonal antibody to HK (C11C1) also recognizes a similar component in chicken plasma as detected by surface plasmon resonance. Angiogenesis induced by FGF2 and VEGF is inhibited by this monoclonal antibody and is a more potent inhibitor of neovascularization induced by VEGF than an integrin α_vβ₃ antibody (LM 609). Our postulate that C11C1 inhibits the stimulation of angiogenesis by HK was confirmed when either C11C1 or D5 completely inhibited angiogenesis in the CAM induced by HK. Growth of human fibrosarcoma (HT-1080) on the CAM was inhibited by GST-D5 and C11C1. These results indicate HK is proangiogenic probably by releasing bradykinin and that a monoclonal antibody directed to HK could serve as an antiangiogenic agent with a potential for inhibiting tumor angiogenesis and other angiogenesis-mediated disorders.     

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.     

Overexpression of the 18A2/mts1 gene and down–regulation of the TIMP–2 gene in invasive human glioma cell lines in vitro

Invasion of the reconstituted extracellular matrix composite, Matrigel, by eight human glioma–derived cell lines and human fetal brain cells was assessed in vitro using 8 um polycarbonate filters in a modified Boyden migration chamber. With the exception of one low grade glioma derived cell line, all lines studied proved to be invasive while normal fetal brain cells failed to invade. This invasive potential was independent of the histological grade of the tumour from which the cell lines originated. In addition, the expression of the metastasis–associated gene 18A2lmts1 as well as the tissue inhibitor of metalloproteinases–2 (TIMP–2) was analysed in each of the glioma–derived cell lines. The 18A2/mtsl was expressed in all the cells studied with the exception of fetal brain cells and the low grade non–invasive glioma derived IPRK–7 cell line. The 18A2/mtsl related genes coding for the S100 subfamily of calcium binding proteins were found to be differentially and overexpressed in invasive cell lines. TIMP–2 was expressed only in noninvasive cell lines. These results suggest that the 18A2/ mtsl and TIMP–2 genes could play an important role in the invasive behaviour of human glioma cells in vitro. .     

Testicular seminoma with human chorionic gonadotropin production

Testicular seminoma with elevated serum human chorionic gonadotropin level (hCG-positive seminoma) is regarded as more malignant than marker-negative seminoma, although Its prognosis is still unclear. To clarify the malignant potential of seminoma with hCG production, the serum levels of the beta subunit of hCG (β-hCG) and lactic acid dehydrogenase (LDH) were examined in 35 and 40 patients, respectively, and the Immunohistochemical expression of β-hCG examined in 45 tumors. The elevation of the LDH serum level correlated to the Invasive status, metestatic status and poor outcome, while that of the serum β-hCG level correlated only to the metastatic status. Immunohistochemical expression of β-hCG was observed in syncytiotrophoblastic giant cells in 11 tumors and a few mononuclear seminoma cells In 36 tumors. Expression was not associated with the malignancy potential, except where the expression In mononuclear cells Inversely correlated to the invasive status. These results suggest that most seminomas produce a slight amount of hCG; that an elevated hCG serum level Indicates the pressnce of metastatic tumors and mainly reflects an increase in tumor volume but not in cellular malignancy potential; and that the LDH serum level, rather than hCG, is more useful as a prognostic indicator for patients with seminoma.     

鼻腔、副鼻窦原发性肿瘤70例CT分析

本文回顾分析了70例经手术病理证实的鼻腔、副鼻窦原发性良恶性肿瘤的临床和CT表现。讨论了良恶性肿瘤的鉴别诊断,不典型的CT表现及CT的检查价值,认为CT检查可做为鼻腔、副鼻窦肿瘤的首选方法。     

胃癌组织内微血管定量的意义

目的：研究胃癌组织中微血管数量（MVC）与临床病理因素及预后的关系。方法：材料取自瑞金医院1988年～1991年胃癌手术切除标本，共128例。抗因子Ⅷ相关抗原（F-ⅧRAg）的单克隆抗体和免疫组化试剂盒购自Dako公司。研究方法按LSAB法免疫组织化学操作技术常规进行；微血管定量以镜下200倍，肿瘤内5个最高微血管密度区的MVC均数表示；分析MVC与临床病理因素之间关系，并对有完整5年随访资料的86例胃癌患者预后与MVC关系进行探讨。结果：所有胃癌组织中的平均MVC为16.5±8．5，MVC随TNM分期增加而增加，有淋巴结转移患者的MVC（18．3±8.7）明显高于无淋巴结转移患者（13．8±7．4）（P＜0．01），高MVC（≥16）胃癌患者比低MVC（＜16）患者预后明显为差，5年生存率分别为42.5％和58．7％（P＜0．05）。结论：MVC在胃癌患者是一个有意义的预后指标．     

Mediastinal lipoma: Report of a case

We experienced a case of mediastinal lipoma, which is considered to be a relatively rare disease. A 3-year-old girl was referred to Gifu University hospital because of fever and an abnormal shadow on her chest X-ray. The chest X-ray clearly showed a well-delineated tumor shadow which seemed to oppress the diaphragm and the right atrium in the right lower lung area. A computed tomogram (CT) of the chest showed a homogeneous mass localized on the right diaphragm and adjoining the right anterior chest wall and heart. The mass showed a fat density measuring about-100 HU. Magnetic resonance imaging (MRI) showed a high-intensity mass which was almost the same level as the subcutaneous fat on both the T₁-weighted and T₂-weighted images. Thoracotomy was performed and a fatty tumor was found. It arose from the right side of the pericardium and adjoined the diaphragm, the anterior chest wall, and the thymus. There was no adhesion between the tumor and the surrounding organs. It was resected easily and its contents were yellowish and homogeneous. The patient made an uneventful recovery and was discharged 10 days after the operation. Light microscopy showed a lipoma consisting of mature adipose tissue and no malignancy was found.     

磷酸钙骨水泥修复良性骨肿瘤骨缺损

目的：研究磷酸钙骨水泥(CPC)修复良性骨肿瘤刮除术后遗留的骨缺损的临床应用。方法：应用CPC修复33例患者良性骨肿瘤刮除术后遗留的骨缺损。患者平均年龄38岁，肿瘤类型依次为骨纤维结构不良、骨巨细胞瘤、骨囊肿、动脉瘤样骨囊肿、软骨粘液样纤维瘤、非骨化性纤维瘤、骨母细胞瘤，观察患者术中CPC固化时间，术后全身及切口局部反应，血钙、磷值变化，X线片和CT扫描，平均随访时间19个月。结果：全部患者未见明显不良反应，血钙、磷值未见升高，X线片显示骨缺损处均填充良好，随访见所有患者均有CPC降解和骨替代现象发生。结论：良性骨肿瘤刮除后利用CPC填充修复骨缺损，可充分填充骨肿瘤刮除后不规则瘤腔，即刻恢复骨的强度．经骨替代后可真正完成骨修复。术式简单．并发症少。     

Relationship between renal capsular artery feeding and size of VX-2 carcinoma implant in the rabbit kidney

When regional intraarterial infusion is applied in the treatment of malignant tumors it is essential to reach the tumor via all its major feeder vessels. In this study VX-2 carcinoma was implanted into the lower pole of the left kidney in 24 rabbits to investigate whether the renal capsular artery takes part in tumor feeding. The rabbits were divided into four groups that were followed for 8, 10, 12 or 14 days after tumor implantation. At that time the renal artery was ligated close to the kidney and subsequently silicone rubber or barium sulfate/gelatin suspension was injected into the capsular artery. The tissue was cleared, and the tumor carefully removed and examined microscopically for traces of silicone rubber. When barium sulfate had been injected, the kidney was examined radiographically in order to detect possible presence of contrast medium in the tumor. This study revealed no vascular supply to the implanted VX-2 carcinoma from the capsular artery when the tumor was confined intracapsularly, i.e., up to 12 days after tumor implantation in untreated rabbits.This investigation was performed at the Oncological Research Laboratory, Department of Diagnostic Radiology, University of Bergen, Bergen, Norway     

Dynamic contrast-enhanced ultrasound with carbon dioxide microbubbles as adjunct to arteriography of liver tumors

Purpose The goal of the study is to evaluate utility of contrast enhanced ultrasound (US) with carbon dioxide microbubbles in evaluation of hepatic lesions.Methods Twenty eight patients with single or multiple t hepatic lesions (11 hepatocellular carcinoma, 8 hemangiomas, 5 metastases, 1 adenoma, 1 focal nodular hyperplasia, 2 regenerative nodules) were examined. US exam was performed during intraarterial injection of 10 ml of CO₂ through the same catheter employed for liver arteriography. The US exam was videotaped in its salient phases. Characteristics of enhancement were evaluated and correlated with histological findings or patient follow up.Results Sonographic angiography clearly demonstrated vascularization of the lesions. Hepatocellular carcinoma, hemangioma, metastases, focal nodular hyperplasia, and regenerative nodules had very characteristic patterns. The injection of CO₂ allowed detection of small additional nodules.Conclusion Sonographic angiography can improve characterization and staging of hepatic tumors. Low cost and the simplicity of the technique should encourage further experimentation.