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ANNALS OF ONCOLOGY 2003年第6期14卷 813-816页

作者： Garattini, S Ist Ric Farmacol Mario Negri Milan Italy

New approaches to cancer therapy S. Garattini Istituto di Ricerche Farmacologiche “Mario Negri”, Via Eritrea 62, 20157 Milano, Italy *E-mail: mapelli@*** Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Garattini Annals of Oncology, Volume 14, Issue 6, 1 June 2003, Pages 813–816, https://***/10.1093/annonc/mdg261 Published: 01 June 2003

关键词：血管生成抑制剂/治疗应用抗肿瘤药/治疗应用化学疗法辅助综合疗法酶抑制剂/治疗应用免疫疗法肿瘤/治疗人类

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Boron neutron capture therapy of the rat 9L gliosarcoma: evaluation of the effects of shark cartilage

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BRITISH JOURNAL OF RADIOLOGY 2000年第868期73卷 429-434页

作者： Morris, GM Coderre, JA Micca, PL Lombardo, DT Hopewell, JW Univ Oxford Churchill Hosp Res Inst Oxford OX3 7LJ England Brookhaven Natl Lab Dept Med Upton NY 11973 USA

A number of anti-angiogenic substances are now under evaluation, both experimentally and clinically, as potential agents for the treatment of cancer. It has recently been demonstrated that anti-angiogenic agents can increase the therapeutic potential of photon irradiation in a range of tumour models. In the present communication a preliminary assessment is made of the effects of shark cartilage on the response of the rat 9L gliosarcoma to boron neutron capture therapy (BNCT). Shark cartilage was administered orally as an aqueous suspension at a daily dose of similar to 2000 mg kg(-1) body weight. The mean survival time of rats receiving no treatment was 20.7+/-0.5 days post intracranial tumour implantation. Administration of shark cartilage alone extended the survival time. Two of the rats treated with shark cartilage were healthy and fully active at the end of the evaluation period (43 days post implantation). At autopsy the brain tumours of these animals were a factor of similar to 4 smaller than controls. In a repeat study with shark cartilage alone the survival time was extended by approximately 30%. After boronophenylalanine-mediated BNCT, with or without shark cartilage, the survival time of rats that eventually became moribund was increased by a factor of similar to 2 relative to controls. In both treatment groups similar to 20% of rats were healthy at 1 year after BNCT. There was no evidence of residual tumour at post-mortem It was concluded that shark cartilage, when given alone, significantly increased the survival time of tumour-bearing rats, presumably owing to an antiangiogenic effect. However, the survival data suggested that boronophenylalanine-mediated BNCT did not appear to be enhanced by the administration of shark cartilage.

关键词：血管生成抑制剂/治疗应用硼中子俘获疗法脑肿瘤/病理学脑肿瘤/放射疗法脑肿瘤/治疗软骨神经胶质肉瘤/病理学神经胶质肉瘤/放射疗法神经胶质肉瘤/治疗肿瘤移植辐射增敏药/治疗应用大鼠近交F344 鲨鱼存活率组织提取物/治疗应用肿瘤细胞培养的动物大鼠

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Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia

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BLOOD 2000年第8期95卷 2637-2644页

作者： Padró, T Ruiz, S Bieker, R Bürger, H Steins, M Kienast, J Büchner, T Berdel, WGE Mesters, RM Univ Munster Dept Med Hematol & Oncol D-48129 Munster Germany Univ Munster Gerhard Domagk Inst Pathol D-48129 Munster Germany

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21;complete remission, n = 20), Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin, Microvessel counts were significantly higher in patients with AML (0 = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2(10.0-12.0)/x500 field, respectively (P < .001), On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P < .001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with greater than or equal to 5% residual blasts (P < .001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML, Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood, 2000;95:2637-2644) (C) 2000 by The American Society of Hematology.

关键词：急性病血管生成抑制剂/治疗应用抗肿瘤药/治疗应用骨髓/血液供给骨髓/病理学白血病髓样/药物疗法白血病髓样/病理学白血病髓样/病理生理学新生血管化病理性青少年成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Angiogenesis: Potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation

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PHARMACOLOGICAL REVIEWS 2000年第2期52卷 237-268页

作者： Griffioen, AW Molema, G Univ Hosp Maastricht Dept Internal Med Tumor Angiogenesis Lab NL-6202 AZ Maastricht Netherlands Univ Groningen Inst Drug Explorat Dept Pathol & Lab Med Tumor Immunol Lab Groningen Netherlands Univ Groningen Dept Pharmacokinet & Drug Delivery Groningen Netherlands

Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is a sequence of events that is fundamental to many physiologic and pathologic processes such as cancer, ischemic diseases, and chronic inflammation. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor, the fibroblast growth factors (like in FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Whereas inhibition of angiogenesis can prevent diseases with excessive vessel growth such as cancer, diabetes retinopathy, and arthritis, stimulation of angiogenesis would be beneficial in the treatment of diseases such as coronary artery disease and critical limb ischemia in diabetes. In this review we highlight the current knowledge on angiogenesis regulation and report on the recent findings in angiogenesis research and clinical studies. We also discuss the potentials, limitations, and challenges within this field of research, in light of the development of new therapeutic strategies for diseases in which angiogenesis plays an important role.

关键词：血管生成抑制剂/药理学血管生成抑制剂/治疗应用心血管疾病/药物疗法心血管疾病/病理学慢性病炎症/药物疗法炎症/病理学肿瘤/血液供给肿瘤/药物疗法肿瘤实验性/血液供给肿瘤实验性/药物疗法新生血管化病理性/药物疗法动物人类

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Efficacy of antiangiogenic therapy with TNP-470 in superficial and invasive bladder cancer models in mice

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UROLOGY 2000年第3期56卷 521-526页

作者： Beecken, WDC Fernandez, A Panigrahy, D Achilles, EG Kisker, O Flynn, E Joussen, AM Folkman, J Shing, Y Childrens Hosp Dept Surg Boston MA 02115 USA Harvard Univ Sch Med Boston MA USA

Objectives. To evaluate the efficacy of antiangiogenic therapy with O-(chloracetyl-carbamoyl) fumagillol (TNP-470) in a superficial and an invasive bladder cancer model in mice. The control of recurrent superficial and metastatic bladder cancer constitutes a major problem in urologic practice. Although the established therapies for these cases (immunotherapy, chemotherapy, and radiation therapy) have improved during the previous decades, further improvement and the reduction of existing side effects are needed. The inhibition of angiogenesis represents a new concept in cancer therapy. Methods. We evaluated the in vitro effect of TNP-470 on the proliferation of bovine capillary endothelial cells (BCE), the superficial transitional cell carcinoma (TCC) cell line (KK-47), and the invasive TCC cell line (MGH-U1). To evaluate the in vivo effect of TNP-470 on the growth of advanced TCCs, both cell lines were injected subcutaneously into SCID mice. When tumors grew to a size of 100 to 200 mm(3), therapy either with TNP-470 or phosphate-buffered saline was initiated. Results. TNP-470 strongly inhibited endothelial cell proliferation in vitro. The in vitro proliferation of both bladder carcinoma cell lines was also inhibited by TNP-470. However, the doses inhibitory to bladder carcinoma cells were 100-fold higher than the doses that were effective in the inhibition of endothelial cell proliferation. In vivo, TNP-470 significantly inhibited the growth of advanced KK-47 (67%) and MGH-U1 (68%) tumors in SCID mice. Conclusions. Our results indicate that antiangiogenic therapy with TNP-470 is equally effective in advanced superficial and invasive bladder carcinoma models in mice. When our results are taken together with the reports of other laboratories, TNP-470 appears to be a promising candidate as a tumor suppressor in superficial and invasive bladder cancer. UROLOGY 56: 521-526, 2000. (C) 2000, Elsevier Science Inc.

关键词：血管生成抑制剂/治疗应用癌移行细胞/血液供给癌移行细胞/药物疗法细胞分裂/药物作用环己烷类药物筛选试验抗肿瘤小鼠 SCID 新生血管化病理性/药物疗法倍半萜类/治疗应用肿瘤细胞培养的/药物作用膀胱肿瘤/血液供给膀胱肿瘤/药物疗法动物牛女(雌)性小鼠

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Thalidomide: Current and potential clinical applications

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AMERICAN JOURNAL OF MEDICINE 2000年第6期108卷 487-495页

作者： Calabrese, L Fleischer, AB Cleveland Clin Fdn Dept Rheumat & Immunol Dis Cleveland OH 44195 USA Wake Forest Univ Sch Med Dept Dermatol Winston Salem NC 27109 USA

More than three decades after its withdrawal from the world marketplace, thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. However, it has long been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behcet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with hu-man immunodeficiency virus (HIV) infection;the drug is efficacious against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. To prevent teratogenicity, a comprehensive program has been established to control access to the drug, including registration of prescribing physicians, dispensing pharmacies, and patients;mandatory informed consent and education procedures;and limitation of the quantity of drug dispensed. Clinical and, in some patients, electrophysiologic monitoring for peripheral neuropathy is indicated with thalidomide therapy. Other adverse effects include sedation and constipation. With appropriate safeguards, thalidomide may benefit patients with a broad variety of disorders for which existing treatments are inadequate. (C) 2000 by Excerpta Medica, Inc.

关键词：血管生成抑制剂/免疫学血管生成抑制剂/药理学血管生成抑制剂/治疗应用抗HIV药/免疫学抗HIV药/药理学抗HIV药/治疗应用关节炎类风湿/药物疗法贝赫切特综合征/药物疗法皮肤科用药/免疫学皮肤科用药/药理学皮肤科用药/治疗应用缺肢/化学诱导红斑结节性/药物疗法移植物抗宿主病/药物疗法 HIV感染/药物疗法免疫抑制剂/免疫学免疫抑制剂/药理学免疫抑制剂/治疗应用麻风抑制药/免疫学麻风抑制药/药理学麻风抑制药/治疗应用麻风瘤型/药物疗法红斑狼疮皮肤/药物疗法肿瘤/药物疗法周围神经系统疾病/化学诱导口炎口疮性/药物疗法致畸剂沙立度胺/免疫学沙立度胺/药理学沙立度胺/治疗应用人类

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康柏西普联合玻璃体切除术治疗增殖期糖尿病性视网膜病变的临床疗效

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医学临床研究 2024年第1期41卷 11-13页

作者：王会艳胡鹏蒋丽娟黄英邵阳学院附属第一医院湖南邵阳422000

【目的】探讨康柏西普联合玻璃体切除术(PPV)治疗增殖期糖尿病性视网膜病变(PDR)的临床疗效。【方法】选取2020年8月至2022年10月在本院就诊的46例(50眼)PDR患者作为研究对象,按照随机数字表法分为观察组和对照组,每组23例(25眼)。对照... 详细信息

【目的】探讨康柏西普联合玻璃体切除术(PPV)治疗增殖期糖尿病性视网膜病变(PDR)的临床疗效。【方法】选取2020年8月至2022年10月在本院就诊的46例(50眼)PDR患者作为研究对象,按照随机数字表法分为观察组和对照组,每组23例(25眼)。对照组患者给予单纯23 G PPV治疗,观察组患者给予康柏西普联合23 G PPV治疗。比较两组患者手术时间及术中和术后情况。【结果】观察组手术时间显著短于对照组(t=2.47,P<0.05);观察组术后最佳矫正视力(BCVA)度数高于对照组(P<0.05);因医源性视网膜裂孔、视网膜脱落实行的硅油填充率低于对照组(P<0.05)。【结论】康柏西普联合23 G PPV治疗PDR患者,可有效缩短手术时间,改善患者术后视力,降低并发症发生率。

关键词：糖尿病视网膜病变/并发症糖尿病,2型/并发症玻璃体切除术血管生成抑制剂/治疗应用

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Antagonising angiogenesis in rheumatoid arthritis

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ANNALS OF THE RHEUMATIC DISEASES 2001年第sup3期60卷 III71-III74页

作者： Brenchley, PEC Univ Manchester Manchester Clin Dept Med Manchester M13 9WL Lancs England

Rheumatoid arthritis (RA) is a chronic systemic disease characterised by an inflammatory erosive synovitis. Early changes in the synovium are marked by neovascularisation, inflammatory cell infiltration, and associated synoviocyte hyperplasia, which produce a pannus of inflammatory vascular tissue. This pannus covers and erodes articular cartilage, eventually leading to joint destruction. Angiogenesis is a complex, highly regulated physiological process, which in normal adults is restricted to the female reproductive cycle and wound healing. A coordinated sequence of endothelial cell division, selective degradation of vascular basement membranes and surrounding extracellular matrix (ECM) with migration of endothelial cells1 results in new capillary growth from existing vessels. Pathological angiogenesis is now recognised as a fundamental component of pannus development in RA,2 with evidence of both focal endothelial proliferation and apoptosis in the synovium.3

关键词：血管生成抑制剂/治疗应用关节炎类风湿/药物疗法关节炎类风湿/代谢关节炎类风湿/病理生理学内皮生长因子/代谢细胞外基质/代谢成纤维细胞生长因子2/代谢葡糖醛酸糖苷酶/代谢葡糖氨基聚糖类/代谢生长物质/代谢硫酸乙酰肝素/代谢关节/代谢关节/病理学关节/病理生理学淋巴因子/代谢新生血管化病理性/代谢新生血管化病理性/预防和控制血管内皮生长因子A 血管内皮生长因子类人类

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New life in a sleeper: Thalidomide and Crohn's disease

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GASTROENTEROLOGY 1999年第6期117卷 1485-1488页

作者： Sands, BE Podolsky, DK Harvard Univ Massachusetts Gen Hosp Sch Med Gastrointestinal Unit Boston MA 02114 USA Harvard Univ Massachusetts Gen Hosp Sch Med Ctr Study Inflammatory Bowel Dis Boston MA 02114 USA

GASTROENTEROLOGY 1999;117:1485-1488

关键词：血管生成抑制剂/副作用血管生成抑制剂/治疗应用 Crohn病/药物疗法致畸剂沙立度胺/副作用沙立度胺/治疗应用肿瘤坏死因子α/拮抗剂和抑制剂肿瘤坏死因子α/代谢女(雌)性人类男(雄)性

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玻璃体内注射康柏西普治疗视网膜分支静脉阻塞继发黄斑水肿的临床研究

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医学临床研究 2016年第1期33卷 83-85页

作者：范金连曾琦段国平湖南师范大学第一附属医院暨湖南省人民医院眼科湖南长沙410005

【目的】初步评价玻璃体腔内注射康柏西普治疗视网膜分支静脉阻塞（BRV0）继发黄斑水肿（ME）的疗效及安全性。【方法】对2014年8月至2015年2月就诊于本院眼科已确诊为BRVO继发ME的患者21例（21眼）的临床资料进行回顾性分析，对患眼均... 详细信息

【目的】初步评价玻璃体腔内注射康柏西普治疗视网膜分支静脉阻塞（BRV0）继发黄斑水肿（ME）的疗效及安全性。【方法】对2014年8月至2015年2月就诊于本院眼科已确诊为BRVO继发ME的患者21例（21眼）的临床资料进行回顾性分析，对患眼均给予玻璃体腔内注射康柏西普，观察术前和术后1d、1周、1个月、3个月时患者的最佳矫正视力，光学相干断层扫描测定黄斑中心区视网膜厚度的变化。【结果】在21眼中有19眼视力提高，2眼视力不变。治疗前的LogMRA视力为0．55±0．74，治疗后1周、1个月、3个月时分别为：0．57±0．70、0．61±0．63、0．62±0．58，其与治疗前相比差异均具有显著性（P〈0．05）。黄斑中心凹平均厚度治疗前为（404．25±62．76）μm，治疗后1周、1个月、3个月时分别为（354．25±64．12）μm、（221．75±37．30）μm、（195．30±24．70）μm，治疗后明显改善，与治疗前相比差异具有显著性（P〈0．05）。未发现与药物相关的眼部并发症及全身的不良反应。【结论】玻璃体内注射康柏西普治疗BRVO继发ME患者中短期内可提高视力、减轻ME，但长期疗效仍需进一步观察。

关键词：玻璃体注射,病灶内血管生成抑制剂/治疗应用抗体,单克隆/治疗应用视网膜静脉闭塞/并发症黄斑水肿/病因学

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