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91.
Michael FINDLAY Katrina SHARPLES Greta A RILEY rew SIMPSON Stephen ACKLAND Katherine HALL Richard ISAACS Gillian HUMM Mark J MCKEAGE 《Asia-Pacific Journal of Clinical Oncology》2007,3(2):99-105
Background: This dose escalation study assessed feasibility of a totally oral chemotherapy regimen using cyclophosphamide and capecitabine. The rationale for this combination was based on the observation that preclinical models of cyclophosphamide up‐regulated tumor thymidine phosphorylase and increased the activation of capecitabine. Methods: Eligible patients with advanced cancer were treated with oral cyclophosphamide and capecitabine on a 28‐day cycle. If no dose limiting toxicities (DLT) were encountered during the first two treatment cycles, the next patient group was assigned to the next highest dose level until the maximum tolerable dose (MTD) was determined. Results: Twenty‐seven patients entered treatment. The majority of non‐DLT were grades 1 and 2. DLT experienced in the first 8‐week observation period were grade 3 diarrhea (one patient, level III) and grade 3 emesis (two patients, level V). MTD was observed at level 5, 1331 mg/m2/day capecitabine days 1–28 with 125 mg/m2/day cyclophosphamide days 1–14 of the 28‐day cycle. The recommended phase II dose is therefore 1331 mg/m2/day capecitabine with 100 mg/m2/day cyclophosphamide. The best response evaluation showed four partial responses (breast, colon, ovary and pancreas). Conclusion: Cyclophosphamide and capecitabine can be combined at their full oral single agent dose with promising tolerability and activity. 相似文献
92.
鼻咽癌血管生成与复发转移的关系初探 总被引:5,自引:0,他引:5
探讨鼻咽癌血管生成与复发转移的关系。方法采用免疫组织化学S-P法对73例NPC石蜡标本组织中的微血管密度及血管内皮细胞生长因子表达进行检测,随访3年,NPC复发转移19例,无复发转移。结果复发转移组的MVD及VEGF表达显著高于无复发转移组,MVD与VEGF的表达相关。结论NPC的MVD及VEGF与复发转移密切相关,有可能作为判断肿瘤生物学行为,转移潜能及预后的指标。 相似文献
93.
血管内皮生长因子在上皮性卵巢癌中的临床病理研究 总被引:1,自引:0,他引:1
目的研究血管内皮生长因子(VEGF)在上皮性卵巢癌组织中的表达状况并分析其与临床病理参数之间的关系。方法采用免疫组化、原位杂交技术分别检测31例上皮性卵巢癌、17例卵巢上皮性良性肿瘤及5例正常卵巢组织中VEGF蛋白质及核酸表达水平。结果上皮性卵巢癌组织中VEGF和VEGF mRNA阳性表达率分别为51.6%(16/31)和48.4%(15/31),与良性肿瘤相比有显著性差异(P〈0.05)。上皮性卵巢癌中VEGF阳性表达率分别与淋巴结转移及腹水量密切相关(P〈0.05),而在不同组织类型、病理分级及临床分期中无明显差异(P〉0.05)。恶性肿瘤患者生存状况与癌组织中VEGF阳性表达率亦无相关性(P〉0.05)。结论VEGF蛋白质及其mRNA在上皮性卵巢癌中高水平表达,且其阳性率与淋巴结转移及腹水量密切相关,可作为卵巢癌侵袭性评估的指标之一,为VEGF及其受体作为卵巢癌的治疗靶点提供科学依据。 相似文献
94.
Kyoko Hida Nako Maishi Kosuke Akiyama Hitomi Ohmura‐Kakutani Chisaho Torii Noritaka Ohga Takahiro Osawa Hiroshi Kikuchi Hirofumi Morimoto Masahiro Morimoto Masanobu Shindoh Nobuo Shinohara Yasuhiro Hida 《Cancer science》2017,108(11):2195-2203
Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TEC contain stem cell‐like populations with high aldehyde dehydrogenase (ALDH) activity (ALDHhigh TEC). ALDHhigh TEC have proangiogenic properties compared with ALDHlow TEC. However, the association between ALDHhigh TEC and drug resistance remains unclear. In the present study, we found that ALDH mRNA expression and activity were higher in both human and mouse TEC than in NEC. Human NEC:human microvascular endothelial cells (HMVEC) were treated with tumor‐conditioned medium (tumor CM). The ALDHhigh population increased along with upregulation of stem‐related genes such as multidrug resistance 1, CD90, ALP, and Oct‐4. Tumor CM also induced sphere‐forming ability in HMVEC. Platelet‐derived growth factor (PDGF)‐A in tumor CM was shown to induce ALDH expression in HMVEC. Finally, ALDHhigh TEC were resistant to fluorouracil (5‐FU) in vitro and in vivo. ALDHhigh TEC showed a higher grade of aneuploidy compared with that in ALDHlow TEC. These results suggested that tumor‐secreting factor increases ALDHhigh TEC populations that are resistant to 5‐FU. Therefore, ALDHhigh TEC in tumor blood vessels might be an important target to overcome or prevent drug resistance. 相似文献
95.
EZH2 promotes angiogenesis through inhibition of miR-1/Endothelin-1 axis in nasopharyngeal carcinoma
96.
Lorelei A. Mucci Jennifer R. Stark William D. Figg Fredrick Schumacher Haojie Li Miyako Abe Kristen Hennessy Meir J. Stampfer John Michael Gaziano Jing Ma Philip W. Kantoff 《International journal of cancer. Journal international du cancer》2009,125(5):1143-1146
Endostatin inhibits endothelial cell proliferation and migration, prerequisites of angiogenesis. A functional missense mutation (D104N) in endostatin was associated with an increased prostate cancer risk in a small study. We undertook a larger, prospective study within the Physicians' Health Study to examine D104N and prostate cancer risk and progression among 544 incident prostate cancer cases (1982–1995) and 678 matched controls. The association between endostatin genotype and cancer risk was estimated using logistic regression models. Among cases, Cox models were used to assess D104N and lethal prostate cancer. Given the role of endostatin in neovascularization of adipose tissue, we cross classified individuals on D104N genotype and body mass index (BMI). The genotype frequency was 1.3% homozygous (NN), 14.5% heterozygous (DN) and 84.2% wildtype homozygous (DD). There was no overall association between carriage of the N allele and prostate cancer risk (RR = 1.2, 95% CI: 0.9–1.6) or cancer‐specific mortality (HR = 1.2, 0.7–1.8). Cases with the polymorphic allele were less likely to be overweight (BMI 25 kg/m2 or greater, 26%) compared to men wildtype homozygous (48%), p < 0.0001. Being overweight was associated with a 60% greater prostate cancer risk among those who were wildtype homozygous. In contrast, being overweight was associated with a 50% lower risk of cancer among those with the N allele. We did not confirm an earlier observation between the D104N polymorphism and prostate cancer. However, our data indicate that prostate cancer cases who carry the variant N allele are more likely to be overweight, and may be more susceptible to the angiogenic influences of obesity in prostate cancer pathogenesis. © 2009 UICC 相似文献
97.
98.
Role of Incipient Angiogenesis in Cancer Metastasis 总被引:7,自引:0,他引:7
Metastasis is the primary cause of mortality in cancer patients. Angiogenesis is intimately involved in metastasis at the site of entry of tumor cells into the vasculature and at the site of eventual metastasis growth. In this commentary, we review current paradigms regarding angiogenesis in metastatic sites. Recent discoveries challenge some of the existing paradigms.Significant prior data suggest that successful formation of metastases requires: 1) angiogenesis in the primary tumor site; 2) downregulation of cohesive molecules and tumor cell increased motility, resulting in invasion into neovessels; 3) tumor cell embolism; 4) arrest and attachment in capillary beds of distant organs; 5) extravasation and proliferation in the organ parenchyma; and 6) re-establishment of angiogenesis when the tumor reaches >1–2mm in size [1].While most recent data largely confirm the aforementioned sequence of events, a few reports have revealed new knowledge about the earliest phases of angiogenesis of metastases. Of particular importance has been the ability to create tumor cell lines that are stably transfected with reporter genes, such as green fluorescence protein. With these tools it is now literally possible to monitor tumor formation from a single cell [2–7]. 相似文献
99.
ADAMTS4 and its proteolytic fragments differentially affect melanoma growth and angiogenesis in mice
Nithya Rao Zhiyuan Ke Hongrui Liu Chao‐Jin Ho Saran Kumar Wei Xiang Yizhun Zhu Ruowen Ge 《International journal of cancer. Journal international du cancer》2013,133(2):294-306
The metalloproteinase ADAMTS4 (ADAMTS, a disintegrin‐like and metalloproteinase with thrombospondin motif)/aggrecanase‐1 is highly expressed in cartilage and has been implicated in human arthritis. Although abundantly expressed in many types of cancer, its role in cancer remains unknown. In this work, we demonstrate for the first time that full‐length ADAMTS4 and its catalytically more active N‐terminal 53 kDa autocatalytic fragment both promote B16 melanoma growth and angiogenesis in mice. In contrast, overexpression of its catalytically inactive E362A mutant or truncated fragments containing only the C‐terminal ancillary domains suppresses melanoma growth and angiogenesis under similar conditions. Structure–function mapping revealed that the single thrombospondin‐type 1 repeat domain is essential and sufficient for the antitumorigenic activity displayed by the catalytically inactive ADAMTS4 isoforms. Suppression of tumor growth and angiogenesis in mice is accompanied by a significant increase in tumor cell apoptosis, whereas tumor cell proliferation is not affected. Importantly, we identified and demonstrated the presence of novel proteolytic fragments of ADAMTS4 containing essentially only the C‐terminal ancillary domains in cultured cells, and also in human cancer tissues, coexisting with full‐length and catalytically active N‐terminal fragments. The contrasting functions toward tumor growth in mice by the wild‐type proteinase and its catalytically inactive mutant correlate with their contrasting influences on angiogenesis signaling pathway molecules in B16 melanoma in mice. Our results suggest a complex role for ADAMTS4 in cancer with the functional balance of protumorigenic and antitumorigenic isoforms likely to act as an important parameter in determining the net influence of this metalloproteinase on tumor growth in vivo. 相似文献
100.
目的:研究人骨肉瘤细胞系OS-732血管生成相关作用。方法:应用鸡胚绒毛尿囊膜模型,通过解剖显微镜及透射电镜观察该细胞系促血管生成特点,并以免疫组化方法检测人骨肉瘤细胞系OS-732鸡胚绒毛尿囊膜移植瘤中血管内皮生长因子(vascular endothelial growth factor,VEGF),碱性成纤维细胞生长因子(Basic fibroblast growth factor,bFGF)的表达。结果:该细胞系具较强的诱导血管生成能力,解剖显微镜下可见血管辐辏现象,透射电镜下可见新生血管壁由单层内皮细胞构成,内皮细胞裂隙增宽,基底膜不完整,缺乏平滑肌成分,移植瘤组织发VEGF和bFGF均呈阳性表达,其中VEGF呈高表达。结论:肿瘤诱导的新生血管在病理,生理及形态功能方面都具有特征性,其诱导血管生成过程中可能有多种血管生长因子的共同参与,针对血管生长因子为靶点进行抗血管生成治疗对改善骨肉瘤预后可能具有重要意义。 相似文献