Progress in Tumor Research最新文献_第8页

Transglutaminases of lower organisms. 低等生物的谷氨酰胺转氨酶。

Progress in Tumor Research Pub Date : 2005-01-01 DOI: 10.1159/000084242

Ramakrishna U Rao, Ramaswamy Chandrashekar, Kapil Mehta

引用次数: 2

Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis. 选择性环氧化酶-2抑制剂在肿瘤血管生成管理中的治疗潜力。

Progress in Tumor Research Pub Date : 2003-01-01 DOI: 10.1159/000071373

Stephen Gately, Robert Kerbel

{"title":"Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis.","authors":"Stephen Gately, Robert Kerbel","doi":"10.1159/000071373","DOIUrl":"https://doi.org/10.1159/000071373","url":null,"abstract":"It is clear that COX-2 plays an important role in tumor and endothelial cell biology. Increased expression of COX-2 occurs in multiple cells within the tumor microenvironment that can impact on angiogenesis. COX-2 appears to: (a) play a key role in the release and activity of proangiogenic proteins; (b) result in the production of eicosanoid products TXA2, PGI2, PGE2 that directly stimulate endothelial cell migration and angiogenesis in vivo, and (c) result in enhanced tumor cell, and possibly, vascular endothelial cell survival by upregulation of the antiapoptotic proteins Bcl-2 and/or activation of PI3K-Akt. Selective pharmacologic inhibition of COX-2 represents a viable therapeutic option for the treatment of malignancies. Agents that selectively inhibit COX-2 appear to be safe, and well tolerated suggesting that chronic treatment for angiogenesis inhibition is feasible [107-110]. Because these agents inhibit angiogenesis, they should have at least additive benefit in combination with standard chemotherapy [111] and radiation therapy [24, 112]. In preclinical models, a selective inhibitor of COX-2 was shown to potentiate the beneficial antitumor effects of ionizing radiation with no increase in normal tissue cytotoxicity [113-115]. More recently, metronomic dosing regimens of standard chemotherapeutic agents without extended rest periods were shown to target the microvasculature in experimental animal models and result in significant antitumor activity [116-118]. This antiangiogenic chemotherapy regimen could be enhanced by the concurrent administration of an angiogenesis inhibitor [116-119]. Trials that will evaluate continuous low dose cyclophosphamide in combination with celecoxib are underway in patients with metastatic renal cancer, and non-Hodgkin's lymphoma [120]. Given the safety and tolerability of the selective COX-2 inhibitors, and the potent antiangiogenic properties of these agents, the combination of antiangiogenic chemotherapy with a COX-2 inhibitor warrants clinical evaluation [118, 121, 122]. The effects of selective COX-2 inhibitors on angiogenesis may also be due, in part, to COX-independent mechanisms [123-125]. Several reports have confirmed COX-independent effects of celecoxib, at relatively high concentrations (50 microM), where apoptosis is stimulated in cells that lack both COX-1 and COX-2 [126]. More recently, Song et al. [127] described structural modifications to celecoxib that revealed no association between the COX-2 inhibitory and proapoptotic activities of celecoxib [125]. Some of the COX-independent mechanisms for NSAIDs and selective COX-2 inhibitors include activation of protein kinase G, inhibition of NF-kappa B activation, downregulation of the antiapoptotic protein Bcl-XL, inhibition of PPAR delta, and activation of PPAR gamma. One or more of these COX-independent effects could contribute to the antiangiogenic properties of NSAIDs and selective COX-2 inhibitors. In order to take advantage of both the","PeriodicalId":49661,"journal":{"name":"Progress in Tumor Research","volume":"37 ","pages":"179-92"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000071373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22427233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 122

Potential for combined modality therapy of cyclooxygenase inhibitors and radiation. 环加氧酶抑制剂和放射联合治疗的潜力。

Progress in Tumor Research Pub Date : 2003-01-01 DOI: 10.1159/000071374

Debabrata Saha, Hak Choy

{"title":"Potential for combined modality therapy of cyclooxygenase inhibitors and radiation.","authors":"Debabrata Saha, Hak Choy","doi":"10.1159/000071374","DOIUrl":"https://doi.org/10.1159/000071374","url":null,"abstract":"In conclusion, COX-2 inhibitors have potent anti-tumorigenic activity. Results from animal studies strongly indicate that the likely mechanism for enhanced TGD and TCD50 in tumors treated with radiation and COX-2 inhibitors was the inhibition of angiogenesis. In our recent findings we observed that the antagonists of angiogenesis also inhibited the endogenous as well as phorbol-ester-mediated induction of COX-2 expression in human lung cancer cell lines and that in the xenograft model a combination of angiogenic antagonists and radiation significantly delayed tumor growth [ASCO 2002, Vol. 21 (Part 1); p445a, #1779]. In human tumor models, apoptosis was another mechanism of cell death. Furthermore, it was demonstrated that COX-2 inhibitors could change the intrinsic radiosensitivity of human cancer cells [41]. Therefore, inhibition of angiogenesis by COX-2 inhibitors may be the major mechanism for increased radiation effects in tumors. However, other mechanisms such as changes in tumor perfusion, apoptosis, and an increase in intrinsic radiation sensitivity must also be considered. Inhibitors of COX-2 in combination with radiation therapy may be an alternative strategy that can be tested in clinical trials. The combination of COX-2 inhibitors and radiation suggest a complementary strategy to target angiogenesis while potentially minimizing the impact on quality of life. Currently, the Radiation Therapy Oncology Group [www.rtog.org] is just one of the National Cancer Institute sponsored cooperative groups conducting clinical trials in cervix cancer, lung cancer and brain tumors, using inhibitors of COX-2 in combination with chemotherapy and radiation therapy. These clinical trials will help elucidate the role of this interesting class of agents in combination with cytotoxic therapy for the treatment of cancer.","PeriodicalId":49661,"journal":{"name":"Progress in Tumor Research","volume":"37 ","pages":"193-209"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000071374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22427234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Cyclooxygenase-2: a target for the prevention and treatment of cancers of the upper digestive tract. 环氧化酶-2:预防和治疗上消化道癌症的靶点。

Progress in Tumor Research Pub Date : 2003-01-01 DOI: 10.1159/000071369

Nasser K Altorki, Kotha Subbaramaiah, Andrew J Dannenberg

引用次数: 6

Role of COX-independent targets of NSAIDs and related compounds in cancer prevention and treatment. 非甾体抗炎药cox非依赖性靶点及相关化合物在癌症防治中的作用

Progress in Tumor Research Pub Date : 2003-01-01 DOI: 10.1159/000071377

Jae-Won Soh, I Bernard Weinstein

引用次数: 81

Regulation of COX-2 expression in human cancers. COX-2在人类癌症中的表达调控。

Progress in Tumor Research Pub Date : 2003-01-01 DOI: 10.1159/000071363

Dan A Dixon