Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team.

Dezube, Bruce J.; Roenn, Jamie H. Von; Holden‐Wiltse, Jeanne; Cheung, Tony; Remick, S. C.; Cooley, Timothy P.; Moore, Jonathan M.; Sommadossi, Jean Pierre; Shriver, S.; Suckow, Carol; Gill, Parkash S.

doi:10.1200/jco.1998.16.4.1444

Cited by 117 publications

(35 citation statements)

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“…Indeed clinical trials utilizing two such agents (TNP 470 and thalidomide) are currently ongoing (6,8,9). Recently, lead compounds based on a strategy that aims to cause direct damage to the tumor endothelium resulting in rapid and catastrophic shutdown in the vascular function of the tumor and leading to extensive secondary tumor cell death (11) also have entered clinical trials.…”

Section: Discussionmentioning

confidence: 99%

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Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Rojiani

Rise

et al. 2002

Acta Oncologica

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Section: Discussionmentioning

confidence: 99%

“…When administered once weekly by intravenous infusion, this agent gave partial responses in KS patients (6). More recently, there has been some interest in exploring the clinical utility of thalidomide as an anti-KS agent.…”

mentioning

confidence: 99%

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Rojiani

Rise

et al. 2002

Acta Oncologica

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“…Angiogenesis inhibitors are one group of investigational agents currently being tested in patients with AIDS-related KS. These include fumagillin, thalidomide, the MMP inhibitor COL-3, and imatinib mesylate [23,[75][76][77][78][79]. In the phase I trial of the MMP inhibitor COL-3, tumor response rate was encouraging (44%) and correlated with biomarker evidence of decreased angiogenesis [77].…”

Section: Prognosis and Treatmentmentioning

confidence: 99%

AIDS-Related Malignancies: Emerging Challenges in the Era of Highly Active Antiretroviral Therapy

2005

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Human immunodeficiency virus (HIV)-infected patients are at increased risk of developing cancer, particularly in the later stages of acquired immune deficiency syndrome (AIDS). LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the pathogenesis and clinical presentation of Kaposi's sarcoma, with a special emphasis on Kaposi's sarcoma herpesvirus/human herpesvirus-8, and outline treatment approaches.2. Discuss the pathogenesis, epidemiology, and treatment of AIDS-related lymphomas.3. Discuss the increasing incidence of non-AIDS-defining malignancies such as Hodgkin's lymphoma and plasma cell disorders in patients with HIV infection.4. Explain how, in the era of highly active antiretroviral therapy, both AIDS-related lymphoma and Hodgkin's lymphoma patients may be treated with therapies previously reserved for their immunocompetent counterparts.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on May 11, 2018http://theoncologist.alphamedpress.org/ Downloaded fromThis material is protected by U.S.

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“…A 1ϫ1-cm grid was then added to the digital CAM images and the average number of vessels within 5-7 grids counted as a measure of vascularity. AGM-1470 (a kind gift of the NCI Developmental Therapeutics testing program), a very active anti-angiogenic agent currently undergoing clinical trials for cancer, 51,52) was used as a positive control. Ten ng/embryo AGM-1470 caused 60-70% suppression in angiogenesis in all experiments (data not shown).…”

Section: Synthesis Of Thalidomide Metabolitesmentioning

confidence: 99%

Effects of Putative Hydroxylated Thalidomide Metabolites on Blood Vessel Density in the Chorioallantoic Membrane (CAM) Assay and on Tumor and Endothelial Cell Proliferation.

Marks

Shi

Fry

et al. 2002

Biological & Pharmaceutical Bulletin

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Angiogenesis, the process of blood vessel formation from pre-formed vessels, has recently become a primary target of anticancer therapy. This is due in part to the finding that removing the blood supply to a tumor can not only prevent further growth but can also starve the existing cells to death.2) In the past several years there have been many potential anti-angiogenic agents developed acting by many mechanisms including interruption of growth factor receptor phosphorylation, [3][4][5] growth factor-receptor binding, 6,7) cell adhesion molecule expression and signaling 8,9) and alterations in endothelial cell apoptosis. 10,11) In addition, several agents such as thalidomide have been shown to inhibit angiogenesis by an as yet not fully understood mechanism.12-18) Furthermore, thalidomide has been shown to reduce tumor growth both in model systems [19][20][21] and in patients. [22][23][24][25][26][27][28] Clinically, however, thalidomide has a fairly weak effect as a monotherapy in patients with solid tumors [22][23][24] but is showing tremendous promise against multiple myeloma.25-28) It has been shown that activation of thalidomide by human or rabbit liver enzymes, but not by rat liver enzymes, significantly enhances the anti-angiogenic effect of the drug in rat aortic sections or isolated endothelial cells.29) This is very interesting because thalidomide is virtually non-toxic to rats when given orally (PO). Intraperitoneal (IP), administration however, commonly associated with "first-pass" hepatic metabolism, 30) recapitulates the teratogenic effect of thalidomide in rats. 31)Kenyon et al. 19) also showed that thalidomide given IP was effective as an anti-angiogenic agent in the mouse corneal model, whereas thalidomide given PO was inactive. In addition, thalidomide teratogenesis was only found to occur after activation of the drug by liver enzymes. 13,[32][33][34][35] Furthermore, in a Xenopus oocyte assay of teratogenesis, activation of thalidomide by a single cytochrome P450 enzyme, CYP2E1, lead to a teratogenic compound whereas unactivated thalidomide was non-teratogenic.35) Thus metabolism of thalidomide is critical to its anti-angiogenic and teratogenic activity. However, the identity of the active anti-angiogenic and teratogenic moiety or moieties of thalidomide are still unknown.The goal of this work was to explore the effect of putative hydroxylated thalidomide metabolites on blood vessel density and target cell proliferation. Since the anti-angiogenic activity of thalidomide was first reported, 36) only a limited number of thalidomide metabolites have been tested for antiangiogenic activity. Figure 1 shows known and hypothesized metabolites of thalidomide (structures M1-M8) based on extensive literature review. [37][38][39][40][41][42][43][44][45] Thalidomide can be metabolized through hydrolysis at the glutarimide and/or phthalimide ring to yield metabolites such as M6-M8. Its hydroxylation can occur on glutarimide or phthalimide ring to yield metabolites M1-M5. Interestingly, only metabolites M5...

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Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team.

Cited by 117 publications

References 6 publications

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

Activity of the Vascular Targeting Agent Combretastatin A-4 Disodium Phosphate in a Xenograft Model of AIDS-Associated Kaposi's Sarcoma

AIDS-Related Malignancies: Emerging Challenges in the Era of Highly Active Antiretroviral Therapy

Effects of Putative Hydroxylated Thalidomide Metabolites on Blood Vessel Density in the Chorioallantoic Membrane (CAM) Assay and on Tumor and Endothelial Cell Proliferation.

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