Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 11 to 20 of 92

Publication Record

Connections

Targeting angiogenesis in advanced non-small cell lung cancer.
Lammers PE, Horn L
(2013) J Natl Compr Canc Netw 11: 1235-47
MeSH Terms: Angiogenesis Inhibitors, Antineoplastic Agents, Biomarkers, Carcinoma, Non-Small-Cell Lung, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Humans, Lung Neoplasms, Neoplasm Staging, Neovascularization, Pathologic, Prognosis, Treatment Outcome
Show Abstract · Added June 26, 2014
Lung cancer is the leading cause of cancer-related mortality in the United States. Over the past 40 years, treatments with standard chemotherapy agents have not resulted in substantial improvements in long-term survival for patients with advanced lung cancer. Therefore, new targets have been sought, and angiogenesis is a promising target for non-small cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody targeted against the vascular endothelial growth factor, is the only antiangiogenic agent currently recommended by NCCN for the treatment of advanced NSCLC. However, several antibody-based therapies and multitargeted tyrosine kinase inhibitors are currently under investigation for the treatment of patients with NSCLC. This article summarizes the available clinical trial data on the efficacy and safety of these agents in patients with advanced lung cancer.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Tumour angiogenesis regulation by the miR-200 family.
Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, Bottsford-Miller J, Liu Y, Kim SB, Unruh A, Gonzalez-Villasana V, Huang L, Zand B, Moreno-Smith M, Mangala LS, Taylor M, Dalton HJ, Sehgal V, Wen Y, Kang Y, Baggerly KA, Lee JS, Ram PT, Ravoori MK, Kundra V, Zhang X, Ali-Fehmi R, Gonzalez-Angulo AM, Massion PP, Calin GA, Lopez-Berestein G, Zhang W, Sood AK
(2013) Nat Commun 4: 2427
MeSH Terms: Angiogenesis Inhibitors, Breast Neoplasms, Cell Movement, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Interleukin-8, Lung Neoplasms, MicroRNAs, Models, Biological, Nanoparticles, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Oligonucleotides, Pericytes, Treatment Outcome
Show Abstract · Added March 10, 2014
The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Retinal angiogenesis suppression through small molecule activation of p53.
Chavala SH, Kim Y, Tudisco L, Cicatiello V, Milde T, Kerur N, Claros N, Yanni S, Guaiquil VH, Hauswirth WW, Penn JS, Rafii S, De Falco S, Lee TC, Ambati J
(2013) J Clin Invest 123: 4170-81
MeSH Terms: Angiogenesis Inhibitors, Animals, Apoptosis, Cell Proliferation, Cell Survival, Cells, Cultured, Hindlimb, Human Umbilical Vein Endothelial Cells, Humans, Imidazoles, Ischemia, Macular Degeneration, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Myocytes, Smooth Muscle, Neovascularization, Physiologic, Piperazines, Rats, Retinal Vessels, Transcriptional Activation, Tumor Suppressor Protein p53
Show Abstract · Added October 9, 2013
Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies.
1 Communities
1 Members
0 Resources
22 MeSH Terms
Emerging paradigms in cardiomyopathies associated with cancer therapies.
Ky B, Vejpongsa P, Yeh ET, Force T, Moslehi JJ
(2013) Circ Res 113: 754-64
MeSH Terms: Angiogenesis Inhibitors, Animals, Anthracyclines, Cardiomyopathies, Cardiotoxins, Humans
Show Abstract · Added March 4, 2015
The cardiovascular care of cancer patients (cardio-oncology) has emerged as a new discipline in clinical medicine, given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies such as anthracyclines and radiation have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of targeted cancer therapies, which were initially thought to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, or overexpression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting human epidermal growth factor receptor-2 (mutated or overexpressed in breast cancer), BCR-ABL (chronic myelogenous leukemia and some cases of acute lymphoblastic leukemia), and c-Kit (gastrointestinal stromal tumor). Other agents targeting more complex malignancies, such as advanced solid tumors, have had successes, but have not extended life to the degree seen with chronic myelogenous leukemia. Years before the first targeted therapy, Judah Folkman correctly proposed that to address solid tumors one had to target the inherent neoangiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the catch-22. Nevertheless, cardio-oncology has the potential to be transformative as the human cardiomyopathies that arise from targeted therapies can provide insights into the normal function of the heart.
0 Communities
1 Members
0 Resources
6 MeSH Terms
Cardio-oncology: it takes two to translate.
Moslehi J, Cheng S
(2013) Sci Transl Med 5: 187fs20
MeSH Terms: Angiogenesis Inhibitors, Animals, Coronary Vessels, Heart, Indoles, Microvessels, Pericytes, Pyrroles, Sunitinib
Added March 4, 2015
0 Communities
1 Members
0 Resources
9 MeSH Terms
Peroxisome proliferator-activated receptor-β/δ regulates angiogenic cell behaviors and oxygen-induced retinopathy.
Capozzi ME, McCollum GW, Savage SR, Penn JS
(2013) Invest Ophthalmol Vis Sci 54: 4197-207
MeSH Terms: Angiogenesis Inhibitors, Animals, Cells, Cultured, Disease Models, Animal, Endothelial Cells, Humans, Oxygen, PPAR delta, PPAR-beta, Rats, Retinal Diseases, Retinal Neovascularization, Retinal Vessels, Sulfones, Thiazoles, Thiophenes
Show Abstract · Added October 9, 2013
PURPOSE - To develop new therapies against ocular neovascularization (NV), we tested the effect of peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) agonism and antagonism on angiogenic behaviors and in human retinal microvascular endothelial cells (HRMEC) and on preretinal NV in rat oxygen-induced retinopathy (OIR).
METHODS - HRMECs were treated with the PPAR-β/δ agonist GW0742 and the antagonist GSK0660. Messenger RNA levels of a PPAR-β/δ target gene, angiopoietin-like-4 (angptl4) were assayed by qRT-PCR. HRMEC proliferation and tube formation were assayed according to standard protocols. OIR was induced in newborn rats by exposing them to alternating 24-hour episodes of 50% and 10% oxygen for 14 days. OIR rats were treated with GW0742 or GSK0660. Angptl4 protein levels were assessed by ELISA and preretinal NV was quantified by adenosine diphosphatase staining.
RESULTS - GW0742 significantly increased angptl4 mRNA, and GSK0660 significantly decreased angptl4 mRNA. GW0742 had no effect on HRMEC proliferation, but caused a significant and dose-responsive increase in tube formation. GSK0660 significantly reduced serum-induced HRMEC proliferation and tube formation in a dose-dependent manner. Intravitreal injection of GW0742 significantly increased total retinal Angptl4 protein, but intravitreal injection of GSK0660 had no effect. Intravitreal injection of GW0742 significantly increased retinal NV, as did GW0742 administered by oral gavage. Conversely, both intravitreal injection and intraperitoneal injection of GSK0660 significantly reduced retinal NV.
CONCLUSIONS - PPAR-β/δ activation exacerbates, and its inhibition reduces, preretinal NV. PPAR-β/δ may regulate preretinal NV through a prodifferentiation/maturation mechanism that depends on Angptl4. Pharmacologic inhibition of PPAR-β/δ may provide a rational basis for therapeutic targeting of ocular NV.
1 Communities
1 Members
0 Resources
16 MeSH Terms
The effect of intracellular protein delivery on the anti-tumor activity of recombinant human endostatin.
Lim J, Duong T, Lee G, Seong BL, El-Rifai W, Ruley HE, Jo D
(2013) Biomaterials 34: 6261-71
MeSH Terms: Amino Acid Sequence, Angiogenesis Inhibitors, Animals, Antineoplastic Agents, Endostatins, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Inbred BALB C, Molecular Sequence Data, NIH 3T3 Cells, Neoplasms, Protein Structure, Tertiary, Recombinant Fusion Proteins
Show Abstract · Added September 3, 2013
Endostatin (ES), a 20 kDa protein derived from the carboxy-terminus of collagen XVIII is a potent angiogenesis inhibitor, but clinical development has been hindered by poor clinical efficacy and insufficient functional information from which to design agents with improved activity. The present study investigated protein uptake by cells as a determinant of ES activity. We developed a cell-permeable ES protein (HM73ES) with enhanced capacity to enter cells by adding a macromolecule transduction domain (MTD). HM73ES inhibited angiogenesis-associated phenotypes in cultured endothelial cells [as assessed by tube formation, wound-healing, cell proliferation and survival assays]. These effects were accompanied by reductions in MAPK signaling (ERK phosphorylation), and in β-Catenin, c-Myc, STAT3, and VEGF protein expression. The cell-permeable ES displayed greater tissue penetration in mice and suppressed the growth of human tumor xenografts to a significantly greater extent than ES protein without the MTD sequence. Our results suggest that anti-angiogenic activities of native ES are limited at the level of protein uptake and/or subcellular localization, and that much of the activity of ES against tumors depends on one or more intracellular functions. This study will inform future efforts to understand ES function(s) and suggest strategies for improving ES-based cancer therapeutics.
Copyright © 2013 Elsevier Ltd. All rights reserved.
0 Communities
3 Members
0 Resources
14 MeSH Terms
Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives.
Bair SM, Choueiri TK, Moslehi J
(2013) Trends Cardiovasc Med 23: 104-13
MeSH Terms: Angiogenesis Inhibitors, Antineoplastic Agents, Cardiotoxins, Cardiovascular Diseases, Humans, Medication Therapy Management, Neovascularization, Pathologic, Patient Care Team, Signal Transduction, Translational Medical Research, Vascular Endothelial Growth Factor A
Show Abstract · Added March 4, 2015
Novel cancer therapies targeting tumor angiogenesis have revolutionized treatment options in a variety of tumors. Specifically, VEGF signaling pathway (VSP) inhibitors have been introduced into clinical practice at a rapid pace over the last decade. It is becoming increasingly clear that VSP inhibitors can cause cardiovascular toxicities including hypertension, thrombosis, and heart failure. This review highlights these toxicities and proposes several strategies in their prevention and treatment. However, we recognize the dearth of data in this area and advocate a multi-disciplinary approach involving cardiologists and oncologists, as well as clinical and translational studies, in understanding and treating VSP-inhibitor associated toxicities.
Copyright © 2013 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
11 MeSH Terms
The novel antiangiogenic VJ115 inhibits the NADH oxidase ENOX1 and cytoskeleton-remodeling proteins.
Venkateswaran A, Friedman DB, Walsh AJ, Skala MC, Sasi S, Rachakonda G, Crooks PA, Freeman ML, Sekhar KR
(2013) Invest New Drugs 31: 535-44
MeSH Terms: Angiogenesis Inhibitors, Cells, Cultured, Cytoskeletal Proteins, Human Umbilical Vein Endothelial Cells, Humans, Indoles, NAD, NADH, NADPH Oxidoreductases, Proteomics, Quinuclidines
Show Abstract · Added March 7, 2014
Targeting tumor vasculature represents a rational strategy for controlling cancer. (Z)-(+/-)-2-(1-benzylindol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol (denoted VJ115) is a novel chemical entity that inhibits the enzyme ENOX1, a NADH oxidase. Genetic and small molecule inhibition of ENOX1 inhibits endothelial cell tubule formation and tumor-mediated neo-angiogenesis. Inhibition of ENOX1 radiosensitizes tumor vasculature, a consequence of enhanced apoptosis. However, the molecular mechanisms underlying these observations are not well understood. Herein, we mechanistically link ENOX1-mediated regulation of cellular NADH concentrations with proteomics profiling of endothelial cell protein expression following exposure to VJ115. Pathway Studios network analysis of potential effector molecules identified by the proteomics profiling indicated that a VJ115 exposure capable of altering intracellular NADH concentrations impacted proteins involved in cytoskeletal reorganization. The analysis was validated using RT-PCR and immunoblotting of selected proteins. RNAi knockdown of ENOX1 was shown to suppress expression of stathmin and lamin A/C, proteins identified by the proteomics analysis to be suppressed upon VJ115 exposure. These data support the hypothesis that VJ115 inhibition of ENOX1 can impact expression of proteins involved in cytoskeletal reorganization and support a hypothesis in which ENOX1 activity links elevated cellular NADH concentrations with cytoskeletal reorganization and angiogenesis.
0 Communities
2 Members
0 Resources
10 MeSH Terms
Management of antiangiogenic therapy-induced hypertension.
de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD
(2012) Hypertension 60: 607-15
MeSH Terms: Angiogenesis Inhibitors, Antihypertensive Agents, Carcinoma, Renal Cell, Combined Modality Therapy, Humans, Hypertension, Indoles, Kidney Neoplasms, Lisinopril, Male, Middle Aged, Nephrectomy, Pyrroles, Sunitinib, Treatment Outcome, Withholding Treatment
Added March 4, 2015
0 Communities
1 Members
0 Resources
16 MeSH Terms