Abstract:
:Approval of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab by the FDA in 2004 reflected the success of this vascular targeting strategy in extending survival in patients with advanced cancers. However, consistent with previous reports that experimental tumors can grow or recur during VEGF blockade, it has become clear that many patients treated with VEGF inhibitors will ultimately develop progressive disease. Previous studies have shown that disruption of VEGF signaling in tumors induces remodeling in surviving vessels, and link increased expression of angiopoietin-1 (Ang-1) with this process. However, overexpression of Ang-1 in different tumors has yielded divergent results, restricting angiogenesis in some systems while promoting it in others. These data raise the possibility that effects of Ang-1/Tie-2 may be context-dependent. Expression of an Ang-1 construct (Ang1*) did not significantly change tumor growth in our model prior to treatment, although vessels exhibited changes consistent with increased Tie-2 signaling. During inhibition of VEGF, however, both overexpression of Ang1* and administration of an engineered Ang-1 agonist (Bow-Ang1) strikingly protected tumors and vasculature from regression. In this context, Ang-1/Tie-2 activation limited tumor hypoxia, increased vessel caliber, and promoted recruitment of mural cells. Thus, these studies support a model in which activation of Tie-2 is important for tumor and vessel survival when VEGF-dependent vasculature is stressed. Understanding such mechanisms of adaptation to this validated form of therapy may be important in designing regimens that make the best use of this approach.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Huang J,Bae JO,Tsai JP,Kadenhe-Chiweshe A,Papa J,Lee A,Zeng S,Kornfeld ZN,Ullner P,Zaghloul N,Ioffe E,Nandor S,Burova E,Holash J,Thurston G,Rudge J,Yancopoulos GD,Yamashiro DJ,Kandel JJsubject
Has Abstractpub_date
2009-01-01 00:00:00pages
79-87issue
1eissn
1019-6439issn
1791-2423journal_volume
34pub_type
杂志文章abstract::Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer (GC) compared with intestinal-type GC; however, histological typing is currently the only method for distinguishing these two major types of GC. We compared t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2387
更新日期:2014-06-01 00:00:00
abstract::One hundred five patients with clinical stage T2-T4 transitional cell bladder carcinoma who completed either low-dose (20-26 Gy) or high dose (40-50 Gy) preoperative radiotherapy (RT) followed by cystectomy were reviewed. Five-year actuarial survival was 42%, 52%, and 17% for stages T2, T3, and T4, respectively. Five-...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.1.5.555
更新日期:1992-10-01 00:00:00
abstract::Telomeres, repeated DNA sequences (T2AG3)n that guard the ends of chromosomes, serve as a checkpoint for cell-cycle progression and regulate cell senescence and apoptosis. Loss of the telomeric repeats promotes genomic instability, which is the hallmark of most cancer cells. Whether this loss differs among tumor cells...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.15.3.423
更新日期:1999-09-01 00:00:00
abstract::The aim of the present work is to investigate whether microtubule-affecting drugs including vincristine, vinblastine, vindesine and vinorelbine are able to produce an anti-angiogenic effect at non-cytotoxic doses in the same way of taxol. The cytotoxic effects were determined by means of the colorimetric MTT assay, an...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with broad resistance to chemotherapeutic drugs. Krüppel-like factor 4 (KLF4) is a candidate tumor suppressor in PDAC. However, the precise role of KLF4 in gemcitabine resistance of PDAC remains largely unclear. In this study, we demonstrat...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4099
更新日期:2017-10-01 00:00:00
abstract::Induction of differentiation in a variety of model systems is accompanied by cell cycle exit and inhibition of Cdk2 kinase activity. We asked whether inhibition of Cdk2 activity is sufficient to allow differentiation to occur in a non-small cell lung cancer cell line. Treatment of NCI-H358 with flavopiridol, an inhibi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::The Equiguard is a dietary supplement comprised of standardized extracts from nine herbs, respectively, Herba epimedium brevicornum Maxim (stem and leaves), Radix morindae officinalis (root), Fructus rosa laevigatae michx (fruit), Rubus chingii Hu (fruit), Schisandra chinensis (Turz.) Baill (fruit), Ligustrum lucidum ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Peptide hormone relaxin produced in normal and cancer prostate cells can stimulate prostate cancer progression. Suppression of relaxin or relaxin receptor RXFP1 expression inhibited prostate cancer both in vitro and in vivo. RXFP1 is a G protein-coupled receptor with the extracellular low density lipoprotein A (LDL-A)...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1159
更新日期:2011-12-01 00:00:00
abstract::The epidermal growth factor (EGF) receptor (EGFR) is activated by EGF and other EGF-like growth factors, including amphiregulin (AR). We characterized the localization and mitogenic action of AR in T3M4 and COLO-357 human pancreatic cancer cell lines and determined whether the presence of AR in human pancreatic cancer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.6.3.625
更新日期:1995-03-01 00:00:00
abstract::The presence of S-100 protein positive dendritic cells (S-100(+)DC) in primary hepatocellular carcinoma (HCC) were immunohistochemically investigated in relation to clinicopathological factors. The patients who showed a marked infiltration of S-100(+)DC survived longer especially in the group of non-curative resection...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.2.231
更新日期:1994-08-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1112
更新日期:2011-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-07-01 00:00:00
abstract::Phosphorylation of histone H2AX (gammaH2AX) is a sensitive marker of DNA damage, particularly induction of DNA double-strand breaks. Using multiparameter cytometry we explored the effects of doxorubicin (DOX), cisplatin (CDDP) and 5-fluorouracil (5-FU) on four types of endometrioid adenocarcinoma cell lines (HEC-1A, H...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000589
更新日期:2010-05-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF), a secreted endothelial-specific growth factor, and microvessel density was examined in 204 primary non-small cell lung carcinomas. The expression of VEGF was evaluated by immunohistochemical staining using an anti-VEGF antibody. Positive staining was obtained in 125 out of 20...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.6.5.1059
更新日期:1995-05-01 00:00:00
abstract::Medulloblastoma is the most common malignant brain tumor in childhood. The most prevalent chromosomal abnormalities are isochromosome 17q and loss of 17p, the location of the tumor suppressor gene p53. Mutations in the p53 gene in medulloblastoma are relatively infrequent but have recently been correlated to poor prog...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2010.884
更新日期:2011-03-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.2.329
更新日期:1997-02-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.7.4.825
更新日期:1995-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 已发布勘误
doi:10.3892/ijo.2015.3315
更新日期:2016-03-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1860
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000431
更新日期:2009-11-01 00:00:00
abstract::The p53-induced wig-1 gene encodes an unusual nuclear zinc finger protein with high sequence similarity between human, rat and mouse. Wig-1 belongs to a group of proteins with widely spaced zinc fingers that bind double stranded (ds) RNA. We show here that wig-1 is present in Gallus gallus (chicken), Silurana tropical...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract::The potential of arsenic trioxide (As2O3) as a novel therapy against ovarian cancer has been progressively recognized. Its prospective usefulness for treatment of this malignancy either alone or in combination with other chemotherapeutic agents has been increasingly explored. In this study, we attempted to enhance the...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.986
更新日期:2011-06-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4523
更新日期:2018-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1168
更新日期:2012-01-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2009-08-01 00:00:00
abstract::Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.4.883
更新日期:1998-04-01 00:00:00