Abstract:
:TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF its biological effect on tumor vasculature should be measured rather than its effect on tumor growth. The aim of this study was to assess the effects of a low dose of NGR-TNF (5 ng/kg) on vascular permeability, tumor hypoxia, perfusion and proliferation in lymphoma bearing mice. MRI measurements with blood pool contrast agent showed an increased leakage of the contrast agent from the vasculature in NGR-TNF treated tumors compared with controls (p < 0.05), suggesting NGR-TNF-induced vascular permeability. Immunohistochemical analysis two hours after NGR-TNF treatment showed a decrease in tumor hypoxia (p < 0.1) and an increase in labeling index of the S-phase marker bromodeoxyuridine (p < 0.1), possibly due to an increase in tumor blood flow after NGR-TNF treatment. Although a decrease in tumor hypoxia and an increase in labeling index could have lead to increased tumor growth, in this experiment after one day a decrease in tumor volume was measured. Possibly, the effects on tumor hypoxia and proliferation two hours after treatment are transient and overruled by other, more longlasting effects. For example, the observed increase in vascular permeability may lead to haemoconcentration and increased interstitial pressure, ultimately resulting in an reduction of tumor blood flow and thus a decrease in tumor growth. A beneficial effect of NGR-TNF in combination with other therapeutical agents may therefore critically depend on the sequence and timing of the regimens. Currently, NGR-TNF is being tested in clinical studies.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJdoi
10.1007/s10637-005-4540-2subject
Has Abstractpub_date
2006-01-01 00:00:00pages
27-36issue
1eissn
0167-6997issn
1573-0646journal_volume
24pub_type
杂志文章abstract::In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m2/wk with escalation to 75 mg/m2/wk if there were no adverse effects. Twenty-seven patients were evaluab...
journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
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abstract::Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...
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pub_type: 临床试验,杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,评审
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abstract::In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elem...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00751-1
更新日期:2019-12-01 00:00:00
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0240-8
更新日期:2015-06-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0569-x
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journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
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更新日期:2013-04-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01044-8
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pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00
abstract::Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the ac...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0470-z
更新日期:2017-10-01 00:00:00
abstract::Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2017-06-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
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