Abstract:
PURPOSE:Phosphatidylinositol (PtdIns) 3-kinase is an important mediator of many cellular functions. The study of PtdIns 3-kinase has been facilitated by the existence of the potent irreversible inhibitor of p110 PtdIns 3-kinase, wortmannin. The purpose of the study was to investigate the relationship between the cell growth inhibitory activity and antitumor activity of wortmannin and inhibition of PtdIns 3-kinase. METHODS:PtdIns 3-kinase activity was measured in cells and tumors and the effects of wortmannin investigated. RESULTS:Wortmannin inhibited the growth of murine C3H and human MCF-7 mammary tumors in vivo. However, the ability of wortmannin to inhibit C3H tumor growth was not related to inhibition of tumor PtdIns 3-kinase activity. The existence of wortmannin-insensitive PtdIns 3-kinase activity was demonstrated in C3H and MCF-7 cell culture lysates and solid tumors, and normal mouse tissue homogenates. In addition to being resistant to inhibition by wortmannin, MCF-7 cell lysate total PtdIns 3-kinase activity was also resistant to five additional known inhibitors of p110 PtdIns 3-kinase. Partial purification of wortmannin-insensitive PtdIns 3-kinase from MCF-7 cell lysate showed the activity to be independent of the PtdIns 3-kinase p85 regulatory subunit. CONCLUSION:The results of the current study demonstrate that wortmannin can inhibit the growth of murine and human mammary tumors despite the presence of novel wortmannin-insensitive PtdIns 3-kinases in these tissues suggesting that some other target is responsible for wortmannin's antitumor activity.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Lemke LE,Paine-Murrieta GD,Taylor CW,Powis Gdoi
10.1007/s002800051123keywords:
subject
Has Abstractpub_date
1999-01-01 00:00:00pages
491-7issue
6eissn
0344-5704issn
1432-0843pii
90440491.280journal_volume
44pub_type
杂志文章abstract:PURPOSE:Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (U...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-006-0377-4
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND AND AIMS:oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2005-12-01 00:00:00
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doi:10.1007/s00280-015-2869-6
更新日期:2015-11-01 00:00:00
abstract::We studied bioavailability, treatment schedule dependence, and therapeutic efficacy of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine), against murine tumors and human tumor xenografts. The rate of its intestinal absorption was about 50%, and it was immediately metabolized to its parent comp...
journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2001-12-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2010-10-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686012
更新日期:1992-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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更新日期:2006-05-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1999-01-01 00:00:00
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更新日期:2009-12-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1997-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1355-4
更新日期:2011-03-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686174
更新日期:1993-01-01 00:00:00
abstract::Sodium cyanate (NaOCN) at a dose of 250 mg/kg was shown to decrease protein synthesis in P388 leukemia tumor cells to approximately 52% of control values at 2 h and 32% at 5 h after NaOCN administration, without a corresponding decrease in various normal tissues of the tumor-bearing CD2Fl mice. CD2Fl mice that had rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254597
更新日期:1984-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1361-6
更新日期:2011-03-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2014-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2017-10-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
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更新日期:1989-01-01 00:00:00
abstract::Epirubicin (4'-epidoxorubicin), an analogue of doxorubicin (Adriamycin), has established activity in the treatment of small-cell lung cancer (SCLC) when used at doses of 75 to 120 mg/m2 in previously untreated patients. We completed a phase II study of epirubicin (85 mg/m2 given intravenously at 3-week intervals) in 2...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685514
更新日期:1991-01-01 00:00:00
abstract::The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685942
更新日期:1992-01-01 00:00:00
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journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
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更新日期:2016-06-01 00:00:00