Abstract:
:Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galβ1-3GalNAcα-O-TVPAAVVVA) was previously shown to inhibit both normal bladder epithelial as well as T24 bladder carcinoma cell proliferation and heparin-binding epidermal growth factor-like growth factor (HB-EGF) production at low nanomolar concentrations, and an L: -pipecolic acid derivative (Galβ1-3GalNAcα-O-TV-pipecolic acid-AAVVVA) was also shown to inhibit normal bladder epithelial cell proliferation. To better determine their spectrum of activity, we measured the effects of these APF derivatives on the proliferation of cells derived from additional urologic carcinomas (bladder and kidney), non-urologic carcinomas (ovary, lung, colon, pancreas, and breast), and melanomas using a (3)H-thymidine incorporation assay. We also measured the effects of as-APF on cell HB-EGF and matrix metalloproteinase (MMP2) secretion plus cell invasion, using qRT-PCR, Western blot and an in vitro invasion assay. L: -pipecolic acid as-APF and/or as-APF significantly inhibited proliferation of each cell line in a dose-dependent manner with IC(50)'s in the nanomolar range, regardless of tissue origin, cell type (carcinoma vs. melanoma), or p53 or ras mutation status. as-APF also inhibited HB-EGF and MMP2 production plus in vitro invasion of tested bladder, kidney, breast, lung, and melanoma tumor cell lines, in a dose-dependent manner (IC(50) = 1-100 nM). Synthetic APF derivatives are potent inhibitors of urologic and non-urologic carcinoma plus melanoma cell proliferation, MMP2 production, and invasion, and may be useful for development as adjunctive antitumor therapy(ies).
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Koch KR,Zhang CO,Kaczmarek P,Barchi J Jr,Guo L,Shahjee HM,Keay Sdoi
10.1007/s10637-011-9746-xsubject
Has Abstractpub_date
2012-10-01 00:00:00pages
1849-64issue
5eissn
0167-6997issn
1573-0646journal_volume
30pub_type
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journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9130-7
更新日期:2008-10-01 00:00:00
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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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abstract:BACKGROUND AND RATIONALE:Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. METHODS:The primary endpoi...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
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更新日期:2012-02-01 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
doi:10.1007/s10637-009-9237-5
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:To analyze the feasibility of capecitabine with weekly irinotecan and concurrent radiotherapy followed by laparoscopic-total mesorectal excision (LTME) in rectal cancer patients. METHODS:Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (u), spiral abdominal and pe...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9192-6
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abstract::The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synerg...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9727-0
更新日期:2012-08-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1023/a:1010687017717
更新日期:2001-05-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9228-6
更新日期:2009-12-01 00:00:00
abstract::Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173788
更新日期:1984-01-01 00:00:00
abstract::A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicit...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF01275473
更新日期:1992-04-01 00:00:00
abstract:PURPOSE:BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a con...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-010-9498-z
更新日期:2011-12-01 00:00:00
abstract::Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a pha...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-005-2908-y
更新日期:2005-10-01 00:00:00
abstract::Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanom...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9614-0
更新日期:2012-04-01 00:00:00
abstract:PURPOSE:Erlotinib (Tarceva®, OSI-774) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. As high-grade gliomas frequently show amplification, overexpression and/or mutation of EGFR, this drug has been tested in several clinical trials with glioblastoma patients, but unfortunat...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9569-1
更新日期:2012-04-01 00:00:00
abstract::Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0431-6
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
doi:10.1007/BF00874426
更新日期:1993-11-01 00:00:00
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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: 临床试验,杂志文章
doi:10.1007/BF02614222
更新日期:1995-01-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/B:DRUG.0000026259.28395.c2
更新日期:2004-08-01 00:00:00
abstract::Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00177255
更新日期:1990-05-01 00:00:00
abstract::Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00840-1
更新日期:2020-06-01 00:00:00
abstract::A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat wa...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-013-9983-2
更新日期:2014-04-01 00:00:00
abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00179430
更新日期:1985-01-01 00:00:00
abstract::Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9768-4
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-014-0199-x
更新日期:2015-04-01 00:00:00
abstract::We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectiv...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006327302041
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9766-6
更新日期:2012-12-01 00:00:00
abstract:INTRODUCTION:Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-s...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0268-9
更新日期:2015-08-01 00:00:00