Abstract：
:A common form of multidrug resistance in human cancer results from expression of the MDR1 gene which encodes a plasma membrane energy-dependent multidrug efflux pump. We have engineered transgenic mice which express this multidrug transporter in their bone marrow cells and demonstrated that peripheral WBC of these animals provide a rapid and reliable system for assessing the bioactivity of agents that reverse multidrug resistance. Immunocytochemical analysis of bone marrow smears suggests that the activation of the MDR1 transgene has probably occurred at a very early stage of bone marrow differentiation since most bone marrow cells express the transporter. Expression of this transgene in bone marrow produces about 10-fold resistance to leukopenia induced by taxol compared to normal bone marrow. Chemosensitization of MDR1 mice to daunomycin and taxol, measured by a fall in WBC, is detectable at a dose as low as 0.01 mg/kg R-verapamil. A dose of 0.5 mg/kg R-verapamil reduces the WBC by nearly 50%. Chemosensitization of MDR-transgenic mice with 5 mg/kg R-verapamil, which is highly effective in reversing MDR and readily tolerated by mice, necessitates a reduction of the maximum tolerated dose of most chemotherapeutic agents by only 20%. In addition, detailed histopathological examination shows that treatment of mice with chemotherapeutic drugs and R-verapamil does not change the organ-related toxicity pattern but only moderately accentuates inherent toxic side effects of the chemotherapeutic agents. We conclude that MDR1-transgenic mice represent a valid model for evaluating efficacy, potency, and toxicity associated with chemotherapy and chemosensitization of multidrug-resistant cells in animals.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mickisch GH,Licht T,Merlino GT,Gottesman MM,Pastan Isubject
Has Abstractpub_date
1991-10-01 00:00:00pages
5417-24issue
19eissn
0008-5472issn
1538-7445journal_volume
51pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proli...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:The effect of "antiangiogenesis" therapy using cortisone acetate (CA) with or without heparin on tumor growth as well as in combination with chemotherapy was investigated. C3H mice were implanted intradermally with N-[4-(5-nitro-2-furyl)-thiazolyl]formamide induced undifferentiated transitional cell carcinoma, MBT-2, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:To improve tumor:tissue ratios in immunoscintigraphy, a three-step targeting method has been developed. The reagents used were (a) a radioactive, low molecular weight chelate prepared from ionic gallium and a phenolic polyaminocarboxylic acid, which can be labeled either with the single-photon emitter 67Ga or with the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in patients with VHL disease and in the majority of patients with sporadic clear cell renal carcinoma (RCC). Overexpression of transforming growth factor (TGF) beta1 has been observed in patients with several cancers, including RCCs, with serum and urine lev...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:The purpose of these studies was to examine the antiproliferative properties of 16 recombinant human IFN-alpha B/D hybrids against various human tumor lines of different histological origin and to determine whether any of the hybrid molecules possessed immunomodulating activity that could active antitumor properties i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-04-15 00:00:00
abstract：:Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-3163
更新日期：2008-02-15 00:00:00
abstract：:Although apoptosis and necrosis are morphologically distinct manifestations of cell death, apoptosis and some necroses share common features in the death signaling pathway involving functional steps of death-driving interleukin 1beta-converting enzyme family proteases and anti-cell death protein Bcl-2. One evident phy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-15 00:00:00
abstract：:A novel metastasis-associated gene was identified with a differential display system in murine carcinoma cells showing a high rate of metastasis to the liver. A human homologue was also identified using a PCR-based strategy. The protein coded by this gene was named cystatin-like metastasis-associated protein (CMAP) an...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-10-15 00:00:00
abstract：:Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally i...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0412
更新日期：2010-08-01 00:00:00
abstract：:We recently reported that LY294002 (LY29) and LY303511 (LY30) sensitized tumor cells to drug-induced apoptosis independent of the phosphoinositide 3-kinase/Akt pathway. Here, we investigated the mechanism of LY30-induced sensitization of human neuroblastoma cells to TRAIL-mediated apoptosis. We provide evidence that L...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-1996
更新日期：2009-03-01 00:00:00
abstract：:A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
abstract：:Previous results have suggested that methotrexate (MTX) could interfere with the repair of spontaneous DNA damage. To determine its effects on induced DNA damage, MTX was compared to hydroxyurea and arabinofuranosylcytosine (H/A), a drug combination known to block the DNA polymerase step of excision repair, for its ab...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-03-15 00:00:00
abstract：:It had been shown previously that the ribonucleotide reductase from mouse tumor consisted of two nonidentical components (Tris and dye fractions, each prepared from the 20 to 40% (NH/)2SO4 protein fraction containing the ribonucleotide reductase activity by blue dextran-Sepharose chromatography). The individual compon...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-11-01 00:00:00
abstract：:The effect of Adriamycin on the invasive capacity of rat ascites hepatoma cells, W1, was studied. The invasive capacity of W1 cells was estimated in vitro by counting the number of penetrated single tumor cells and tumor cell colonies formed from the penetrated cells underneath a cultured mesothelial cell monolayer (H...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithel...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1807
更新日期：2014-09-15 00:00:00
abstract：:mtCLIC/CLIC4 is a p53 and tumor necrosis factor alpha (TNFalpha) regulated intracellular chloride channel protein that localizes to cytoplasm and organelles and induces apoptosis when overexpressed in several cell types of mouse and human origin. CLIC4 is elevated during TNFalpha-induced apoptosis in human osteosarcom...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2005-01-15 00:00:00
abstract：:The cell cycle stimulation of individual species of the uracil DNA glycosylase was examined in WI-38 normal diploid fibroblasts. The nuclear uracil DNA glycosylase was induced as WI-38 cells traversed the cell cycle. In contrast, the specific activity of the mitochondrial glycosylase remained constant during cell prol...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. ATP citrate lyase (ACLY) is a key enzyme of de novo fatty acid synthesis responsible for generating cytosolic acetyl-CoA and oxaloacetate. To evaluate its role in lung cancer progression, we here analyzed ACLY expression in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-1235
更新日期：2008-10-15 00:00:00
abstract：:Membrane-bound complement inhibitors protect host cells from inadvertent complement attack, and complement inhibitors are often up-regulated on tumors, possibly representing a selective adaptation by tumors to escape elimination by a host antitumor immune response. Relevant in vivo studies using rodent models of human...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-02-15 00:00:00
abstract：:Migration from the primary tumor is a crucial step in the metastatic cascade. Cells with various degrees of adhesion and motility migrate and are launched into the bloodstream as single circulating tumor cells (CTC) or multicellular CTC clusters. The frequency and size distributions of these clusters have been recentl...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-1726
更新日期：2019-11-01 00:00:00
abstract：:Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-10-01 00:00:00
abstract：:Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpressed in human cancer and play an important role in survival signaling. In addition to its involvement with cell survival, VEGFR-3 is a primary factor in lymphatic angiogenesis. Because...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1661
更新日期：2006-02-01 00:00:00
abstract：:The effect of pretreatment with L-asparaginase on the cytotoxicity of methotrexate (MTX) was studied in L5178Y murine leukemic cells and L-929 cells grown in vitro. The results were correlated with the effects of L-asparaginase on DNA synthesis. At low concentrations of the enzyme, pretreatment of cells enhanced the e...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-06-01 00:00:00
abstract：:Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens. Hypersensitivity of beta-pol-deficient cells to methylating agents is because of induction of apoptosis (Ochs et al., Cancer Res., 59: 1544-155...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:Integrins interact with extracellular matrix (ECM) and deliver intracellular signaling for cell proliferation, survival, and motility. During tumor metastasis, integrin-mediated cell adhesion to and migration on the ECM proteins are required for cancer cell survival and adaptation to the new microenvironment. Using st...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-2515
更新日期：2009-04-15 00:00:00
abstract：:Topotecan, a water-soluble semisynthetic analogue of camptothecin, is the first topoisomerase I inhibitor to undergo evaluation in pediatric patients with refractory malignancies. A phase I and pharmacokinetic study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities, the incidence...
journal_title：Cancer research
pub_type： 临床试验,杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:In a preceding paper (D. B. Alexander et al., Cancer Res., 53: 1808-1815, 1993), we demonstrated that the in vitro glucocorticoid inhibition of Con8 mammary tumor cell growth is accompanied by the disruption of a transforming growth factor alpha (TGF-alpha) autocrine loop. This growth suppression response functions in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-04-15 00:00:00
