Abstract：
:Two human ovarian cancer cell lines were established from a patient before (PEO1) and after (PEO4) the onset of resistance to 5-fluorouracil (5-FU)/cisplatin-based chemotherapy. Using growth inhibition assays, we determined that the PEO4 line was almost 5-fold more resistant to 5-FU than the PEO1 line. The addition of either 1 or 20 microM leucovorin did not enhance the growth-inhibitory effects of 5-FU against the resistant PEO4 line. In characterizing the potential mechanisms of 5-FU resistance, we found no differences in thymidylate synthase activity between the two lines using both the 5-fluoro-2'-deoxyuridine-5'-monophosphate-binding and catalytic assays. A 4-hr exposure to 1 microM 5-FU resulted in greater ternary complex formation in the resistant line, and we observed no differences between the two lines in 5-FU incorporation into RNA. However, a 4-hr exposure to 1 microM [3H]5-FU resulted in a 3-fold decrease in 5-FU accumulation in the DNA of the resistant PEO4 line. Cesium sulfate gradient centrifugation was used to more accurately separate and analyze for DNA-incorporated 5-FU metabolites and confirmed that the absolute level of 5-FU in the DNA of the PEO4 cells was markedly decreased (6.5-fold) compared with that of the sensitive PEO1 cell line. Moreover, time course studies demonstrated that the accumulated 5-FU in the DNA of the PEO4 cells was more rapidly removed compared with that in the PEO1 cells. Our findings suggest that decreased 5-FU levels in DNA, in part due to an enhanced removal from DNA, represent a mechanism by which the human ovarian cancer PEO4 line expresses decreased sensitivity to 5-FU.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Chu E,Lai GM,Zinn S,Allegra CJsubject
Has Abstractpub_date
1990-09-01 00:00:00pages
410-7issue
3eissn
0026-895Xissn
1521-0111journal_volume
38pub_type
杂志文章abstract：:The blocking effects of guanethidine on electrically induced, neurally mediated, contractions of the guinea pig vas deferens in vitro could be markedly antagonized by the bee venom polypeptide apamin (20-60 nM), by 0.1 mM methylene blue, and (less regularly) by 0.1-0.15 mM quinine, three substances known to inhibit ca...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:A methylcholanthrene-induced rat sarcoma that can be propagated in vitro or in vivo was evaluated for resistance to antifolates and was found to be relatively resistant to methotrexate and 10-ethyl-10-deazaaminopterin but sensitive to trimetrexate. Rat sarcoma cell extracts contained low levels of dihydrofolate reduct...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:The 5'-flanking region of the mouse mu opioid receptor (MOR) gene has two promoters, referred to as distal and proximal. MOR mRNA is predominantly initiated by the proximal promoter. Previously, several important cis-elements and trans-factors have been shown to play a functional role in the proximal promoter of the M...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008284
更新日期：2005-05-01 00:00:00
abstract：:The activities of phosphorylase kinase and myosin light-chain kinase are regulated by Ca2+ binding to calmodulin. However, differences in the activation properties of the purified enzymes are apparent, since calmodulin binds to phosphorylase kinase in the absence of Ca2+ whereas prior formation of a Ca2+ . calmodulin ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:We studied the mechanism by which the peptide omega-grammotoxin-SIA inhibits voltage-dependent calcium channels. Grammotoxin at concentrations of > 50 nM completely inhibited inward current carried by 2 mM barium through P-type channels in rat cerebellar Purkinje neurons when current was elicited by depolarizations up...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1095
更新日期：1997-12-01 00:00:00
abstract：:The N-methyl-D-aspartate (NMDA) receptor is believed to play a major role in learning and in excitotoxic neuronal damage associated with stroke and epilepsy. Pregnenolone sulfate, a neurosteroid, specifically enhances NMDA-gated currents in spinal cord neurons, while inhibiting receptors for the inhibitory amino acids...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:Cardiac-directed expression of AC6 has pronounced favorable effects on cardiac function possibly not linked with cAMP production. To determine rigorously whether cAMP generation is required for the beneficial effects of increased AC6 expression, we generated a catalytically inactive AC6 mutant (AC6mut) that has marked...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.067298
更新日期：2011-03-01 00:00:00
abstract：:Recent clinical studies reveal that selective agonists of group II metabotropic glutamate (mGlu) receptors have robust efficacy in treating positive and negative symptoms in patients with schizophrenia. Group II mGlu receptor agonists also modulate the in vivo activity of psychotomimetic drugs and reduce the ability o...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.035170
更新日期：2007-08-01 00:00:00
abstract：:Both human ether-à-go-go-related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malig...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.091439
更新日期：2014-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The toxicity of acetaminophen (4'-hydroxyacetanilide), 3,5-dimethylacetaminophen (3'-5'-dimethyl-4'-hydroxyacetanilide), and 2,6-dimethylacetaminophen (2',6'-dimethyl-4'-hydroxyacetanilide) was investigated in hepatocytes isolated from phenobarbital-pretreated rats. At a concentration of 5 mM, acetaminophen was found ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:The cDNA for the rat alpha 1c-adrenergic receptor (AR) has been cloned using a probe derived from the bovine alpha 1c-AR sequence. Clone rB7a has a 2.6-kilobase insert with a 1390-base pair open reading frame and encodes a receptor of 466 amino acids. The cloned receptor has 91% amino acid identity with the bovine alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:In vivo administration of the porphyrogenic agent allylisopropylacetamide (AIA) to phenobarbital-pretreated rats results in marked loss of hepatic cytochrome P-450 content. Using isozyme-selective functional markers, we now show that such loss reflects inactivation of several phenobarbital-inducible and constitutive i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.816
更新日期：1997-05-01 00:00:00
abstract：:The aim of the current study is to determine whether butein (3,4,2',4'-tetrahydroxychalcone) exhibits antiproliferative effects against tumor cells through suppression of the signal transducer and activator of transcription 3 (STAT3) activation pathway. We investigated the effects of butein on constitutive and inducib...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052548
更新日期：2009-03-01 00:00:00
abstract：:We investigated the mechanisms of MDR1 gene activation by CCAAT/enhancer binding protein beta (C/EBPbeta, or nuclear factor for interleukin 6) in human cancer cells. Transfection of the breast cancer cell line MCF-7 and its doxorubicin-selected variant MCF-7/ADR by either C/EBPbeta or C/EBPbeta-LIP (a dominant-negativ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.4.906
更新日期：2004-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:The X-ray and NMR structural study of 3-carbomethoxy rifamycin S5 was undertaken in order to determine whether its low antimicrobial activity was related to a conformation of the molecule which was unfavorable for interaction with bacterial DNA-dependent RNA polymerase. However, the molecule assumes a conformation sim...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Ovarian cancer is the leading cause of death from gynecological malignancy and has the worst prognosis of all gynecological cancers. Vascular endothelial growth factor (VEGF) plays an important role in ovarian cancer development. 9-beta-D-Arabinofuranosyl-2-fluoroadenine (Fara-A), a nucleotide analog, is frequently us...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.66.1.178
更新日期：2004-07-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Small-molecule restoration of wild-type structure and function to mutant p53 (so-called mutant reactivation) is a highly sought-after goal in cancer drug development. We previously discovered that small-molecule zinc chelators called zinc metallochaperones (ZMCs) reactivate mutant p53 by restoring zinc binding to zinc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107409
更新日期：2017-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.018333
更新日期：2006-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:S-Adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) inhibit mitogen-induced proliferative response in liver and colon cancer cells. SAMe and MTA are also proapoptotic in liver cancer cells by selectively inducing Bcl-x(S) expression. The aims of this work were to assess whether these agents are...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054411
更新日期：2009-07-01 00:00:00
abstract：:The seven-transmembrane receptor Smoothened (Smo) is the major component involved in signal transduction of the Hedgehog (Hh) morphogens. Smo inhibitors represent a promising alternative for the treatment of several types of cancers linked to abnormal Hh signaling. Here, on the basis of experimental data, we generated...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.065102
更新日期：2010-10-01 00:00:00
abstract：:We have cloned new 5-Hydroxytryptamine 4 (5-HT4) receptor splice variants from mouse (m5-HT4(e)R and m5-HT4(f)R), rat (r5-HT4(e)R), and human brain tissue (h5-HT4(e)R) which differ, as do the previously described 5-HT4 receptor variants, in the length and composition of their intracellular C termini after the common s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:[3H]Dihydroalprenolol ([3H]DHA) has been used extensively in receptor binding studies to measure beta-adrenergic receptors in the central nervous system. Usually, nonspecific binding has been defined by high concentrations of the beta-adrenergic receptor agonist isoproterenol or antagonists such as alprenolol or propr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
