Abstract:
:Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles from multidrug-resistant cells were exposed to two analogs of vinblastine, N-(p-azido-[3,5-3H]benzoyl)-N'-(beta-aminoethyl)vindesine and N-(p-azido-[3-125I]salicyl)-N'-(beta-aminoethyl)vindesine, that could be photoactivated. Our studies show the specific labeling of a 150- to 170-kDa protein in membrane vesicles from two independently selected multidrug-resistant KB cell lines, which was not seen in drug-sensitive parental or revertant cell lines. The labeling of the high molecular weight protein was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at about 1 microM. Photolabeling was also inhibited by 100 microM vincristine or 100 microM verapamil but not by 100 microM colchicine or 100 microM dexamethasone. The data suggest that the 150- to 170-kDa protein may play an important role in the multidrug-resistance phenotype.
journal_name
Proc Natl Acad Sci U S Aauthors
Cornwell MM,Safa AR,Felsted RL,Gottesman MM,Pastan Idoi
10.1073/pnas.83.11.3847subject
Has Abstractpub_date
1986-06-01 00:00:00pages
3847-50issue
11eissn
0027-8424issn
1091-6490journal_volume
83pub_type
杂志文章abstract::The kinetics and order of rearrangements in the gene complex encoding T-cell-receptor beta chains were studied by Southern blot hybridization in a collection of hybridomas derived from fetal thymocytes at various stages of ontogeny (day 14 to day 17). Our results show a steady increase in the frequency of rearranged b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.9.2925
更新日期:1985-05-01 00:00:00
abstract::GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activation of GTPases and may also be critical for the cellular compartmentalization of GTPases. RhoGDI and GDI/D4 are two currently known GDIs for the Rho-subfamily of GTPases. Using their cDNAs to screen a human brain cDNA library under low str...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.9.4279
更新日期:1997-04-29 00:00:00
abstract::The Escherichia coli flagellar motor senses the intracellular concentration of the response regulator CheY-P and responds by varying the bias between its counterclockwise (CCW) and clockwise (CW) rotational states. The response is ultrasensitive with a large Hill coefficient (approximately 10). Recently, the detailed ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804641105
更新日期:2008-08-19 00:00:00
abstract::Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomize...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.15.6868
更新日期:1991-08-01 00:00:00
abstract::We have found a soluble cyclase, using for assay radioactively marked ATP as precursor. The reaction product was isolated by thin-layer chromatography and identified by specific degradation. After homogenization, part of the activity remained in the particulate fraction but could be easily extracted. The cyclase was c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.63.1.86
更新日期:1969-05-01 00:00:00
abstract::Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1408018111
更新日期:2014-07-01 00:00:00
abstract::We compared folding properties of designed protein Top7 and natural protein S6 by using coarse-grained chain models with a mainly native-centric construct that accounted also for nonnative hydrophobic interactions and desolvation barriers. Top7 and S6 have similar secondary structure elements and are approximately equ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0911844107
更新日期:2010-02-16 00:00:00
abstract::Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutraliz...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1707369114
更新日期:2017-07-25 00:00:00
abstract::We report the development of a practical ultrafast allelic profiling assay for the analysis of short tandem repeats (STRs) by using a highly optimized microfluidic electrophoresis device. We have achieved baseline-resolved electrophoretic separations of single-locus STR samples in 30 sec. Analyses of PCR samples conta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.19.10273
更新日期:1997-09-16 00:00:00
abstract::We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.9.3410
更新日期:1990-05-01 00:00:00
abstract::The conversion of cells from a normal phenotype to full malignancy apparently requires multiple genetic events. Efforts to reconstruct multistep tumorigenesis in cell culture have shown that two types of oncogenes (typified by HRAS and MYC) can cooperate to elicit complete transformation. Transformation of embryonic r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.12.4355
更新日期:1988-06-01 00:00:00
abstract::The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1914112117
更新日期:2020-01-07 00:00:00
abstract::The influenza virus hemagglutinin polypeptides, HA1 and HA2, have been purified by gel filtration in the presence of sodium dodecyl sulfate from a vaccine preparation of the recombinant strain Heq1N2. Use of this technique for purification of the hemagglutinin polypeptides eliminated the need for proteolytic agents fo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.1.238
更新日期:1976-01-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717802115
更新日期:2018-02-06 00:00:00
abstract::Retroviruses undergo a high frequency of genetic alterations during the process of copying their RNA genomes. However, little is known about the replication fidelity of other elements that transpose via reverse transcription of an RNA intermediate. The complete sequence of 29 independently integrated copies of the yea...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.15.7767
更新日期:1996-07-23 00:00:00
abstract::Hypnotic analgesia in some respects resembles opiate analgesia. We tested the hypothesis that some features of hypnotic analgesia are mediated through neuronal pathways activating specific opiate receptors in brain. The opiate antagonist naloxone had no effect on hypnotic analgesia in three subjects. Thus, the hypothe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.6.2041
更新日期:1975-06-01 00:00:00
abstract::The complex cooperative behavior exhibited by wild chimpanzees generates considerable theoretical and empirical interest, yet we know very little about the mechanisms responsible for its evolution. Here, we investigate the influence of kinship on the cooperative behavior of male chimpanzees living in an unusually larg...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611449104
更新日期:2007-05-08 00:00:00
abstract::Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for developmen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0409482102
更新日期:2005-05-24 00:00:00
abstract::Marine Archaea are important players among microbial plankton and significantly contribute to biogeochemical cycles, but details regarding their community structure and long-term seasonal activity and dynamics remain largely unexplored. In this study, we monitored the interannual archaeal community composition of abun...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1216863110
更新日期:2013-04-09 00:00:00
abstract::The Watson-Crick model for DNA duplex duplication proposes that the two parental chains separate and that each directs the synthesis of a complementary chain with which it is found associated after the duplication act. Previous experiments have left unchallenged alternative models which propose that in any single act ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.65.2.363
更新日期:1970-02-01 00:00:00
abstract::Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities [Straus, S.E. (1988) J. Inf. Dis. 157, 405-412]. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.7.2922
更新日期:1991-04-01 00:00:00
abstract::Lod scores provide a method to unify linkage tests based on identity by descent and identity in marker state while permitting selection of the most informative individuals through their disease-related phenotypes and markers in relatives. After parametric lods are reviewed, a nonparametric approach that depends on a s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.8.3471
更新日期:1996-04-16 00:00:00
abstract::Enterohemorrhagic Escherichia coli O157 is one of the leading worldwide public health concerns, causing large outbreaks of hemorrhagic colitis as well as numerous small outbreaks and sporadic cases. The variability of restriction enzyme-digestion patterns of O157 genomes, which is widely used to distinguish strains in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.262441699
更新日期:2002-12-24 00:00:00
abstract::Understanding how institutional changes within academia may affect the overall potential of science requires a better quantitative representation of how careers evolve over time. Because knowledge spillovers, cumulative advantage, competition, and collaboration are distinctive features of the academic profession, both...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1121429109
更新日期:2012-04-03 00:00:00
abstract::Among 21 human mammary tumors analyzed for transforming genes by transfection of NIH/3T3 cells, only DNA of a carcinosarcoma cell line, HS578T, registered as positive. A Harvey (H)-ras oncogene identified in this line was cloned in biologically active form and the activating lesion was identified as a single nucleotid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.17.5384
更新日期:1984-09-01 00:00:00
abstract::Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid-protein interactions, and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1611096114
更新日期:2017-02-14 00:00:00
abstract::Exposure of cholera toxin to membrane particles prepared from sarcoma 180 cells gives rise to a variety of fragments which are capable of activating adenylate cyclase [ATP:pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. A major component of these fragments has an apparent molecular weight in the 8,000-10,000 range. The ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.8.2654
更新日期:1976-08-01 00:00:00
abstract::We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.15.7386
更新日期:1993-08-01 00:00:00
abstract::Two deletion-substitution mutations of phage lambda, spi-113 and spi-274, are shown to remove about half of the rightward operator OR. Physiological studies show that spi-113 is still repressible. Thus, the 50 or so nucleotides of OR deleted in this mutant are not absolutely essential for repression. prm-116, which in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.3.712
更新日期:1976-03-01 00:00:00
abstract::Epstein-Barr virus (EBV)-genome-negative human lymphoma lines, Ramos and BJAB, can be converted by EBV in vitro into EBV-genome-positive virus nonproducer lines. These cell lines have been used to identify surface antigens unique to EBV, with the expectation that such determinants might be related to the antigenic tar...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.1.33
更新日期:1984-01-01 00:00:00