Role of symmetric and asymmetric division of stem cells in developing drug resistance.

Abstract:

:Often, resistance to drugs is an obstacle to a successful treatment of cancer. In spite of the importance of the problem, the actual mechanisms that control the evolution of drug resistance are not fully understood. Many attempts to study drug resistance have been made in the mathematical modeling literature. Clearly, in order to understand drug resistance, it is imperative to have a good model of the underlying dynamics of cancer cells. One of the main ingredients that has been recently introduced into the rapidly growing pool of mathematical cancer models is stem cells. Surprisingly, this all-so-important subset of cells has not been fully integrated into existing mathematical models of drug resistance. In this work we incorporate the various possible ways in which a stem cell may divide into the study of drug resistance. We derive a previously undescribed estimate of the probability of developing drug resistance by the time a tumor is detected and calculate the expected number of resistant cancer stem cells at the time of tumor detection. To demonstrate the significance of this approach, we combine our previously undescribed mathematical estimates with clinical data that are taken from a recent six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myelogenous leukemia. Based on our analysis we conclude that leukemia stem cells must tend to renew symmetrically as opposed to their healthy counterparts that predominantly divide asymmetrically.

authors

Tomasetti C,Levy D

doi

10.1073/pnas.1007726107

subject

Has Abstract

pub_date

2010-09-28 00:00:00

pages

16766-71

issue

39

eissn

0027-8424

issn

1091-6490

pii

1007726107

journal_volume

107

pub_type

杂志文章
  • Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells.

    abstract::Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity...

    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.75.12.6130

    authors: Seifert SC,Gelehrter TD

    更新日期:1978-12-01 00:00:00

  • Spectrum and chemical composition of the remarkable planetary nebula NGC 6537.

    abstract::Observations with the image tube scanner at the Shane 3-m telescope are combined with data obtained with the International Ultraviolet Explorer to assess the spectrum of the remarkable high-excitation planetary nebula NGC 6537. We have analyzed the spectrum of this nitrogen-rich object with the aid of the theoretical ...

    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.82.8.2202

    authors: Feibelman W,Aller LH,Keyes CD,Czyzak SJ

    更新日期:1985-04-01 00:00:00

  • The initial steps of biogenesis of cyanobacterial photosystems occur in plasma membranes.

    abstract::During oxygenic photosynthesis in cyanobacteria and chloroplasts of plants and eukaryotic algae, conversion of light energy to biologically useful chemical energy occurs in the specialized thylakoid membranes. Light-induced charge separation at the reaction centers of photosystems I and II, two multisubunit pigment-pr...

    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.241503898

    authors: Zak E,Norling B,Maitra R,Huang F,Andersson B,Pakrasi HB

    更新日期:2001-11-06 00:00:00

  • Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

    abstract::In the retinae of many vertebrates, there are classes of horizontal cell that probably utilize gamma-aminobutyric acid (GABA) as a neurotransmitter. As with other amino acid transmitter agents, the postsynaptic action of GABA is thought to be terminated by uptake into neurons and glia surrounding the release site. 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.87.22.8945

    authors: Malchow RP,Ripps H

    更新日期:1990-11-01 00:00:00

  • Use of a foreign epitope as a "tag" for the localization of minor proteins within a cell: the case of the immunity protein to colicin A.

    abstract::The immunity protein to colicin A (Cai), which is constitutively expressed at a very low level in Escherichia coli strains, has been studied in recombinant plasmid constructs allowing expression of various immunity fusion proteins under the control of inducible promoters. The 13-amino acid NH2-terminal region of Cai w...

    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.85.3.689

    authors: Geli V,Baty D,Lazdunski C

    更新日期:1988-02-01 00:00:00

  • Crystal structure of lipid phosphatase Escherichia coli phosphatidylglycerophosphate phosphatase B.

    abstract::Membrane-integrated type II phosphatidic acid phosphatases (PAP2s) are important for numerous bacterial to human biological processes, including glucose transport, lipid metabolism, and signaling. Escherichia coli phosphatidylglycerol-phosphate phosphatase B (ecPgpB) catalyzes removing the terminal phosphate group fro...

    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.1403097111

    authors: Fan J,Jiang D,Zhao Y,Liu J,Zhang XC

    更新日期:2014-05-27 00:00:00

  • Brain-wide genetic mapping identifies the indusium griseum as a prenatal target of pharmacologically unrelated psychostimulants.

    abstract::Psychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreERT2-based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetam...

    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.1904006116

    authors: Fuzik J,Rehman S,Girach F,Miklosi AG,Korchynska S,Arque G,Romanov RA,Hanics J,Wagner L,Meletis K,Yanagawa Y,Kovacs GG,Alpár A,Hökfelt TGM,Harkany T

    更新日期:2019-12-17 00:00:00

  • Mutation of gene-proximal regulatory elements disrupts human epsilon-, gamma-, and beta-globin expression in yeast artificial chromosome transgenic mice.

    abstract::Previous studies have defined transcriptional control elements, in addition to the promoters, that both lie near individual human beta-globin locus genes and have been implicated in their differential stage-specific regulation during development (i.e., are believed to directly participate in hemoglobin switching). We ...

    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.94.1.169

    authors: Liu Q,Bungert J,Engel JD

    更新日期:1997-01-07 00:00:00

  • Equitable decision making is associated with neural markers of intrinsic value.

    abstract::Standard economic and evolutionary models assume that humans are fundamentally selfish. On this view, any acts of prosociality--such as cooperation, giving, and other forms of altruism--result from covert attempts to avoid social injunctions against selfishness. However, even in the absence of social pressure, individ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1112324108

    authors: Zaki J,Mitchell JP

    更新日期:2011-12-06 00:00:00

  • DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite.

    abstract::The free radicals nitric oxide and superoxide anion react to form peroxynitrite (ONOO-), a highly toxic oxidant species. In vivo formation of ONOO- has been demonstrated in shock and inflammation. Herein we provide evidence that cytotoxicity in cells exposed to ONOO- is mediated by DNA strand breakage and the subseque...

    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.93.5.1753

    authors: Szabó C,Zingarelli B,O'Connor M,Salzman AL

    更新日期:1996-03-05 00:00:00

  • Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1.

    abstract::Sulfoquinovose (SQ; 6-deoxy-6-sulfoglucose) is the polar head group of the plant sulfolipid SQ-diacylglycerol, and SQ comprises a major proportion of the organosulfur in nature, where it is degraded by bacteria. A first degradation pathway for SQ has been demonstrated recently, a "sulfoglycolytic" pathway, in addition...

    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.1507049112

    authors: Felux AK,Spiteller D,Klebensberger J,Schleheck D

    更新日期:2015-08-04 00:00:00

  • Glutathione transport by inside-out vesicles from human erythrocytes.

    abstract::Purified inside-out vesicles from human erythrocytes were used to investigate the active transport of oxidized glutathione (GSSG). Incubation of vesicles and GSSG in the presence of ATP resulted in the transport of GSSG into the vesicles. When vesicles were incubated with reduced glutathione (GSH), no transport was ob...

    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.77.11.6359

    authors: Kondo T,Dale GL,Beutler E

    更新日期:1980-11-01 00:00:00

  • Intramolecular phenotypic capacitance in a modular RNA molecule.

    abstract::Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mec...

    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.1420902112

    authors: Hayden EJ,Bendixsen DP,Wagner A

    更新日期:2015-10-06 00:00:00

  • Septin assemblies form by diffusion-driven annealing on membranes.

    abstract::Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin filaments elongate and are knitted together into higher-order a...

    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.1314138111

    authors: Bridges AA,Zhang H,Mehta SB,Occhipinti P,Tani T,Gladfelter AS

    更新日期:2014-02-11 00:00:00

  • Neurons in the human amygdala selective for perceived emotion.

    abstract::The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We invest...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1323342111

    authors: Wang S,Tudusciuc O,Mamelak AN,Ross IB,Adolphs R,Rutishauser U

    更新日期:2014-07-29 00:00:00

  • Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice.

    abstract::The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies, including myelody...

    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.1112317108

    authors: Ko M,Bandukwala HS,An J,Lamperti ED,Thompson EC,Hastie R,Tsangaratou A,Rajewsky K,Koralov SB,Rao A

    更新日期:2011-08-30 00:00:00

  • Mercuric ion reduction and resistance in transgenic Arabidopsis thaliana plants expressing a modified bacterial merA gene.

    abstract::With global heavy metal contamination increasing, plants that can process heavy metals might provide efficient and ecologically sound approaches to sequestration and removal. Mercuric ion reductase, MerA, converts toxic Hg2+ to the less toxic, relatively inert metallic mercury (Hg0) The bacterial merA sequence is rich...

    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.93.8.3182

    authors: Rugh CL,Wilde HD,Stack NM,Thompson DM,Summers AO,Meagher RB

    更新日期:1996-04-16 00:00:00

  • A model of the cell-autonomous mammalian circadian clock.

    abstract::Circadian timekeeping by intracellular molecular clocks is evident widely in prokaryotes and eukaryotes. The clockworks are driven by autoregulatory feedback loops that lead to oscillating levels of components whose maxima are in fixed phase relationships with one another. These phase relationships are the key metric ...

    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.0904837106

    authors: Mirsky HP,Liu AC,Welsh DK,Kay SA,Doyle FJ 3rd

    更新日期:2009-07-07 00:00:00

  • ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response.

    abstract::The ATM gene is mutated in the syndrome of ataxia telangiectasia (AT), associated with neurologic dysfunction, growth abnormalities, and extreme radiosensitivity. Insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor with tyrosine kinase activity that can mediate mitogenesis, cell transformation, a...

    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.041416598

    authors: Peretz S,Jensen R,Baserga R,Glazer PM

    更新日期:2001-02-13 00:00:00

  • Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry.

    abstract::Chemical cross-linking mass spectrometry (CXMS) is being increasingly used to study protein assemblies and complex protein interaction networks. Existing CXMS chemical cross-linkers target only Lys, Cys, Glu, and Asp residues, limiting the information measurable. Here we report a "plant-and-cast" cross-linking strateg...

    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.1813574115

    authors: Yang B,Wu H,Schnier PD,Liu Y,Liu J,Wang N,DeGrado WF,Wang L

    更新日期:2018-10-30 00:00:00

  • Rapid, high-level expression of biologically active alpha-trichosanthin in transfected plants by an RNA viral vector.

    abstract::alpha-Trichosanthin, a eukaryotic ribosome-inactivating protein from Trichosanthes kirilowii, inhibits the replication of the human immunodeficiency virus (HIV) in vitro. The alpha-trichosanthin gene was placed under the transcriptional control of a tobamovirus subgenomic promoter in a plant RNA viral vector. Two week...

    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.90.2.427

    authors: Kumagai MH,Turpen TH,Weinzettl N,della-Cioppa G,Turpen AM,Donson J,Hilf ME,Grantham GL,Dawson WO,Chow TP

    更新日期:1993-01-15 00:00:00

  • Deletions of bases in one strand of duplex DNA, in contrast to single-base mismatches, produce highly kinked molecules: possible relevance to the folding of single-stranded nucleic acids.

    abstract::A 32-base-pair (bp) DNA duplex with deletions in one strand, and thus extra bases in the opposing strand, was ligated head-to-tail to produce linear and circular multimers. The electrophoretic mobility of the linear multimers was analyzed in polyacrylamide gels and the size of the circular DNA was determined by electr...

    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.86.13.4833

    authors: Hsieh CH,Griffith JD

    更新日期:1989-07-01 00:00:00

  • Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates.

    abstract::A complete experimental format is given for the reconstitution of human hemoglobin from the separated heme-free alpha- and beta-globin chains (alpha degrees, beta degrees) and hemin, by two alternative routes. Based on their oxygen binding properties, the reaction of the ferri-forms with reducing agent, and the respon...

    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.74.1.64

    authors: Yip YK,Waks M,Beychok S

    更新日期:1977-01-01 00:00:00

  • Cofilin expression induces cofilin-actin rod formation and disrupts synaptic structure and function in Aplysia synapses.

    abstract::Cofilin-actin rods are inclusion-like structures that are induced by certain chemical or physical stresses in cultured cells, and the rods formed in neurons are thought to be associated with neurodegeneration. Here, we cloned an Aplysia cofilin homolog and overexpressed it in cultured neurons. Overexpressed cofilin 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.0507675102

    authors: Jang DH,Han JH,Lee SH,Lee YS,Park H,Lee SH,Kim H,Kaang BK

    更新日期:2005-11-01 00:00:00

  • Antagonistic role of vega1 and bozozok/dharma homeobox genes in organizer formation.

    abstract::During zebrafish development, zygotic gene expression initiated at the midblastula transition converts maternal information on embryo polarity into a transcriptional read-out. Expression of a homeobox gene, vega1, is activated at midblastula transition in all blastomeres, but is down-regulated dorsally before gastrula...

    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.97.22.12121

    authors: Kawahara A,Wilm T,Solnica-Krezel L,Dawid IB

    更新日期:2000-10-24 00:00:00

  • Optical control of an ion channel gate.

    abstract::The powerful optogenetic pharmacology method allows the optical control of neuronal activity by photoswitchable ligands tethered to channels and receptors. However, this approach is technically demanding, as it requires the design of pharmacologically active ligands. The development of versatile technologies therefore...

    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.1318715110

    authors: Lemoine D,Habermacher C,Martz A,Méry PF,Bouquier N,Diverchy F,Taly A,Rassendren F,Specht A,Grutter T

    更新日期:2013-12-17 00:00:00

  • Specific interaction of mutant p53 with regions of matrix attachment region DNA elements (MARs) with a high potential for base-unpairing.

    abstract::Mutant, but not wild-type p53 binds with high affinity to a variety of MAR-DNA elements (MARs), suggesting that MAR-binding of mutant p53 relates to the dominant-oncogenic activities proposed for mutant p53. MARs recognized by mutant p53 share AT richness and contain variations of an AATATATTT "DNA-unwinding motif," w...

    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.95.23.13681

    authors: Will K,Warnecke G,Wiesmüller L,Deppert W

    更新日期:1998-11-10 00:00:00

  • The N terminus of the Drosophila Numb protein directs membrane association and actin-dependent asymmetric localization.

    abstract::Drosophila Numb is a membrane associated protein of 557 amino acids (aa) that localizes asymmetrically into a cortical crescent in mitotic neural precursor cells and segregates into one of the daughter cells, where it is required for correct cell fate specification. We demonstrate here that asymmetric localization 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.94.24.13005

    authors: Knoblich JA,Jan LY,Jan YN

    更新日期:1997-11-25 00:00:00

  • Gene activation in somatic nuclei after injection into amphibian oocytes.

    abstract::Genes that are unexpressed in somatic cells have been activated by injecting cultured cell nuclei of the frog Xenopus laevis into oocytes of the newt Pleurodeles waltlii. The genes that were activated are normally expressed in oocytes but not in cultured cells. Conversely, genes that are normally expressed in cultured...

    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.74.6.2470

    authors: De Robertis EM,Gurdon JB

    更新日期:1977-06-01 00:00:00

  • Cysteine-rich intestinal protein 2 (CRIP2) acts as a repressor of NF-kappaB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis.

    abstract::Chromosome 14 was transferred into tumorigenic nasopharyngeal carcinoma and esophageal carcinoma cell lines by a microcell-mediated chromosome transfer approach. Functional complementation of defects present in the cancer cells suppressed tumor formation. A candidate tumor-suppressor gene, cysteine-rich intestinal pro...

    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.1101747108

    authors: Cheung AK,Ko JM,Lung HL,Chan KW,Stanbridge EJ,Zabarovsky E,Tokino T,Kashima L,Suzuki T,Kwong DL,Chua D,Tsao SW,Lung ML

    更新日期:2011-05-17 00:00:00