Abstract：
:Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; however, too often these responses are followed by eventual regrowth of the tumor. This clinical conundrum could be explained by the existence of a tumorigenic cell population that is relatively resistant to these therapies and retains pluripotent status in order to repopulate the original tumor and/or contribute to distant metastasis following treatment. Compelling data from liquid tumors, and more recently from studies focused on solid tumors, now support the existence of such tumorigenic cells (i.e., cancer stem cells) as a distinct subpopulation within the total tumor cell mass. These cancer stem cells (CSCs), as compared to the non-CSC population, have the ability to reconstitute the primary tumor phenotype when transplanted into recipient animals. In addition, data are beginning to emerge demonstrating that many standard-of-care chemotherapeutics are less effective in promoting cell death or cytostasis in these putative cancer stem cells as compared to effects in the non-stem cell cancerous cells. Therefore, targeting these locomotive drivers of tumors, the cancer stem cell population, should be considered a high priority in the continued pursuit of more effective cancer therapies.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Winquist RJ,Boucher DM,Wood M,Furey BFdoi
10.1016/j.bcp.2009.03.020subject
Has Abstractpub_date
2009-08-15 00:00:00pages
326-34issue
4eissn
0006-2952issn
1873-2968pii
S0006-2952(09)00196-8journal_volume
78pub_type
杂志文章abstract：:Resistance to anti-cancer chemotherapies often leads to regional failure, and can be caused by biochemical and/or physiological mechanisms. Biochemical mechanisms include the overexpression of resistance-conferring proteins. In contrast, physiological resistance involves the tumor microenvironment, and can be caused b...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00467-2
更新日期：2003-10-01 00:00:00
abstract：:It is believed that chemotherapeutic agents can enhance the malignancy of treated cancer cells in clinical situations, which is a major problem for chemotherapy. However, the underlying molecular mechanisms are still not fully understood. Here, we demonstrated that chemotherapy up-regulates the levels of spermatogenic...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.07.046
更新日期：2018-10-01 00:00:00
abstract：:Recent studies in our laboratory have revealed that Mn2+ is capable of promoting cell spreading and neurite outgrowth in PC12 cells, a process which is dependent on Mn2+ stimulation of the interaction between extracellular matrix (ECM) components and their corresponding integrin receptors. Since the major ECM proteins...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90534-7
更新日期：1994-04-29 00:00:00
abstract：:[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+) (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase II clinical trials for treatment of lung and ovarian cancers. The structure and DNA binding profile of BBR3464 is different from drugs commonly used clinica...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.12.016
更新日期：2007-05-01 00:00:00
abstract：:To test the association between flavin-containing monooxygenases (FMOs) and osmoregulation, saltwater-adapted euryhaline flounder (Platichthys flesus) were statically exposed to 34 (ambient), 25, and 15 parts per thousand (/1000) salinity for 1 or 2 weeks. FMO activity (thiourea S-oxidase) was assayed in gill and live...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00358-9
更新日期：1996-09-13 00:00:00
abstract：:Caco-2 cells are a widely used model in drug development to study intestinal drug transport and metabolism. Recently, serotonin (5-hydroxytryptamine, 5-HT) has been characterized as a highly selective substrate of human UDP-glucuronosyltransferase UGT1A6 [Krishnaswamy S, Duan SX, von Moltke LL, Greenblatt DJ, Court MH...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.02.010
更新日期：2005-05-01 00:00:00
abstract：:The p53 tumor suppressor protein provides a major anti-cancer defense mechanism, as underscored by the fact that the p53 gene is the most frequent target for genetic alterations in human cancer. Recent work has led to the realization that p53 lies at the hub of a very complex network of signaling pathways, which integ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,收录出版
doi：10.1016/s0006-2952(02)01149-8
更新日期：2002-09-01 00:00:00
abstract：:We report here studies on the regulation of the metabolism of adenosine 3',5'-monophosphate (cAMP) in established and primary cultures of rat pulmonary microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required to achiev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00914-5
更新日期：2002-02-15 00:00:00
abstract：:It has become apparent of late that even in tamoxifen and/or aromatase resistant breast cancers, ERα remains a bona fide therapeutic target. Not surprisingly, therefore, there has been considerable interest in developing Selective ER Degraders (SERDs), compounds that target the receptor for degradation. Currently, ICI...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.03.031
更新日期：2011-07-15 00:00:00
abstract：:The cytoprotective effect of the natural dietary constituent indole-3-carbinol (I-3-C) on carbon tetrachloride (CCl4) mediated hepatotoxicity in mice was examined. I-3-C pretreatment by gavage 1 hr prior to intraperitoneal injection of CCl4 produced a 63% decrease in CCl4-mediated centrolobular necrosis and a related ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90737-x
更新日期：1988-01-15 00:00:00
abstract：:The effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione lev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90419-x
更新日期：1989-06-01 00:00:00
abstract：:gamma-Aminobutyric acid (GABA) uptake was studied in bovine chromaffin cells maintained in primary culture. Uptake was found to be dependent on Na+, but not on K+ and Ca2+ ions; it was found that 2 Na+ ions were necessary for each molecule of GABA transported. 2,4-Dinitrophenol, ouabain and vanadate inhibited GABA upt...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90459-0
更新日期：1989-07-15 00:00:00
abstract：:Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased the expression of tissue factor, a membrane-anchored glycoprotein that initiates blood coagulation on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human monocyte/macrophages. On monocyte/macrophages, oleic acid strongly inhibite...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90118-x
更新日期：1994-07-19 00:00:00
abstract：:Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2005.11.006
更新日期：2006-03-30 00:00:00
abstract：:Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mecha...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90342-g
更新日期：1992-12-01 00:00:00
abstract：:Ephedrine and its alkaloids are used for the treatment of asthma, nasal congestion, and obesity. Ephedrine, with two chiral centers, exists as four isomers that exhibit direct and indirect effects on both alpha- and beta-adrenergic receptors (AR). Our main goal was to study the direct effects of the ephedrine isomers ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00152-5
更新日期：1999-09-01 00:00:00
abstract：:EM012, a semisynthetic phthalideisoquinoline alkaloid, has been recently found to target microtubules and possess anti-cancer activity. In this study, we evaluated the effects of EM012 in combination with the classic microtubule-targeting agent paclitaxel. Our results demonstrated that EM012 enhanced the anti-prolifer...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.08.032
更新日期：2004-12-15 00:00:00
abstract：:3-Morpholino-sydnonimine (SIN-1) is a NO-releasing compound which mimics the effects of cGMP through activation of soluble guanylyl cyclase. Its prodrug, molsidomine (SIN-10), does not release NO but does modulate various cell functions. These findings prompted us to study the effects of SIN-10 and SIN-1 on the respir...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90397-2
更新日期：1992-08-18 00:00:00
abstract：:Several monoclonal antibodies against human liver glutathione S-transferase mu were developed. One of these monoclonal antibodies, called GST-3H4 was further characterized and used in this study. In hepatic tissue, after immunoblotting, GST-3H4 strains a 27 kDa protein with a pI value of 6.2. GST-3H4 recognizes other ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90068-v
更新日期：1990-02-01 00:00:00
abstract：:The N-type voltage-gated calcium channel (Ca(v)2.2) functions in neurons to regulate neurotransmitter release. It comprises a clinically relevant target for chronic pain. We have validated a calcium mobilization approach to assessing Ca(v)2.2 pharmacology in two stable Ca(v)2.2 cell lines: alpha1(B), alpha2delta, beta...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.06.003
更新日期：2006-09-14 00:00:00
abstract：:N-Trifluoroacetyladriamycin-14-valerate (AD 32), a lipophilic, DNA non-binding analog of Adriamycin (ADR), was found to be a potent inhibitor of the membrane-bound enzyme, protein kinase C (PKC). PKC was isolated and purified from human leukemia ML-1 cells, and the enzyme activity was shown to be activated by the tumo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90254-g
更新日期：1992-02-18 00:00:00
abstract：:Understanding the mechanism of resistance to tubulin-targeted anticancer drugs is important for improved chemotherapy. In this work, a colchicine-resistant MCF-7 cell line (MCF-7Col30) was generated by the gradual increment of colchicine treatment and the MCF-7Col30 showed ∼8-fold resistance towards colchicine. MCF-7C...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.02.018
更新日期：2017-05-15 00:00:00
abstract：:A major problem in the treatment of cancer is cellular resistance to cytotoxic drugs. In tumor cells in vitro, the development of multidrug resistance is usually accompanied by increased expression of drug transporters, either P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP(1)). Both proteins bel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00453-6
更新日期：2000-11-15 00:00:00
abstract：:Current epidemiological and experimental studies support a beneficial role of dietary polyphenols in several gastrointestinal diseases, including inflammatory bowel disease. The aim of this study was to gain a better understanding of the effects of a naturally occurring polyphenol, ellagic acid, present in some fruits...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.06.043
更新日期：2011-10-01 00:00:00
abstract：:The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate the genes for proinflammatory mediators and protective antioxidant genes. GSH, a ubiquitous tripeptide t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(00)00392-0
更新日期：2000-10-15 00:00:00
abstract：:The possible role of fluroacetate in the toxicity and antitumour activity of the fluroethylnitrosoureas, BFNU and FCNU has been studied in CBA mice bearing the TLX5 lymphoma either sensitive (TLXS) or resistant (TLXRT) to nitrosoureas. Treatment of mice bearing either TLXS or TLXRT tumours with either BFNU or FCNU cau...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90353-3
更新日期：1985-09-15 00:00:00
abstract：:The cytotoxicity of paracetamol and of its putative toxic metabolite, N-acetyl-p-benzo-quinoneimine (NABQI) have been investigated in hepatocytes from hamster, mouse, rat and human liver. Whereas paracetamol readily caused cell blebbing and a loss of viability in hepatocytes from mouse and hamster, human and rat hepat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90412-6
更新日期：1987-04-01 00:00:00
abstract：:We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90039-l
更新日期：1992-07-07 00:00:00
abstract：:JG-03-14, a substituted pyrrole that inhibits microtubule polymerization, was screened against MCF-7 (p53 wild type), MDA-MB231 (p53 mutant), MCF-7/caspase 3 and MCF-7/ADR (multidrug resistant) breast tumor cell lines. Cell viability and growth inhibition were assessed by the crystal violet dye assay. Apoptosis was ev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.07.003
更新日期：2007-10-01 00:00:00
abstract：:Although clofibrate has been shown to inhibit platelet aggregation that is caused by thrombin, ADP and epinephrine, by blocking the release of arachidonic acid from platelet phospholipids [8], here we have demonstrated that clofibrate enhanced platelet aggregation by arachidonic acid and PLC and reversed the effects o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90434-8
更新日期：1982-06-01 00:00:00
