SEARCH · PubMed Health

Results for “anticancer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources

PubMed2005

Electrochemical approach of anticancer drugs--DNA interaction.

The interaction of drugs with DNA is among the most important aspects of biological studies in drug discovery and pharmaceutical development processes. In recent years there has been a growing interest in the electrochemical investigation of interaction between anticancer drugs and DNA. Observing the pre and post electrochemical signals of DNA or drug interaction provides good evidence for the interaction mechanism to be elucidated. Also this interaction could be used for the quantification of these drugs and for the determination of new drugs targeting DNA. Electrochemical approach can provide new insight into rational drug design and would lead to further understanding of the interaction mechanism between anticancer drugs and DNA.

Antineoplastic Agents↗

PubMed2005

Molecular organization of the antifungal and anticancer drug 2-(2,4-dihydroxyphenylo)-5,6-dichlorobenzothiazole in solution and in monolayers: an effect of pH.

2-(2,4-Dihydroxyphenylo)-5,6-dichlorobenzothiazol (dHBBT) is a new anticancer, antifungal and antibacterial drug characterised also by cytostatic and anticancer activity. The effect of pH on the molecular organization of dHBBT in monomolecular layers and in solution has been studied by electronic absorption and FT-IR spectroscopies. The analysis of the spectroscopic data suggests that at neutral and at high pH values (pH 6-8) dHBBT appears in the anionic form that prevents the formation of dimers due to the electrostatic repulsion between the molecules.

Antifungal Agents↗

PubMed2006

Cell resensitization after delivery of a cycle-specific anticancer drug and effect of dose splitting: learning from tumour cords.

After a single dose of an anticancer agent, changes due to cell death are expected to occur in the distribution of cells between proliferating and quiescent compartment as well as in the oxygenation and nutritional state of surviving cells. These changes are transient because tumour regrowth tends to restore the pretreatment status. The reoxygenation due to the decrease of oxygen consumption is expected to induce cell recruitment from quiescence into proliferation, and consequently to increase the sensitivity of the cell population to a successive treatment by a cycle-specific drug. In previous papers we proposed a model of the response of tumour cords (cylindrical arrangements of tumour cells growing around a blood vessel of the tumour) to single-dose treatments. The model included the motion of cells and oxygen diffusion and consumption. On the basis of that model suitably extended to better account for the action of anticancer drugs, we study the time course of the oxygenation and of the redistribution of cells between the proliferating and quiescent compartments. By means of simulations of the response to a dose delivered as two spaced equal fractions, we investigate the dependence of tumour response on the spacing between the fractions and on the main parameters of the system. A time window may be found in which the delivery of two fractions is more effective than the delivery of the undivided dose.

Antineoplastic Agents↗

PubMed2004

Antioxidant and anticancer activity of extract from Betula platyphylla var. japonica.

The antioxidant and anticancer properties of a medicinal plant, Betula platyphylla var. japonica were investigated. The total methanol extract of B. platyphylla var. japonica had protective effects against hydrogen peroxide (H2O2) in the Chinese hamster lung fibroblast (V79-4) cell line and induced apoptotic cell death in human promyelocytic leukemia (HL-60) cells, a cancer cell line. B. platyphylla var. japonica extract significantly increased cell viability against H2O2. The extract also showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (IC50 2.4 microg/ml) and lipid peroxidation inhibitory activity (IC50 below 4.0 microg/ml). Furthermore, B. platyphylla var. japonica extract reduced the number of V79-4 cells arrested in G2/M in response to H2O2 treatment and increased the activities of several cellular antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase. Treatment with B. platyphylla var. japonica extract induced cytotoxicity and apoptosis in HL-60 cells, as shown by nucleosomal DNA fragmentation, increases in the subdiploid cell population, and fluorescence microscopy. B. platyphylla var. japonica extract gradually increased the expression of pro-apoptotic Bax and led to the activation of caspase-3 and cleavage of PARP. These findings suggest that B. platyphylla var. japonica exhibits potential antioxidant and anticancer properties.

Animals↗

PubMed2004

Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer.

Cancer prevention and treatment using traditional Chinese medicines have attracted increasing interest. This study characterizes antioxidant activity and phenolic compounds of traditional Chinese medicinal plants associated with anticancer, comprising 112 species from 50 plant families. The improved ABTS(*+) method was used to systematically assess the total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC) of the medicinal extracts. The TEAC values and total phenolic content for methanolic extracts of herbs ranged from 46.7 to 17,323 micromol Trolox equivalent/100 g dry weight (DW), and from 0.22 to 50.3 g of gallic acid equivalent/100 g DW, respectively. A positive, significant linear relationship between antioxidant activity and total phenolic content (all R(2) values>/=0.95) showed that phenolic compounds were the dominant antioxidant components in the tested medicinal herbs. Major types of phenolic compounds from most of the tested herbs were preliminarily identified and analyzed, and mainly included phenolic acids, flavonoids, tannins, coumarins, lignans, quinones, stilbenes, and curcuminoids. These medicinal herbs exhibited far stronger antioxidant activity and contained significantly higher levels of phenolics than common vegetables and fruits. Traditional Chinese medicinal plants associated with anticancer might be potential sources of potent natural antioxidants and beneficial chemopreventive agents.

Antineoplastic Agents, Phytogenic↗

PubMed2006

A new classification system of anticancer drugs - based on cell biological mechanisms.

The arrival of a great number of new anticancer agents has made it necessary to reclassify all of them. We established a new classification system based on cell biological mechanisms. Anticancer drugs were grouped as cytotoxic drug and modifier, which could regulate the interaction of tumor, host and drugs. The modifiers were subdivided into three groups: cell biological modifier which reverses the abnormal biological behaviour of tumor cells, biological response modifier which regulates the host response of tumor and biochemical modulator which affects the host's metabolic pathway of cytotoxic drug to enhance the chemosensitivity or reduce the adverse reaction. Combination with cell biological modifiers and cytotoxic drugs play a double role of killer and rectifier for tumor cells, whereas biological response modifiers and cytotoxic drugs are combined to regulate the tumor-host interaction. Biochemical modulators and cytotoxic drugs are combined to enhance the chemosensitivity or improve the dose of cytotoxic drugs.

Animals↗

PubMed2006

Treatment of solid tumors and metastases by fibrinogen-targeted anticancer drug therapy.

The accumulation of fibrin/fibrinogen and other coagulation factors in and around solid tumors and metastatic foci has been recognized for a century as an aspect of cancer pathology. On this basis, anticoagulants and fibrinolytic agents have been deployed as adjuvant anticancer therapies, but they have proved clinically useful for only a small proportion of tumors and they only control the functions of the coagulant components. Overuse or long-term application of anticoagulants and fibrinolytic agents often lead to undesirable side-effects. Here, we propose that anticancer drugs that act by different mechanisms can inhibit tumor-associated coagulation, and it may be possible to develop drugs that specifically targeting tumor-related coagulation, have specific cytotoxic effects on tumor and metastatic cells. We provide laboratory and clinical evidence supporting the hypothesis and offer proposals for future applications.

Animals↗

PubMed2005

Chemical composition and anticancer activity of leaf essential oil of Myrica gale L.

Myrica gale L. (Myricaceae), a native plant from Canada used in traditional medicine, was extracted by hydrodistillation and the oil was collected after 30 and 60 min. The chemical composition of these two extracts was determined using GC-MS analysis. We identified 53 components and myrcene (23.18-12.14%), limonene (11.20-6.75%), alpha-phellandrene (9.90-6.49%) and beta-caryophyllene (9.31-10.97%) were the major components in the 30- and 60-min fractions, respectively, whereas higher caryophyllene oxide content was detected in the 60-min fraction (9.94%) than in the 30-min fraction (3.47%). The anticancer activities of these extracts were assessed against human lung carcinoma cell line A-549 and human colon adenocarcinoma cell line, DLD-1. The 60-min fraction showed higher anticancer activity against both tumor cell lines with an IC50 value of 88 +/- 1 microg/ml. The 30-min fraction had an IC50 value of 184 +/- 4 microg/ml for A-549 and 160 +/- 3 microg/ml for DLD-1. The higher cell growth inhibition induced by the 60-min fraction, as compared to the 30-min fraction, could be due to sesquiterpene enrichment.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Embryotoxic effects of CKD-602, a new camptothecin anticancer agent, in rats.

CKD-602 is a newly developed camptothecin anticancer agent. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than other camptothecin anticancer agents. The potential of CKD-602 to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred mated females (sperm in vaginal lavage=day 0) were distributed among three treatment groups and a control group. CKD-602 was administered intravenously at dose levels of 0, 5, 20 and 80 microg/kg/d to pregnant rats from days 6 to 15 of gestation. The vehicle control rats received an equivalent volume of 1 ml distilled water with d-mannitol 50mg and tartaric acid 0.06 mg. All dams were subjected to the caesarean section on day 20 of gestation. There were no signs of maternal toxicity or embryotoxicity at 5 microg/kg/d, but at 20 microg/kg/d, there was an increase in relative brain weight. At 80 microg/kg/d, reduced food intake, suppressed body weight and increased weight of spleen were observed in dams. An increase in the resorptions and dead fetuses, a decrease in litter size, fetal and placental weights were also found. In addition, various types of external, visceral and skeletal malformations occurred. Characteristic malformations included absent eye bulge, agnathia, dilated cerebral ventricle, anophthalmia, absent thoracic centrum, fused vertebral arch, fused rib, among others. Visceral and skeletal variations were observed. Retarded ossification of several skeletal districts and delayed ossification of sternebrae, metatarsals and sacrocaudal vertebrae were also observed. The results show that CKD-602 is embryotoxic and teratogenic at a minimally maternally toxic dose, i.e. at 80 microg/kg/d in rats. The no-observed-adverse-effect level (NOAEL) of CKD-602 for developmental toxicity was considered to be 20 microg/kg/d, however, the NOAEL for maternal toxicity was 5 microg/kg/d.

Abnormalities, Drug-Induced↗

PubMed2006

Selecting new health technologies for evaluation: can clinical experts predict which new anticancer drugs will impact Danish health care?

Several countries have systems in place to support the managed entry of new health technologies. The big challenge for these so-called horizon-scanning systems is to select those technologies that require decision support by means of an early evaluation. Clinical experts are considered a valuable source of information on new health technologies, but research on the relevance of their input is scarce. In 2000, we asked six Danish expert oncologists to predict whether a sample of 19 new anticancer drugs would impact Danish health care over the next 5 years. In 2005, we assessed the accuracy of these predictions in a delayed type cross-sectional study. The specificity of the Danish experts' prediction was 1 (95% confidence interval 0.74-1.00) and the sensitivity was 0.63 (0.31-0.86). The negative predictive value was 0.79 (0.52-0.92) and the positive predictive value was 1 (0.57-1.00). This indicates that clinical experts have the ability to predict which new anticancer drugs are unlikely to have an impact. This information can be used to increase the efficiency of selecting new technologies for evaluation. As the experts missed 37% of drugs that are in need of guidance, they should not be relied upon to select drugs relevant for evaluation.

Antineoplastic Agents↗

PubMed2005

Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs.

P-glycoprotein (ABCB1) and breast cancer resistance protein [BCRP (also known as ABCG2)] are drug efflux transporters of the ATP binding cassette (ABC) family of proteins. Both P-glycoprotein and BCRP are located in the apical membrane of epithelial cells (e.g. in the intestinal wall and blood-brain barrier), where they can actively extrude a variety of structurally diverse drugs and drug metabolites. Consequently, the oral uptake and CNS penetration of substrate drugs can be low and variable. Inhibition of P-glycoprotein and/or BCRP is therefore a logical strategy to improve oral absorption, CNS penetration and delivery of anticancer agents to brain tumors or CNS metastases. As outlined in this review, this concept of improved oral pharmacokinetics has been demonstrated extensively for the anticancer drugs paclitaxel and topotecan both in preclinical models and in patients, and improved CNS penetration has been shown for paclitaxel, docetaxel and imatinib in preclinical models.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Multilevel modulation of the mevalonate and protein-prenylation circuitries as a novel strategy for anticancer therapy.

The important role of the mevalonate and protein-prenylation circuitries in the process of carcinogenesis is increasingly being recognized. Accordingly, several enzymes within these pathways have been pharmacologically targeted for anticancer drug development. Despite promising activity in a plethora of preclinical models, clinical evaluation of these agents as monotherapy against various malignancies has been disappointing. Appropriate combinations of inhibitors of isoprenoid biosynthesis, inhibitors of prenylation and postprenylation modifications might be a more clinically effective strategy for anticancer therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties.

It is believed that anticancer and apoptosis inducing properties of green tea are mediated by it's polyphenolic constituents particularly catechins. A number of reports have shown that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is among the most effective chemopreventive and apoptosis-inducing agents present in the beverage. Plant polyphenols are naturally occurring antioxidants but they also exhibit prooxidant properties. Over the last several years we have shown that various classes of plant polyphenols including flavonoids, curcuminoids and tannins are capable of catalyzing oxidative DNA cleavage particularly in the presence of transition metal ions such as copper and iron. With a view to understand the chemical basis of various pharmacological properties of green tea, in this paper we have compared the prooxidant properties of green tea polyphenols--EGCG and EC ((-)-epicatechin). The rate of oxidative DNA degradation as well as hydroxyl radical and superoxide anion formation was found to be greater in the case of EGCG as compared with EC. It was also shown that copper mediated oxidation of EC and EGCG possibly leads to the formation of polymerized polyphenols. Further, it was indicated that copper oxidized catechins were more efficient prooxidants as compared with their unoxidized forms. These results correlate with the observation by others that EGCG is the most effective apoptosis inducing polyphenol present in green tea. They are also in support of our hypothesis that prooxidant action of plant polyphenols may be an important mechanism of their anticancer properties. A model for binding of Cu(II) to EC has been presented where the formation of quinone and a quinone methide has been proposed.

Animals↗

PubMed2003

Hematotoxicity response in rats by the novel copper-based anticancer agent: casiopeina II.

The in vivo toxicity of the novel copper-based anticancer agent, casiopeina II (Cu(4,7-dimethyl-1,10-phenanthroline)(glycine)NO3) (CII), was investigated. Casiopeinas are a family of copper-coordinated complexes that have shown promising anticancer activity. The major toxic effect attributed to a single i.v. administration of CII (5 mg/kg dose) in the rat was an hemolytic anemia (reduced hemoglobin concentration (HB), red blood cell (RBC) count and packed cell volume (PCV) accompanied by a marked neutrophilic leukocytosis) 12 h and 5 days after administration, attributed to a direct erythrocyte damage. Increased reticulocyte levels and presence of normoblasts in peripheral blood 5 days post-administration indicated an effective erythropoietic response with recovery at 15 days. Increase in spleen weight and the morphological evidence of congestion of the red pulp (RP) with erythrocytes (E) resulting in a higher ratio of red to white pulp (WP) was consistent with increased uptake of damaged erythrocytes by the reticuloendothelial system observed by histopathology and electron microscopy. Extramedullary hemopoiesis was markedly increased at 5 days giving further evidence of a regenerative erythropoietic response that had an effective recovery by 15 days. Morphological changes in spleen cellularity were consistent with hematotoxicity, mainly a reduction of the red pulp/white pulp ratio, increase in erythrocyte content at 12 h, and an infiltration of nucleated cells in the red pulp at 5 days, with a tendency towards recovery 15 days after administration. The erythrocyte damage is attributed to generation of free radicals and oxidative damage on the membrane and within cells resulting from the reduction of Cu(II) and the probable dissociation of the CII complex.

Animals↗

PubMed2004

Primary cultures of microglial cells for testing toxicity of anticancer drugs.

Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.

Animals↗

PubMed2005

Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway.

When exposed to DNA-damaging insults such as ionizing radiation (IR) or ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell cycle progression or induce cell death. Here we examined the ability of five commonly used anticancer drugs with different mechanisms of action to activate the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Unexpectedly, although the alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed, after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a phenomena that correlated with increased E2F1 protein levels and consequently enhanced expression of cyclin E. These results reveal a differential impact of various classes of anticancer chemotherapeutics on the Cdc25A-degradation pathway, and indicate that the kinetics of checkpoint induction, and the relative balance of key components within the DNA damage response network may dictate whether the treated cells arrest their cell cycle progression.

Antibiotics, Antineoplastic↗

PubMed2002

Topoisomerase II antagonism and anticancer activity of coordinated derivatives of [RuCl(2)(C(6)H(6))(dmso)].

Topoisomerase II poisoning and anticancer activity by the organometallic compound [RuCl(2)(C(6)H(6))(dmso)] was shown by us in an earlier study [Biochemistry 38 (1999) 4382]. Since high concentrations of this complex were required to achieve either effects, we have synthesized four derivatives of this complex in which the dimethyl sulphoxide group on the ruthenium atom was replaced with pyridine, 3-aminopyridine, p-aminobenzoic acid, and aminoguanidine. Three of these molecules showed enhanced potency of topoisomerase II poisoning and consequently also showed higher anticancer activity in breast and colon carcinoma cells in vitro. Detailed analysis of the molecular action of these compounds on topoisomerase II activity was carried out using the classical relaxation and cleavage activity of the enzyme, which revealed that the compounds poison topoisomerase II by freezing the enzyme and enzyme-cleaved DNA in a ternary "cleavage complex". The cleavage complex is implicated in the anti-neoplastic activity of these compounds. DNA interaction studies showed that these compounds interact with DNA in much the same way as [RuCl(2)(C(6)H(6))(dmso)], by external binding of the DNA helix. This is unlike most other topoisomerase II poisons, which predominantly interact with DNA through intercalation with the double helix.

Animals↗

PubMed2002

Cell-cycle-dependent regulation of CNT1, a concentrative nucleoside transporter involved in the uptake of cell-cycle-dependent nucleoside-derived anticancer drugs.

Most nucleoside-derived anticancer drugs are taken up by the high-affinity Na-dependent nucleoside transporter CNT1. Since such drugs are to some extent cell-cycle-dependent in their cytotoxic action, we examined the relationship between CNT1 expression and cell-cycle progression in the rat hepatoma cell line FAO. Cell cultures were synchronized either at late G1 or early S stages by combining mimosin treatment with either previous synchronization or not by serum starvation. Cell-cycle progression was then assessed by measuring [methyl-3H]thymidine incorporation into DNA and monitoring cyclin E and A protein levels. In these conditions, CNT1 protein amounts increase at the G1-S transition. When cells were synchronized using hydroxyurea (HU), which directly interacts with nucleotide metabolism by inhibiting ribonucleotide reductase, CNT1 protein amounts increased in synchronized cells and remained high during cell-cycle progression. These data indicate that CNT1 adapts to cell-cycle progression and responds to nucleos(t)ide metabolism status, a feature that might contribute to the cytotoxic action of cell-cycle-dependent anticancer drugs.

Animals↗