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 685 records · Page 38Linked to original sources

PubMed2002

Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometry.

Kahalalide F (KF) is a novel cyclic depsipeptide anticancer drug, which has shown anticancer activity both in vitro and in vivo especially against human prostate cancer cell lines. To characterize the pharmacokinetics of KF during a phase I clinical trial in patients with androgen refractory prostate cancer, a method was developed and validated for the quantitative analysis of KF in human plasma using high-performance liquid chromatography (HPLC) coupled to positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). Microbore reversed-phase liquid chromatography (LC) performed with mobile phases containing trifluoroacetic acid, an additive commonly used for separating peptides, resulted in substantial suppression of the signal for KF on ESI-MS/MS. An alternative approach employing a basic mobile phase provided an excellent response for KF when detected in the positive ion mode. Plasma samples were prepared for LC MS/MS by solid-phase extraction on C(18) cartridges. The LC separation was performed on a Zorbax Extend C(18) column (150 x 2.1 mm i.d., particle size 5 micro m) with acetonitrile -10 mM aqueous ammonia (85 : 15, v/v) as the mobile phase, at a flow-rate of 0.20 ml min(-1). A butyric acid analogue of KF was used as the internal standard. The lower limit of quantitation (LLQ) using a 500 micro l sample volume was 1 ng ml(-1) and the linear dynamic range extended to 1000 ng ml(-1). The inter-assay accuracy of the assay was -15.1% at the LLQ and between -2.68 and -9.05% for quality control solutions ranging in concentration from 2.24 to 715 ng ml(-1). The inter-assay precision was 9.91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature.

Antineoplastic Agents↗

PubMed1992

Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic.

We have developed a new delivery system for sustained release of an anticancer drug (cis-platinum) by enclosure into blocks of porous calcium hydroxyapatite ceramic. The slow release of this drug from this system was confirmed in in vitro experiments. When this system was implanted into normal back muscle, or the tibia, sustained release of cis-platinum was observed during a 12-week period after implantation. The diffusion rate of cis-platinum into blood and other organs (liver, kidney, brain) was less than 10% of that at the implanted site. This delivery system placed into experimental tumors of mice also showed a uniform release of anticancer drug for more than 3 months. Inhibition of tumor growth was more marked after local implantation of this system than after intraperitoneal administration of cis-platinum. These results indicate that this new approach to a drug delivery system may well have an important role in cancer chemotherapy. In bone tumors it is attractive because the mechanical strength of calcium hydroxyapatite ceramic permits partial surgical excision and replacement of the bone defect at the same time.

Animals↗

PubMed2006

Anticancer effects of zoledronic acid against human osteosarcoma cells.

Based on neoadjuvant chemotherapy, the prognosis of osteosarcoma patients has improved dramatically. However, due to therapy resistance in patient subgroups, the development of new treatment strategies is still of utmost importance. The aim of our study was to test the effects of the nitrogen-containing bisphosphonate zoledronic acid (ZOL) on osteosarcoma cell lines (N = 9). Exposure to ZOL at low micromolar concentrations induced a dose- and time-dependent block of DNA synthesis and cell cycle progression followed by microfilament breakdown and apoptosis induction. The ZOL-induced cell cycle accumulation in S phase was accompanied by significant changes in the expression of cyclins and cyclin-dependent kinase inhibitors with a prominent loss of cyclin E and D1. ZOL not only inhibited growth but also migration of osteosarcoma cells. The mevalonate pathway intermediary geranyl-geraniol (GGOH) but not farnesol (FOH) significantly inhibited the anticancer effects of ZOL against osteosarcoma cells. Correspondingly, ZOL sensitivity correlated with the blockade of protein geranylgeranylation indicated by unprenylated Rap1. Overexpression of even high levels of P-glycoprotein, as frequently present in therapy-resistant osteosarcomas, did not impair the anticancer activity of ZOL. Summarizing, our data suggest that ZOL, which selectively accumulates in the bone, represents a promising agent to improve osteosarcoma therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1982

Synthesis, hydrolytic reactivity, and anticancer evaluation of N- and O-triorganosilylated compounds as new types of potential prodrugs.

N- and O-Triorganosilylated compounds related to various anticancer agents were synthesized for evaluation as potential anticancer prodrugs. 1H-NMR and UV kinetic measurements of hydrolytic desilylation were used to correlate relative rates of structural unmasking with steric bulk about the silicon reaction center. The tert-butyldimethylsilyl ester of chlorambucil and a number of O- triorganosilylated carbamate derivatives of nor-nitrogen mustard showed significant activity against P-388 lymphocytic leukemia in mice.

Animals↗

PubMed1987

Cyclic voltammetry of quinolinium salts and related compounds: correlation with structure and anticancer activity.

Cyclic voltammetry data were obtained for 12 salts of quinolines, one pyridine, and one open-chain imine which possess varying degrees of anticancer activity. The structural features include sidechain bis(2-methylthio)vinyl, 2-methylthio-2-aminovinyl, dithioacetic acid, 2-quinolylvinyl, 2-styrylvinyl, and guanidine sulfide functionalities. Reduction potentials ranged from -0.43 to -1.08 V. The electrochemical results are correlated with structure. A possible mechanism of anticancer action is addressed.

Antineoplastic Agents↗

PubMed1975

Oxygen consumption by acrylamide polymerization: a method for rapid screening of anticancer agents.

We have developed a rapid and sensitive method to measure oxygen consumption of tumor cells by acrylamide polymerization. This method could be used as an in vitro screen for potential chemotherapeutic agents. Previous techniques have lacked either the sensitivity or the speed required for use as an effective clinical tool. This method was modified from a technique previously developed in our laboratory for measuring oxygen in blood. Standard anticancer agents were tested against Walker 256 ascites tumor. Ascites was harvested from 20 rats on each of 50 days, incubated briefly with drugs, and acrylamide polymerization time was measured hourly. Individual controls were established for each drug-treated group, and oxygen uptake measured after one hour of incubation. Actinomycin, cyclohexamide, and cytosine arabinoside inhibited tumor cell oxygen consumption by 80%, 40%, and 30%, respectively. These results correlated with the known in vivo effects of these drugs on Walker carcinosarcoma. Therefore, this sensitive method could potentially be used directly on tumor cells removed from biopsy material so that the testing of anticancer drugs could be completed on the day of biopsy.

Acrylamides↗

PubMed1990

Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats.

Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.

Animals↗

PubMed2006

Development and validation of a liquid chromatography method for the simultaneous determination of alpha-tocopherol, retinol and retinyl esters in human serum using a monolithic column for the monitoring of anticancer therapy side effects.

Among other side effects, administration of anticancer agents is accompanied by manifestations of gastrointestinal toxicity and disturbances of antioxidant balance. The monitoring of these toxic effects in clinical practice is impeded by a dearth of reliable laboratory methods. Therefore, a simple and rapid reversed-phase high-performance liquid chromatography procedure for selective and sensitive determination of retinol, a-tocopherol, and retinyl esters (retinyl-palmitate and retinyl-stearate) in blood serum has been developed and presented in this study. A Series 200 LC HPLC instrument from Perkin Elmer (Norwalk, USA) with diode-array detector (DAD) was used for the analysis. Separations of retinol, alpha-tocopherol, retinyl-palmitate, and retinyl-stearate were performed using a Chromolith Performance RP-18e, 100 x 4.6 mm monolithic column from Merck (Darmstadt, Germany). Gradient elution was used at a flow rate of 3 mL/min; the mobile phase was methanol-water (95:5, v/v) for 0-2.1 min and methanol-2-propanol (60:40, v/v) for 2.1-4.9 min. The total time of analysis was 6 min. The injection volume was 20 microL and the analysis was performed at ambient temperature. Detection of retinol, alpha-tocopherol, and retinyl esters was carried out at 325, 295, and 330 nm, respectively. For practical assessment of the method, the vitamin A absorption test was performed on seven healthy controls as well as on six patients with non-small cell lung carcinoma or head and neck carcinoma previously treated by chemotherapy and/or radiotherapy, six patients with rectal carcinoma before chemoradiotherapy, four patients with gastrointestinal stromal tumor (GIST) before treatment with imatinib, and a breast cancer patient with chemotherapy-induced diarrhea. Present data demonstrate the feasibility of large scale HPLC determination of vitamin E, vitamin A, and retinyl esters in human serum using a silica monolithic column, and this method may represent a valuable aid in the laboratory monitoring of the toxicity of anticancer therapy.

Absorption↗

PubMed2005

Histone deacetylation in epigenetics: an attractive target for anticancer therapy.

The reversible histone acetylation and deacetylation are epigenetic phenomena that play critical roles in the modulation of chromatin topology and the regulation of gene expression. Aberrant transcription due to altered expression or mutation of genes that encode histone acetyltransferase (HAT) or histone deacetylase (HDAC) enzymes or their binding partners, has been clearly linked to carcinogenesis. The histone deacetylase inhibitors are a new promising class of anticancer agents (some of which in clinical trials), that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell-cycle arrest, terminal differentiation, and/or apoptosis. This report reviews the chemistry and the biology of HDACs and HDAC inhibitors, laying particular emphasis on agents actually in clinical trials for cancer therapy and on new potential anticancer lead compounds more selective and less toxic.

Acetylation↗

PubMed1995

Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer.

The anticancer agent temozolomide labeled with 13C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-o ne), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization 13C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal models of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.

Animals↗

PubMed2006

Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug.

There has been increasing interest in the potential applications of gold (III) complexes as anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs. Our previous findings demonstrated that gold (III) porphyrin 1a preferentially induced apoptosis in a cancer cell line (SUNE1). In this study, we identified differentially expressed proteins related to the drug's cytotoxic action by comparing the protein alterations induced by gold (III) porphyrin 1a and cisplatin treatments. Several clusters of altered proteins were identified, including cellular structure and stress-related chaperone proteins, proteins involved in reactive oxygen species and enzyme proteins, translation factors, proteins that mediate cell proliferation or differentiation, and proteins participating in the internal degradation systems. Our results indicated that multiple factors leading to apoptosis were involved in drug cytotoxicity in SUNE1 cells. The balance between pro-apoptotic and anti-apoptotic signals determined the final fate of cancer cells.

Antineoplastic Agents↗

PubMed2004

Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cells.

OBJECTIVES: We analyzed the actions of zoledronic acid (10-250 microM) and doxorubicin (10-250 nM) on PC-3 prostate cancer cells using both continuous (48-96 hr) and pulsatile exposures (15 min/day for up to three consecutive days). RESULTS: The proliferation of PC-3 cells was inhibited by either continuous or pulsatile exposures of zoledronic acid in a dose-dependent manner. In contrast, pulsatile exposures of doxorubicin failed to inhibit the growth of PC-3 cells. In addition, the inhibition of PC-3 cells by zoledronic acid was partially neutralized by exogenous administration of geranylgeranyl pyrophosphate (GGPP), however, not by farnesyl pyrophosphate (FPP). Furthermore, exogenous administration of transforming growth factor beta 1 (TGF-beta1), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), and more potently, insulin-like growth factor 1 (IGF-1) inhibited the doxorubicin-induced apoptosis of PC-3 cells. Under identical experimental conditions, these growth factors failed to alter the cytotoxicity of PC-3 cells induced by zoledronic acid. CONCLUSIONS: These data suggest that (i) repetitive and pulsatile (15 min/day) exposure to zoledronic acid inhibited the growth of PC-3 cells, (ii) this anticancer action of zoledronic acid was partially mediated by the attenuation of GGPP production, and (iii) bone microenvironment-related growth factors do not alter the anticancer actions of zoledronic acid on PC-3 cells.

Antibiotics, Antineoplastic↗

PubMed2007

Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer activity.

Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha-aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6, desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2 (P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of the analogs was butanoylated at the N-terminus. The antiproliferative activity of the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer (SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer activity in the above cell lines at concentrations ranging from 0.01 nM to 1 microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a xenograft model of human primary colon cancer in athymic nude mice and was found to cause significant reduction in tumor volume. NMR and molecular dynamics (MD) simulation studies for this analog revealed the presence of a mixed 3(10)/alpha-helical structure. This study demonstrates that the designed BN analogs retain their anticancer activity after the incorporation of the constrained amino acid, Aib, and are potential molecules for future use in cancer therapy and drug targeting.

Amino Acid Sequence↗

PubMed2006

Cytotoxic assays for screening anticancer agents.

In the process of identifying potential anticancer agents, the ability of a new agent is tested for cytotoxic activity against a panel of standard cancer cell lines. The National Cancer Institute (NCI) present the cytotoxic profile for each agent as a set of estimates of the dose required to inhibit the growth of each cell line. The NCI estimates are obtained from a linear interpolation method applied to the dose-response curves. In this paper non-linear fits are proposed as an alternative to interpolation. This is illustrated with data from two agents recently submitted to NCI for potential anticancer activity. Fitting of individual non-linear curves proved difficult, but a non-linear mixed model applied to the full set of cell lines overcame most of the problems. Two non-linear functional forms were fitted using random effect models by both maximum likelihood and a full Bayesian approach. Model-based toxicity estimates have some advantages over those obtained from interpolation. They provide standard errors for toxicity estimates and other derived quantities, allow model comparisons. Examples of each are illustrated.

Antineoplastic Agents↗

PubMed1990

Induction of micronuclei and toxic effects in embryos of pregnant rats treated before implantation with anticancer drugs: cyclophosphamide, cis-platinum, adriamycin.

To evaluate a possible relationship of maternal exposure to anticancer drugs during the preimplantation period to blastopathies and postimplantation embryotoxicity, CD female rats were injected intraperitoneally on day 3 of pregnancy with 15 and 30 mg/kg of cyclophosphamide (CPA), 2 and 4 mg/kg of Adriamycin (ADR), 3 and 6 mg/kg of cis-platinum (Cis-Pt), or with 5 ml/kg of saline. Blastocysts were collected on day 5 of gestation and evaluated for gross morphology, cell number, and micronuclei. Some females were sacrificed on day 21 of pregnancy in order to evaluate postimplantation embryotoxicity. A reduction in cell number/blastocyst was observed only in animals exposed to Cis-Pt 6 mg/kg; vice versa, a dose-related increase of micronuclei and of blastocysts with micronuclei was found in all groups treated with the anticancer agents. A significant increase of postimplantation loss was recorded in the groups treated with high doses of Cis-Pt and ADR, but no clear signs of teratogenicity were observed.

Animals↗

PubMed1995

Charge-transfer chromatographic study of the complex formation of some anticancer drugs with gamma-cyclodextrin.

The interaction between 23 anticancer drugs and gamma-cyclodextrin (gamma-CD) was studied by reversed-phase charge-transfer thin-layer chromatography and the relative strength of interaction was calculated. gamma-CD formed inclusion complexes with 14 compounds, the complex always being more or less hydrophobic than the uncomplexed drug. The inclusion-forming capacity of a drug differed considerably depending on its chemical structure. The linear correlation between the hydrophobicity and the specific hydrophobic surface area of anticancer drugs indicated that they can be considered a homologous series of compounds, although their chemical structures are highly different.

Antineoplastic Agents↗

PubMed2000

Cytotoxicity and biotransformation of the anticancer drug perillyl alcohol in PC12 cells and in the rat.

The cytotoxic monoterpene perillyl alcohol (POH) has anticancer properties. We investigated its cytotoxicity in PC12 cells in relation to its biotransformation. POH is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase to perillaldehyde (PCO) and perillic acid (PCOOH), respectively. Apoptosis was determined by cell cycle (subG(0)G(1)) analysis and AnnexinV staining followed by flow cytometry. PCO caused apoptosis at 200 microM, POH caused apoptosis from 500 microM on, while PCOOH had no effect. The caspase inhibitor zVAD prevented apoptosis. Inhibition of POH oxidation by 4-methylpyrazol did not prevent the apoptotic effect of POH indicating that POH itself is also apoptotic. To find out to what extent POH is metabolized to PCO, the metabolism of POH, PCO, and PCOOH was determined after intravenous injection in the rat and in isolated hepatocytes. Although PCO can form a glutathione conjugate(s), no indication of the formation of GSH conjugates was found either in vivo or in hepatocytes. About 70% of the dose was recovered as glucuronides in bile and urine. PCOOH generated only the acyl glucuronide, while POH and PCO formed both acyl and ether glucuronides. These results indicate that PCO is a major intermediary metabolite of POH in the rat in vivo and suggest that PCO may contribute to the anticancer effect of POH.

Animals↗

PubMed2006

Targeting NF-kappaB in anticancer adjunctive chemotherapy.

After more than three decades of its declaration, the war against cancer still appears far from being won. Although there have been decisive victories in a few battles, such as the one against testicular cancer, the overall result is sobering. Hopes for an imminent cure had been raised among the public by the promises of molecular biology, combinatorial chemistry and high-throughput screening. These promises have manifested themselves in the widely proclaimed strategy of rationally targeted anticancer drug discovery, which may be summarized as the 'one-gene-one target-one drug' approach. Over the years, however, it has gradually become clear that, in most cases, treatment of cancer with a single drug may at best delay progression of the disease but is unlikely to lead to a cure. Thus, it appears that rationally targeted monotherapy will have to be replaced by rationally targeted combination therapy. Inhibitors of NF-kappaB look likely to become an important weapon in the anticancer combination therapy arsenal.

Antineoplastic Agents↗