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 541 records · Page 30Linked to original sources

PubMedDate not supplied

Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells.

Genistein, a principal soy isoflavone, has recently aroused interest in medical research owning to its numerous biochemical properties such as: inhibition of the activity of tyrosine-specific protein kinases and topoisomerase II, estrogenic and antioxidant activity as well as antiproliferative and antiangiogenic effects. Therefore, genistein is extensively investigated as a novel anticancer drug. To improve physicochemical properties of genistein (e.g., water solubility) we have synthesized its complexes with amines. Genistein-piperazine complex (GP) has been then examined whether it exhibits anticancer action against human promyelocytic leukemia cell line (HL-60) cultured in vitro. The parallel study with pure genistein has also been undertaken. Cell proliferation, viability, apoptosis and cell cycle kinetics have been assayed for various drugs concentrations (10-40 microM) and periods of exposure (1-6 days). GP reduced proliferation rate, decreased cell viability and induced apoptotic cell death, in a dose- and time-dependent manner. Flow-cytometric analysis of cell cycle distribution revealed a progressive and sustained accumulation of cells in the G2/M phase that was accompanied by unperturbed protein synthesis. The measured anticancer effects of GP and genistein were qualitatively and quantitatively similar, indicating that genistein-amine complex does not loose the activity of the parent compound.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation?

The cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of procarcinogens and xenobiotics. Human CYP1B1 protein has been detected in a variety of tumors but is not detected in adjacent normal tissues or in liver. This suggests that CYP1B1 could biotransform anticancer agents specifically in the target cells. The interaction between CYP1B1 and 12 commonly used anticancer drugs was screened using an ethoxyresorufin deethylase assay. Four agents were competitive inhibitors of CYP1B1 activity: flutamide (K(i) = 1.0 microM), paclitaxel (K(i) = 31.6 microM), mitoxantrone (K(i) = 11.6 microM), and docetaxel (K(i) = 28.0 microM). Doxorubicin (K(i) = 2.6 microM) and daunomycin (K(i) = 2.1 microM) were mixed inhibitors, while tamoxifen was a noncompetitive inhibitor (K(i) = 5.0 microM). Vinblastine, vincristine, 5-fluorouracil, etoposide, and cyclophosphamide did not inhibit CYP1B1 activity. In vitro incubations with flutamide and CYP1B1 produced a metabolite consistent with 2-hydroxyflutamide. Comparison of kinetic parameters (K(m), K(i), V(max)) for flutamide 2-hydroxylation by CYP1B1, CYP1A1, and CYP1A2 indicate that CYP1B1 could play a major role for flutamide biotransformation in tumors. The results obtained indicate that several anticancer agents inhibit CYP1B1 activity. Drug inactivation by CYP1B1 may represent a novel mechanism of resistance, influencing the clinical outcome of chemotherapy.

Antineoplastic Agents↗

PubMed2001

In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B.

Halichondrin B is a highly potent anticancer agent originally found in marine sponges. Although scarcity of the natural product has hampered efforts to develop halichondrin B as a new anticancer drug, the existence of a complete synthetic route has allowed synthesis of structurally simpler analogues that retain the remarkable potency of the parent compound. In this study, we show that two macrocyclic ketone analogues of halichondrir B, ER-076349 and ER-086526, have sub-nM growth inhibitory activities in vitro against numerous human cancer cell lines as well as marked in vivo activities at 0.1-1 mg/kg against four human xenografts: MDA-MB-435 breast cancer, COLO 205 colon cancer, LOX melanoma, and NIH: OVCAR-3 ovarian cancer. ER-076349 and ER-086526 induce G2-M cell cycle arrest and disruption of mitotic spindles, consistent with the tubulin-based antimitotic mechanism of halichondrin B. This is supported further by direct binding of the biotinylated analogue ER-040798 to tubulin and inhibition of tubulin polymerization in vitro by ER-076349 and ER-086526. Retention of the extraordinary in vitro and in vivo activity off halichondrin B in structurally simplified, fully synthetic analogues establishes the feasibility of developing halichondrin B-based agents as highly effective, novel anticancer drugs.

Animals↗

PubMed2001

4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548), a novel anticancer agent active against tumor cell lines with different resistance mechanisms.

The activity of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548), a new alkycycline with high antitumor activity against a broad range of cancer cells, was evaluated in vitro and in vivo in cells selected for resistance to different anticancer agents. Both in vitro and in vivo, PNU-159548 did retain its activity in cells expressing the multidrug resistance (MDR) phenotype, associated to MIDR-1 gene overexpression or with an alteration in the topoisomerase II gene (altered MDR), independently on the drug used for the selection of the resistant cell line. According to these data, the intracellular uptake of PNU-159548 is not influenced by the presence of MDR-1. PNU-159548 was also active, both in vitro and in vivo, against cells showing resistance to various alkylating agents iincluding cisplatin, cyclophosphamide, and melphalan) and topoisomerase I-inhibitors. Cells defective in nucleotide excision repair, which did show hypersensitivity to treatment with UV irradiation and alkylating agents, showed only a marginally increased sensitivity to PNU-159548. Similarly, the activity of the drug was not influenced by the mismatch repair system, as assessed in two different cellular systems deficient in hMLH1 expression and in which hMLH1 activity was restored by chromosome 3 transfer. The results obtained clearly indicate that the new anticancer agent PNU-159548 is able to overcome the classical mechanisms of resistance emerging after treatment with the most clinically used anticancer agents, and it could represent an alternate choice in the treatment of those tumors refractory to conventional therapy.

Animals↗

PubMed2000

Analysis of the structure-anticancer activity relationship in a set of Schiff bases of macrocyclic 2,6-bis(2- and 4-formylaryloxymethyl)pyridines.

Quantitative estimation of the structure-anticancer activity relationship in a series of macrocyclic Schiff bases of 2,6-bis(formylaryloxymethyl)pyridines was carried out by the topological approach. Correlation equations describing the relationship between the anticancer activity and structural parameters of the molecules studied and descriptors characterizing their structure were obtained on the basis of in vitro screening data. The influence of structure of the investigated substances as reflected by the parameters studied on the anticancer activity, was established.

Antineoplastic Agents↗

PubMed2001

Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation.

The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor (PPAR) gamma ligands, known for their ability to induce adipocyte differentiation and increase insulin sensitivity, also exhibits anticancer properties. Currently, TZDs are being tested in clinical trials for treatment of human cancers expressing high levels of PPARgamma because it is assumed that activation of PPARgamma mediates their anticancer activity. Using PPARgamma(-/-) and PPARgamma(+/+) mouse embryonic stem cells, we report here that inhibition of cell proliferation and tumor growth by TZDs is independent of PPARgamma. Our studies demonstrate that these compounds block G(1)-S transition by inhibiting translation initiation. Inhibition of translation initiation is the consequence of partial depletion of intracellular calcium stores and the resulting activation of protein kinase R that phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2), thus rendering eIF2 inactive. PPARgamma-independent inhibition of translation initiation most likely accounts for the anticancer properties of thiazolidinediones.

3T3 Cells↗

PubMed2001

Anticancer effect of a lentiviral vector capable of expressing HIV-1 Vpr.

A lentiviral vector capable of expressing the HIV-1 vpr gene (Vpr lentiviral vector) was constructed, and its in vivo anticancer effect was determined against cutaneous tumors derived from the AT-84 oral cancer cells in immunocompetent mice. A single intratumoral injection of the Vpr lentiviral vector not only significantly reduced the primary tumor volume but also completely regressed tumors in >40% of animals. More interestingly, the mice of which the primary tumors were completely regressed by the Vpr lentiviral vector were additionally protected from a secondary challenge of AT-84 cells. These data suggest that the Vpr lentiviral vector elicits its anticancer activity in part by the activation of the immune system. The above suggestion is additionally supported by the failure of the lentiviral vector to demonstrate anticancer activity in immunocompromised nude or SCID mice. The Vpr lentiviral vector offers a powerful new strategy for cancer gene therapy and may be useful for the control of solid tumors, such as human oral squamous cell carcinomas.

Animals↗

PubMedDate not supplied

Clinical evaluation of granisetron as an inhibitor of nausea and vomiting induced by oral anticancer drugs.

In order to inhibit the nausea and vomiting induced by oral anticancer drugs, granisetron was administered orally at a dose of 2 mg once a day, and its usefulness and safety were evaluated. The subjects were 26 outpatients with gastric or colon cancer receiving chemotherapy with oral anticancer drugs and complaining of gastrointestinal symptoms. A record sheet was handed to the patients. In comparison with the condition before treatment, the patients were instructed to indicate on the record sheet the severity of nausea (4 grades), presence or absence of vomiting, and degree of appetite (4 grades) after treatment, and thereby to evaluate the clinical efficacy or antiemetic effect every day in accordance with clinical efficacy evaluation criteria of 4 grades (very effective, effective, slightly effective, and ineffective). i) Nausea disappeared in 47.8% of the patients on the 1st day of treatment and in 65.2% on the 5th day of treatment. ii) Vomiting was observed in 2 and 3 patients on the 1st and 3rd day, respectively, but not on the 4th day of treatment or thereafter. iii) The efficacy rate, comprising both very effective and effective, was 69.5% on the 1st day of treatment, and increased gradually to reach 78.2% on the 5th day of treatment. iv) There was no adverse reaction or abnormality of laboratory test values attributable to granisetron. Granisetron was safe and effective against nausea and vomiting induced by oral anticancer drugs.

Administration, Oral↗

PubMed2002

The role of the proteasome in apoptosis induced by anthracycline anticancer agents.

To elucidate the involvement of proteasome inhibition in apoptosis induced by anthracycline anticancer agents, we investigated the interaction between the proteasome and anthracycline anticancer agents, and the function of the proteasome in apoptosis. Exposure of L1210 mouse lymphocytic leukemia cells to adriamycin (ADM) or 4'-O-tetrahydropyranyladriamycin (THP) resulted in apoptosis in a dose-dependent manner: 5 microM ADM and 0.5 microM THP induced apoptosis efficiently, but the effects of 10 microM ADM and 5 microM THP were markedly decreased or completely absent. Carbobenzoxy-leucyl-leucyl-leucinal (Z-LLLal), a specific proteasome inhibitor, also induced dose-dependent apoptosis of the cells. The inhibitory effect of THP on chymotrypsin-like protease activity of proteasomes purified from the cytosol of L1210 cells was stronger than that of ADM. Both of these agents showed reversible non-competitive inhibitory effects. The intracellular content of ubiquitinated protein increased in ADM-, THP- or Z-LLLal-treated L1210 cells during apoptosis. These results suggested that anthracycline anticancer agents induce apoptosis by interacting, at least in part, with proteasomes.

Animals↗

PubMed2002

[Anticancer chemotherapy containing cisplatin in patients with lung cancer and kidney function].

To carry out safe anticancer chemotherapy one should consider the kidney function. Insufficiency of that main organ responsible for drugs excretion, caused either by neoplastic disease or by chemotherapy, can diminish the possibility or even make impossible of carrying out a complete treatment cycle. The aim of our work was to evaluate the kidney function in patients with lung cancer during anticancer chemotherapy containing cisplatin. The tubular function was studied by estimation the activity of N-acetyl-beta-D-glucosaminidase in urine and glomerular function was studied by estimation the concentration of creatinine in urine, urea, uric acid and electrolytes in plasma. The observations have recorded that neoplastic process, as well as chemotherapy impaired the tubular function. It has showed that it does exist a necessity of detailed estimation of kidney excretory function before, during and after the end of anticancer therapy. Determination of NAG activity in urine may be helpful for the recognition of the patients at high nephrotoxicity risk, who need special care.

Acetylglucosaminidase↗

PubMed2002

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents.

This study reports that a selective COX-2 inhibitor JTE-522inhibits both in vitro and in vivo growth of human lung cancer cells as a single agent. Furthermore, the adjunct use of JTE-522 is shown to significantly enhance treatment efficacy of conventional anticancer drugs not only in vitro but also in vivo without causing any noticeable side effects. Indeed, IC(50)s of various anticancer agents in vitro were reduced by up to 70%, whereas the combination therapy of JTE-522 with docetaxel and vinorelbine inhibited tumor growth in vivo by 65 and 55%, respectively. Taken together, these findings suggest that the use of a selective COX-2 inhibitor in the treatment of lung cancer may be promising, especially because of its enhancement of the treatment efficacy of conventional anticancer agents without compromising quality of life.

Adenocarcinoma↗

PubMed2002

Effect of dosage of anticancer agents during transcatheter arterial chemoembolization on T cell subsets in patients with hepatocellular carcinoma.

OBJECTIVE: To investigate the effects of the dosage of anticancer agents during transcatheter arterial chemoembolization (TACE) on the T cell subsets in patients with hepatocellular carcinoma (HCC). METHODS: Thirty-six patients with unresectable HCC were randomly divided into 2 groups to receive superselective TACE. Patients in group A (n=18) received low-dose (2-4 mg) mitomycin C (MMC) as the anticancer drug when the tumor was less than 5 cm in diameter; when the tumor ranged from 5 and 8 cm in diameter, 4-6 mg MMC along with 10 mg epirubicin (EPI) was given, and in cases of even larger tumors, 6-8 mg MMC, 10 mg EPI and 100 mg CBP were prescribed. Conventional chemotherapy regimen constituted by 10 mg MMC, 40 mg PI and 300 mg CBP was adopted in group B (n=18). The peripheral blood T cell subsets including CD3(+), CD4(+), CD8(+), NK, CD4(+)/CD8(+) ratio, CD4(+)CD45(+), CD4(+)CD29(+), CD8(+)CD28(+) and CD8(+)CD28- were measured by flow cytometry in both groups before and one week after treatment. RESULTS: The T cell subsets were comparable in the 2 groups before the treatment. After TACE, no significant changes occurred in CD3(+), CD4(+), CD8(+), NK, CD4(+)/CD8(+), CD4(+)CD29(+) or CD8(+)CD28- cells in group A, while significant decrease in CD4(+)CD45(+) and increase in CD8(+)CD28(+) cells were observed (P<0.05 and P<0.001, respectively). In group B, CD4(+) and CD4(+)CD29(+) levels, together with CD4(+)/CD8(+) ratio, were significantly lower than those before treatment (P<0.05), but CD8(+) and CD8(+)CD28- subsets were significantly higher (P<0.05). CONCLUSIONS: The cellular immune function of HCC patients is significantly impaired by anticancer drugs for TACE at conventional dose, while low-dose of the drugs may enhance the cellular immune function.

Adult↗

PubMed2002

Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.

The PRL family oncogenic phosphatases are attractive targets for developing inhibitors as anticancer therapeutics given their potentially pathogenic role in human malignancies. Herein we demonstrate that pentamidine, an anti-protozoa drug with an unknown mechanism of action, is an inhibitor of PRLs with anticancer potential. Pentamidine at its therapeutic doses inhibited recombinant PRL phosphatases in vitro and inactivated ectopically expressed PRLs in NIH3T3 transfectants with an effective duration more than 24 h after a pulse cell treatment. The drug had in vitro growth-inhibitory activity against human cancer cell lines that express the endogenous PRLs. Pentamidine at a tolerable dose markedly inhibited the growth of WM9 human melanoma tumors in nude mice coincident with the induction of tumor cell necrosis and is capable of inactivating ectopically expressed PRL-2 in the cancer cells. These observations suggest the potential of pentamidine in anticancer therapies and may provide a basis for developing novel PTPase-targeted therapeutics.

3T3 Cells↗

PubMed2002

[Practical control methods for the dose individualization of anticancer drugs].

Most anticancer drugs are characterized by a narrow therapeutic index, wide inter-patient variability of pharmacokinetic parameters and high toxicity. The need for dose individualization of anticancer drugs is now well accepted. The strategies that can be employed for optimizing dosage regimen were reviewed. The aim of this paper was to provide an insight into the feasibility of these techniques in anticancer chemotherapy and their application at all stages of clinical trials and practice.

Antineoplastic Agents↗

PubMed2001

[Study on anticancer activity of Syngnathus in vitro].

OBJECTIVE: To study the anticancer activity of Syngnathus in vitro. METHOD: Observing the influence of different extracts from Syngnathus on growth of different cancer cell strains by MTT method. RESULT: It has been found out that the fat-soluble nonsaponified extract from Temminck et Schlegel and the alcoholic extract from Syngnathus acus have cytotoxic activities. The nonsaponified extract from Temminck et Schlegel can inhibit the growth of cancer cell strains KB, Hela, PAA, K562, and Bcap37, and the alcoholic extract from Syngnathus acus can inhibit the growth of cancer cell strin KB, But Bloch shows no apparent anticancer activity. CONCLUSION: Syngnathus has promising prospects as an anticancer Chinese medicine.

Animals↗

PubMed2002

Synthesis of some new bis-thiazoles as possible anticancer agents.

Several new 5-(2,3-dihydrothiazol-2-yledinyl)rhodanines 3a-c and 5-(4-oxothiazolidinon-2-ylidenyl)rhodanine 4 were synthesized through the reaction of 5-thiocarbamoyl rhodanines 2 with phenacyl bromides or chloroacetic acid, respectively. The synthesis of the arylidene derivatives 5a-c were also described. The 5-(4-amino-5-cyano-2,3-dihydrothiazol-2-yledinyl)rhodanines 10a, b were obtained through reaction of rhodanines 1a, b with thiazolium salt 9. All the prepared compounds were screened for their anticancer activity using the NCI in vitro anticancer screening program. Three compounds showed promising anticancer activity against particular human cell lines used in the assay.

Antineoplastic Agents↗

PubMed2002

[The anticancer effect of artesunate and its mechanism].

AIM: To study the anticancer effect of artesunate and its mechanism. METHODS: To observe the effect of artesunate on the growth of solid tumor and the expression of PCNA, Bcl-2 and Bax genes in mice bearing H22 solid hepatic carcinoma. RESULTS: After administration of artesunate (ig, 300 mg.kg-1.d-1 x 7 d), growth of solid tumor was obviously inhibited, the tumor inhibitory rates were 49.1%, 48.7% and 46.6% and 46.6% in 3 experiments. The apoptosis of liver cancer cells were increased. Immunohistochemical staining showed that the number of Bcl-2 protein positive cells were decreased, but the number of Bax protein positive cells were increased. The PCNA positive cells were significantly lower than those in the control group. CONCLUSION: Artesunate showed obvious anticancer activity on H22 hepatic carcinoma bearing mice and undergo apoptosis of liver cancer cells. The mechanism of anticancer effect of artesunate may be related to down-regulation of the expression of PCNA and Bcl-2 genes and up-regulation of the expression of Bax gene.

Animals↗

PubMed2002

[Synthesis of 4-, 6- or 7-substituted phenyliminomethylenecoumarins and their anticancer activities].

AIM: A series of substituted phenyliminomethylenecoumarins derivatives was designed in order to find compounds possessing anticancer activities. METHODS: Title compounds (1a-b, 2a-b and 3a-q) were synthesized and screened by several anticancer models in vitro. RESULTS: Twenty-one new compounds (1a-b, 2a-b and 3a-q) were synthesized and screened. Structures of the new compunds were determined by MS, HNMR and elemental analysis. Twelve compounds (3c, 3d, 3e, 3f, 3g, 3h, 3j, 3k, 3m, 3o, 3p, 3q) showed inhibitory effects on HCT-8, KB and Bel7402 cell lines in vitro. CONCLUSION: Some compounds had certain anticancer activities and were worth further studying.

Antineoplastic Agents↗