salicylates has been researched along with Lung-Neoplasms* in 13 studies
1 trial(s) available for salicylates and Lung-Neoplasms
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A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations.
KRAS mutations are present in 30% of lung adenocarcinomas. Salirasib prevents Ras membrane binding thereby blocking the function of all Ras isoforms. This phase II study determined the activity of salirasib in patients with advanced lung adenocarcinomas with KRAS mutations.. Two cohorts of patients with stage IIIB/IV lung adenocarcinoma were eligible: patients with tumors with KRAS mutations who were previously treated with chemotherapy and patients receiving initial therapy who had ≥15 pack-year smoking history. Salirasib was given orally from days 1 to 28 of a 35-day cycle. The primary end point was the rate of nonprogression at 10 weeks.. Thirty-three patients were enrolled. Thirty patients had KRAS mutations (23 patients who were previously treated and 7/10 patients who had no prior therapy). Of the previously treated patients, 7 of 23 (30%) had stable disease at 10 weeks, and 4 of 10 (40%) previously untreated patients had stable disease at 10 weeks. No patient had a radiographic partial response (0% observed rate, 95% confidence interval 0-12%). The median overall survival was not reached (>9 months) for previously untreated patients and it was 15 months for patients who received prior chemotherapy. Diarrhea, nausea, and fatigue were the most common toxicities.. Salirasib at the current dose and schedule has insufficient activity in the treatment of KRAS mutant lung adenocarcinoma to warrant further evaluation. The successful enrollment of 30 patients with tumors with KRAS mutant lung adenocarcinoma over 15 months at a single site demonstrates that drug trials directed at a KRAS-specific genotype in lung cancer are feasible. Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; DNA, Neoplasm; Farnesol; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Polymerase Chain Reaction; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Salicylates; Survival Rate; Treatment Outcome | 2011 |
12 other study(ies) available for salicylates and Lung-Neoplasms
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Ginkgolic Acid Inhibits Invasion and Migration and TGF-β-Induced EMT of Lung Cancer Cells Through PI3K/Akt/mTOR Inactivation.
Epithelial-to-mesenchymal transition (EMT) is a critical cellular phenomenon regulating tumor metastases. In the present study, we investigated whether ginkgolic acid can affect EMT in lung cancer cells and the related underlying mechanism(s) of its actions. We found that ginkgolic acid C15:1 (GA C15:1) inhibited cell proliferation, invasion, and migration in both A549 and H1299 lung cancer cells. GA C15:1 also suppressed the expression of EMT related genes (Fibronectin, Vimentin, N-cadherin, MMP-9, MMP-2, Twist and Snail) and suppressed TGF-β-induced EMT as assessed by reduced expression of mesenchymal markers (Fibronectin, Vimentin, N-cadherin), MMP-9, MMP-2, Twist and Snail. However, GA C15:1 did not affect the expression of various epithelial marker proteins (Occludin and E-cadherin) in both A549 and H1299 cells. TGF-β-induced morphologic changes from epithelial to mesenchymal cells and induction of invasion and migration were reversed by GA C15:1. Finally, GA C15:1 not only abrogated basal PI3K/Akt/mTOR signaling cascade, but also reduced TGF-β-induced phosphorylation of PI3K/Akt/mTOR pathway in lung cancer cells. Overall, these findings suggest that GA C15:1 suppresses lung cancer invasion and migration through the inhibition of PI3K/Akt/mTOR signaling pathway and provide a source of potential therapeutic compounds to control the metastatic dissemination of tumor cells. J. Cell. Physiol. 232: 346-354, 2017. © 2016 Wiley Periodicals, Inc. Topics: Cell Line, Tumor; Cell Movement; Cell Survival; Down-Regulation; Enzyme Activation; Epithelial-Mesenchymal Transition; Humans; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Salicylates; Signal Transduction; TOR Serine-Threonine Kinases; Transforming Growth Factor beta | 2017 |
5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA): showing a strategy of designing drug to block lung metastasis of tumors.
Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients. By analyzing the structures and comparing the docking scores of the known pharmacophores, the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA) as a promising lead compound to develop metastasis inhibitors. In vitro 5, 10, and 20 µM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells. In vivo 0.4, 2.0, and 8.9 µmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC (Lewis Lung Carcinoma) toward lung. In vivo, 2 µmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice. Therefore, BHIMHA simultaneously blocked tumor metastasis toward lung, slowed the primary tumor growth, and limited the inflammation. These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Drug Design; Humans; Indoles; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Neoplasm Metastasis; NF-kappa B; Protein Kinase C-alpha; Salicylates | 2016 |
Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity.
Fatty acid synthase (FAS) has been proposed to be a new drug target for the development of anticancer agents because of the significant difference in expression of FAS between normal and tumour cells. Since a n-hexane-soluble extract from Ginkgo biloba was demonstrated to inhibit FAS activity in our preliminary test, we isolated active compounds from the n-hexane-soluble extract and evaluated their cytotoxic activity in human cancer cells. Three ginkgolic acids 1-3 isolated from the n-hexane-soluble extract inhibited the enzyme with IC(50) values 17.1, 9.2 and 10.5 µM, respectively, and they showed cytotoxic activity against MCF-7 (human breast adenocarcinoma), A549 (human lung adenocarcinoma) and HL-60 (human leukaemia) cells. Our findings suggest that alkylphenol derivatives might be a new type of FAS inhibitor with cytotoxic activity. Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Fatty Acid Synthases; Female; Ginkgo biloba; Hexanes; HL-60 Cells; Humans; Inhibitory Concentration 50; Lung Neoplasms; Molecular Structure; Plant Extracts; Plant Leaves; Salicylates | 2013 |
Downregulation of survivin and aurora A by histone deacetylase and RAS inhibitors: a new drug combination for cancer therapy.
Histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA), constitute a novel class of anticancer agents that cause an increase in acetylated histones and thus restore the expression of dormant tumor-suppressor and other genes related to cell differentiation, cell-cycle arrest or apoptosis of tumor cells. The Ras inhibitor farnesylthiosalicylic acid (FTS, salirasib) attenuates cancer cell proliferation in vitro and in vivo and, under certain circumstances, induces cell death. FTS by itself does not induce differentiation or complete growth arrest. The abovementioned activity of VPA as a differentiation agent suggested that it might be worth investigating its possible therapeutic potential in synergistic combination with FTS. Here, we examined whether the combined application of VPA and FTS could synergistically inhibit the proliferation of cancer cells that express oncogenic K-Ras (A549 nonsmall-cell lung carcinoma cells), DLD1 (colon carcinoma cells) or chronically active wild-type K-Ras and constitutively active B-Raf (ARO, thyroid carcinoma cells). The results showed that combined treatment with VPA and FTS synergistically reduces proliferation in all of these cancer cell lines by downregulating Ras and blocking the expression of Survivin and Aurora A. These alterations, which were most pronounced following the combined treatment, led to a mitotic crisis, as reflected by mislocalization of the chromosomal passenger complex. Our findings thus demonstrate that combination therapy with VPA and FTS might offer a promising therapeutic approach to the treatment of epithelial tumors. Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aurora Kinases; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Down-Regulation; Farnesol; Flow Cytometry; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Microtubule-Associated Proteins; Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Salicylates; Survivin; Valproic Acid | 2011 |
Synthesis and in vitro cytotoxicity of novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives.
Novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives as the leaving groups were synthesized and characterized by elemental analysis, FAB(+)-MS, FT-IR, and (1)H NMR spectroscopy. Most of the resulting platinum complexes had high solubility in organic solvents such as ethanol, acetone, and ether, and had right partition coefficient suited to be encapsulated in liposomes. The pertinent complexes were evaluated for their in vitro cytotoxicity against A549 human lung carcinoma and SGC-7901 human gastric carcinoma cell lines. They showed better cytotoxic activity than carboplatin and oxaliplatin. Topics: Antineoplastic Agents; Cell Line, Tumor; Diamines; Drug Screening Assays, Antitumor; Humans; Liposomes; Lung Neoplasms; Platinum; Salicylates; Solubility; Solvents; Spectrum Analysis; Stomach Neoplasms | 2007 |
Willow bark extract (BNO1455) and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells.
Recently, there have been extensive efforts to evaluate the chemopreventive role of substances present in natural products. The aim of this study was to examine the effects of the main groups of compounds (salicylalcohol derivates, flavonoids, proanthocyanidins), and salicin isolated from willow bark extract BNO 1455 on proliferation and apoptosis in human colon and cancer cells.. We used human colon cyclooxygenase-2 (COX-2)-positive HT 29 and (COX-2)-negative HCT 116 or lung COX-2 proficient A 549 and low COX-2 expressing SW2 cells. After treatment for 72 h with various concentrations of single substances and acetylsalicylic acid (ASA) as control, inhibition of cell growth and cytotoxicity were measured by colorimetric WST-1 assay and propidium iodide uptake by flow cytometry, respectively. Apoptotic cells were identified by annexin V adhesion using flow cytometry.. Studies on dose-dependent effects of BNO 1455 and its fractions showed anti-proliferative activity of all compounds with 50% maximal growth inhibitory concentrations (GI(50)) between 33.3 and 103.3 microg/ml for flavonoids and proanthocyanidins fractions and 50.0-243.0 microg/ml for salicylalcohol derivates and extract. Apoptosis induction was confirmed by annexin V adherence and analysis of cell morphology based on light scattering characteristics using flow cytometry in all cell lines at GI(50).. We showed that willow bark extract BNO 1455 an its fractions inhibit the cell growth and promote apoptosis in human colon and lung cancer cell lines irrespective of their COX-selectivity. Topics: Apoptosis; Carcinoma, Small Cell; Cell Proliferation; Cell Survival; Colonic Neoplasms; Cyclooxygenase 1; Cyclooxygenase 2; Flavonoids; Flow Cytometry; HT29 Cells; Humans; Lung Neoplasms; Membrane Proteins; Plant Bark; Plant Extracts; Proanthocyanidins; Salicylates; Salix; Tumor Cells, Cultured | 2007 |
Suppression of lung cancer tumor growth in a nude mouse model by the Ras inhibitor salirasib (farnesylthiosalicylic acid).
Aberrant Ras pathway functions contribute to the malignant phenotype of lung cancers. Inhibitors of Ras might therefore be considered as potential drugs for lung cancer therapy. Here, we show that the Ras inhibitor farnesylthiosalicylic acid (salirasib) inhibits proliferation of human lung cancer cells harboring a mutated K-ras gene (A549, H23, or HTB54) or overexpressing a growth factor receptor (H1299 or HTB58) and enhances the cytotoxic effect of the chemotherapeutic drug gemcitabine. Salirasib inhibited active K-Ras in A549 cells, reversed their transformed morphology, and inhibited their anchorage-independent growth in vitro. Tumor growth in A549 and HTB58 cell nude mouse models was inhibited by i.p. administration of salirasib. P.o. formulated salirasib also inhibited A549 cell tumor growth. Our results suggest that p.o. salirasib may be considered as a potential treatment for lung cancer therapy. Topics: Animals; Antineoplastic Agents; Cell Division; Cell Line, Tumor; Farnesol; Humans; Lung Neoplasms; Mice; Mice, Nude; ras Proteins; Salicylates | 2007 |
Hypoxia enhances metastatic efficiency in HT1080 fibrosarcoma cells by increasing cell survival in lungs, not cell adhesion and invasion.
This study examined possible mechanisms for hypoxia-increased metastasis in a green fluorescent protein-labeled human fibrosarcoma cell line (HT1080). The efficiency of the lung arrest of tumor cells, which can be dependent on the adhesive potential of the tumor cells, was assessed by measuring the level of integrin alpha3beta1 protein and by adhesion assays, whereas the extravasation potential was examined by an invasion assay. These properties were not changed by exposure to hypoxia, indicating that lung arrest and extravasation are unlikely to play a major role in the effect of hypoxia on metastasis in this model. The main effect of hypoxic exposure was found to be increased survival after lung arrest as determined by clonogenic assay of tumor cells recovered from mouse lungs after i.v. injection. Concomitantly, apoptosis was identified as responsible for the death of lung-arrested cells, suggesting the involvement of an altered apoptotic response following hypoxic exposure of these cells. Consistent with this finding, we found that the effect of hypoxia on both increased metastasis and survival of arrested cells was inhibited by treatment with farnesylthiosalicylic acid. However, this effect was not due to down-regulation of hypoxia-inducible factor-1alpha, a mechanism of action of this drug reported by previous studies. Further detailed studies of the mechanisms of action of the drug are needed. Topics: Animals; Antineoplastic Agents; Cell Adhesion; Cell Hypoxia; Cell Line, Tumor; Cell Survival; Farnesol; Fibrosarcoma; Green Fluorescent Proteins; Humans; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Salicylates; Transplantation, Heterologous | 2007 |
Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species (ROS).
Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto-oncogene and abnormal generation of intracellular oxygen species (reactive oxygen species (ROS)) have been linked, by independent lines of evidence, to cell transformation and to malignant growth. By comparing two subpopulations of the B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis capacities (low and high, respectively) we found that both the expression/phosphorylation of c-Met and the steady-state levels of ROS positively correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10 cells led to a parallel decrease in the generation of oxygen species and in metastatic capacity, suggesting that oxidants may mediate the pro-metastatic activity of the HGF receptor. c-Met activation by a ligand elicits the formation of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the anchorage-independent growth of F10 cells, consistent with a critical role for oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic manipulation of the Rac-ROS cascade at different levels demonstrated its crucial role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and potentially targetable by new antimetastatic, redox-based therapies. Topics: Animals; Free Radical Scavengers; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neoplasm Metastasis; Neuropeptides; Organometallic Compounds; Oxidation-Reduction; Phosphorylation; Proto-Oncogene Proteins c-met; rac GTP-Binding Proteins; rac1 GTP-Binding Protein; Reactive Oxygen Species; Salicylates; Signal Transduction; Superoxides | 2006 |
[Study on antitumor activities of ginkgolic acids from Ginkgo sarcotestas in vitro].
To study the influence of ginkgolic acids on human tumor cells and normal cells.. Ginkgolic acids (total concentration 90%) was prepared from ginkgo sarcotestas. The inhibitive effect of ginkgolic acids on human tumor cells and normal cells lines was examined by MTT assay.. When the concentration was 5.0 micrograms/ml, ginkgolic acids obviously inhibited the growth of tumor cells and didn't influence the normal cells. Inhibitive rate of ginkgolic acids on LTEP-a-2 was 59.1%. High-concentration ginkgolic acids had inhibitive effect on the growth of tumor cells and normal cells.. Ginkgolic acids had a obvious inhibitive effect on tumor cells in vitro. When the concentration was under 5.0 micrograms/ml, ginkgolic acids didn't influence the growth of normal cells. Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Division; Chromatography, High Pressure Liquid; Ginkgo biloba; Humans; Lung Neoplasms; Mice; Plant Bark; Plant Extracts; Plants, Medicinal; Salicylates; Seeds; Tumor Cells, Cultured | 2004 |
The quinoline-based drug, N-[4-[1-hydroxy-2-(dibutylamino)ethyl] quinolin-8-yl]-4-azidosalicylamide, photoaffinity labels the multidrug resistance protein (MRP) at a biologically relevant site.
MRP is a member of the ABC trafficking proteins thought to mediate the transport of glutathione S-conjugates and amphiphilic natural products. However, unlike P-glycoprotein, the biochemical mechanism by which MRP mediates the resistance to cytotoxic drugs is not clear. In this report, we describe the interactions of a quinoline-based drug, N-{4-[1-hydroxy-2-(dibutylamino)ethyl] quinolin-8-yl}-4-azidosalicylamide (IAAQ), with MRP. Our results demonstrate the ability of IAAQ to photoaffinity label a 190 kDa protein in resistant Small Cell Lung Cancer cells (H69/AR) but not in the parental H69 cells. The photoaffinity labeling of the 190 kDa protein with IAAQ was both saturable and specific. The identity of the 190 kDa protein, as MRP, was confirmed by immunoprecipitation with the monoclonal antibody, QCRL-1. Furthermore, a molar excess of LTC4, MK 571 or vinblastine inhibited the photoaffinity labeling of MRP with IAAQ in intact cells and plasma membranes. Cell growth and drug transport studies showed H69/AR cells to be less sensitive to and to accumulate less IAAQ than the parental H69 cells. In addition, MK 571 and doxorubicin increased the sensitivity to and the accumulation of IAAQ in H69/AR cells. Together, the results of this study show for the first time the direct binding of unaltered cytotoxic drug to MRP. Moreover, given the structural similarities between IAAQ and MK 571, we suggest that MK 571 modulates MRP-mediated resistance by direct binding to MRP. Topics: Affinity Labels; Antibodies, Monoclonal; ATP-Binding Cassette Transporters; Binding Sites; Carcinoma, Small Cell; Cell Division; Doxorubicin; Drug Resistance, Multiple; Humans; Kinetics; Lung Neoplasms; Multidrug Resistance-Associated Proteins; Propionates; Quinolines; Salicylates; Tumor Cells, Cultured; Vinblastine | 1997 |
Immunologic studies of glycoproteins isolated from cell membranes of human lung carcinomas.
Topics: Adenocarcinoma; Antigen-Antibody Complex; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Membrane; Cross Reactions; Electrophoresis, Starch Gel; Epitopes; Fluorescent Antibody Technique; Glycoproteins; Humans; Immunodiffusion; Immunoelectrophoresis; Lung Neoplasms; Microsomes; Salicylates; Sodium Dodecyl Sulfate | 1974 |