Search results for "synergism"
showing 10 items of 153 documents
PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer
2017
AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoprote…
In vitro activity of anidulafungin in combination with amphotericin B or voriconazole against biofilms of five Candida species
2016
Objectives: To evaluate the in vitro activity of anidulafungin combined with amphotericin B or voriconazole against Candida spp. biofilms. Methods: Four Candida albicans, four Candida tropicalis, four Candida glabrata, two Candida parapsilosis and two Candida orthopsilosis blood isolates were tested by the microdilution chequerboard method combined with the XTT metabolic assay. Biofilm MIC was defined as the lowest concentration producing 50% metabolic inhibition with respect to control (BMIC50). Concentrations in the combinations ranged from 1/8xBMIC(50) to 4xBMIC(50) found for each antifungal tested alone. Results: Anidulafungin plus amphotericin B acted synergistically against C. albican…
Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer
2017
Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their…
Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
2019
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. In addition, late relapses are emerging suggesting the development of acquired resistances that compromise the anticancer efficacy of ICI. How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating…
Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in C…
2017
ABSTRACT Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions. Here we investigated chemoprofiles of three Curcuma species and observed a great variety of phytochemicals with curcumin being among the few present in all three species. On the other hand ascorbic acid (AA) was a compound that was solely found in Curcuma longa. In the present study we explored the cytotoxic effect of a curcumin/AA combination toward human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model. The drug combination showed additive cytotoxicity towards CCRF-CEM and CEM/ADR…
Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer
2018
Although many anticancer agents for gastric cancer have been developed, the prognosis for many patients remains poor. Recently, costimulatory immune molecules that reactivate antitumor immune responses by utilizing the host immune system have attracted attention as new therapeutic strategies. CD137 is a costimulatory molecule that reportedly potentiates the antitumor activity of tumor-targeting monoclonal antibodies (mAbs) by enhancing antibody-dependent cellular cytotoxicity. However, it remains unclear whether CD137 stimulates tumor-regulatory activity in gastric cancer. In this study, we investigated the antitumor effects of CD137 stimulation on gastric cancer cells administered tumor-ta…
Combined immunotherapy: CTLA-4 blockade potentiates anti-tumor response induced by transcutaneous immunization.
2017
Abstract Background The epidermal application of the Toll Like Receptor 7 agonist imiquimod and a T-cell peptide epitope (transcutaneous immunization, TCI) mediates systemic peptide-specific cytotoxic T-cell (CTL) responses and leads to tumor protection in a prophylactic tumor setting. However, it does not accomplish memory formation or permanent defiance of tumors in a therapeutic set-up. As a distinct immunologic approach, CTLA-4 blockade augments systemic immune responses and has shown long-lasting effects in preclinical experiments as well as in clinical trials. Objective The study investigates the vaccination capacity of TCI in combination with the checkpoint inhibitor CTLA-4 in matter…
Effect of Buthionine Sulfoximine on the Sensitivity to Doxorubicin of Parent and MDR Tumor Cell Lines
1994
We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more…
9-cis-Retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene
1997
The role of retinoic acids (RA) on liver fatty acid- binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-ci's-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10 -6 M 9-CK-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-c/s-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome prol…
Isoquercitrin and polyphosphate co-enhance mineralization of human osteoblast-like SaOS-2 cells via separate activation of two RUNX2 cofactors AFT6 a…
2014
Isoquercitrin, a dietary phytoestrogen, is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. Here we studied the combined effects of isoquercitrin, a cell membrane permeable 3-O-glucoside of quercetin, and polyphosphate [polyP], a naturally occurring inorganic polymer inducing bone formation, on mineralization of human osteoblast-like SaOS-2 cells. Both compounds isoquercitrin and polyP induce at non-toxic concentrations the mineralization process of SaOS-2 cells. Co-incubation experiments revealed that isoquercitrin (at 0.1 and 0.3μM), if given simultaneously with polyP (as Ca(2+) salt; at 3, 10, 30 and 100μM) amplifies the mineralization-enhanci…