Search results for "Neoplastic"
showing 10 items of 2901 documents
Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View
2020
Multidrug resistance (MDR), of the innate and acquired types, is one of major problems in treating tumor diseases with a good chance of success. In this review, we examine the key role of nuclear factor-kappa B (NF-κB) to induce MDR in three tumor models characterized precisely by innate or acquired MDR, in particular triple negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and acute myeloid leukemia (AML). We also present different pharmacological approaches that our group have employed to reduce the expression/activation of this transcriptional factor and thus to restore chemo-sensitivity. Finally, we examine the latest scientific evidence found by other groups, the most sign…
Pharmacogenomic and molecular docking studies on the cytotoxicity of the natural steroid wortmannin against multidrug-resistant tumor cells
2014
Wortmannin is a cytotoxic compound derived from the endophytic fungi Fusarium oxysporum, Penicillium wortmannii and Penicillium funiculosum that occurs in many plants, including medicinal herbs. The rationale to develop novel anticancer drugs is the frequent development of tumor resistance to the existing antineoplasic agents. Therefore, it is mandatory to analyze resistance mechanisms of novel drug candidates such as wortmannin as well to bring effective drugs into the clinic that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients. In the present project, we found that P-glycoprotein-overexpressing tumor cells…
Pathophysiology of anthracycline cardiotoxicity.
2016
Anthracyclines (ANTs) are powerful drugs that have reduced the mortality of cancer patients. However, their use is limited by the development of cardiotoxicity (CTX), which is dose dependent and may lead to left ventricular dysfunction and heart failure. Although various strategies have been suggested to reduce the negative effects of ANTs, CTX is still an important unresolved clinical issue. This may be due at least partly to the incomplete characterization of the molecular and cellular mechanisms of ANT-induced CTX. In addition, although various forms of cardiac damage have been demonstrated with the use of these drugs in experimental studies, it is not yet clear how these translate to th…
5-Fluorouracil Buccal Tablets for Locoregional Chemotherapy of Oral Squamous Cell Carcinoma: Formulation, Drug Release and Histological Effects on Re…
2010
5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is associated with severe toxic effects and no topical formulations of 5-FU for buccal drug delivery have been reported. In this study we would report the development of buccal tablets suitable for direct application of low-doses of 5-FU on cancer lesions. The topical administration could be effective on tumor area while systemic undesired side effects are avoided. Preliminarily, the limited tendency of 5-FU to cross the buccal tissue was established using reconstituted human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vi…
Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile …
2012
Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …
Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy
2016
The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of …
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
2009
Abstract Coadministration of the iron chelator dexrazoxane reduces by 80% the incidence of heart failure in cancer patients treated with anthracyclines. The clinical application of dexrazoxane is limited, however, because its ability to inhibit topoisomerase IIα (TOP2A) is feared to adversely affect anthracycline chemotherapy, which involves TOP2A-mediated generation of DNA double-strand breaks (DSB). Here, we investigated the apoptotic effects of dexrazoxane and the anthracycline doxorubicin, alone and in combination, in a tumor cell line with conditionally regulated expression of TOP2A. Each drug caused apoptosis that was only partly dependent on TOP2A. Unexpectedly, dexrazoxane was found…
The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin.
1989
The therapeutic efficacy of 5-fluorouracil (FUra) and cis-dichlorodiamine-platinum (cis-DDP) in mice bearing transplantable leukemia and solid tumors was evaluated using different sequences of combination of these agents. The optimal sequence was cis-DDP administered 24 h after FUra. The administration of FUra at its maximally tolerated dose (MTD) followed 24 h later by low doses of cis-DDP yielded less toxicity and higher response rate against L1210 and colon 26 than the administration of these two agents in the opposite sequence or concurrently at the MTD. The sequence of administration of these two agents was not therapeutically important when the antitumor activity was evaluated against…
Could resveratrol be a useful drug for the treatment of malignant hemopathies?
2013
Resveratrol is a poly-phenol with many beneficial effects: not only as an antioxidant, anti-inflammatory, and antiatherogenic agent, as well as a platelet aggregation inhibitor, but also as an antiproliferative and proapoptotic factor in various types of cancers. There are reviews about the mechanisms responsible for its effects in leukemia and lymphomas, emphasizing the chemosensitizing role of resveratrol, which allows overcoming the multidrug resistance of cancers. The action of resveratrol occurs preferentially on leukemic cells, and not on the normal ones. In addition, it is one of the few drugs that act on leukemic stem cells. If experimental results are promising, its application in …
Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells
2014
Background: In hepatocellular carcinoma (HCC), different signaling pathways are de-regulated, and among them, the expression of the epidermal growth factor receptor (EGFR). Tyrphostin AG-1478 is a lipophilic low molecular weight inhibitor of EGFR, preferentially acting on liver tumor cells. In order to overcome its poor drug solubility and thus improving its anticancer activity, it was entrapped into nanostructured lipid carriers (NLC) by using safe ingredients for parenteral delivery. Results: Nanostructured lipid carriers (NLC) carrying tyrphostin AG-1478 were prepared by using the nanoprecipitation method and different matrix compositions. The best system in terms of mean size, PDI, zeta…