Search results for "Antineoplastic agent"
showing 10 items of 1538 documents
SYNTHESIS, CHARACTERIZATION AND IN VITRO CYTOTOXICITY STUDIES OF A MACROMOLECULAR CONJUGATE OF PACLITAXEL BEARING OXYTOCIN AS TARGETING MOIETY.
2007
The present study describes the experimental synthetic procedure and the characterization of a new polyaspartamide macromolecular prodrug of paclitaxel, bearing oxytocin residues as targeting moieties. In vitro stability studies of bioconjugate, performed in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma, evidenced the high stability of the targeting portion (oxytocin)-polymer linkage and the ability of this conjugate to release linked paclitaxel in a prolonged way in plasma. Moreover, preliminary in vitro antiproliferative studies, carried out on MCF-7 cells, that are oxytocin receptor positive cells, showed that the polymeric conjugate has the s…
Stability of irinotecan-loaded drug eluting beads (DC BeadTM) used for transarterial chemoembolization
2009
Purpose. The aim of this study was to determine the loading efficiency, physicochemical stability, and release of irinotecan-loaded DC BeadsTM (bead size 100—300 μm, 300—500 μm) before and after mixing with nonionic contrast medium (Accupaque® 300, Imeron® 300, Ultravist ® 300) during a prolonged period of time (28 days) when stored at room temperature or refrigerated. Methods. DC Beads TM were loaded with 50 mg irinotecan (Campto®) per milliliter beads in a 2 h loading period. Drug loading efficiency and stability were determined by measuring the irinotecan concentration in the excess solution. A free-flowing in vitro elution method for a period of 2 h and phosphate buffered solution (PBS…
Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells
2015
Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 an…
Paclitaxel and beta-lapachone synergistically induce apoptosis in human retinoblastoma Y79 cells by downregulating the levels of phospho-Akt.
2009
Paclitaxel (PTX) and beta-lapachone (LPC) are naturally occurring compounds that have shown a large spectrum of anticancer activity. In this article we show for the first time that PTX/LPC combination induces potent synergistic apoptotic effects in human retinoblastoma Y79 cells. Combination of suboptimal doses of PTX (0.3 nM) and LPC (1.5 microM) caused biochemical and morphological signs of apoptosis at 48 h of treatment. These effects were accompanied by potent lowering in inhibitor of apoptosis proteins and by activation of Bid and caspases 3 and 6 with lamin B and PARP breakdown. PTX/LPC combination acted by favoring p53 stabilization through a lowering in p-Akt levels and in ps166-MDM…
Long-term stability study of clofarabine injection concentrate and diluted clofarabine infusion solutions
2011
Purpose: The aim of this study was to investigate the physicochemical stability of clofarabine (CAFdA) injection concentrate and ready-to-use CAFdA infusion solutions over a prolonged period of 28 days. Methods: To determine the stability of CAFdA infusion solutions, the injection concentrate (Evoltra®, 1 mg/mL, Genzyme) was diluted either with 0.9% sodium chloride or 5% glucose infusion solution. The resulting concentrations of 0.2 mg/mL or 0.6 mg/mL, respectively, were chosen to represent the lower and upper limit of the ordinary concentration range. Test solutions were stored under refrigeration (2–8°C) or at room temperature either light protected or exposed to light. CAFdA concentrati…
Acrylamide catalytically inhibits topoisomerase II in V79 cells.
2010
The vinyl monomer acrylamide is characterized by the presence of an alpha,beta-unsaturated carbonyl group that makes it reactive towards thiol, hydroxyl or amino groups and towards the nucleophilic centers in DNA. The ability of acrylamide to chemically modify protein thiols has prompted us to consider topoisomerase II as one possible target of acrylamide, since agents targeting protein sulfhydryl groups act as either catalytic inhibitors or poisons of topoisomerase II. Nuclear extracts from V79 Chinese hamster cells incubated with acrylamide reduced topoisomerase II activity as inferred by an inability to convert kinetoplast DNA to the decatenated form. Nuclear extracts incubated with acry…
Heterocycle-containing retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptos…
2001
In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the C9-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, …
Proteomic profiling of Trastuzumab (Herceptin(R))-sensitive and -resistant SKBR-3 breast cancer cells.
2013
BACKGROUND: The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear. Aim: To study the effects of short and prolonged trastuzumab treatment on the proteomic profiles of HER-2-overexpressing SKBR-3 BC cells. MATERIALS AND METHODS: Cells were treated with trastuzumab to obtain sensitive and resistant clones. The drug effects were evaluat…
Synthesis of 5H-pyrido[3,2-b]pyrrolizin-5-one tripentone analogs with antitumor activity
2018
Abstract Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61–91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (hum…
Cytotoxic activity of secondary metabolites derived from Artemisia annua L. towards cancer cells in comparison to its designated active constituent a…
2010
Artemisia annua L. (sweet wormwood, qinhao) has traditionally been used in Chinese medicine. The isolation of artemisinin from Artemisia annua and its worldwide accepted application in malaria therapy is one of the showcase success stories of phytomedicine during the past decades. Artemisinin-type compounds are also active towards other protozoal or viral diseases as well as cancer cells in vitro and in vivo. Nowadays, Artemisia annua tea is used as a self-reliant treatment in developing countries. The unsupervised use of Artemisia annua tea has been criticized to foster the development of artemisinin resistance in malaria and cancer due to insufficient artemisinin amounts in the plant as c…