Biomedical subjects

Konstantinos Dimas

Publications and source records attributed to Konstantinos Dimas.

4 recordsLinked to original sources

PubMed2005

A liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC): physicochemical characterization and cytotoxic activity against human cancer cell lines.

The overall goal of this study was to prepare a novel liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC), as a combined formulation and to study its activity against cancer cells and peripheral blood mononuclear cells (PBMCs), in terms of efficacy and toxicity. Liposomes composed of HePC/egg phosphatidylcholine/stearylamine (HePC/EPC/SA) 10:10:0.1 (molar ratio) (1) and EPC/SA 10:0.1 (molar ratio) (2) were prepared and doxorubicin was encapsulated using the pH gradient method. Determination of lipids and doxorubicin has been achieved by high-performance thin-layer chromatography coupled with a flame-ionization detector. Prepared liposomes were characterized for their size distribution and their zeta-potential at each step of the preparation procedure. In vitro release studies have been evaluated in buffer and culture medium at 25 and 37 degrees C for 24 hours period. Liposomal formulations, free doxorubicin and HePC were tested against cancer cell lines and PBMCs, using sulforhodamine B (SRB) assay. Doxorubicin was encapsulated into the liposomes 1 and 2 at a drug to lipid molar ratio of 1.08 and 0.77, respectively, with an entrapping efficiency almost 100% in both cases. Doxorubicin was retained into liposome 1 up to 70% at 25 degrees C in TES, while up to 80% was released from 1 when liposomes were incubated at 37 degrees C either in culture medium or in the TES buffer at 24 hours. The activity of doxorubicin was retained or slightly improved when entrapped into liposomes 1 and 2, while liposomal formulation 1 encapsulating doxorubicin was found to be less toxic against normal cells (PBMCs). The combination of HePC and doxorubicin in one combined formulations justified as an improvement of the therapeutic index (TI) of doxorubicin in terms of efficacy and toxicity.

Amines↗

PubMed2005

Cytotoxic and antitumor activity of liposome-incorporated sclareol against cancer cell lines and human colon cancer xenografts.

The aim of this study was to design and prepare liposome-incorporated sclareol--a highly lipophilic natural product-to overcome its water insolubility and develop suitable formulations for in vivo administration. The bioactive labdane-type diterpene sclareol was incorporated into liposomes composed of egg phosphatidylcholine and dipalmitoylphosphatidylglycerol prepared by the thin-film hydration method followed by sonication. A formulation of egg phosphatidylcholine/dipalmitoylphosphatidylglycerol/sclareol (9:0.1:5 molar ratio) was developed and characterized. The lipid recovery and the sclareol to lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection. In vitro drug release was measured in supplemented RPMI-1640 at 37 degrees C. The liposomal and the free sclareol were initially tested in vitro for their activity against human cancer cell lines using the sulphorhodamine B assay. Liposomes incorporating sclareol at a drug to lipid molar ratio of 0:43, suggesting an incorporation efficiency of almost 80%, showed reduced growth rate of human colon cancer tumors (HCT116) developed in SCID mice, without any significant side effects.

Animals↗

PubMed2005

Brain tuberculomas due to miliary tuberculosis.

Brain tuberculomas are a rare complication of tuberculosis arising through hematogenous spread from an extracranial source, most often of pulmonary origin. The clinical course is usually subacute or chronic, lasting weeks or months, and they typically occur in immunocompromised patients. Recognition and prompt diagnosis of this disorder is important because early treatment can prevent patient worsening and lead to clinical improvement. The authors report a 68-year-old diabetic man with headache and cognitive/behavioral changes in whom investigation revealed disseminated brain tuberculomas resulting from miliary tuberculosis. He received antituberculous treatment and had an excellent recovery.

Aged↗

PubMed2003

The cytoprotective aminothiol WR1065 activates p53 through a non-genotoxic signaling pathway involving c-Jun N-terminal kinase.

WR1065 is an aminothiol with selective cytoprotective effects in normal cells compared with cancer cells. In a previous study (North, S., El-Ghissassi, F., Pluquet, O., Verhaegh, G., and Hainaut, P. (2000) Oncogene 19, 1206-1214), we have shown that WR1065 activates wild-type p53 in cultured cells. Here we show that WR1065 induces p53 to accumulate through escape from proteasome-dependent degradation. This accumulation is not prevented by inhibitors of phosphatidylinositol 3-kinases and is not accompanied by phosphorylation of Ser-15, -20, or -37, which are common targets of the kinases activated in response to DNA damage. Furthermore, WR1065 activates the JNK (c-Jun N-terminal kinase), decreases complex formation between p53 and inactive JNK, and phosphorylates p53 at Thr-81, a known site of phosphorylation by JNK. A dominant negative form of JNK (JNK-APF) reduces by 50% the activation of p53 by WR1065. Thus, WR1065 activates p53 through a JNK-dependent signaling pathway. This pathway may prove useful for pharmacological modulation of p53 activity through non-genotoxic mechanisms.

3T3 Cells↗