PURPOSE Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. EXPERIMENTAL DESIGN We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they m...

The phenotypic distinction between naive T lymphocytes, before primary activation by antigen, and previously stimulated memory T cells has remained elusive until recently. Although several surface markers phenotypically subdivide CD4+ or CD8+ cells (1-6), or are transiently expressed by T cells upon activation (7-12), none ofthese determinants has been formally shown to identify a subset ofmuri...

The recently determined C. elegans P-glycoprotein (Pgp) structure revealed significant deviations compared to the original mouse Pgp structure, which suggested possible misinterpretations in the latter model. To address this concern, we generated an experimental electron density map from single-wavelength anomalous dispersion phasing of an original mouse Pgp dataset to 3.8 Å resolution. The map...

Background:Punica granatum var. pleniflora (PGP) has been used for thousands of years as an effective agent to treat various types of diseases. However, there are a few new evidences addressing its therapeutic effects and related mechanisms. Therefore, the aim of this study was to investigate the cytotoxic, antioxidant, antibacterial, and anti-inflammatory effects of ethanolic (ET), dichloromet...

One of the best-characterized resistance mechanisms in acute myeloid leukemia (AML) is the drug extrusion mediated by P-glycoprotein (Pgp). Recently the results of workshops organized by several groups concluded that accurate measurement of low activity of Pgp is a difficult goal in clinical samples. Therefore, highly sensitive and specific assays were developed to assess the functionality of P...

Current cytotoxic chemotherapy produces clinical benefit in patients with breast cancer but the survival impact is modest. To explore novel cytotoxic agents for the treatment of advanced disease, we have characterized a new and pharmacokinetically improved Hec1-targeted compound, TAI-95. Nine of 11 breast cancer cell lines tested were sensitive to nanomolar levels of TAI-95 (GI50 1⁄4 14.29–73.6...

The pharmacodynamics of taxol in human head and neck squamous cell carcinoma were studied using histocultures of surgical specimens from patients (n = 22). Tumors were treated with taxol for 24 h. The inhibition of DNA synthesis was determined by 48 h cumulative bromodexyuridine (BrdUrd) incorporation. The induction of apoptosis was measured by morphological changes, in situ DNA end labeling, p...

Current cytotoxic chemotherapy produces clinical benefit in patients with breast cancer but the survival impact is modest. To explore novel cytotoxic agents for the treatment of advanced disease, we have characterized a new and pharmacokinetically improved Hec1-targeted compound, TAI-95. Nine of 11 breast cancer cell lines tested were sensitive to nanomolar levels of TAI-95 (GI(50) = 14.29-73.6...

Milk thistle (Silybum marianum) is a native plant of Mediterranean Sea areas. Silymarin, an extract from its seeds, is used in various liver diseases for its hepatoprotective effects. It contains silymarin flavonoids (SF) such as silybin, silydianin and silychristin. Cyclosporin A (CsA) is widely used as an immunosuppressant in organ transplantations. Its other applications in many autoimmune d...