C-X-C motif chemokine 12 influences the development of extramedullary hematopoiesis in the spleens of myelofibrosis patients.

Myelofibrosis (MF) is characterized by the constitutive mobilization of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) and the establishment of extramedullary hematopoiesis. The mechanisms underlying this abnormal HSC/HPC trafficking pattern remain poorly understood. We demonstrated that both splenic and peripheral blood (PB) MF CD34(+) cells equally share a defective ability to home to the marrow, but not to the spleens, of NOD/LtSz-Prkdc(scid) mice.

Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.

Rigosertib (ON 01910.Na), a synthetic novel benzyl styryl sulfone, was administered to 28 patients with advanced cancer in a Phase I trial in order to characterize its pharmacokinetic profile, determine the dose-limiting toxicities (DLT), define the recommended phase II dose (RPTD) and to document any antitumor activity. Patients with advanced malignant neoplasms refractory to standard therapy were given escalating doses of rigosertib (50, 100, 150, 250, 325, 400, 650, 850, 1,050, 1,375, 1,700 mg/m(2)/24h) as a 3-day continuous infusion (CI) every 2 weeks.

Determination of the glucuronide metabolite of ON 013100, a benzylstyrylsulfone antineoplastic drug, in colon cancer cells using LC/MS/MS.

ON 013100, (E)-2,4,6-trimethoxystyryl-3-hydroxy-4-methoxybenzyl sulfone, is a potent kinase inhibitor whose phosphate form is in Phase I clinical trials in lymphoma and acute lymphoid leukemia. The objectives were to: (a) investigate the possible presence of the glucuronide metabolite of the drug in two representative colon cancer cell lines, a drug resistant (colo-205) and a drug sensitive (colo-320); (b) quantify the glucuronide metabolite and the unchanged drug in the cells after treatment with ON 013100. The glucuronide was synthesized and a selective LC/MS/MS method was developed and validated for the characterization and quantification of the metabolite.

Discontinuous drug binding to proteins: binding of an antineoplastic benzyl styryl sulfone to albumin and enzymes in vitro and in phase I clinical trials.

Sodium (E)-{N-[2-methyloxy-5-(2',4',6'-trimethoxy-styrylsulfonyl) methylenephenyl]amino}acetate (C(21)H(24)NNaO(8)S, ON 01910.Na) is a novel, synthetic benzyl styryl sulfone, currently in phase I clinical trials in cancer patients. Our objective was to use electrospray mass spectrometry to determine, in intact complexes, the number of drug molecules bound to albumin and selected enzymes.

The effect of CXCL12 processing on CD34+ cell migration in myeloproliferative neoplasms.

Primary myelofibrosis (PMF) and polycythemia vera (PV) are chronic myeloproliferative neoplasms. PMF and, to a lesser degree, PV are characterized by constitutive mobilization of hematopoietic stem cells (HSC) and progenitor cells (HPC) into the peripheral blood (PB). The interaction between the chemokine CXCL12 and its receptor CXCR4 plays a pivotal role in determining the trafficking of CD34(+) cells between the bone marrow (BM) and the PB.

Resveratrol in raw and baked blueberries and bilberries.

Resveratrol in the fruits of bilberry (Vaccinium myrtillus L.), the lowbush "wild" blueberry (Vaccinium angustifolium Aiton), the rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry (Vaccinium corymbosum L.) were measured using a new assay based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Cytotoxic dammarane glycosides from processed ginseng.

Steaming ginseng at high temperature increased its cytotoxicity to SK-Hep-1 hepatoma cancer cells. HPLC separation and fractionation followed by MTT assay revealed that ginsenosides Rg3, Rg5, Rk1, Rs5, and Rs4 are the active principles. Their 50% growth inhibition concentration (GI50) values were 41, 11, 13, 37, and 13 microM, respectively.