The effect of melphalan on mouse myeloma and hemopoietic progenitor cells was studied with a primary cell culture assay for mouse myeloma stem cells developed by Park, Bergsagel, and McCulloch and bone marrow cell culture and spleen colony assays for hemopoietic progenitor cells. Myeloma and bone marrow cells were exposed in vivo to graded doses of melphalan and harvested 3 and 24 hr later for ...

We investigated the transport of [chloroethyl-14C]melphalan with lymphocytes from three groups of patients with chronic lymphocytic leukemia (untreated, treated sensitive, and treated resistant). There was no significant difference in the Km or Vmax of melphalan transport in lymphocytes from the three groups. In addition, there were no significant differences in intracellular melphalan levels a...

PURPOSE We did a randomized phase I/II trial designed to evaluate the safety and efficacy of combining the proteasome inhibitor bortezomib with high-dose melphalan as the conditioning for high-dose therapy and autologous transplant for myeloma. EXPERIMENTAL DESIGN Enrolled patients were limited to those who did not achieve a very good partial remission (VGPR) following one or more induction r...

Melphalan is an alkylating agent frequently used in an intravenous formulation to treat hematologic malignancies and solid tumors in both adults and children. According to the manufacturer, melphalan is stable in sterile 0.9% sodium chloride for 90 min at room temperature (RT). Several authors have studied the stability of different concentrations of melphalan; however, most were not adapted to...

Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases. The chemical name for melphalan, is 4-bis (2-chloroethyl) amino-L-phenylalanine, it has a molecular weight of 305.20, and its molecular formula i...

We report the activity and toxicity of intrathecal melphalan in the treatment of human neoplastic meningitis in the subarachnoid space of athymic nude rats. Animals received injections via chronic indwelling subarachnoid catheters with 5 x IO5 or 5 x IO6 TE-67I human rhabdomyosarcoma cells or 5 x 10'' D-54 MG human glioma cells and were treated with melphalan on days 8. 5, or 5, respectively. M...

Melphalan (L-phenylalanine mustard), a cytostatic drug used in treatment of human breast cancer, was injected into mice bearing preneoplastic hyperplastic alveolar nodule mammary outgrowth line D2. Melphalan, doses of either 2.5 or 5.0 mg/kg, markedly enhanced tumor formation in its mammary nodule outgrowth line. Samples of nodule outgrowths in untreated mice produced 13% tumors by 9 months aft...

Melphalan transport, glutathione levels, and glutathione-S-transferase activity were measured in two continuous human medulloblastoma cell lines and transplantante xenografts in attiviminude mice, TE-671 and Dany. In vitro mean glutathione levels were 10.06 nmol/10' cells in TE671 and 2.96 nmol/106 cells in Daoy. In vitro mean glutathione-.?transferase values were 91.52 nmol/min/mg protein in T...

A melphalan-resistant human rhabdomyosarcoma xenograft, TE-671 MR, was established in athymic mice by serial melphalan treatment of the parent xenograft, TE-671, at the 10% lethal dosage (LD10); significant resistance was evident after ten passages of the tumor. TE-671 MR demonstrated a doubling time of 3.5 days and a latency period to 1000-mm3 tumors of 27.5 days. The glutathione level of TE-6...

OBJECTIVES Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. METHODS RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or bortezomib. Cell proliferat...