BACKGROUND Recent reports indicate that in vitro drug screens combined with gene expression profiles (GEP) of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM) a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive sign...

Investigation of the mechanism of uptake of melphalan by L5178Y lymphoblasts has been extended with particular emphasis on the chemical specificity of the transport mech anism. Evidence was obtained that uptake of melphalan was an active carrier-mediated process. Uptake appeared to proceed “uphill― against a concentration gradient of approximately eight-fold and was temperature sensitive, p...

Malignant transformation in melanoma is characterized by a phenotype "switch" from E- to N-cadherin, which is associated with increased motility and invasiveness of the tumor and altered signaling, leading to decreased apoptosis. We hypothesized that the novel pentapeptide (ADH-1), which disrupts N-cadherin adhesion, could sensitize melanoma tumors to the cytotoxic effects of chemotherapy. N-ca...

Melphalan (L-phenylalanine mustard, L-PAM, alkeran; molecular weight, 305,000) is transported across tumor cell membranes and the blood-brain barrier by the large neutral amino acid (LNAA) transport system. Normally, plasma LNAA levels are high enough and the affinity low enough that this system does not transport much melphalan into the brain. However, plasma amino acids can be reduced by fast...

We tested the hypothesis that bifunctional DNA adducts formed by a nitrogen mustard-based anticancer drug were more efficient than monofunctional adducts at causing elevation of p53, consistent with the difference in cytotoxicity. Human leukemia cell line ML-1 was exposed for 1 h to melphalan or its monofunctional derivative monohydroxymelphalan. Levels of DNA adducts, measured by specific immu...

Five different human melanoma xenografts were used in a xenograft model of extremity melanoma to evaluate the variability of tumor response to regionally administered melphalan or temozolomide and to determine if various components of pertinent drug resistance pathways for melphalan [glutathione S-transferase (GST)/glutathione] and temozolomide [O(6)-alkylguanine DNA alkyltranferase (AGT)/misma...

The pharmacokinetics of melphalan following high-dose p.o. administration were determined in 17 patients with various malignancies for the purpose of assessing interpatient and intrapatient pharmacokinetic variability. All patients underwent bone marrow harvest on day -8 (relative to bone marrow reinfusion). On days -7, -6, and -5, melphalan was given p.o. and the dose was escalated on each coh...

Previous studies have shown that uptake of several alkylating agents occurs by independent transport mechanisms. Uptake of one of these agents, the phenylalanine derivative of nitrogen mustard (melphalan), has been investigated in LPC-1 plasmacytoma cells in vitro. Evidence suggesting that melphalan uptake is an active process is that uptake of free intact melphalan proceeds "uphill" against a ...

Melphalan has been shown to effectively improve cancers by inhibiting deoxyribonucleic acid synthesis. However, it some obvious drawbacks such as short plasma half-life, non-target selectivity and serious adverse reactions. Because of these shortcomings, its clinical application is limited. In the present research work, we have tried obtain polyethylene glycol-hyaluronic modifying hyaluronic wi...

Melphalan combined with prednisone (MP) has long been the historical treatment of reference for a large proportion of elderly myeloma (MM) patients ineligible for autologous stem cell transplantation, and is still the backbone of new regimens that include the new era of novel agents. Melphalan-prednisone-thalidomide (MPT) and melphalan-prednisone-bortezomib (Velcade((R)), MPV), proved superior ...