1.PJ34, a poly(ADP-ribose) polymerase (PARP) inhibitor, reverses melphalan-resistance and inhibits repair of DNA double-strand breaks by targeting the FA/BRCA pathway in multidrug resistant multiple myeloma cell line RPMI8226/R.
Xiong T1, Wei H1, Chen X1, Xiao H1. Int J Oncol. 2015 Jan;46(1):223-32. doi: 10.3892/ijo.2014.2726. Epub 2014 Oct 23.
There is still no ideal treatment for multidrug resistant multiple myeloma, looking for drugs which can reverse chemotherapy resistance and enhance curative effects of chemotherapy drugs becomes a problem that needs to be solved urgently. Poly(ADP-ribose) polymerase inhibitors appear to be an important tool for medical therapy of several malignancies. In the present study, we investigated the potential of the PARP-1 inhibitor PJ34, in vitro, to further enhance the efﬁcacy of the traditional chemotherapy drug melphalan in the multidrug-resistant multiple myeloma cell line RPMI8226/R. The effects of different concentrations of PJ34 and melphalan on cell proliferation were determined by the CCK-8 assay. The expressions of FA/BRCA pathway-related factors were detected by western blotting and RT-PCR. The percentage of cell apoptosis was measured with flow cytometry. DNA double-strand break (DSB) repair was quantiﬁed by γH2AX immunoﬂuorescence.
2.Influence of PJ34 on the genotoxicity induced by melphalan in human multiple myeloma cells.
Xiong T1, Chen X1, Wei H1, Xiao H1. Arch Med Sci. 2015 Apr 25;11(2):301-6. doi: 10.5114/aoms.2014.43164. Epub 2015 Apr 23.
INTRODUCTION: The aim of this study was to evaluate the potential biological activity of N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride (PJ34) on the genotoxicity induced by melphalan in human multiple myeloma cells.
3.A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation.
Hari P1, Aljitawi OS2, Arce-Lara C3, Nath R4, Callander N5, Bhat G6, Allen LF6, Stockerl-Goldstein K7. Biol Blood Marrow Transplant. 2015 Dec;21(12):2100-5. doi: 10.1016/j.bbmt.2015.08.026. Epub 2015 Aug 29.
Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran.