PhysEmp :: Medicine :: Medical Specialties :: Hematology :: Journals

Hematological Oncology

Silibinin can induce differentiation as well as enhance vitamin D3-induced differentiation of human AML cells ex vivo and regulates the levels of differentiation-related transcription factors
Jing Zhang, Jonathan S Harrison, Milan Uskokovic, Michael Danilenko, George P Studzinski Wed, 28 Oct 2009 04:28:00 -0000
Induction of terminal differentiation is a conceptually attractive approach for the therapy of neoplastic diseases. Although vitamin D derivatives (deltanoids) can induce differentiation of AML cells in vitro, so far deltanoids have not been successfully brought to the clinic, due to the likelihood of life-threatening hypercalcemia. Here, we incubated freshly obtained blood cells from patients with AML with a plant antioxidant (PAOx), silibinin (SIL), alone or together with a deltanoid. Twenty patients with AML (all subtypes except M3) were available for this study, and in 14 (70%), SIL (60 µM) either induced differentiation ex vivo, or enhanced differentiation induced by deltanoids, or both. Interestingly, SIL acting alone induced differentiation only in cases in which chromosome aberrations could not be detected. In eleven samples sufficient material was available for a limited analysis of the underlying events. Quantitative RT-PCR showed that differentiation markers were upregulated at the mRNA level by both SIL and deltanoids, suggesting that intracellular signaling pathways upstream of transcription factors (TFs) were activated by these agents. Western analysis for proteins which function as TFs in deltanoid-induced monocytic differentiation, such as members of Jun and C/EBP families, surprisingly demonstrated that SIL upregulated all these TFs in the cases tested. This suggests that although the presence of SIL may not always be sufficient to induce differentiation, it can serve as a differentiation enabling factor for blasts obtained from a large proportion of patients with AML. Thus, SIL/deltanoid combinations warrant further consideration as preventive/therapeutic regimens in human leukaemia. Copyright © 2009 John Wiley & Sons, Ltd.

Annals of Hematology

Salvage treatment with upfront melphalan 100 mg/m2 and consolidation with novel drugs for fulminant progression of multiple myeloma
Wed, 18 Nov 2009 19:15:05 -0000
Abstract  Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m2 (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n = 16) or bortezomib (n = 15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2–15 months), and the median OS was 8 months (range, 3–23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0862-zAuthors Marta Krejci, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicZdenek Adam, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicTomas Buchler, Thomayer University Hospital 1st Faculty of Medicine, Department of Oncology Prague Czech RepublicAndrea Krivanova, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicLudek Pour, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicLenka Zahradova, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicMichal Holanek, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicViera Sandecka, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicJiri Mayer, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlav Subscribe to Journals RSS feed