Emerging strategies for high-risk and relapsed/refractory acute myeloid leukemia: Novel agents and approaches currently in clinical trials

Sasine, Joshua P.; Schiller, Gary J.

doi:10.1016/j.blre.2014.07.002

Cited by 51 publications

(47 citation statements)

References 83 publications

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“…28,29 In addition, treatment with sorafenib has been discouraged in elderly patients due to signs of cardiac toxicity. 30 The encapsulation of sorafenib and nilotinib into nanoparticles may improve the drugs solubility and stability, minimize the toxic side effects, and allow the drug to accumulate at the tumor site through the enhanced permeability and retention (EPR) effect. 31 In this study, we prepared sorafenib-and nilotinib-loaded poly(styrene-co-maleic acid [SMA]) micelles.…”

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confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene- co -maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing.

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confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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“…Vosaroxin has been shown to be active against various in vitro and in vivo tumor models including breast, bladder, pancreas, colon, ovarian, gastric, and lung cancer [29][30][31][32][33][34][35]. It has also shown synergistic activity with platinum agents, anthracyclines, antimetabolites, and targeted therapies in tumor models [36]. In a recently completed pivotal phase 3 study in relapsed or refractory acute myeloid leukemia (N = 711), no increase in organspecific toxicities (cardiac, renal, hepatic, or pulmonary) was observed with vosaroxin/cytarabine treatment in comparison with placebo/cytarabine treatment [37].…”

Section: Research Papermentioning

confidence: 99%

“…Tumor weight was calculated according to the formula tumor weight (mg) = tumor volume (mm 3 ) = d2 × D/2, where d and D are the shortest and longest diameters, respectively. The effects of the treatments were assessed as previously described [36]. At about 10 days after the tumor injection, 30 mice with tumor volumes of 0.5-0.8 cm 3 were randomly divided into 6 groups (5 mice per group with 2 tumors each): (1) control (vehicle); (2) vosaroxin (10 mg/kg every 5 days for 5 weeks intravenous [IV] injection into tail vein; (3) radiotherapy (RT; 4 Gy delivered in a single fraction) [59]; (4) vosaroxin in combination with RT; (5) temozolomide (16 mg/kg 5 consecutive days) and (6) temozolomide in combination with RT.…”

Section: Mouse Glioblastoma Xenograft Modelmentioning

confidence: 99%

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Festuccia¹,

Gravina²,

Mancini³

et al. 2016

European Journal of Cancer

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“…Recently, targeted molecular therapies and immunebased therapies, such as the leukemia-associated antigen vaccine and antigen-specific cytotoxic T cells, are under investigation for the management of high-risk AML (Greiner et al, 2008;Sasine and Schiller, 2015). Long-term complete remission was demonstrated for some AML cases with cellular cytotoxic activity against myeloid leukemia cells (Müller-Schmah et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction

Shi

Chen

Zha

et al. 2015

DNA and Cell Biology

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Defective T cell receptor (TCR) signaling resulting in lower T cell function plays a crucial role in the pathogenesis of T cell immunodeficiency in leukemia. Previous studies have indicated that lower TCRf levels are a common characteristic of patients with leukemia, and upregulating TCRz could partially recover T cell function. In this study, we characterized the effect of the stimulating factor induction on the TCRf, Zap-70, and FceRIc levels, IFN-g secretion, and the distribution and clonal expansion of TCR Vb subfamilies in CD3 + T cells sorted from peripheral blood from acute myeloid leukemia (AML) patients. The induction included single stimulating factor or a combination with different cytokines (IL-2, IL-7, IL-2 + IL-7, IL-7 + IL-12, CD3, CD3 + CD28 antibody, CD3 + CD28 antibody + IL-2, and CD3 + CD28 antibody + IL-7) at 72 h. The results showed that increased TCRf and Zap-70 levels with deceased FceRIc in T cells after induction, and different responses to cytokine in T cell from different cases may indicate the heterogeneity of T cells and different immune statuses in different AML cases. Increased IFN-g levels in T cells from AML patients were detected after induction in the IL-12 + IL-7, CD3 + CD28 + IL-2, and CD3 + CD28 + IL-7 groups. Moreover, the number of TCR Vb subfamily T cells expressed was increased; however, all of the TCR Vb subfamily T cells in the AML patients could not be completely recovered after induction. In conclusion, the cytotoxicity and activation function of T cells could be enhanced after induction by different stimuli accompanied by an increase in TCRf and Zap-70 and recovery of the TCR Vb repertoire in AML patients.

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Emerging strategies for high-risk and relapsed/refractory acute myeloid leukemia: Novel agents and approaches currently in clinical trials

Cited by 51 publications

References 83 publications

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction

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