1 to assess the role of p21(WAF1) induction by
perifosine.
2 s in nude mice was dramatically inhibited by
perifosine.
3 blocked by treatment with the AKT inhibitor
perifosine.
4 nes lacking p21(waf1/cip1) are refractory to
perifosine.
5 nized HN12 cells released in the presence of
perifosine (
10 microM) demonstrated increased expression
6 Perifosine +
10 Gy did not result in a significantly inc
7 The dose selected for the phase II study was
perifosine 50 mg/d plus bortezomib 1.3 mg/m(2), with the
8 In this study, we investigated the effect of
perifosine,
a p.o.-bioavailable ALK, on the cell cycle k
9 pands our understanding of the mechanisms of
perifosine action in neuroblastoma.
10 ciferase reporter plasmids, we observed that
perifosine activates the 2.4-kb full-length p21(waf1/cip
11 Moreover, we showed that
perifosine activates the mitogen-activated protein/extra
12 t lacking p53-binding sites, suggesting that
perifosine activates the p21(waf1/cip1) promoter indepen
13 72-h exposure of the MDA468 and PC3 cells to
perifosine alone resulted in cell death in a dose-depend
14 Additional ATLs, including miltefosine and
perifosine,
also displaced Pma1p from rafts to the vacuo
15 Perifosine,
an Akt inhibitor, has been shown to be effec
16 Perifosine,
an inhibitor of AKT signaling, significantly
17 Akt is strongly inhibited by
perifosine,
an orally active alkyl-lysophospholipid curr
18 data were obtained using the AKT inhibitors
perifosine and 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-
19 sm accounting for the anticancer activity of
perifosine and a potential strategy to enhance the antic
20 We demonstrated that
perifosine and bortezomib both targeted NF-kappaB throug
21 cells (in which the PTEN gene is deleted) to
perifosine and cetuximab, alone and in combination.
22 ersed by cotreatment with the Akt inhibitors
perifosine and GSK69069 or by the addition of neutralizi
23 With these results, we combined
perifosine and temozolomide as treatment of platelet-der
24 Animal studies showed that
perifosine and temozolomide combination therapy was more
25 A mutants greatly sensitized SW1736 cells to
perifosine and temsirolimus.
26 MK-2206 and GSK690693 but not the compounds (
perifosine and triciribine) targeting the PH domain of A
27 To gain insight into
perifosine anti-tumor activity in neuroblastoma we have
28 Novel agents such as bortezomib,
perifosine,
atacicept, oblimersen sodium, and tositumoma
29 Furthermore,
perifosine augments dexamethasone, doxorubicin, melphala
30 These data, therefore, indicate that
perifosine blocks cell cycle progression of head and nec
31 Perifosine-
bortezomib +/- dexamethasone demonstrated enc
32 A phase III trial is underway comparing
perifosine-
bortezomib plus dexamethasone with bortezomib
33 rategy to enhance the anticancer efficacy of
perifosine by preventing autophagy.
34 signal-related kinase (ERK) is increased by
perifosine;
conversely, MEK inhibitor synergistically en
35 Finally,
perifosine demonstrates significant antitumor activity i
36 y prolonged survival by 27% (P = 0.0002) but
perifosine did not (P = 0.92).
37 Perifosine does not induce cytotoxicity in peripheral bl
38 Taken together, the data showed that
perifosine enhances the antitumor activity of cetuximab
39 hat the novel signal transduction modulator,
perifosine,
enhances the cytotoxicity of dexamethasone a
40 but was ultimately ineffective in preventing
perifosine/
HDACI-mediated apoptosis.
41 Genetic-dependent apoptosis was induced by
perifosine in cells selectively tested.
42 Clinical data suggest that
perifosine in combination with dexamethasone has activit
43 nt of gliomas, we investigated the effect of
perifosine in combination with temozolomide.
44 However, the efficacy of
perifosine in human gliomas has not been established.
45 ndicate that coadministration of HDACIs with
perifosine in human leukemia cells leads to Akt and MEK/
46 ide the framework for clinical evaluation of
perifosine in WM patients.
47 Perifosine induced significant reduction in WM tumor gro
48 ggesting that JNK plays an essential role in
perifosine-
induced apoptosis.
49 SP600125) did not attenuate sodium butyrate/
perifosine-
induced apoptosis.
50 of xenografts in nude mice, suggesting that
perifosine-
induced autophagy protects cells from undergo
51 uction of p21(waf1/cip1) is required for the
perifosine-
induced cell cycle arrest because cell lines
52 sely, MEK inhibitor synergistically enhances
Perifosine-
induced cytotoxicity in MM cells.
53 tingly, MEK inhibitor significantly enhanced
perifosine-
induced cytotoxicity in WM cells.
54 Inhibition of JNK abrogates
perifosine-
induced cytotoxicity, suggesting that JNK pla
55 nsulinlike growth factor 1 (IGF-1) overcomes
Perifosine-
induced cytotoxicity.
56 The minimal p21 promoter region required for
perifosine-
induced p21 promoter activation contains four
57 Mutations in each particular Sp1 site block
perifosine-
induced p21(waf1/cip1) expression.
58 Importantly,
Perifosine induces apoptosis even of MM cells adherent t
59 ribose) polymerase cleavage, suggesting that
perifosine induces both apoptosis and autophagy.
60 We have shown previously that
perifosine induces p21(waf1/cip1) in a p53-independent f
61 port, we investigated the mechanism by which
perifosine induces p21(waf1/cip1) protein expression.
62 Perifosine induces significant cytotoxicity in both MM c
63 We observed that
perifosine induces the accumulation of p21(waf1/cip1) mR
64 In addition to inhibition of Akt,
perifosine inhibited the assembly of both mTOR/raptor an
65 ent study reveals a novel mechanism by which
perifosine inhibits Akt and the mTOR axis.
66 Collectively, we conclude that
perifosine inhibits mTOR signaling and induces autophagy
67 These results thus suggest that
perifosine inhibits the mTOR axis through a different me
68 Perifosine is a synthetic novel alkylphospholipid, a new
69 Perifosine is an alkylphospholipid exhibiting antitumor
70 These results indicate that
perifosine is an effective drug in gliomas in which Akt
71 Perifosine is an oral Akt inhibitor which exerts a marke
72 egulation by Akt knockdown and the inhibitor
perifosine leads to significant inhibition of proliferat
73 both conventional (dexamethasone) and novel (
perifosine,
lenalidomide, and bortezomib) therapies.
74 Some examples include
perifosine,
lovastatin, and UCN-01.
75 To determine whether
perifosine may enhance the antitumor activity of the ant
76 inase inhibitor desipramine attenuated HDACI/
perifosine-
mediated ceramide and ROS production as well
77 e (MEK) 1 or myristoylated Akt blocked HDACI/
perifosine-
mediated ceramide production and cell death,
78 yeloma (MM) cells is completely inhibited by
perifosine [
octadecyl-(1,1-dimethyl-piperidinio-4-yl)-ph
79 glioblastomas, we investigated the impact of
perifosine on glia in culture and on a mouse glioma mode
80 This study details the impact of
perifosine on proteome and lysine acetylome in SK-N-AS c
81 Ectopic Mcl-1 expression potently inhibited
perifosine/
PD184352-induced apoptosis, as did Bak or Bax
82 shed Bax/Bak binding, and sharply attenuated
perifosine/
PD184352-induced apoptosis.
83 pathways plays a critical functional role in
perifosine/
PD184352-mediated lethality.
84 ethasone at 20 mg if progression occurred on
perifosine plus bortezomib alone.
85 rial, we compared the efficacy and safety of
perifosine plus capecitabine (P-CAP) with placebo plus c
86 Treatment of the cells with
perifosine reduced baseline levels of phosphorylated Akt
87 Strikingly,
perifosine reduced the levels of Akt and other major com
88 inhibit Akt, other mechanisms contribute to
perifosine'
s anti-tumor activity.
89 PD184352 or U0126 and the PI3K/Akt inhibitor
perifosine strikingly induced apoptosis in multiple mali
90 Here we show that
perifosine strongly reduces phosphorylation levels of Ak
91 Moreover,
perifosine substantially increased the levels of type II
92 tified other signaling pathways modulated by
perifosine,
such as activation of ERK MAPK pathway, whic
93 hydroxamic acid (SAHA), or trichostatin with
perifosine synergistically induced mitochondrial dysfunc
94 Perifosine,
the only available oral ALK, is being studie
95 Addition of subtoxic doses of
perifosine to cetuximab treatment also enhanced the cetu
96 provide the rationale for clinical trials of
perifosine to improve patient outcome in MM.
97 horylation of SAPK/JNK that was activated by
perifosine treatment alone.
98 changes in the proteome and acetylome after
perifosine treatment in SK-N-AS neuroblastoma cells usin
99 Perifosine triggers c-Jun N-terminal kinase (JNK) activa
100 of cdk complexes in vitro demonstrated that
perifosine,
up to 20 microM, did not directly interfere
101 effect, rather than feedback activation, of
perifosine upstream ERK pathway.
102 Inhibition of Akt phosphorylation by
perifosine was seen in these cells.
103 tors (HDACIs) and the alkyl-lysophospholipid
perifosine were examined in human leukemia cells.
104 was potently inhibited by the Akt inhibitor
perifosine,
whereas SW1736, Hth74, WRO, KAT18, and TAD2
105 The combination of
perifosine with a lysosomal inhibitor enhanced apoptosis
106 itive to the antiproliferative properties of
perifosine with an IC(50) of similar0.6-8.9 microM.