ライフサイエンスコーパス: IMiD

1 IMiD-induced decrease of C/EBPbeta protein led to impair

2 IMiDs also block the stimulatory effect of insulinlike g

3 IMiDs diminished interleukin-2, interferongamma, and IL-

4 IMiDs display pronounced antiproliferative effect agains

5 IMiDs immunomodulatory drugs, including lenalidomide and

6 IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN

7 IMiDs, including lenalidamide and thalidomide, are also

8 opment stage of the model, we identified 176 IMiD response genes that were differentially expressed b

9 ever, IKZF1 is substantially lower in 3 of 5 IMiD-resistant MM cell lines.

10 re differentially expressed before and after IMiD exposure using pharmacogenomic GEP data from patien

11 Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune

12 kylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase

13 86.5% were double refractory to a PI and an IMiD.

14 and 88%, 78%, and 68% were refractory to an IMiD, a PI, or both, respectively.

15 The subgroup with an IMiD-14 score higher than the cutoff was deemed to be IM

16 5013 (Revlimid), an immunomodulatory analog (IMiD) of thalidomide, in multiple myeloma (MM).

17 that Thal and its immunomodulatory analogs (IMiDs) directly induce apoptosis or growth arrest of MM

18 e hypothesize that proteasome inhibitors and IMiDs are highly active because malignant plasma cells a

19 sphodiesterase (PDE) type IV inhibitors, and IMiDs, which have unknown mechanism(s) of action.

20 core higher than the cutoff was deemed to be IMiD-resistant.

21 105 patients (75%), were administered before IMiD-based salvage therapy.

22 immediately before sampling, with 43% being IMiD refractory and 46% being PI refractory in the most

23 nd use of IMiD-based therapy, delays between IMiD refills, and select health outcomes during the firs

24 thin CRL4(CRBN) and enantioselectively binds IMiDs.

25 Emerging evidence suggests that both IMiDs and PIs can have cardiovascular (CV) sequelae, whi

26 e, inhibition of the eIF4E-C/EBPbeta axis by IMiD compounds was not observed in IMiD-resistant MM cel

27 combined the 14 genes to create a continuous IMiD-14 score and an optimal cutoff.

28 Immunomodulatory derivatives (IMiDs), along with proteasome inhibitors, are key compon

29 (Thal) and its immunomodulatory derivatives (IMiDs), proteasome inhibitor PS-341, and As(2)O(3) act d

30 eblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM).

31 The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomid

32 of which had received immunomodulatory drug (IMiD) therapy.

33 Lenalidomide is an immunomodulatory drug (IMiD) with activity in lymphoid malignancies occurring p

34 otent analog of Thal, immunomodulatory drug (IMiD), on T cells.

35 had received both an immune modulatory drug (IMiD) and proteasome inhibitor: (35 [73%] of 48) were re

36 Lenalidomide is an immunomodulatory drug (IMiDs) with clinical efficacy in multiple myeloma (MM) a

37 inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory.

38 of retreatment with immunomodulatory drugs (IMiDs) among patients with multiple myeloma who received

39 The introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has greatly impro

40 pretreated with both immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs), and 88%, 78%, an

41 lidomide and related immunomodulatory drugs (IMiDs) exert their antitumor effects remains unclear.

42 Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are Food and Drug A

43 The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide yield high response

44 pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for mult

45 and lenalidomide are immunomodulatory drugs (IMiDs) that produce high remission rates in the treatmen

46 asome inhibitors and immunomodulatory drugs (IMiDs), resulting in a significant improvement in overal

47 ntitumor activity of immunomodulatory drugs (IMiDs).

48 he use of novel oral immunomodulatory drugs (IMiDs; lenalidomide and thalidomide) among beneficiaries

49 000 (introduction of immunomodulatory drugs [IMiDs]), respectively.

50 its potent analogs (immunomodulatory drugs [IMiDs]).

51 l and its analogues (immunomodulatory drugs, IMiDs) on MM cells was demonstrated, suggesting multiple

52 hese mutations were undetectable at earlier, IMiD-sensitive time points.

53 We establish ZFP91 as a bona fide IMiD-dependent CRL4(CRBN) substrate and further show tha

54 Median out-of-pocket cost for the first IMiD prescription was $3,178 for LIS nonrecipients and $

55 if, related to the IKZF1/3 ZnF, critical for IMiD-dependent CRBN binding.

56 eblon (CRBN) is an essential requirement for IMiD action, the complete molecular and biochemical mech

57 ummary, CRBN is an essential requirement for IMiD activity and a possible biomarker for the clinical

58 in the model could provide novel targets for IMiD resistance and therapeutic intervention.

59 A role for IMiDs, perhaps in combination with chemotherapy or andro

60 xpression of C/EBPbeta rescued MM cells from IMiD-induced inhibition of proliferation, indicating tha

61 ggest which patients would benefit most from IMiD-based therapies.

62 dentify patients most likely to benefit from IMiDs and suggest direct TrxR or Trx inhibitors for MM t

63 ral new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib

64 including epothilones and immunomodulators (IMiDs), as well as other novel agents within the new lan

65 a axis by IMiD compounds was not observed in IMiD-resistant MM cells.

66 3,038 beneficiaries, 41% received first-line IMiDs.

67 utic efficacy of microenvironment-modulating IMiDs.

68 Pomalidomide is a new IMiD with high in vitro potency.

69 rt investigating the underlying mechanism of IMiD-induced neutropenia and increased risk of VTE in mu

70 ined validation cohorts from four studies of IMiD combination regimens: the TT3a trial (thalidomide i

71 in 3 patients with CRBN mutations at time of IMiD resistance confirmed that these mutations were unde

72 yzed associations between the LIS and use of IMiD-based therapy, delays between IMiD refills, and sel

73 es both delineate the mechanism of action of IMiDs against MM cells in vitro and form the basis for c

74 myeloma; however, the mechanism of action of IMiDs is largely unknown.

75 ecent findings on the mechanism of action of IMiDs, its use as a new treatment modality for various h

76 thway did not block the anti-PEL activity of IMiDs.

77 thalidomide, in the antimyeloma activity of IMiDs.

78 nockdown of MYC enhanced the cytotoxicity of IMiDs.

79 on the recent advances in the development of IMiDs.

80 The anti-PEL effects of IMiDs involved cereblon-dependent suppression of IRF4 an

81 Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of

82 may enhance immune response and efficacy of IMiDs in MM.

83 es investigated the pleiotropic functions of IMiDs, with a particular focus on immune modulation, the

84 rtance to clarify the antitumor mechanism of IMiDs.

85 compelling evidence for clinical testing of IMiDs alone and in combination with BRD4 inhibitors for

86 order to establish better clinical usage of IMiDs, it is of utmost importance to clarify the antitum

87 More and more indications for the use of IMiDs in hematologic malignancies have been identified.

88 tients with multiple myeloma, but the use of IMiDs in multiple myeloma is associated with neutropenia

89 s derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of haematologic malignan

90 ast to down-regulation of C/EBPbeta protein, IMiD compounds did not alter C/EBPbeta mRNA levels or pr

91 95% CI, 16% to 47%) probability of receiving IMiDs among beneficiaries age 75 to 84 years and a signi

92 erapy of multiple myeloma followed by repeat IMiD (thalidomide [34; 24%] or lenalidomide [106; 76%])

93 ieved less than a partial response to repeat IMiD.

94 epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re

95 Although Thal/IMiDs, PS-341, and As(2)O(3) inhibit nuclear factor (NF)

96 e potential immunomodulatory effects of Thal/IMiDs in MM were examined.

97 It was demonstrated that Thal/IMiDs do not induce T-cell proliferation alone but act a

98 mononuclear cells (PBMCs) treated with Thal/IMiDs demonstrated significantly increased lysis of MM c

99 cells by autologous PBMCs treated with Thal/IMiDs was also observed.

100 Immunomodulatory derivatives of thalidomide (IMiD compounds), such as pomalidomide and lenalidomide,

101 immunomodulatory derivative of thalidomide (IMiD) CC-5013 induces apoptosis or growth arrest even in

102 Immunomodulatory derivatives of thalidomide (IMiDs) have been used for the treatment of myelodysplast

103 immunomodulatory derivatives of thalidomide (IMiDs), but not proteasome inhibitor PS-341, augmented M

104 Here we show that IMiD compounds down-regulate CCAAT/enhancer-binding prot

105 Here, we report that IMiDs work primarily via inhibition of peroxidase-mediat

106 We show that IMiDs down-regulate PU.1, a key transcription factor inv

107 It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX

108 Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding t

109 The IMiD-14 model warrants evaluation in prospective studies

110 free survival was 52% (95% CI 42-64) for the IMiD-14 high group versus 85% (78-92) for the IMiD-14 lo

111 MiD-14 high group versus 85% (78-92) for the IMiD-14 low group, with a hazard ratio (HR) of 2.51 (95%

112 ed to characterize second tumor risks in the IMiD era.

113 oint was to show the prognostic value of the IMiD-14 gene signature for progression-free survival.

114 INTERPRETATION: Our results suggest that the IMiD-14 model has prognostic value in patients with mult

115 Moreover, Thal and the IMiDs enhance the anti-MM activity of Dex and, conversel

116 the development and testing of Thal and the IMiDs in a new treatment paradigm to target both the tum

117 poptotic signaling triggered by Thal and the IMiDs is associated with activation of related adhesion

118 osts for expensive anticancer drugs like the IMiDs may improve access to oral therapy for patients wi

119 n the present study, we demonstrate that the IMiDs trigger activation of caspase-8, enhance MM cell s

120 an time from diagnosis to repeat exposure to IMiD was 28 months.

121 nsitivity of human multiple myeloma cells to IMiDs.

122 hat we believe a critical mechanism by which IMiDs drugs function as therapeutic immunomodulatory age

123 ignificantly shorter in the 83 patients with IMiD-14 high scores than in the 92 patients with IMiD-14

124 -14 high scores than in the 92 patients with IMiD-14 low scores; 3 year progression-free survival was

125 oma who were treated in clinical trials with IMiD-containing regimens.

126 evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM.

127 e-binding pocket but is not competitive with IMiDs.

128 Patients treated with IMiDs had significantly fewer emergency department visit

129 s with multiple myeloma who are treated with IMiDs.

130 n effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression.

131 with patients receiving bortezomib (without IMiDs), but 1-year overall survival and cumulative Medic