1 MTSEA(+) modification of the dimer occurs in
two hits.
2 Interestingly, a distinct
two-hit activation process has been recently described f
3 y (ALI): LPS-induced inflammatory injury and
two-hit ALI caused by suboptimal mechanical ventilation
4 The availability of this ras and p53
two-hit animal model system recapitulating HNSCC progres
5 oteins probably retain some function and the
two hits are co-selected to produce an optimal level of
6 gression, leading to selection for more than
two hits at the APC locus.
7 ary models, such as oncogene activation and "
two hits"
at tumor suppressor loci.
8 The '
two hits'
at APC are coselected so as to produce an opti
9 Two hits,
ATA and NF023, obtained in both screens were c
10 are induced by paracrine factors released by
two-hit cells in the dermis and that proliferation with
11 Two-hit cells were not detected in the epidermis.
12 location of cells with biallelic mutations ("
two-hit"
cells) was unclear.
13 Both EMyT and cilium loss require
two-hit conditions: disassembly/absence of intercellular
14 o initiate tumorigenesis through the classic
two-hit CRC pathway.
15 We employed a
two-hit endotoxemia/pneumonia model, whereby administrat
16 In this article, we describe
two hit finding approaches leading to the discovery of n
17 Two hits from commercial sources (1, 2) were found activ
18 in vivo activity of hsp110 (CG6603) or tra1,
two hits from the screen, affects neurodegeneration in a
19 cular and immunohistochemical evidence for a
two-hit (
germline plus somatic) mutation mechanism.
20 The '
two-hit'
group exposed to KA on both P15 and P45 had hig
21 res, and the greater neuronal injury in the '
two-hit'
group.
22 ses for 3p12 markers hence obeying Knudson's
two hit hypothesis.
23 These data support a
two-hit hypothesis as a mechanism of cystogenesis.
24 al mitotic alterations in AD and explain the
two-hit hypothesis by describing how both mechanisms are
25 r initiation of disease, evidence suggests a
two-hit hypothesis for antibody attack on the valve endo
26 In this study, we investigate the
two-hit hypothesis for CCM pathogenesis.
27 ction comprising the second hit of Knudson's
two-hit hypothesis is important in human cancer.
28 Knudson's
two-hit hypothesis postulates that genetic alterations i
29 ignant transformation, and suggest Knudson's
two-hit hypothesis should now be expanded to include epi
30 This work provided the foundation for the
two-hit hypothesis that explained the role of recessive
31 ss signalling pathways in AD, we proposed a "
two-hit hypothesis" which states that although either ox
32 The seminal '
two-hit hypothesis' implicitly assumes that bi-allelic t
33 According to Knudson's
two-hit hypothesis, the remaining allele is lost, either
34 Based on the
two-hit hypothesis, we attempted to improve the penetran
35 These findings support a
two-hit hypothesis, whereby cytoplasmic mislocalization
36 genomic DNA, apparently violating Knudson's
two-hit hypothesis.
37 genetic silencing, thus fulfilling Knudson's
two-hit hypothesis.
38 A "
two-hit"
hypothesis predicts a second somatic hit, in ad
39 ibit embryonic lethality; this supports the "
two-hit"
hypothesis, which proposes that a germline muta
40 lcoholic fatty liver disease (NAFLD) is the "
two-hit"
hypothesis.
41 causes rather than the long-held Knudson's '
two-hit'
hypothesis; the evidence that retinoma may repr
42 Here we use a '
two-hit'
immune-activation paradigm to determine whether
43 IT may be inactivated in accordance with the
two-hit inactivation model, involving deletion of one al
44 that malignant transformation requires full "
two-hit"
inactivation of a tumor-suppressor gene.
45 enes predispose kindreds to HNPCC suggest a "
two-hit"
inactivation of both alleles of a particular MM
46 ealthy volunteer monocytes using an in vitro
two-hit inflammation model.
47 sruption of tight junction integrity after a
two-hit injury with burn and E. faecalis infection, but
48 nst Hsp90 and the subsequent optimization of
two hits into leads with inhibitory activities in the lo
49 Thus, for both L9 and L26 genes, we observe "
two hit"
kinetics commonly observed in genes suppressing
50 the canonical substrate group for PTP1B; the
two hit lists were also very different from each other.
51 variably Rb1(-/-), modeling tumorigenesis by
two-hit loss of RB1 in humans.
52 c inactivation of 1p36 genes in the classic "
two-hit"
manner is scarce; however, many tumor suppresso
53 ns confirm that rhabdomyomas occur through a
two hit mechanism of pathogenesis.
54 in mouse knockout models strongly supports a
two-hit mechanism for cyst formation.
55 n human cancer and typically occur through a
two-hit mechanism involving a missense mutation in one a
56 These results suggest that if a
two-hit mechanism is required for cyst formation in PKD2
57 In keeping with the
two-hit mechanism of cyst formation, approximately 70% o
58 oss-of-function mutations in PRKCSH, and the
two-hit mechanism operational in dominant polycystic kid
59 the malignant transformation of NSCLC via a
two-hit mechanism, including epigenetic changes and alle
60 ic kidney disease, ADPLD may also occur by a
two-hit mechanism.
61 t of benign tumors, hamartomas, occurs via a
two-hit mechanism.
62 or suppressor gene is altered in PNTs by the
two-hit mechanism.
63 ical manifestation of ADPKD also occurs by a
two-hit mechanism.
64 associated with Pkd2 deficiency occurs by a
two-hit mechanism.
65 and produce susceptibility to cancer by the
two-hit mechanism.
66 cer genomes are often thought to arise as a "
two-hit"
mechanism in the process of tumor-suppressor ge
67 Our study identifies a potential "
two-hit"
mechanism in which tau acetylation disengages t
68 Our data support a "
two-hit"
mechanism of CTF aggregation dependent on TDP-4
69 lts suggest that (a) RASSF1A inactivation by
two hits (
methylation and loss) is a critical step in SC
70 1 gene usually behave according to Knudson's
two hit model for tumor suppressor genes, seven of eight
71 The results indicate that the "
two hit model" is equally applicable to patients with VH
72 to the view of LIP-driven autoimmunity as a
two hit model; however, not all cofactors have equal abi
73 Our data support a
two-hit model in which the 16p12.1 microdeletion both pr
74 th variable expressivity indicates that this
two-hit model might be more generally applicable to neur
75 s one of the original paradigms of Knudson's
two-hit model of cancer formation, it has become apparen
76 en prion/amyloid disease development and the
two-hit model of cancer progression.
77 ith the unstable Pkd2(WS25) allele suggest a
two-hit model of cystogenesis.
78 These findings challenge the assumed
two-hit model of Emu-Myc lymphoma and demonstrate a func
79 retch) and thrombin in a previously verified
two-hit model of in vitro ventilator-induced lung injury
80 Using a clinically relevant
two-hit model of sepsis, i.e., cecal ligation and punctu
81 The proposed
two-hit model of TRALI is also supported by animal studi
82 view article by Brux and Sachs clarified the
two-hit model of TRALI pathogenesis.
83 We have shown that the
two-hit model requires modification for the APC TSG, bec
84 ific deletion of Adora2b to ALI, utilizing a
two-hit model where intratracheal LPS treatment is follo
85 Recently, the '
Two-hit model' was used to explain the phenotypic variab
86 According to a
two-hit model, antigen exposure associated with genetic
87 These results suggest a
two-hit model, in which the synergistic induction of bot
88 n ADPKD cyst epithelia in the context of the
two-hit model.
89 enetic predisposition and an immune-mediated
two-hit model.
90 or gain of function, thereby introducing a "
two-hit model." This is highly relevant for cancer resea
91 Consistent with Knudson's "
two hit"
model of tumor suppressor genes, leukemias and
92 The general miRNA patterns followed a "
two-hit"
model as a function of nicotine exposure and ab
93 d within a neurodevelopmental/vulnerability "
two-hit"
model for the etiology of schizophrenia.
94 These data extend the "
two-hit"
model of cystogenesis to include a second focal
95 We propose a "
two-hit"
model of ER stress-induced cell death involving
96 Taken together these findings implicate a "
two-hit"
model of inflammatory resolution, whereby activ
97 The '
two-hit'
model is a widely accepted genetic mechanism fo
98 suggests that CCM pathogenesis may follow a
two-hit molecular mechanism, similar to that seen for tu
99 In a
two-hit mouse model of sepsis, we show that tolerance to
100 Testing the
two-hit mouse model should both add new knowledge to the
101 ally, in vivo confirmation was obtained in a
two-hit murine model of VILI where pharmacological inhib
102 ms of CCM have a genetic underpinning of the
two-hit mutation mechanism in the known CCM genes.
103 ns, indicating that CCM follows a Knudsonian
two-hit mutation mechanism.
104 loss of CCM protein staining, supporting the
two-hit mutation mechanism.
105 rine glycine receptor beta subunit gene is a
two-hit mutation, where the hypomorphic alteration in an
106 Therefore,
two "hits,"--
often, but not always, two cleavage events-
107 or cell have been sequentially inactivated ("
two-hit"
oncogenesis mechanism).
108 ce of loss of heterozygosity, the biallelic (
two-hit)
or maximal silencing of LOT1 requires both proc
109 ng through TAS-like genes (TASL), one-hit or
two-hit,
or even two layers of tasiRNA-TASL interactions
110 New data from animal models suggest a
two hit origin of leukemic translocations, where there m
111 form/obliterative arteriopathy induced via a
two-hit pathophysiological mechanism without hypoxia pro
112 In addition, a new example of apparent "
two-hit"
phasiRNA processing was identified.
113 econd, often trivial, stimulus (a so-called "
two hit"
phenomenon).
114 Rb1(+/-) mice incur "
two-hit"
pituitary tumorigenesis; Skp2(-/-);Rb1(+/-) mic
115 Furthermore, in a '
two-hit'
pneumonia model in mice, we have been able to d
116 oncogenic events in such cancers because of
two-hit precursor lesions that have a low probability of
117 ppressor is completely inactivated through a
two-hit process involving a point mutation in one allele
118 Our findings support a
two-hit process of cuprizone-induced demyelination, supp
119 ose that autophagy-mediated cell death is a "
two-hit"
process: Following the cellular stress of the a
120 Further characterization of
two hits revealed that the small molecule HDAC inhibitor
121 targets should permit the extension of this "
two-hit"
reverse genetics methodology to other RV genes.
122 Instead neurodegeneration may involve a
two-hit scenario where interference with OPC differentia
123 ing a kainic acid (KA)-induced, established '
two-hit'
seizure model in rats.
124 Here we establish a "
two-hit"
stress model in mice wherein stress at a specif
125 ative stress and chelatable iron thus act as
two "hits"
synergistically promoting toxic radical forma
126 throughput screening (HTS) campaign revealed
two hits that were nominated for further optimization st
127 My analysis supports Knudson's
two-hit theory but is much simpler and easier to underst
128 t for an extra genetic "hit" contradicts the
two-hit theory for the accelerated carcinogenesis associ
129 al microcirculation are in concert with the "
two-hit"
theory for MSOF.
130 clinical scenario has led to the idea of a "
two-hit"
theory for the development of MSOF, the hallmar
131 esis, we optimized the binding affinities of
two hits to the low nanomolar range.
132 ), demonstrating for the first time that the
two-hit tumor suppressor gene model applies to the TSC-a
133 plastic complications arise from a classical
two-hit tumor suppressor gene model.
134 t in part, by differences in the location of
two-hit tumor suppressor genes across the genome.
135 f clear-cell type (the most common type) are
two-hit tumor suppressor genes, and they cluster in a 43
136 t allele ratios) identified several putative
two-hit tumor suppressor genes, including BAP1.
137 These results support a
two-hit tumor suppressor model for the pathogenesis of S
138 n, implying that ARF can act as a canonical "
two-hit"
tumor suppressor gene.
139 tudies, suggesting that p19ARF is a classic '
two hit'
tumor suppressor.
140 As few as one or
two "hits"
with methylglyoxal per protein molecule have