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Targeted disruption of the Akt gene in
2023-12-22
Targeted disruption of the Akt1 gene in mice induces a growth retardation phenotype [4,19]. Akt2 KO mice reveal mild growth retardation and insulin resistance [4,20,21]. Akt1/2 double KO (DKO) mice display severe growth deficiency and die shortly after birth. These mice exhibit impaired bone and ski
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Interestingly intermittent high doses of
2023-12-22
Interestingly, intermittent high doses of AKT inhibitors have been shown to be a more effective strategy both clinically and pre-clinically. High doses appear to be required for induction of apoptosis and intermittent schedules overcome the low therapeutic index of these compounds. This is particula
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TPMPA Growing evidence indicates that GRKs can exert
2023-12-22
Growing evidence indicates that GRKs can exert different effects within the cell depending on the stimulus, cell type, and localization [97], [121]. In this sense, we were the first to demonstrate a mitochondrial localization for GRK2 [122], later confirmed by other investigators [123], establishing
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Renal cell carcinoma RCC accounts for more than cancer death
2023-12-22
Renal cell carcinoma (RCC) accounts for more than 12,000 cancer deaths in the United States (Jemal et al., 2003). The current treatment includes surgical resection followed by interleukin-2 or Interferon-α treatment. Some patients experience distant metastatic lesions of RCC. In the last 5 years, re
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br LOX in esophageal cancer Various studies
2023-12-22
5-LOX in esophageal cancer Various studies suggest that abnormal levels of AA metabolites play an essential role in human esophageal adenocarcinogenesis (EAC). The key AA derivatives of 5-LOX signaling molecules namely include, 5-HETE, LTB4, and cysteinyl LTs, which are well-known to initiate inf
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In addition to the above mentioned synaptic mechanisms
2023-12-22
In addition to the above-mentioned synaptic mechanisms, the serotonergic system also has a critical role in the antidepressant effects of mGlu2/3 receptor antagonists. Indeed, we previously reported that mGlu2/3 receptor antagonists increased the firing rate of serotonin neurons in the dorsal raphe
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The first description of autophagy as
2023-12-22
The first description of autophagy as a tumour suppression process arises from the observation that the initial step regulatory gene, Atg6/BECN1, was monoallelically lost in 40% to 75% of human prostate, breast, and ovarian cancers [31]. However, while BECN1 heterozygous mutant mice develop, with lo
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At first the APC is a kDa protein divided into
2023-12-22
At first, the APC is a 310kDa protein divided into three domains such as N-terminal, central core and C-terminal domain [102], plays a major role to regulate the Wnt signaling pathway in human cancer by translating β-catenin from the rapamycin price to the nucleus [103]. The SIRT1 regulates the Wnt
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Aurora A overexpression is also related to the
2023-12-22
Aurora-A overexpression is also related to the activation of NF-κB, a potent anti-apoptotic effector that may play a role in preventing apoptosis in cancer Phorbol 12,13-dibutyrate sale [18]. These data show that we are still at the beginning of unraveling the complex mechanism by which these gene
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Deoxycholic acid Purification of Rv c In order to investigat
2023-12-22
Purification of Rv2477c. In order to investigate the catalytic capabilities of Rv2477c, we expressed the protein as an N-terminal histidine-tagged fusion protein in E. coli BL21 cells and purified the protein by cobalt-affinity chromatography. As shown in Fig. 2A, the 65 kDa fusion protein was expre
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br ACL Regulation and Role in Lipid Metabolism
2023-12-22
ACL Regulation and Role in Lipid Metabolism ACL is a ubiquitous enzyme at the nexus of nutrient catabolism and synthesis of cholesterol and fatty acids. In mammals, it is highly expressed in lipogenic tissues including adipose, liver, and lactating mammary glands [9]. In the presence of ATP and C
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Transient transfection with ATR kinase dead D
2023-12-22
Transient transfection with ATR kinase-dead (D2475→A) [30] and ATM kinase-dead (D2870→Ala and N2875→K) [31] constructs was performed using Fugene 6 (Roche Applied Science, Indianapolis). Three microliters of fugene 6+1μg plasmid was used in transfections using 6-well plates at 2×105 cells/well and a
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Treatment of all of the GYN cancer cells
2023-12-22
Treatment of all of the GYN cancer m6A in this study with ATRi not only reduced phosphorylation of Chk1 at Ser345 following genotoxic stress, but also phosphorylation of ATM. Loss of phospho-ATM following ATRi treatment is not likely due to non-specific targeting of ATM by ETP-46464 [28]. While ATR
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Crystal structures were obtained of
2023-12-22
Crystal structures were obtained of sulfonamide 18 and amide 19 as a derivative of amide 36 (Fig. 7A and B). The precise rotameric orientation of amide 36 was of significant interest to understand the compound's interaction with the protein. As it would be difficult to assign the rotomer of 36, the
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Hepatoid adenocarcinoma closely resembles HCC and in some
2023-12-22
Hepatoid adenocarcinoma closely resembles HCC and in some cases can be indistinguishable morphologically. Hepatoid adenocarcinoma is an aggressive neoplasm, and metastasis to the liver is common [12]. Gastric metastasis from HCC has also been reported [27]. Distinguishing hepatoid adenocarcinoma fro
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