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AKT Phosphorylation - Crossref

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Last Updated: 13 June 2022

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Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation

"Abstract Purpose: Mutations in the epidermal growth factor receptor are strongly predictive of gefitinib action in non-u2013small-cell lung cancer non-cell lung cancer. " Conclusions: EGFR mutation and high gene copy number were both correlated with improved objective response in univariate tests. Patients with either K-ras mutation or p-Akt overexpression in EGFR nonmutants and time-to-progression had poor reaction and time-to-progression, causing poor response and time-to-progression, but patients with high gene copy number had improved outcomes in univariate testing. Gefitinib was not given by a patient with a HER2 mutation. Conclusion: The single most significant predictor of gefitinib sensitivity is a GEFITinib-sensitive EGFR mutation. In addition to EGFR mutation, K-ras mutation, and Akt phosphorylation, an EGFR mutation, K-ras mutation, and Akt phosphorylation aid can help with the prediction of gefitinib response in non-u2013small-cell lung cancer non-u2013small cell lung cancer.

Source link: https://doi.org/10.1158/1078-0432.ccr-05-2845


Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK–Mediated Phosphorylation of Akt

"Abstract Purpose: Although a previous research found that nerve ending-u2013-derived acetylcholine promoted prostate cancer proliferation and metastasis by altering cancer cells' microenvironment, the present study seeks to determine whether autocrine cholinergic signaling in prostate epithelial cells promotes prostate cancer proliferation and castration resistance. In this research, IHC was used to detect protein expression in mouse prostate tissue sections and human prostate cancer tissue sections. The role of autocrine cholinergic signaling in controlling prostate cancer development and castration resistance was tested in subcutaneously and orthotopically xenografted tumor models. Result: We discovered the expression of choline acetyltransferase, the mishylogue secretion of acetylcholine, and the expression of CHRM3 in prostate epithelial cells, contributing to the presence of autocrine cholinergic signaling in prostate epithelium. In addition, we found that CHRM3 was elevated in clinical prostate cancer tissues compared to nearby non-cancer tissues. ".

Source link: https://doi.org/10.1158/1078-0432.ccr-14-3163


7-Hydroxystaurosporine (UCN-01) Inhibition of Akt Thr308 but not Ser473 Phosphorylation

"We investigated the effect of UCN-01 on insulin-stimulated glucose transport activity in isolated rat adipose cells to determine the mechanism for this study. " Increasing numbers of UCN-01 up to 2. 5 bcmol/L progressively raise the insulin dose-response curve even higher. We also investigated the effects of UCN-01 on Akt activation in whole-cell homogenates of these cells as Akte is known to mediate in part. Decreased glucose transport activity directly parallels reduced Akt Thr308 phosphorylation in both an insulin and UCN-01 dose-dependent manner, but not so much, when phosphatation is limited only to the lowest insulin level, and then modestly. As expected from the glucose transport activity results, UCN-01 also inhibits insulin-induced Thr308 but not Ser473 phosphorylation of Akt associated with the plasma membranes and low-density microsomes and inhibits translocation of GLUT4 from low-density microsomes to plasma membranes, as expected from insulin-induced Thr308 and ser473 inhibitions.

Source link: https://doi.org/10.1158/1078-0432.ccr-04-0772


Cytoplasmic Sequestration of p27 via AKT Phosphorylation in Renal Cell Carcinoma

"Little is known about p27 expression in renal cell carcinoma or how p27 plays a role in disease progression or response to therapy. " P27 was found in tumors in comparison to matched controls, and cytoplasmic mislocalization of p27 was related to rising tumor grade. Localization of p27 at T157, an AKT phosphorylation site in the p27 NLS, correlates with phosphorylation at T157. p27 activation and phosphorylation of p27 was associated with resistance to apoptosis, and small interfering RNA knockdown of p27 or relocalization to the nucleus raised apoptosis in RCC cells, as shown by increased apoptosis. P27 delocalization of p27 was achieved by pyrolytic inhibition by rapamycin, but mTOR inhibition by rapamycin did not occur. PI3K inhibition reduces T157 phosphorylation and leads to nuclear relocalization of p27, while mTOR inhibition does not. These results should support a clinically appropriate strategy for using mTOR and PI3K/AKT pathway inhibitors in patients with RCC. ".

Source link: https://doi.org/10.1158/1078-0432.ccr-08-0170


Phosphorylation of Akt (Ser473) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer

"We wanted to determine the prognostic value of Akt activation in a cohort of patients with OSCC, as well as the relationship between phosphorylated Akt and PTEN levels. " Methods: We investigated the protein expression levels of phosphorylated Akt and PTEN on a tissue microarray using a novel approach to in situ quantitative protein expression analysis. Patients with tumor p-Akt levels had lower 5-year local recurrence rates compared to patients with tumor p-Akt levels. PTEN and nuclear PTEN were found in a strong inverse relation between nuclear p-Akt and nuclear PTEN: Tumors with elevated nuclear p-Akt had low nuclear PTEN and vice versa. Akt activation in OSCC is linked to adverse patient outcomes, indicating that Akt is a promising molecular target in OSCC. PTEN depletion could be one of the underlying causes of Akt activation in OSCC," says the OSCC's PTEN depletion.

Source link: https://doi.org/10.1158/1055-9965.epi-06-0121


Motexafin gadolinium modulates levels of phosphorylated Akt and synergizes with inhibitors of Akt phosphorylation

"MGd treatment of the follicular lymphoma cell line HF-1 resulted in growth inhibition and apoptosis, but not apoptosis," the Burkitt's lymphoma-u2013-derived cell line Ramos resulted in growth inhibition and apoptosis, but not apoptosis. " Before cell function deregulation, cells increased within 30 minutes after MGd's treatment of HF-1, but after four hours, they began to decline to below baseline values. The addition of specific inhibitors of Akt phosphorylation in MGd-treated HF-1 and Ramos cells reduced pAkt levels in MGd-treated HF-1 and Ramos cells, which synergistically increased cell death. MGd was also tested in combination with celecoxib, an Akt phosphorylation inhibitor, or docetaxel, a microtubule inhibitor that can reduce Akt phosphorylation. These results point to a potential role for pAkt in MGd-induced apoptosis, suggesting that MGd's activity could be enhanced by mixing pAkt with agents that inhibit Akt phosphorylation. ".

Source link: https://doi.org/10.1158/1535-7163.mct-05-0280


Abstract C51: eIF2alpha phosphorylation determines cell susceptibility to oxidative stress via Akt activation.

"Specifically, genetic inactivation of either eIF2u03b1P or the ER-resident kinase PERK in primary mouse or human fibroblasts leads to increased reactive oxygen species production leading to increased DNA loss, Akt hyperactivation, and senescence induction. " Intrinsic ROS created by eIF2P inactivation, according to the primary cells, immortalized and tumor cells are tolerant to elevated levels of intrinsic ROS caused by elevated levels of intrinsic ROS. Nevertheless, immortalized or tumor cells treated by eIF2u03b1P-deficient immortalized or tumor cells are more vulnerable than eIF2u03b1P-proficient cells to extrinsic oxidative stress induced by hydrogen peroxide or doxorubicin therapy. Both in vitro and in vivo by impaired Akt activation, extrinsic oxidative stress leads to the induction of either senescence or death in eIF2u03B1P-deficient tumor cells in vitro and in vivo. Akt responds to oxidative stress in a cell-context dependent manner, according to our findings. Also, eIF2b1P is a potential pharmacological target for tumor treatment in combinational therapies with drugs that stimulate oxidative stress. ".

Source link: https://doi.org/10.1158/1535-7163.targ-13-c51


Abstract A40: Detection of Erk1/2, Mek1/2, and Akt isoform phosphorylation in tumors of 115 patients with different cancer types using the NanoPro™1000 technology.

"Abstract Prostract network analysis has greatly increased in importance in the field of cancer research and therapy. " In particular, the activation status of growth factor receptor-related signal cascades identified by phosphoproteins as a key mediators of cellular signaling is being scrutinized. The activation status of cell signaling proteins must be investigated in order to determine this heterogeneity on the proteome level. Using the NanoPro1000u2122 technology, we investigated selected key proteins from two EGF-receptor downstream pathways in breast cancer, non-small cell lung cancer, colorectal cancer, and liver metastases of colorectal cancer. The statistical analysis of results revealed that isoform phosphorylation of Erk1/2, Mek1/2, and Akt significantly differed among individual patients but not between tumor entities, but not between tumor entities. The degree of overall phosphorylation, as well as individual patterns of isoform phosphorylation, were characterized by differences in phosphorylation patterns. This means that in-depth examination of isoform phosphorylation can reveal significant biological differences and may lead to therapeutically useful, predictive signatures independent of mutation status. The analysis of patients on the proteome level may help to determine predictive biomarker for the onset of resistance to anti-EGF-receptor therapy, which may help to determine personalized medicine. Using the NanoProu21221000 technology, detects Erk1/2, Mek1/2, and Akt isoform phosphorylation in tumors of 115 patients with various cancer types.

Source link: https://doi.org/10.1158/1535-7163.targ-13-a40


Abstract C227: Doxorubicin induces AKT phosphorylation through activation of the aryl hydrocarbon receptor in the heart

"Abstract Doxorubicin is one of the most potent anticancer drugs for treating various types of tumors. " However, the cardiovascular responses of the heart to DOX therapy are also unknown. Aryl hydrocarbon receptor, a ligand-activated transcription factor that is mainly involved in the detoxification of xenobiotic agents that produce ROS, is a ligand-activated transcription factor. We hypothesize that DoX treatment activates AhR and initiates Akt phosphorylation as a defense mechanism against oxidant stress. A significant rise in AhR protein levels in the nuclear fraction incubated with 2. 5 M DOX for 4 hours, which then returned to baseline levels after 24 hours of therapy, which then decreased to baseline levels by 24 hours of therapy. After 4 hours of DOX therapy, immunoprecipitation of the nuclear protein fraction with AhR antibodies and subsequent immunoblotting with ARNT1 antibodies revealed increased binding between these proteins. During 4 hours of DOX therapy, phosphatation of Akt in Ser473 was found, which decreased by 24 hours. Following DOX treatment in H9C2 cells, increased ROS production, as well as cytotoxicity, transfection with either AhR or ARNT1 siRNAs inhibited the phosphorylation of Akt following DOX treatment in H9C2 cells. Separate adult rat cardiomyocytes received a similar pattern of change in Akt phosphorylation and its downstream targets, as well as increased oxidative stress. After 4 hours, Oxidative stress was much higher in mice treated with DOX. In addition, silencing AhR leads to elevated respiratory stress and elevated cell toxicity, which may lead to increased oxidative stress and increased cellular toxicity. ".

Source link: https://doi.org/10.1158/1535-7163.targ-09-c227


Abstract C200: Effects of PI3K/Akt pathway inhibition on global proteome levels and phosphorylation signaling in patient-derived xenograft models of triple negative breast cancer

"Abstract AIM: The aim of this study was to find markers that may have the ability to predict BKM120 safety in triple negative breast cancer. INTRODUCTION: Triple negative breast cancer is the most common subtype of breast cancers, accounting for around 20% of all breast cancers. The absence of estrogen-, progesterone, and HER2/neu expression is characterized by this subtype of breast cancer. Since these are the operational receptors for targeted breast cancer treatments, the new standard therapy instead insists on conventional cytotoxic chemotherapy. Unfortunately, the overwhelming majority of triple negative breast cancer patients does not have a positive response, and new therapeutic agents are needed. Differential analysis of BKM120-treated responsive and resistant tumors' global proteome and phosphoproteome may reveal genes, colors, and pathways related to clinical response to precision therapy. After BKM120 therapy, we obtained tumor tissue from three negative breast cancer xenografts that were propagated in the mammary fat pads of NOD SCID mice. Tumor tissue from six different mouse models under five experimental conditions was lysed and digested into peptides for mass spectrometry experiments. Samples were labeled with TMT6-plex reagents and analyzed in concert with one reference sample in a total of 6 TMT6-plex experiments. Further canonical pathways were discovered using Gene Set Enrichment Analysis on a sample-by-sample basis, and additional network and pathway analyses were done using the network analysis program GeNets, as well as Ingenuity Pathway Analysis. In patient-derived xenograft models of triple negative breast cancer, the effects of PI3K/Akt pathway inhibition on global proteome levels and phosphorylation signaling have been shown.

Source link: https://doi.org/10.1158/1535-7163.targ-15-c200

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions