Search results for "mek"
showing 10 items of 844 documents
Zvaigžņotā Debess: 2013/14, Ziema (222)
2013
Latvijas Universitāte
Izmeklētāja lēmumi un to pārsūdzība kriminālprocesā
2017
Bakalaura darbam tika izvēlēta šāda tēma, jo 2005. gadā, stājoties spēkā Kriminālprocesa likumam, likumdevējs paredzējis, ka vairākus, ar pirmstiesas kriminālprocesa izmeklēšanu saistītus lēmumus, procesā iesaistītās personas nevar pārsūdzēt. Kā rezultātā, darba mērķis bija noskaidrot, vai likumdevējs liedzot personām pārsūdzēt pirmstiesas procesa izmeklēšanā lēmumus, nav ierobežojis personu tiesības uz taisnīgumu, vai ierobežojums ir samērīgs un vai tas nerada šķēršļus lietas savlaicīgai un taisnīgai atrisināšanai. Autore veica aptauju, kuras laikā ieguva prokuroru un izmeklētāju viedokli par izmeklētāju lēmumu pārsūdzību kriminālprocesā. Veicot literatūras analīzi, apkopojot pieejamo info…
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health
2011
William H. Chappell 1 , Linda S. Steelman 1,2 , Jacquelyn M. Long 2 , Ruth C. Kempf 2 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Jorg Basecke 3 , Franca Stivala 4 , Marco Donia 4 , Paolo Fagone 4 , Graziella Malaponte 4 , Maria C. Mazzarino 4 , Ferdinando Nicoletti 4 , Massimo Libra 4 , Danijela Maksimovic-Ivanic 5 , Sanja Mijatovic 5 , Giuseppe Montalto 6 , Melchiorre Cervello 7 , Piotr Laidler 8 , Michele Milella 9 , Agostino Tafuri 10 , Antonio Bonati 11 , Camilla Evangelisti 12 , Lucio Cocco 12 , Alberto M. Martelli 12,13 , and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University 2 Department of Physics, Greenville, N…
Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition …
2007
The molecular mechanisms behind the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are not completely understood and cannot be explained by the inhibition of the cyclooxygenase (COX) enzymes COX-1 and COX-2 alone. We previously reported that both the selective COX-1 inhibitor SC-560 and the selective COX-2 inhibitor CAY10404 exhibit anti-tumor effects in human hepatoma cells. NSAID inhibitors have many COX-independent actions and, among others, the mitogen-activated protein kinase (MAPK) pathways are targets for NSAIDs. Here, we examined the role of MEK/ERK1/2 signaling in the anti-neoplastic effects of both selective COX-1 and COX-2 inhibitors in two human hepato…
The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.
2011
Lung cancer is a malignant disease with poor outcome, which has led to a search for new therapeutics. The PI3K/Akt/mTOR and Ras/raf/Erk pathways are key regulators of tumor growth and survival. In the present study, their roles were evaluated by MTT assay, flow cytometry and Western blotting in lung cancer cells. We found that a high efficacy of antitumor activity was shown with GDC-0941 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In addition, H460 cells with activating mutations of PIK3CA were relatively more sensitive to GDC-0941 than A549 cells with wild-type PIK3CA. Furthermore, GDC-0941 was highly efficacious in combination with U0…
Emerging MEK inhibitors
2010
IMPORTANCE OF THE FIELD: The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways. This pathway can often be effectively silenced by MEK inhibitors. AREAS COVERED BY THIS REVIEW: This review will discuss targeting of MEK which could lead to novel methods to control abnormal proliferation which arises in cancer and other proliferative diseases. This review will cover the scientific literature from 1980 to present and is a follow on from a review which fo…
Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prost…
2020
Background TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging. Results Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemothera…
Emerging Raf inhibitors
2009
The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs.This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evalua…
Synergistic Growth Inhibitory Activity of Combined Mek/Mtor Pathway Blockade in Pten-Null Cancers
2014
ABSTRACT Aim: We have recently shown that induction of PTEN expression plays an integral role in MEK inhibitors' antitumor activity. Here we hypothesize that PTEN status critically influences the functional outcome of combined MEK and PI3K/mTOR inhibition. Methods: Single and combined MEK (trametinib, T) and mTOR (everolimus, E) blockade were assessed in a panel of cancer cell lines and in patient-derived lung and colon cancer stem cells (L- or C-CSC). Pharmacologic interactions were analyzed by conservative isobologram analysis. PTEN role was assessed by shRNA-mediated silencing or overexpression by stable transfection. Treatment-induced changes in the phosphoproteome were analyzed by anti…
Nelielas tīmekļa lietotnes neformālās izstrādes vadlīnijas
2015
Darba ietvaros, pamatojoties uz tīmekļa lietotņu un to ieviešanas pieeju analīzi, tiek definētas vadlīnijas nelielas tīmekļa lietotnes ieviešanai, izmantojot neformālu pieeju. Balstoties uz definētajām vadlīnijām, kā prototips tiek izstrādāta neliela un nesarežģīta tīmekļa lietotne elektronisko pieprasījumu pārvaldībai, kuras izveides apraksts ir sniegts darbā, tādējādi ilustrējot izstrādāto vadlīniju izmantošanu lietotnes izstrādes procesā. Lai nodrošinātu noteiktu darba mērķu sasniegšanu, darba sākumā ir analizēta tīmekļa lietotņu būtība, īsi apskatīta to vēsture, analizētas tīmekļa lietotņu tehnoloģijas, kā arī iztirzāti tīmekļa lietotņu arhitektūras varianti. Darba turpinājumā ir definē…