Search results for " ERK"

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…

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…

Manganese overload affects p38 MAPK phosphorylation and metalloproteinase activity during sea urchin embryonic development.

2014

Abstract In the marine environment, manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. In earlier reports we found that the exposure of Paracentrotus lividus sea urchin embryos to manganese produced phenotypes with no skeleton. In addition, manganese interfered with calcium uptake, perturbed extracellular signal-regulated kinase (ERK) signaling, affected the expression of skeletogenic genes, and caused an increase of the hsc70 and hsc60 protein levels. Here, we extended our studies focusing on the temporal activation of the p38 mitogen-activated protein kinase (p38 MAPK) and the proteolytic activity of metalloprot…

Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways.

2011

Chemotherapy remains a commonly used therapeutic approach for many cancers. Indeed chemotherapy is relatively effective for treatment of certain cancers and it may be the only therapy (besides radiotherapy) that is appropriate for certain cancers. However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant patients. Unfortunately most of these drug transporter inhibitors have not proven effective for ther…

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…

Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model

2006

Several studies have shown that HER-2/neu (erbB-2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER-2-mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER-2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching-off HER-2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching-off HER-2. Interestingly, HER-2 downregulation caused a dephosphorylation of p-ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein…

Manganese interferes with calcium, perturbs ERK signaling, and produces embryos with no skeleton.

2011

Manganese (Mn) has been associated with embryo toxicity as it impairs differentiation of neural and skeletogenic cells in vertebrates. Nevertheless, information on the mechanisms operating at the cellular level remains scant. We took advantage of an amenable embryonic model to investigate the effects of Mn in biomineral formation. Sea urchin (Paracentrotus lividus) embryos were exposed to Mn from fertilization, harvested at different developmental stages, and analyzed for their content in calcium (Ca), expression of skeletogenic genes, localization of germ layer markers, and activation of the extracellular signal-regulated kinase (ERK). By optical and immunofluorescence microscopy, we found…

Harmaa eminenssi : Erkki Reijosen poliittinen toiminta Suomen historian murrosvuosina 1891-1923

1999

The effect of the HDACi JAHA on DNA methylation of breast cancer cells by down-regulating DNMT1 through ERK signaling

2014

Rigasches Wörterbuch

1913

Vorwort: "Der Zweck diese Büchleins ist, Rigasche Zustände und Rigasche Volksart in der Zeit um das Jahr 1869 und die Volkssprache, welche damals besonders am Dünaufer gebräuchlich war, frölich der volkommenen Vergessenheit einstweilen zu entziehen."