Search results for " signaling."
showing 10 items of 1032 documents
Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.
2008
Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr-abl-driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr-abl dependent- and independent-signaling pathways in imatinib-resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STAT5 and CrkL a…
Identification of the Weevil immune genes and their expression in the bacteriome tissue
2008
Abstract Background Persistent infections with mutualistic intracellular bacteria (endosymbionts) are well represented in insects and are considered to be a driving force in evolution. However, while pathogenic relationships have been well studied over the last decades very little is known about the recognition of the endosymbionts by the host immune system and the mechanism that limits their infection to the bacteria-bearing host tissue (the bacteriome). Results To study bacteriome immune specificity, we first identified immune-relevant genes of the weevil Sitophilus zeamais by using suppressive subtractive hybridization (SSH) and then analyzed their full-length coding sequences obtained b…
Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer
2020
The multifaceted nature of ovarian cancer has severely hampered the development of effective therapeutics over the years. The complicate nature of ovarian cancer makes it therapeutically challenging, therefore, there has been a renewed interest in phytochemistry. Phytochemicals have emerged as a potential therapeutic option due to less side effects. Moreover, the signaling inhibition properties have also been studied extensively in recent times. A growing number of data obtained via high-throughput technologies has started to delineate the complex oncogenic signaling networks, thus broadening the therapeutic opportunities. Within the network, microRNAs (miRNAs) have been shown to play a ve…
Interleukin 23p19 inhibitors in chronic plaque psoriasis with focus on mirikizumab: A narrative review.
2020
Psoriasis, a T-cell mediated chronic dermatosis, has a complex etiopathogenesis. There has been extensive research into the aberrant immune response, which leads to the formation of clinical lesions, and the need for developing better and safer drugs has been unrelenting. The past two decades of research has opened up new areas of the immune pathway that can be targeted in order to control the disease. Therefore, we have seen the emergence of biologics which either target T-cell receptors or inhibit Tumor Necrosis Factor-alpha (TNF-α) or inhibit interleukins (IL) like IL-12, IL-17, IL-17 receptor, and more recently IL-23. Drugs specifically targeting the p19 subunit of IL-23 have shown prom…
Effect of estrogen in malignant melanoma
2021
Background Melanoma is associated with poor prognosis in its advanced stages. Potential influence of estrogen and its metabolites on melanoma growth has been suggested. Aims The objective of this review was to provide an overview on the evidence related to estrogen in malignant melanoma. Materials and methods Literature search using PubMed, Google Scholar and relevant cross-references of the retrieved articles was performed to review relevant published articles related to estrogen and its effects in malignant melanoma. Results Effect of estrogen signaling on a tissue largely depends on the relative expression of estrogen receptors (ER) α and β. Gender differences in melanoma may be explaine…
Expression of the Sonic Hedgehog Embryonic Signalling Pathway Components in Matched Pre-Treatment and Relapsed Small Cell Lung Cancer Biopsies
2021
Abstract Cancer stem cells may be responsible for tumour regrowth and acquisition of resistance in small cell lung cancer (SCLC). The Hedgehog pathway regulates survival and proliferation of tissue progenitor and stem cell populations, promoting the expression of stem cell related and proliferative genes. We evaluated the Sonic Hedgehog (Shh) embryonic signalling pathway in relapsed SCLC. Expression levels of Shh related genes GLI1, SMO, SUFU, PTCH1, HHIP, BCL2, BMI, ZEB1, ZEB2, N-MYC, Twist1 were analysed by qRT-PCR in matched pre-treatment and relapsed tumour fresh frozen biopsies of three SCLC patients. Expression of each gene was compared using the paired samples t-test, as well as comp…
Cell fate regulation upon DNA damage : p53 Serine 46 kinases pave the cell death road
2019
Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho-isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferropt…
Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling pathways
2011
Hepatocellular carcinoma (HCC) remains a disease with a poor prognosis despite recent advances in the pathophysiology and treatment. Although the disease is biologically heterogeneous, dysregulation of cellular proliferation and apoptosis both occur frequently and contribute to the malignant phenotype. Chronic liver disease is associated with intrahepatic inflammation which promotes dysregulation of cellular signaling pathways; this triggers proliferation and thus lays the ground for expansion of premalignant cells. Cancer emerges when immunological control fails and transformed cells develop resistance against cell death signaling pathways. The same mechanisms underlie the poor responsiven…
Heat shock proteins: essential proteins for apoptosis regulation
2008
Abstract Many different external and intrinsic apoptotic stimuli induce the accumulation in the cells of a set of proteins known as stress or heat shock proteins (HSPs). HSPs are conserved proteins present in both prokaryotes and eukaryotes. These proteins play an essential role as molecular chaperones by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and by preventing their aggregation. HSPs have a protective function, that is they allow the cells to survive to otherwise lethal conditions. Various mechanisms have been proposed to account for the cytoprotective functions of HSPs. Several of these proteins have demonstrated to directly interact with compo…
Ferroptosis Meets Cell–Cell Contacts
2021
Ferroptosis is a regulated form of cell death characterized by iron dependency and increased lipid peroxidation. Initially assumed to be selectively induced in tumour cells, there is increasing evidence that ferroptosis plays an important role in pathophysiology and numerous cell types and tissues. Deregulated ferroptosis has been linked to human diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Along these lines, ferroptosis is a promising pathway to overcoming therapy resistance of cancer cells. It is therefore of utmost importance to understand the cellular signalling pathways and the molecular mechanisms underlying ferroptosis regulation, including cont…