Search results for "progress"
showing 10 items of 1620 documents
Why do I treat my patients with mild hepatitis C?
2015
The major advances achieved in the treatment of HCV by the development of new direct-acting antiviral agents (DAAs) allow treatment of almost the entire spectrum of patients with chornic infection. As a result of the exceedingly high cost of DAAs in many countries, IFN-free DAA regimens are mostly reserved to patients with advanced fibrosis or cirrhosis. Hence, treatment of patients with milder liver disease is often deferred. This could ultimately result in an increased burden of advanced liver disease and in increased long-term costs of management. Moreover, studies performed during the 'interferon era' and the early data on interferon-free regimens show that patients without severe fibro…
Antifibrotic therapies in the liver.
2015
Significant progress has been made in understanding the principles underlying the development of liver fibrosis. This includes appreciating its dynamic nature, the importance of active fibrolysis in fibrosis regression, and the plasticity of cell populations endowing them with fibrogenic or fibrolytic properties. This is complemented by an increasing array of therapeutic targets with known roles in the progression or regression of fibrosis. With a key role for fibrosis in determining clinical outcomes and encouraging data from recently Food and Drug Administration-approved antifibrotics for pulmonary fibrosis, the development and validation of antifibrotic therapies has taken center stage i…
Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment.
2013
SummaryLiver fibrosis results from an excessive wound healing response in most chronic liver diseases, such as hepatitis C. Despite great advances in antiviral therapy in recent years, progressive liver fibrosis remains a major problem for patients with recurrent hepatitis C after liver transplantation. Liver biopsy remains a central tool in the management of HCV-positive liver transplant recipients, but reliable non-invasive methods for the assessment of liver fibrosis, such as ultrasound elastography, are increasingly being incorporated in the management of post-transplant patients, helping predict prognosis, guide treatment decisions, and stratify patients for emerging antifibrotic thera…
Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases
2022
Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. Thes…
Fibroblast Growth Factor 21 Limits Lipotoxicity by Promoting Hepatic Fatty Acid Activation in Mice on Methionine and Choline-Deficient Diets
2014
Background & Aims Nonalcoholic fatty liver disease is a common consequence of human and rodent obesity. Disruptions in lipid metabolism lead to accumulation of triglycerides and fatty acids, which can promote inflammation and fibrosis and lead to nonalcoholic steatohepatitis. Circulating levels of fibroblast growth factor (FGF)21 increase in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis; therefore, we assessed the role of FGF21 in the progression of murine fatty liver disease, independent of obesity, caused by methionine and choline deficiency. Methods C57BL/6 wild-type and FGF21-knockout (FGF21-KO) mice were placed on methionine- and choline-deficient (MCD)…
Synthetic (glyco-)peptides of the homophilic recognition domain of E-cadherin lead to increased E-cadherin mRNA synthesis and are inductors of cell d…
2010
E-cadherin is one of the critical molecules involved in the metastatic process in many types of cancer. Once combined, E-cadherin exceeds the amount of membranous E-cadherin on the cellular surface by activation of intracellular signaling cascades. Studies on transformed keratinocytes of the HaCat cell line showed induction of differentiation by synthetical partial structures of the homophilic binding region of E-cadherin. The knowledge of effects in lung cancer cells is sparse. Therefore, the effects in primary lung cancer cell lines were investigated. Four primary lung cancer cell lines were incubated for 3, 6, 12, 15, 18, and 24h with synthetic partial structures (peptide and glycopeptid…
Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer
2013
Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6(-/-) mice with Kras(G12D) mutant mice, which develop lung tumors after activation of mutant Kras(G12D), to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. Kras(G12D); IL-6(-/-) mice exhibited increased tumor…
BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy.
2011
BRAFV600E is the most common mutation found in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)-κB have been shown to play an important role in thyroid cancer. In particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates Akt signaling pathway, which is eventually responsible for its anti-apoptotic activity. The aim of our study was to evaluate whether interplay among these three factors exists and exerts a functional role in PTCs. To this purpose, 56 PTC specimens were analyzed for BRAFV600E mutation, TIMP-1 expression, and NF-κB activation. We found that BRAFV600E mutation occurs selectively in PTC nodules an…
Inhibitory effects of cynaropicrin on human melanoma progression by targeting MAPK, NF-κB, and Nrf-2 signaling pathways in vitro
2021
Malignant melanoma is the deadliest skin cancer, due to its propensity to metastasize. MAPKs and NF-κB pathways are constitutively activated in melanoma and promote cell proliferation, cell invasion, metastasis formation, and resistance to therapeutic regimens. Thus, they represent potential targets for melanoma prevention and treatment. Phytochemicals are gaining considerable attention for the management of melanoma because of their several cellular and molecular targets. A screening of a small library of sesquiterpenes lactones selected cynaropicrin, isolated from the aerial parts of Centaurea drabifolia subsp. detonsa, for its potential anticancer effect against melanoma cells. Treatment…
Erythropoietin activates cell survival pathways in breast cancer stem-like cells to protect them from chemotherapy
2013
Abstract Recombinant erythropoietin (EPO) analogs [erythropoiesis-stimulating agents (ESA)] are clinically used to treat anemia in patients with cancer receiving chemotherapy. After clinical trials reporting increased adverse events and/or reduced survival in ESA-treated patients, concerns have been raised about the potential role of ESAs in promoting tumor progression, possibly through tumor cell stimulation. However, evidence is lacking on the ability of EPO to directly affect cancer stem–like cells, which are thought to be responsible for tumor progression and relapse. We found that breast cancer stem–like cells (BCSC) isolated from patient tumors express the EPO receptor and respond to …