Search results for "Targeted therapy"
showing 10 items of 297 documents
Molecular dynamics, dynamic site mapping, and highthroughput virtual screening on leptin and the Ob receptor as anti-obesity target.
2014
Body weight control is a mechanism finely regulated by several hormonal, metabolic, and nervous pathways. The leptin receptor (Ob-R) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream, and under normal circumstances, circulating levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased concentrations lead to opposite effects. Therefore rational design of leptin agonists constitute an appealing challenge in the battle against ob…
Plasma PLTP (phospholipid-transfer protein): an emerging role in ‘reverse lipopolysaccharide transport’ and innate immunity
2011
Plasma PLTP (phospholipid-transfer protein) is a member of the lipid transfer/LBP [LPS (lipopolysaccharide)-binding protein] family, which constitutes a superfamily of genes together with the short and long PLUNC (palate, lung and nasal epithelium clone) proteins. Although PLTP was studied initially for its involvement in the metabolism of HDL (high-density lipoproteins) and reverse cholesterol transport (i.e. the metabolic pathway through which cholesterol excess can be transported from peripheral tissues back to the liver for excretion in the bile), it displays a number of additional biological properties. In particular, PLTP can modulate the lipoprotein association and metabolism of LPS …
Liver fibrosis: Direct antifibrotic agents and targeted therapies
2018
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases. Moreover, drugs that would speed…
The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success
2020
Contains fulltext : 229341.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals. AREAS COVERED: This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program has been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development. EXPERT OPINION: The main goal of NASH pharmacotherapy is to halt or reverse hepati…
Targeted therapy of liver fibrosis/cirrhosis and its complications.
2011
Department of Pharmacokinetics, Toxicology, and Targeting, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA; Division of Molecular and Translational Medicine, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany
Bioanalytical system for detection of cancer cells with photoluminescent ZnO nanorods
2016
Using photoluminescent ZnO nanorods and carbohydrate marker SSEA-4, a novel cancer cell recognition system was developed. Immobilization of SSEA-4 antibodies (αSSEA-4) on ZnO nanorods was performed in buffer solution (pH = 7.1) over 2 h. The cancer cell line probes were fixed on the glass slide. One hundred microliters of ZnO-αSSEA-4 conjugates were deposited on the cell probe and exposed for 30 min. After washing photoluminescence spectra were recorded. Based on the developed methodology, ZnO-αSSEA-4 probes were tested on patient-derived breast and colorectal carcinoma cells. Our data clearly show that the carbohydrate SSEA-4 molecule is expressed on cancer cell lines and patient-derived c…
Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma
2010
The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…
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…
An update on the xenograft and mouse models suitable for investigating new therapeutic compounds for the treatment of B-cell malignancies
2008
B-cell malignancies account for over the 90% of all lymphoid neoplasms. The clonal proliferations of B-cells show a high degree of variation in terms of clinical and presenting features, histopathology, immuophenotype, and genetics. Primary tumor samples are useful for examining the characteristics of a patients own tumor, although both primary leukemic cells and cell lines provide an initial step for screening novel compounds for their activity in some hematological malignancies, they should be followed by models in intact animals. In this review, we try to summarize the animal models generated to study B-cell malignancies, in particular, B-cell lymphoma, B-cell CLL and MM that represent t…
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…