Search results for "Pathway"

New molecular targets for the treatment of osteoarthritis.

2009

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Current treatments are focused on symptomatic relief but they lack efficacy to control the progression of this disease which is a leading cause of disability. Therefore, the development of effective disease-modifying drugs is urgently needed. Different initiatives are in progress to define the molecular mechanisms involved in the initiation and progression of OA. These studies support the therapeutic potential of pathways relevant in joint metabolism such as Wnt/beta-catenin, discoidin domain receptor 2 or proteinase-activated rece…

The Wnt/beta-Catenin Pathway Attenuates Experimental Allergic Airway Disease

2014

Abstract Signaling via the Wnt/β-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/β-catenin pathway has been implicated in remodeling processes, development of emphysema, and fibrosis. However, its relevance for the modulation of allergic responses in the lung remains unclear. Using genetically modified mice with lung-specific inducible (doxycycline) Wnt-1 expression (CCSP-rtTA × tetO-Wnt1), the impact of Wnt on the development of allergic airway disease was analyzed. Overexpression of Wnt during the allergen challenge phase attenuated the development of airway inflammation in an acute model, as well as in a more therapeut…

Impact of Ozone on Crops

2004

Tropospheric O3 has a negative impact on growth, development, and productivity of crops. Effects of O3 have been observed in a wide range of physiological characteristics, such as accelerated senescence, decreased photosynthetic assimilation, decreased productivity, and reduced carbon allocation to roots. Different responses to O3 have been observed in related species and, hence, it is thought that the initial mechanism of O3-induced stress on crops is uniform. A better understanding of the effect of O3 and O3-generated reactive oxygen species is necessary for an insight into the impact of O3 in crops. A great effort must be made in order to decrease the concentrations of O3 air pollution. …

Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium

2015

<b><i>Background:</i></b> The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. <b><i>Objectives:</i></b> To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. <b><i>Methods:</i></b> Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in pat…

18P In vitro analysis of the combination of APR-246 and carboplatin in triple negative breast cancer (TNBC) and high grade serous ovarian cancer (HGS…

2021

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

Through Predictive Personalized Medicine.

2020

Neuroblastoma (NBM) is a deadly form of solid tumor mostly observed in the pediatric age. Although survival rates largely differ depending on host factors and tumor-related features, treatment for clinically aggressive forms of NBM remains challenging. Scientific advances are paving the way to improved and safer therapeutic protocols, and immunotherapy is quickly rising as a promising treatment that is potentially safer and complementary to traditionally adopted surgical procedures, chemotherapy and radiotherapy. Improving therapeutic outcomes requires new approaches to be explored and validated. In-silico predictive models based on analysis of a plethora of data have been proposed by Lomba…

The dark side of the moon: The PI3K/PTEN/AKT pathway in colorectal carcinoma

2009

Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR …

Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy

2012

An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the or…

Peripheral Acute Pain Mechanisms

1995

Many studies in several species, including humans, have identified a subset of primary afferent nerve fibres that are activated by potential or actual tissue-damaging stimuli. Discharge patterns of these nociceptive afferents faithfully reproduce some aspects of the applied stimuli (e.g. shape of the stimulus-response function) but not others (e.g. time-course of a sustained stimulus). Since primary nociceptive afferents provide the input to the central nervous system, their encoding properties have to be considered when studying central processing. On the other hand, pain perception correlates with some aspects of nociceptor discharges (e.g. fatigue with repetition of brief heat pulses), b…