Search results: Found 9

Listing 1 - 9 of 9
Sort by
Targeting PI3K/mTOR signaling in cancer

Author:
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192441 Year: Pages: 93 DOI: 10.3389/978-2-88919-244-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Medicine (General) --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
License:

Loading...
Export citation

Choose an application

Abstract

The phosphatidylinositol 3-kinase (PI3K)/mTOR pathway integrates signals from growth factors with nutrient signals and other conditions and controls multiple cell responses, including proliferation, survival and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer. Somatic or inherited mutations frequently occur in tumor suppressor genes (PTEN, TSC1/2, LKB1) and oncogenes (PIK3CA, PIK3R1, AKT) in the PI3K/mTOR pathway. The fact that the PI3K/mTOR pathway is deregulated in a large number of human malignancies, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. Rapamycin and its analogs targeting mTOR are effective in many preclinical cancer models. Although rapalogs are approved for the treatment of some cancers, their efficacy in clinical trials remains the subject of debate. Due to the complexity of the PI3K/mTOR signaling pathway, developing an effective anti-cancer therapy remains a challenge. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments.

2015: Which new directions for Alzheimer's disease?

Author:
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195350 Year: Pages: 122 DOI: 10.3389/978-2-88919-535-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
License:

Loading...
Export citation

Choose an application

Abstract

According to the World Health Organization, more than 40 million people in the world are affected with dementia. To date, 60-70% of the cases of dementia are attributed to the Alzheimer's disease (AD). This neurodegenerative disorder gradually takes place over a period of at least 20 years before the onset of symptoms, which are impaired memory, apathy and depression. The characteristics of AD consist in neurofibrillary tangles (intraneuronal aggregates of hyperphosphorylated tau proteins) and senile plaques (dense extraneuronal deposits composed of amyloid ß (Aß)). The other features linked to these two core pathological hallmarks of AD are inflammation, oxidative stress, progressive synaptic and neuronal loss. In past years, some of the emerging therapeutic strategies against AD were employed to deal with the pathological hallmarks of the disease. Science teams all over the world try to restore the tau phosphorylation equilibrium. Their purpose is to interfere with the aggregation of tau and decrease its amount of proteins per se as well. Furthermore, they are trying either to stimulate the elimination processes of the aggregated tau proteins or to stop the formation of Aß peptides. This could be reached by the stimulation of the classic techniques of protein degradation such as the autophagic pathway, or by the targeted immunotherapy. In this Research Topic, we wish to summarize and review the etiology of AD and the related therapeutic opportunities for the next decades. To fully understand the precise mechanisms underlying AD, research findings, reviews, new insights and new approaches include AD and related tauopathies, tau phosphorylation balance, pharmacological compounds against AD, neuroprotection strategies and new therapeutic ways but also risk factors for AD and AD genetic information are included in this issue.

An Updated View on an Emerging Target: Selected Papers from the 8th International Conference on Protein Kinase CK2

Authors: --- --- ---
ISBN: 9783038424130 9783038424123 Year: Pages: 320 DOI: 10.3390/books978-3-03842-413-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2017-07-12 07:57:21
License:

Loading...
Export citation

Choose an application

Abstract

The 8th International Conference on Protein Kinase CK2 (www.uks.eu/ck2), organized by Matthias Montenarh and Claudia Götz, will be held at the Faculty of Medicine of Saarland University, in Homburg, Germany, from 6–9 September, 2016.Protein kinase CK2 is a serine/threonine kinase, which is highly conserved in evolution. Knock-out experiments have shown that this enzyme is absolutely necessary for cell viability. The enzyme is highly expressed in rapidly proliferating cells, which goes along with an elevated enzyme activity. Protein kinase CK2 is involved in a broad range of signaling pathways, regulating proliferation, differentiation, apoptosis, or senescence. Recent advances towards the characterization of the three-dimensional structure of protein kinase CK2 and its subunits will undoubtedly yield important new insights into its regulation, and the functions of CK2. Moreover, with two inhibitors of the enzyme presently in clinical phase II trials, human protein kinase CK2 has appeared as an emerging target for cancer diseases.

Current challenges in photosynthesis: From natural to artificial

Authors: --- --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192861 Year: Pages: 102 DOI: 10.3389/978-2-88919-286-1 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Botany --- Science (General)
Added to DOAB on : 2015-12-10 11:59:07
License:

Loading...
Export citation

Choose an application

Abstract

Jules Verne (1828-1905), author of Around the World in Eighty Days (1873) and Journey to the Center of the Earth (1864), wrote in 1875:"I believe that water will one day be used as a fuel, because the hydrogen and oxygen which constitute it, used separately or together, will furnish an inexhaustible source of heat and light. I therefore believe that, when coal (oil) deposits are oxidised, we will heat ourselves by means of water. Water is the fuel of the future". Solar energy is the only renewable energy source that has sufficient capacity for the global energy need; it is the only one that can address the issues of energy crisis and global climate change. A vast amount of solar energy is harvested and stored via photosynthesis in plants, algae, and cyanobacteria since over 3 billion years. Today, it is estimated that photosynthesis produces more than 100 billion tons of dry biomass annually, which would be equivalent to a hundred times the weight of the total human population on our planet at the present time, and equal to a global energy storage rate of about 100 TW. The solar power is the most abundant source of renewable energy, and oxygenic photosynthesis uses this energy to power the planet using the amazing reaction of water splitting. During water splitting, driven ultimately by sunlight, oxygen is released into the atmosphere, and this, along with food production by photosynthesis, supports life on our earth. The other product of water oxidation is “hydrogen” (proton and electron). This ‘hydrogen’ is not normally released into the atmosphere as hydrogen gas but combined with carbon dioxide to make high energy containing organic molecules. When we burn fuels we combine these organic molecules with oxygen. The design of new solar energy systems must adhere to the same principle as that of natural photosynthesis. For us to manipulate it to our benefit, it is imperative that we completely understand the basic processes of natural photosynthesis, and chemical conversion, such as light harvesting, excitation energy transfer, electron transfer, ion transport, and carbon fixation. Equally important, we must exploit application of this knowledge to the development of fully synthetic and/or hybrid devices. Understanding of photosynthetic reactions is not only a satisfying intellectual pursuit, but it is important for improving agricultural yields and for developing new solar technologies. Today, we have considerable knowledge of the working of photosynthesis and its photosystems, including the water oxidation reaction. Recent advances towards the understanding of the structure and the mechanism of the natural photosynthetic systems are being made at the molecular level. To mimic natural photosynthesis, inorganic chemists, organic chemists, electrochemists, material scientists, biochemists, biophysicists, and plant biologists must work together and only then significant progress in harnessing energy via “artificial photosynthesis” will be possible. This Research Topic provides recent advances of our understanding of photosynthesis, gives to our readers recent information on photosynthesis research, and summarizes the characteristics of the natural system from the standpoint of what we could learn from it to produce an efficient artificial system, i.e., from the natural to the artificial. This topic is intended to include exciting breakthroughs, possible limitations, and open questions in the frontiers in photosynthesis research.

Regulation of immune system cell functions by protein kinase C

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193264 Year: Pages: 129 DOI: 10.3389/978-2-88919-326-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:32
License:

Loading...
Export citation

Choose an application

Abstract

Members of the protein kinase C (PKC) family of Ser/Thr kinases are encoded by nine distinct but closely related genes, which give rise to more than 12 different protein isoforms via a mechanism of alternative RNA splicing. Most PKC proteins are ubiquitously expressed and participate in a plethora of functions in most cell types. A majority of PKC isoforms is also expressed in cells of the immune system in which they are involved in signal transduction downstream of a range of surface receptors, including the antigen receptors on T and B lymphocytes. PKC proteins are central to signal initiation and propagation, and to the regulation of processes leading to immune cell proliferation, differentiation, homing and survival. As a result, PKC proteins directly impact on the quality and quantity of immune responses and indirectly on the host resistance to pathogens and tendency to develop immune deficiencies and autoimmune diseases. A significant progress was made in recent years in understanding the regulation of PKC enzymes, their mechanism of action and their role in determining immunocyte behavior This volume reviews the most significant contributions made in the field of immune cell regulation by PKC enzymes. Several manuscripts are devoted to the role of distinct PKC isoforms in the regulation of selected immunocyte responses. Additional manuscripts review more general mechanisms of regulation of PKC enzymes, either by post-translational modifications, such as phosphorylation or controlled proteolysis, or by interaction with different binding proteins that may alter the conformation, activity and subcellular location of PKC. Both types of mechanisms can introduce conformational changes in the molecule, which may affect its ability to interact with cofactors, ATP, or substrates. This topic will be followed by a discussion on the positive and negative impact of individual PKC isoforms on cell cycle regulation. A second section of this volume concentrates on selected topics relevant to role of the novel PKC isoform, PKC-theta, in T lymphocyte function. PKC-theta plays important and some non-redundant roles in T cell activation and is a key isoform that recruits to the immunological synapse - the surface membrane area in T cells that comes in direct contact with antigen presenting cells. The immunological synapse is formed in T cells within seconds following the engagement of the TCR by a peptide-bound MHC molecule on the surface of antigen-presenting cells. It serves as a platform for receptors, adaptor proteins, and effector molecules, which assemble into multimolecular activation complexes required for signal transduction. The unique ability of PKC-theta to activate the NF-kB, AP-1 and NF-AT transcription factors is well established, and recent studies contributed essential information on the mechanisms involved in the recruitment of PKC-theta to the center of the immunological synapse and the nature of its substrates and the role of their phosphorylated forms in signal transduction. Additional review manuscripts will describe the unique behavior of PKC-theta in regulatory T cells and its role in the regulation of other cell populations, including those of the innate immune response. This volume brings together leading experts from different disciplines that review the most recent discoveries and offer new perspectives on the contributions of PKC isoforms to biochemical processes and signaling events in different immune cell populations and their impact on the overall host immune response.

Mitogen Activated Protein Kinases

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453399 Year: Pages: 163 DOI: 10.3389/978-2-88945-339-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2018-02-27 16:16:45
License:

Loading...
Export citation

Choose an application

Abstract

Mitogen-activated protein kinase (MAPK) pathways are evolutionarily conserved in all eukaryotes and allow cells to respond to changes in the physical and chemical properties of the environment and to produce an appropriate response by altering many cellular functions. MAPKs are among the most intensively studied signal transduction systems. MAPK research is a very dynamic field in which new perspectives are continuously opening to the scientific community. Importantly, many MAPK inhibitors have been developed during the last years and are currently being tested in preclinical and clinical assays for inflammatory diseases and cancer treatment. In this research topic, we have gathered 14 papers covering recent advances in different aspects of the MAPK research area that have provided valuable insight into the spatiotemporal dynamics, the regulation and functions of MAPK pathways, as well as their therapeutic potential. We hope that this Research Topic helps readers to have a better understanding of the progresses that have been made recently in the field of MAPK signalling. A deeper understanding of the these pathways will facilitate the development of innovative therapeutic approaches.

Keywords

MAPK --- p38 --- ERK --- JNK --- MSK --- kinase --- scaffold --- cancer --- inflammation --- cell differentiation

Current Knowledge in Thyroid Cancer — From Bench to Bedside

Author:
ISBN: 9783038424765 9783038424772 Year: Pages: VIII, 212 DOI: 10.3390/books978-3-03842-477-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-08-11 11:32:17
License:

Loading...
Export citation

Choose an application

Abstract

In recent years, studies in the field of thyroid cancer have been performed in order to identify and verify thyroid specific biomarkers, as well as cancer-specific changes in gene expression patterns and alterations of the protein content. Furthermore, new drugs, small molecules and antibodies were developed and tested in vitro and in vivo. Trials investigated the ratio between therapeutic and adverse effects. Tyrosine kinase inhibitors (TKI) have become a new therapeutic option of both differentiated thyroid cancer and medullary thyroid cancer. In the last few years, new substances for targeted systemic therapy have been approved after their efficacy was demonstrated in Phase III trials. Most of them show a moderate response. However, adverse effects are common. TKI are used in patients with advanced metastatic thyroid cancer that is radioiodine (RAI)-refractory.In this Special Issue, original studies on the pathophysiology, diagnosis, and therapy of thyroid cancer, including genetics, proteomics, metabolomics, molecular and cell biology, will be published. It will also cover reports on patients, providing novel mechanistic insights into the underlying pathogenesis or new aspects that may impact clinical therapy, and recent study results in order to review the current status of new therapy options in thyroid cancer.

Second Line Treatment of Non-Small Cell Lung Cancer: Clinical; Pathological and Molecular Aspects of Novel Promising Drugs

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452637 Year: Pages: 84 DOI: 10.3389/978-2-88945-263-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General)
Added to DOAB on : 2018-02-27 16:16:44
License:

Loading...
Export citation

Choose an application

Abstract

Lung cancer still remains a challenging disease with a higher mortality rate in comparison to other cancers. The discovery of oncogene addicted tumours and targeted therapies responsive to these targets lead to a meaningful change in the prognosis of these diseases. Unfortunately, these newer therapeutic options are reserved to a minor part of lung cancer patients harbouring specific mutations. In the so called wild type population, the first line options bring the median overall survival to go beyond 1 year, and in the population receiving the maintenance therapy over 16 months. Given these results, more than 60% of patients may receive a second line therapy with further opportunities to improve the length and quality of life. For patients not harbouring targetable DNA mutations newer options will be available for second line therapeutic schemes and two major assets seem to be promising: immune modulation and anti-angiogenetic agents. In particular, anti PD1/PDL1 antibodies, VEGFR antibodies and TKIs, these latter combined with standard chemotherapy docetaxel advance the median overall survival of 12 months. These drugs have a different mechanism of action, various adverse events and their activity is different depending on the types of population. However, the biomarkers’ activity and efficacy prediction are not fully or totally understood. In addition, also for patients with DNA targetable mutations new drugs seems to be promising for the use in the second line therapeutic protocols. In particular, drugs selectively directed against ALK translocation and mutational events and EGFR T790M secondary mutations seems to be very promising. In this Research Topic we critically discuss the older therapies and the historical development of second line, putting in to perspective the new agents available in clinical practice. We discuss their importance from a clinical point of view, but also consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena. In this perspective, the undercovering and characterization of novel predictive biomarkers by NGS technology, the characterization of novel actors in the signal transduction pathway modulating the response of the cells, the optimization of new diagnostic tool as the evaluation of liquid biopsy and the implementation of more suitable pre-clinical models are crucial aspects dissected too. Nivolumab, nintedanib and ramucirumab probably will give the opportunity to improve the efficacy outcomes for the treatment of wild type tumours in second line therapeutic schemes, but many aspects should be debated in order that these agents are made available to patients, planning ahead a therapeutic strategy, beginning from the first line therapy, to the subsequent ones in a logical and affordable manner. As well, for treatment of mutated tumours, mutated EGFR irreversible inhibitors such as rociletinib and AZD9291, and ALK targeting drugs ceritinib and alectinib will also play an important role in the immediate future. Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated, and by launching this Research Topic we tried to give some practical insights in this changing landscape.

The Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC) in New Era of Personalised Medicine

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195435 Year: Pages: 140 DOI: 10.3389/978-2-88919-543-5 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
License:

Loading...
Export citation

Choose an application

Abstract

Lung cancer is the leading cause of cancer related mortality in Canada and USA. Majority of the patients present in advanced stage of the disease and of these only about 2% will be alive at 5 years. NSCLC is the most common form of lung cancer, accounting for approximately 87% of cases. Systemic chemotherapies have been used to treat metastatic NSCLC for decades, but the improvements of outcomes have reached a plateau. Recent advances in understanding signalling pathways for malignant cells, their interconections,the importance of various receptors and biomarkers and the interplay between various oncogenes have led to the development of targeted treatments that are improving both efficacy and safety of the treatments. Knowledge about the advantages of treatments with the targeted agents in metastatic NSCLC is growing rapidly. Combining various targeted agents or sequencing them properly will be important in the era of personalised medicine and overcoming development of the resistence to various targeted agents will be challenging. The importance of a team work,from the diagnosis through various treatments, to supportive care, from the interventional radiologists, pneumologists or surgeons, who have to obtain a satisfactory tumor tissue specimen, to pathologists, radiation and medical oncologists, to supportive care specialists, will be described in our publications. We will cover completely present and future approaches to personalised medicine in this rapidly evolving field of metastatic NSCLC.

Listing 1 - 9 of 9
Sort by
Narrow your search

Publisher

Frontiers Media SA (7)

MDPI - Multidisciplinary Digital Publishing Institute (2)


License

CC by (7)

CC by-nc-nd (2)


Language

english (9)


Year
From To Submit

2017 (4)

2015 (2)

2014 (3)