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Cancer Care Delivery and Women's Health

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453092 Year: Pages: 153 DOI: 10.3389/978-2-88945-309-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-02-27 16:16:45
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Cancer care delivery refers to the multiple layers of the health care system that interact to affect outcomes for patients with cancer and the quality of that care. The factors included in the care delivery system that potentially alter outcomes include social dynamics, financing systems, organizational structures and processes, health technologies, provider and individual behaviors. Because women’s health care has its own unique challenges, the intersection between cancer care delivery and women’s health is to be examined in this Frontiers in Oncology issue. The unique opportunities and challenges of improving the health care system for women with breast and gynecologic cancers are to be explored in depth. We will visit many topics of cancer care delivery with the unique perspective geared towards the care of women’s malignancies.

Alterations of Epigenetics and MicroRNAs in Cancer and Cancer Stem Cell

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193455 Year: Pages: 79 DOI: 10.3389/978-2-88919-345-5 Language: English
Publisher: Frontiers Media SA
Subject: Biology --- Genetics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Studies have shown that alterations of epigenetics and microRNAs (miRNAs) play critical roles in the initiation and progression of human cancer. Epigenetic silencing of tumor suppressor genes in cancer cells is generally mediated by DNA hypermethylation of CpG island promoter and histone modification such as methylation of histone H3 lysine 9 (H3K9) and tri-methylation of H3K27. MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis. Important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in activation of target oncogenes in human malignancies. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of various tissues through differentiation. Accumulating evidence suggests that a subpopulation of cancer cells with distinct stem-like properties is responsible for tumor initiation, invasive growth, and metastasis formation, which is defined as cancer stem cells. Cancer stem cells are considered to be resistant to conventional chemotherapy and radiation therapy, suggesting that these cells are important targets of cancer therapy. DNA methylation, histone modification and miRNAs may be deeply involved in stem-like properties in cancer cells. Restoring the expression of tumor suppressor genes and miRNAs by chromatin modifying drugs may be a promising therapeutic approach for cancer stem cells. In this Research Topic, we discuss about alterations of epigenetics and miRNAs in cancer and cancer stem cell and understand the molecular mechanism underlying the formation of cancer stem cell, which may provide a novel insight for treatment of refractory cancer.

Matricellular Receptors as Potential Targets in Anti-Cancer Therapeutic Strategies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450244 Year: Pages: 129 DOI: 10.3389/978-2-88945-024-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2018-02-27 16:16:44
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The invasive character of a primary cancer is greatly dependent on numerous interactions between tumor cells and their extracellular surroundings. Matricellular receptors are defined as (cell-surface) receptors that bind extracellular matrix (ECM) structural proteins and soluble factors dynamically acting on ECM homeostasis. Matricellular receptors mediate numerous signalings from the extracellular environment to cell nucleus and drive main biological functions that are cell growth, survival and migration. Numerous data from the last decade evidence that matricellular receptors are biosensors that allow to a tumor cell answering to microenvironmental variations, and in this sense they are important contributors to tumor cell malignancy. Matricellular receptors represent thus valuable targets for the development of original anti-cancer strategies. Original reports, bibliographic reviews or hypotheses are welcome to improve the basic knowledge of matricellular receptor properties, their spatio-temporal regulation, the dynamic formation of complex receptors and the impact of such interactions on the invasive properties of tumor cells. Biological, biophysical and pharmacological, as well as in silico contributions will be appreciated.

Keywords

Anti-cancer target --- disco

DNA helicases: expression, functions and clinical implications

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195756 Year: Pages: 78 DOI: 10.3389/978-2-88919-575-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2015-10-30 16:33:44
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Helicases are the proteins that bind to double- or single-stranded DNA and/or RNA chains to unwind higher order structures, usually consuming energy from the hydrolysis of ATP molecules. The biological roles of helicases are associated with a variety of DNA and/or RNA metabolisms, including DNA-replication, -repair, -recombination, RNA processing, and transcription. Dysfunctions of helicases cause various diseases, such as xeroderma pigmentosum (XP), premature aging syndrome, cancer and immunodeficiency, in humans. Moreover, recent genetic analyses revealed that mutations in helicase-encoding genes are frequently found in patients of specific diseases. Some helicases regulate cellular senescence by controlling integrity of genomes, and others play a role in neuromuscular functions presumably by modulating processing of mRNAs. However, the molecular mechanisms of how helicases are regulated in order to maintain our health are not yet fully understood. In this research topic, we will focus on the expression and functions of helicases and their encoding genes, reviewing recent research progresses that provide new insights into development of clinical and pharmaceutical treatments targeting helicases.

Keywords

Aging --- Cancer --- DNA Repair --- helicases --- Telomere

Investigating and harnessing T-cell functions with engineered immune receptors and their ligands

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194131 Year: Pages: 191 DOI: 10.3389/978-2-88919-413-1 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-10 11:59:06
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T-cells are an essential component of the immune system that provide protection against pathogen infections and cancer and are involved in the aetiology of numerous autoimmune and autoinflammatory pathologies. Their importance in disease, the relative ease to isolate, expand and manipulate them ex vivo have put T-cells at the forefront of basic and translational research in immunology. Decades of study have shed some light on the unique way T-cells integrate extrinsic environmental cues influencing an activation program triggered by interactions between peptide-MHC complexes and the antigen-recognition machinery constituted of clonally distributed T-cell receptors and their co-receptor CD4 or CD8. The manipulation of these molecular determinants in cellular systems or as recombinant proteins has considerably enhanced our ability to understand antigen-specific T-cell activation, to monitor ongoing T-cell responses and to exploit T-cells for therapy. Even though these principles have given numerous insights in the biology of CD8+ T-cells that translate into promising therapeutic prospects, as illustrated by recent breakthroughs in cancer therapy, they have proven more challenging to apply to CD4+ T-cells.This Research Topics aims to provide a comprehensive view of the recent insights provided by the use of engineered antigen receptors and their ligands on T-cell activation and how they have been or could be harnessed to design efficient immunotherapies.

Multidrug resistance in Cancer: Pharmacological Strategies from Basic Research to Clinical Issues

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196159 Year: Pages: 99 DOI: 10.3389/978-2-88919-615-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology --- Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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More than 40 years ago, the observation that doxorubicin-resistant tumor cells were cross-resistant to several structurally different anticancer agents was the first step in the discovery of P-glycoprotein (P-gp). P-gp belongs to the superfamily of ATP-binding cassette (ABC) transporters;its overexpression has become a therapeutic target for overcoming multidrug resistance in tumors. However, P-gp is also expressed in cells of normal tissues where it plays a physiological role, by protecting them from the toxic effects of xenobiotics. Also, ABCB1 gene polymorphisms may influence the response to anticancer drugs substrate of P-gp. Several strategies to overcome P-gp tumor drug resistance have been suggested. P-gp 'circumvention’ is the most explored and is based on the coadministration of anticancer agents and pump inhibitors (P-gp modulators). Despite the positive findings obtained in preclinical studies, results of clinical trials are not yet successful and clinical research is still ongoing. Other investigational approaches have been studied (e.g. P-gp targeting antibodies, use of antisense strategies or transcriptional regulators targeting ABCB1 gene expression) but their use is still circumscribed to the preclinical setting. A further approach is represented by the encapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles. This strategy has shown higher efficacy in tumor previously treated with the free drug. The reasons explaining the increased efficacy of liposomal/nanoparticle-based drugs in Pgp-overexpressing tumors include the coating with specific surfactants, the composition changes in the plasma membrane microdomains where P-gp is embedded, the direct impairment of P-gp catalytic mechanisms exerted by specific component of the liposomal shell, but are not yet fully understood. A second strategy to overcome P-gp tumor drug resistance is represented by exploiting the P-gp presence. Actually, P-gp-overexpressing cells show increased sensitivity (collateral sensitivity) to some drugs (e.g. verapamil, narcotic analgesics) and to some investigational compounds (e.g. NSC73306). P-gp-overexpressing cell are hypersensitive to reactive oxygen species, to agents perturbing the energetic metabolic pathways, changing the membrane compositions, reducing the efflux of endogenous toxic catabolites. However, the mechanisms explaining collateral sensitivity have not been fully elucidated. Another approach to exploit P-gp is represented by ABCB1 gene transfer to transform bone marrow progenitor cells into a drug resistant state which may allow conventional or higher doses of anticancer drug substrates of P-gp to be administered safely after transplantation. More recently the development and introduction in the clinics of anticancer drugs which are not substrates of P-gp (e.g. new microtubule modulators, topoisomerase inhibitors) has provided a new and promising strategy to overcome P-gp tumor drug resistance (P-gp 'evasion'). This ‘research topic’ issue aims at exploding the above mentioned matters, in particular by: -retracing the history of the first researches on P-gp - describing the physiological role of P-gp - describing the molecular basis, structural features and mechanism of action of P-gp - describing diagnostic laboratory methods useful to determine the expression of P-gp and its transporter function - describing strategies to overcome tumor drug resistance due to P-gp and other ABC transporters - indicating novel approaches to overcome P-gp multidrug resistance, ranging from basic research studies to pre-clinical/clinical studies.

Exploring Cancer Metabolic Reprogramming Through Molecular Imaging

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452347 Year: Pages: 242 DOI: 10.3389/978-2-88945-234-7 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2017-10-13 14:57:01
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The inclusion of oncogene-driven reprogramming of energy metabolism within the list of cancer hallmarks (Hanahan and Weinberg, Cell 2000, 2011) has provided major impetus to further investigate the existence of a much wider metabolic rewiring in cancer cells, which not only includes deregulated cellular bioenergetics, but also encompasses multiple links with a more comprehensive network of altered biochemical pathways. This network is currently held responsible for redirecting carbon and phosphorus fluxes through the biosynthesis of nucleotides, amino acids, lipids and phospholipids and for the production of second messengers essential to cancer cells growth, survival and invasiveness in the hostile tumor environment. The capability to develop such a concerted rewiring of biochemical pathways is a versatile tool adopted by cancer cells to counteract the host defense and eventually resist the attack of anticancer treatments. Integrated efforts elucidating key mechanisms underlying this complex cancer metabolic reprogramming have led to the identification of new signatures of malignancy that are providing a strong foundation for improving cancer diagnosis and monitoring tumor response to therapy using appropriate molecular imaging approaches. In particular, the recent evolution of positron emission tomography (PET), magnetic resonance spectroscopy (MRS), spectroscopic imaging (MRSI), functional MR imaging (fMRI) and optical imaging technologies, combined with complementary cellular imaging approaches, have created new ways to explore and monitor the effects of metabolic reprogramming in cancer at clinical and preclinical levels. Thus, the progress of high-tech engineering and molecular imaging technologies, combined with new generation genomic, proteomic and phosphoproteomic methods, can significantly improve the clinical effectiveness of image-based interventions in cancer and provide novel insights to design and validate new targeted therapies. The Frontiers in Oncology Research Topic “Exploring Cancer Metabolic Reprogramming Through Molecular Imaging” focusses on current achievements, challenges and needs in the application of molecular imaging methods to explore cancer metabolic reprogramming, and evaluate its potential impact on clinical decisions and patient outcome. A series of reviews and perspective articles, along with original research contributions on humans and on preclinical models have been concertedly included in the Topic to build an open forum on perspectives, present needs and future challenges of this cutting-edge research area.

New Therapies and Immunological Findings in Melanoma and Other Skin Cancers

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457120 Year: Pages: 137 DOI: 10.3389/978-2-88945-712-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Oncology
Added to DOAB on : 2019-01-23 14:53:43
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New therapies are currently being developed in the field of skin cancer. In particular, advances in melanoma now represent the frontline of cancer immunotherapy, as immunological findings in the disease have led to the development of highly effective immune-checkpoint inhibitors. However, these immune-checkpoint inhibitors are only effective in a subset of patients, and may not work in other skin cancer types, thus highlighting the need for further innovation in the field of skin cancer treatment.The purpose of this Research Topic is therefore to provide an up-to-date overview of immune processes and new therapies for melanoma and other skin cancers in order to further stimulate the development of new and even more successful treatments.

Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199495 Year: Pages: 107 DOI: 10.3389/978-2-88919-949-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.

Global Challenges in Radiation Oncology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195909 Year: Pages: 66 DOI: 10.3389/978-2-88919-590-9 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:32
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In the United States, much of the research is focused on developing new and very expensive technologies and drugs - often without a major therapeutic benefit. In resource limited countries, basic oncology care is frequently lacking. In addition, the benefits of various chemo-radiotherapy combinations for a number of malignancies are unknown as these populations have not been adequately investigated. For oncologists in these countries who have marginal to adequate resources, accrual to clinical trials is virtually non-existent to minimal, due to the complexities of their population and competing co-morbidities. As a result, there is a tremendous disparity in treatment outcomes for these populations, compared to those in developed countries. Therefore, we have asked a number of oncologists from different parts of the world to report their experience. Topics that will be covered include locally advanced breast and cervical cancer (India, South Africa), human resources for cancer control in India, systematic review of radiation resources in low and middle income countries, planning national radiotherapy services, building sustainable partnerships through the newly formed ICEC (International Cancer Export Corps), cancer disparities among American Indians, and training radiation oncologists in these under served parts of the world. Authors will discuss "lessons learned" from their populations, practical suggestions to address these disparities, and how we as a global oncology community can address, and mitigate these global challenges. The editorial by Dr. Coleman and myself highlights the invaluable contributions from our global contributors. Thank you for taking the time to read this special issue on global cancer disparities. We are all energized to begin addressing the needs of our cancer patients worldwide.

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