scholarly journals Lessons from Cancer Immunoediting in Cutaneous Melanoma

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mariana Aris ◽  
María Marcela Barrio ◽  
José Mordoh
Keyword(s):  
Cutaneous Melanoma ◽  
Tumor Stage ◽  
Experimental Models ◽  
Tumor Evolution ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
Cancer Immunoediting ◽  
Future Challenges ◽  
Continuous Feedback

We will revisit the dual role of the immune system in controlling and enabling tumor progression, known ascancer immunoediting. We will go through the different phases of this phenomenon, exposing the most relevant evidences obtained from experimental models and human clinical data, with special focus on Cutaneous Melanoma, an immunogenic tumorper excellence. We will describe the different immunotherapeutic strategies employed and consider current models accounting for tumor heterogeneity. And finally, we will propose a rational discussion of the progress made and the future challenges in the therapeutics of Cutaneous Melanoma, taking into consideration that tumor evolution is the resulting from a continuous feedback between tumor cells and their environment, and that different combinatorial therapeutic approaches can be implemented according to the tumor stage.

scholarly journals Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 371
Author(s):  
Stephanie Sendker ◽  
Katharina Waack ◽  
Dirk Reinhardt
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Bone Marrow Microenvironment ◽  
Leukemic Cells ◽  
Therapeutic Approaches ◽  
Complex Interplay ◽  
Comprehensive Overview ◽  
Future Challenges ◽  
Cellular Components

Acute myeloid leukemia (AML) is the second most common leukemia among children. Although significant progress in AML therapy has been achieved, treatment failure is still associated with poor prognosis, emphasizing the need for novel, innovative therapeutic approaches. To address this major obstacle, extensive knowledge about leukemogenesis and the complex interplay between leukemic cells and their microenvironment is required. The tremendous role of this bone marrow microenvironment in providing a supportive and protective shelter for leukemic cells, leading to disease development, progression, and relapse, has been emphasized by recent research. It has been revealed that the interplay between leukemic cells and surrounding cellular as well as non-cellular components is critical in the process of leukemogenesis. In this review, we provide a comprehensive overview of recently gained knowledge about the importance of the microenvironment in AML whilst focusing on promising future therapeutic targets. In this context, we describe ongoing clinical trials and future challenges for the development of targeted therapies for AML.

Compliance landscape in central and eastern Europe – the case of Hungary

2017 ◽  
Vol 20 (4) ◽  
pp. 325-333
Author(s):  
Levente Kovács ◽  
Sandor David
Keyword(s):  
Best Practice ◽  
Banking Sector ◽  
Transition Process ◽  
Customer Relationships ◽  
Risk Category ◽  
Special Focus ◽  
Content Type ◽  
Banking Systems ◽  
Future Challenges

Purpose This paper aims to explore how the understanding of the concept of compliance as its own risk category and the role of compliance as a separate internal banking function developed during the central and eastern European (CEE) region’s restoration of the banking systems, both parallel to and as a part of their transition process from their centrally planned economies to market economies, with special focus on the case of Hungary. Design/methodology/approach The paper discusses the transition within CEE and the reconstruction of their banking systems, including that of money and the capital market and the law-abidingness of the banking sector, the role of its reputation, compliance and customer relationships, compliance after 2005, the Bank of International Settlement principles and their implementation, a Hungarian compliance survey conducted in 2009 and future challenges in the field of compliance. Findings There is still not a globally or continentally accepted “best” practice in the field of compliance. It is under these circumstances that banking systems must face the challenges of this new epoch of increasing migration and cybercrime. Originality/value This paper presents the development of compliance in CEE, with special focus on Hungary. The article was written by employees of the Hungarian Banking Association, put together with the help of the vast experience they gained throughout their careers in the banking sector.

Centrosome Aberrations as Drivers of Chromosomal Instability in Breast Cancer

Endocrinology ◽  
2021 ◽  
Author(s):  
Katrina M Piemonte ◽  
Lindsey J Anstine ◽  
Ruth A Keri
Keyword(s):  
Breast Cancer ◽  
Chromosomal Instability ◽  
Dynamic Change ◽  
Structural Defects ◽  
Tumor Evolution ◽  
Therapeutic Approaches ◽  
Cancer Hallmarks ◽  
Aggressive Disease ◽  
Wide Range

Abstract Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers. CIN in cancer often occurs as a result of disrupting key regulators of mitotic fidelity and faithful chromosome segregation. As a consequence of their essential roles in mitosis, dysfunctional centrosomes can induce and maintain CIN. Centrosome defects are common in breast cancer, a heterogeneous disease characterized by high CIN. These defects include amplification, structural defects, and loss of primary cilium nucleation. Recent studies have begun to illuminate the ability of centrosome aberrations to instigate genomic flux in breast cancer cells and the tumor evolution associated with aggressive disease and poor patient outcomes. Here, we review the role of CIN in breast cancer, the processes by which centrosome defects contribute to CIN in this disease, and the emerging therapeutic approaches that are being developed to capitalize upon such aberrations.

Immuno-metabolic interfaces in cardiac disease and failure

2021 ◽  
Author(s):  
Edoardo Bertero ◽  
Jan Dudek ◽  
Clement Cochain ◽  
Murilo Delgobo ◽  
Gustavo Ramos ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Technologies ◽  
Cell Function ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Cardiac Metabolism ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
System Metabolism

Abstract The interplay between the cardiovascular system, metabolism, and inflammation plays a central role in the pathophysiology of a wide spectrum of cardiovascular diseases, including heart failure. Here, we provide an overview of the fundamental aspects of the interrelation between inflammation and metabolism, ranging from the role of metabolism in immune cell function to the processes how inflammation modulates systemic and cardiac metabolism. Furthermore, we discuss how disruption of this immuno-metabolic interface is involved in the development and progression of cardiovascular disease, with a special focus on heart failure. Finally, we present new technologies and therapeutic approaches that have recently emerged and hold promise for the future of cardiovascular medicine.

scholarly journals PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Giovanni Innella ◽  
Elena Bonora ◽  
Iria Neri ◽  
Annalucia Virdi ◽  
Alba Guglielmo ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Suppressor Gene ◽  
Experimental Models ◽  
Special Focus ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Palmoplantar Keratosis ◽  
Pathogenic Process

Germline PTEN pathogenic variants cause a spectrum of disorders collectively labeled PTEN Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that PTEN is a “haploinsufficient” tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of PTEN-associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type PTEN allele was retained and expressed, reinforcing the evidence that PTEN does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the CDH13 gene that might have cooperated with PTEN-haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by PTEN alterations, which may contribute to its understanding.

scholarly journals Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Annagrazia Adornetto ◽  
Carlo Gesualdo ◽  
Maria Luisa Laganà ◽  
Maria Consiglia Trotta ◽  
Settimio Rossi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Neurodegenerative Diseases ◽  
Microvascular Disease ◽  
Experimental Models ◽  
Therapeutic Approaches ◽  
Catabolic Pathway ◽  
Retinal Pathology ◽  
Pharmacological Target

Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.

scholarly journals DDX54 Plays a Cancerous Role Through Activating P65 and AKT Signaling Pathway in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Yu ◽  
Jing-Long Wang ◽  
Li-Li Meng ◽  
Chun-Ting Hu ◽  
Zhao-Wen Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Tumor Stage ◽  
Akt Signaling ◽  
Label Free ◽  
Akt Signaling Pathway ◽  
Therapeutic Approaches ◽  
Phosphorylation Level ◽  
Novel Therapeutic

Colorectal cancer (CRC) is one of the most malignant cancers, and its incidence is still steadily increasing. The DDX RNA helicase family members have been found to play a role in various cancers; however, the role of DDX54 in colorectal cancer is still unclear and needed to be defined. Here, we found DDX54 was overexpressed in CRC tissues by the label-free mass spectrum, which was also verified in tissue microarray of colon cancer, as well as the CRC cell lines and TCGA database. High DDX54 level was correlated with tumor stage and distant metastasis, which always indicated a poor prognosis to the CRC patients. DDX54 could promote the proliferation and mobility of CRC cells through increasing the phosphorylation level p65 and AKT leading to the tumorigenesis. Here, we have preliminarily studied the function of DDX54 in CRC, which would improve our understanding of the underlying biology of CRC and provide the new insight that could be translated into novel therapeutic approaches.

scholarly journals Understanding anemia of chronic disease

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Paula G. Fraenkel
Keyword(s):  
Chronic Disease ◽  
Interleukin 6 ◽  
Severe Infection ◽  
Epidemiologic Studies ◽  
Experimental Models ◽  
Adverse Outcomes ◽  
Therapeutic Approaches ◽  
Anemia Of Chronic Disease ◽  
Iron Sequestration

Abstract The anemia of chronic disease is an old disease concept, but contemporary research in the role of proinflammatory cytokines and iron biology has shed new light on the pathophysiology of the condition. Recent epidemiologic studies have connected the anemia of chronic disease with critical illness, obesity, aging, and kidney failure, as well as with the well-established associations of cancer, chronic infection, and autoimmune disease. Functional iron deficiency, mediated principally by the interaction of interleukin-6, the iron regulatory hormone hepcidin, and the iron exporter ferroportin, is a major contributor to the anemia of chronic disease. Although anemia is associated with adverse outcomes, experimental models suggest that iron sequestration is desirable in the setting of severe infection. Experimental therapeutic approaches targeting interleukin-6 or the ferroportin–hepcidin axis have shown efficacy in reversing anemia in either animal models or human patients, although these agents have not yet been approved for the treatment of the anemia of chronic disease.

ACE2 as therapeutic agent

2020 ◽  
Vol 134 (19) ◽  
pp. 2581-2595
Author(s):  
Qiuhong Li ◽  
Maria B. Grant ◽  
Elaine M. Richards ◽  
Mohan K. Raizada
Keyword(s):  
Therapeutic Agent ◽  
Renin Angiotensin System ◽  
Peptide Hormone ◽  
Experimental Models ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Angiotensin Converting Enzyme 2 ◽  
Beneficial Effects ◽  
Overwhelming Evidence ◽  
Future Challenges

Abstract The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin–angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein–coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

Sign in / Sign up

Export Citation Format

Share Document