scholarly journals MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Salvatore Raieli ◽  
Daniele Di Renzo ◽  
Silvia Lampis ◽  
Camilla Amadesi ◽  
Luca Montemurro ◽  
...  

A wide range of malignancies presents MYCN amplification (MNA) or dysregulation. MYCN is associated with poor prognosis and its over-expression leads to several dysregulations including metabolic reprogramming, mitochondria alteration, and cancer stem cell phenotype. Some hints suggest that MYCN overexpression leads to cancer immune-escape. However, this relationship presents various open questions. Our work investigated in details the relationship of MYCN with the immune system, finding a correlated immune-suppressive phenotype in neuroblastoma (NB) and different cancers where MYCN is up-regulated. We found a downregulated Th1-lymphocytes/M1-Macrophages axis and upregulated Th2-lymphocytes/M2-macrophages in MNA NB patients. Moreover, we unveiled a complex immune network orchestrated by N-Myc and we identified 16 genes modules associated to MNA NB. We also identified a MYCN-associated immune signature that has a prognostic value in NB and recapitulates clinical features. Our signature also discriminates patients with poor survival in non-MNA NB patients where MYCN expression is not discriminative. Finally, we showed that targeted inhibition of MYCN by BGA002 (anti-MYCN antigene PNA) is able to restore NK sensibility in MYCN-expressing NB cells. Overall, our study unveils a MYCN-driven immune network in NB and shows a therapeutic option to restore sensibility to immune cells.

2019 ◽  
Vol 23 (5) ◽  
pp. 503-516 ◽  
Author(s):  
Qiang Zhang ◽  
Xude Wang ◽  
Liyan Lv ◽  
Guangyue Su ◽  
Yuqing Zhao

Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.


Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 159
Author(s):  
Tina Schönberger ◽  
Joachim Fandrey ◽  
Katrin Prost-Fingerle

Hypoxia is a key characteristic of tumor tissue. Cancer cells adapt to low oxygen by activating hypoxia-inducible factors (HIFs), ensuring their survival and continued growth despite this hostile environment. Therefore, the inhibition of HIFs and their target genes is a promising and emerging field of cancer research. Several drug candidates target protein–protein interactions or transcription mechanisms of the HIF pathway in order to interfere with activation of this pathway, which is deregulated in a wide range of solid and liquid cancers. Although some inhibitors are already in clinical trials, open questions remain with respect to their modes of action. New imaging technologies using luminescent and fluorescent methods or nanobodies to complement widely used approaches such as chromatin immunoprecipitation may help to answer some of these questions. In this review, we aim to summarize current inhibitor classes targeting the HIF pathway and to provide an overview of in vitro and in vivo techniques that could improve the understanding of inhibitor mechanisms. Unravelling the distinct principles regarding how inhibitors work is an indispensable step for efficient clinical applications and safety of anticancer compounds.


2021 ◽  
Author(s):  
Linchong Sun ◽  
Huafeng Zhang ◽  
Ping Gao

AbstractMetabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.


Author(s):  
M. G. Monika Bai ◽  
H. Vignesh Babu ◽  
V. Lakshmi ◽  
M. Rajeswara Rao

Fluorescent porous organic polymers are a unique class of materials owing to their strong aggregation induced emission, long range exciton migration and permanent porosity, thus envisioned to possess a wide range of applications (sensing, OLEDs).


2020 ◽  
Vol 8 (1) ◽  
pp. 4
Author(s):  
Devan L. Puhl ◽  
Jessica L. Funnell ◽  
Derek W. Nelson ◽  
Manoj K. Gottipati ◽  
Ryan J. Gilbert

Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidance for regenerating axons. Glia are non-neuronal regulatory cells that maintain homeostasis in the healthy nervous system and regulate regeneration in the injured nervous system. Electrospun fiber scaffolds offer a wide range of characteristics, such as fiber alignment, diameter, surface nanotopography, and surface chemistry that can be engineered to achieve a desired glial cell response to injury. Further, electrospun fibers can be loaded with drugs, nucleic acids, or proteins to provide the local, sustained release of such therapeutics to alter glial cell phenotype to better support regeneration. This review provides the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system both in vitro and in vivo. The information presented can be used to design and optimize electrospun fiber scaffolds to target glial cell response to mitigate nervous system injury and improve regeneration.


2003 ◽  
Vol 01 (03) ◽  
pp. 541-586 ◽  
Author(s):  
Tero Aittokallio ◽  
Markus Kurki ◽  
Olli Nevalainen ◽  
Tuomas Nikula ◽  
Anne West ◽  
...  

Microarray analysis has become a widely used method for generating gene expression data on a genomic scale. Microarrays have been enthusiastically applied in many fields of biological research, even though several open questions remain about the analysis of such data. A wide range of approaches are available for computational analysis, but no general consensus exists as to standard for microarray data analysis protocol. Consequently, the choice of data analysis technique is a crucial element depending both on the data and on the goals of the experiment. Therefore, basic understanding of bioinformatics is required for optimal experimental design and meaningful interpretation of the results. This review summarizes some of the common themes in DNA microarray data analysis, including data normalization and detection of differential expression. Algorithms are demonstrated by analyzing cDNA microarray data from an experiment monitoring gene expression in T helper cells. Several computational biology strategies, along with their relative merits, are overviewed and potential areas for additional research discussed. The goal of the review is to provide a computational framework for applying and evaluating such bioinformatics strategies. Solid knowledge of microarray informatics contributes to the implementation of more efficient computational protocols for the given data obtained through microarray experiments.


2021 ◽  
Vol 83 (4) ◽  
pp. 100-111
Author(s):  
Ahmad Anwar Zainuddin ◽  

Internet of Things (IoT) is an up-and-coming technology that has a wide variety of applications. It empowers physical objects to be organized in a specialized framework to grow its convenience in terms of ease and time utilization. It is to convert the thought of bridging the crevice between the physical world and the machine world. It is also being use in the wide range of the technology in this current situation. One of its applications is to monitor and store data over time from numerous devices allows for easy analysis of the dataset. This analysis can then be the basis of decisions made on the same. In this study, the concept, architecture, and relationship of IoT and Big Data are described. Next, several use cases in IoT and big data in the research methodology are studied. The opportunities and open challenges which including the future directions are described. Furthermore, by proposing a new architecture for big data analytics in the Internet of Things, this paper adds value. Overall, the various types of big IoT data analytics, their methods, and associated big data mining technologies are discussed.


1992 ◽  
Vol 262 (6) ◽  
pp. S9 ◽  
Author(s):  
E Bowdan

Regulation of feeding is a fundamental element of homeostasis. This is reflected in the similarity of control mechanisms in a wide range of animals, including insects and humans. A close examination of feeding behavior can illuminate the physiological processes driving regulation. A simple, inexpensive method for recording fine details of feeding by caterpillars is described. Possible experiments, interpretation of the data, and the relationship of observations to the underlying physiology, are outlined.


Parasitology ◽  
1993 ◽  
Vol 107 (S1) ◽  
pp. S159-S167 ◽  
Author(s):  
P. S. Shetty ◽  
N. Shetty

Interactions between infection and nutrition have been well recognized for several years now since they contribute directly to the health of individuals and communities. Malnourished individuals are specially prone to developing infections while infections themselves can lead to profound changes in the nutritional status of the individual. Health workers in developing countries in the tropics have long recognized the mutually aggravating interactions of malnutrition and infection. The importance of this synergistic relationship between infection and nu-tritional status has been studied extensively in the case of young children. The nutritional status of a young child is a critical determinant of both c morbidity and mortality resulting from a wide range of infections: bacterial, viral, or parasitic. Chandra (1983), in his review on the relationship of nutrition, immunity and infection has categorized the wide range of infectious agents (bacterial, viral, fungal and parasitic) into those that are definitely, variably or minimally influenced by the nutritional status of the child.


1998 ◽  
Vol 44 (12) ◽  
pp. 1115-1136 ◽  
Author(s):  
M J Butler ◽  
A W Day

The relationship of polyketide melanogenesis molecular biology to that of nonmelanin-producing pathways in a wide range of fungi and other organisms is discussed. Analytical methods and fundamental properties of melanins are discussed and fungal melanin properties are compared with those of animal and bacterial melanins. The enzymatic degradation of melanins by lignin peroxidases is described.Key words: fungal melanin, polyketide melanin, DHN melanin, melanin degradation, melanin properties, melanin analysis.


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