scholarly journals NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target

2020 ◽  
Vol 21 (3) ◽  
pp. 753 ◽  
Author(s):  
Alessandro Gambella ◽  
Rebecca Senetta ◽  
Giammarco Collemi ◽  
Stefano Gabriele Vallero ◽  
Matteo Monticelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Chromosomal Rearrangements ◽  
Nervous System Development ◽  
Cns Tumors ◽  
Loss Of Function ◽  
Chimeric Receptors ◽  
Cancer Types ◽  
Trk B

The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.

scholarly journals Functional role of pax6 in eye and central nervous system development in the annelid Capitella teleta

2018 ◽  
Author(s):  
Marleen Klann ◽  
Elaine C. Seaver
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Functional Role ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Loss Of Function ◽  
Downstream Target ◽  
Capitella Teleta

AbstractThe transcription factor Pax6 is an important regulator of early animal development. Loss of function mutations of pax6 in a range of animals results in a reduction or complete loss of the eye, a reduction of a subset of neurons, and defects in axon growth. There are no studies focusing on the role of pax6 during development of any lophotrochozoan representative, however, expression of pax6 in the developing eye and nervous system in a number of species suggest that pax6 plays a highly conserved role in eye and nervous system formation. We investigated the functional role of pax6 during development of the marine annelid Capitella teleta. Expression of pax6 transcripts in C. teleta larvae is similar to patterns found in other animals, with distinct subdomains in the brain and ventral nerve cord as well as in the larval and adult eye. To perturb pax6 function, two different splice-blocking morpholinos were used. Larvae resulting from injections with either morpholino show a reduction of the pax6 transcript, and development of both the larval eyes and the central nervous system architecture are highly disrupted. Preliminary downstream target analysis confirms disruption in expression of some components of the retinal gene regulatory network, as well as disruption of genes involved in nervous system development. Results from this study, taken together with studies from other species, reveal an evolutionarily conserved role for pax6 in eye development, and in neural specification and development.

Antenatal Glucocorticoids Supplementation and Central Nervous System Development

2013 ◽  
Vol 14 (2) ◽  
pp. 160-166
Author(s):  
Diego Gazzolo ◽  
Laura D. Serpero ◽  
Alessandro Frigiola ◽  
Raul Abella ◽  
Alessandro Giamberti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Central Nervous System Development

scholarly journals Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1453
Author(s):  
Joaquín Martí-Clúa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Current Data ◽  
Cellular Mechanisms ◽  
Dividing Cells ◽  
The Central Nervous System ◽  
Repeated Doses ◽  
Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

Antenatal Glucocorticoids Supplementation and Central Nervous System Development

2013 ◽  
Vol 14 (2) ◽  
pp. 160-166
Author(s):  
Diego Gazzolo ◽  
Laura D. Serpero ◽  
Alessandro Frigiola ◽  
Raul Abella ◽  
Alessandro Giamberti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Central Nervous System Development

scholarly journals Growth factors in central nervous system development and tumorigenesis

1997 ◽  
Vol 3 (3) ◽  
pp. E7 ◽  
Author(s):  
Barbara E. Lazio ◽  
Lawrence S. Chin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factors ◽  
Growth Factor ◽  
System Development ◽  
Growth Factor Receptors ◽  
Nervous System Development ◽  
Central Nervous System Tumors ◽  
Central Nervous System Development ◽  
Nervous System Tumors

Growth factors play an important role in the development of the normal central nervous system as well as in the genesis of central nervous system tumors. Some of the more important growth factors and growth factor receptors, as they pertain to neurooncology, are reviewed in this article.

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