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1.
Adv Sci (Weinh) ; 11(18): e2309796, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38384234

RESUMO

Glioblastoma (GBM) remains a challenge in Neuro-oncology, with a poor prognosis showing only a 5% survival rate beyond two years. This is primarily due to its aggressiveness and intra-tumoral heterogeneity, which limits complete surgical resection and reduces the efficacy of existing treatments. The existence of oncostreams-neuropathological structures comprising aligned spindle-like cells from both tumor and non-tumor origins- is discovered earlier. Oncostreams are closely linked to glioma aggressiveness and facilitate the spread into adjacent healthy brain tissue. A unique molecular signature intrinsic to oncostreams, with overexpression of key genes (i.e., COL1A1, ACTA2) that drive the tumor's mesenchymal transition and malignancy is also identified. Pre-clinical studies on genetically engineered mouse models demonstrated that COL1A1 inhibition disrupts oncostreams, modifies TME, reduces mesenchymal gene expression, and extends survival. An in vitro model using GFP+ NPA cells to investigate how various treatments affect oncostream dynamics is developed. Analysis showed that factors such as cell density, morphology, neurotransmitter agonists, calcium chelators, and cytoskeleton-targeting drugs influence oncostream formation. This data illuminate the patterns of glioma migration and suggest anti-invasion strategies that can improve GBM patient outcomes when combined with traditional therapies. This work highlights the potential of targeting oncostreams to control glioma invasion and enhance treatment efficacy.


Assuntos
Neoplasias Encefálicas , Glioma , Camundongos , Animais , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Microambiente Tumoral/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Cadeia alfa 1 do Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I/metabolismo
2.
WIREs Mech Dis ; 16(2): e1636, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38185860

RESUMO

In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.


Assuntos
Sêmen , Diferenciação Sexual , Masculino , Animais , Reprodução , Células Germinativas , Espermatozoides
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