RESUMO
In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction. Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential, rapid growth, and poor prognosis. Due to the rarity of these cancers, the standard therapy is poorly defined. The diagnosis of these tumors is based on combination of morphological features, immunohistochemical and neuroendocrine and epithelial cell markers. Both endocrine and epithelial cell components can act independently of each other and thus, careful grading of each component separately is required. These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response. Regardless of the organ of origin, these tumors portend poor prognosis with increased proportion of neuroendocrine component. Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes. The etiopathogenesis of these mixed tumors remains obscure but poses interesting question. We briefly discuss a few salient points in this editorial.
RESUMO
Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) has emerged as an innovative immunotherapy for hematological cancer treatment. However, the limited effect on solid tumors, complex processes, and excessive manufacturing costs remain as limitations of CAR-T therapy. Nanotechnology provides an alternative to the conventional CAR-T therapy. Owing to their unique physicochemical properties, nanoparticles can not only serve as a delivery platform for drugs but also target specific cells. Nanoparticle-based CAR therapy can be applied not only to T cells but also to CAR-natural killer and CAR-macrophage, compensating for some of their limitations. This review focuses on the introduction of nanoparticle-based advanced CAR immune cell therapy and future perspectives on immune cell reprogramming.
Assuntos
Nanopartículas , Neoplasias , Receptores de Antígenos Quiméricos , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T , Imunoterapia , Neoplasias/terapiaRESUMO
A persistent barrier to the cure and treatment of neurological diseases is the limited ability of the central and peripheral nervous systems to undergo neuroregeneration and repair. Recent efforts have turned to regeneration of various cell types through cellular reprogramming of native cells as a promising therapy to replenish lost or diminished cell populations in various neurological diseases. This review provides an in-depth analysis of the current viral vectors, genes of interest, and target cellular populations that have been studied, as well as the challenges and future directions of these novel therapies. Furthermore, the mechanisms by which cellular reprogramming could be optimized as treatment in neurological diseases and a review of the most recent cellular reprogramming in vitro and in vivo studies will also be discussed.
RESUMO
Induced pluripotent stem cells (iPSCs) was successfully generated from skin fibroblast obtained from patient with cystic fibrosis by using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit, which contain three vectors preparation: polycistronic Klf4-Oct3/4-Sox2, cMyc, and Klf4. Created iPSC lines showed a normal karyotype, expressed pluripotency markers and demonstrated the potential to differentiate into three germ layers in spontaneous differentiation assay.
Assuntos
Fibrose Cística , Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Mutação , Diferenciação Celular , Fibroblastos/metabolismoRESUMO
Nonsense-mediated mRNA decay (NMD) is a post-transcriptional mechanism that targets aberrant transcripts and regulates the cellular RNA reservoir. Genetic modulation in vertebrates suggests that NMD is critical for cellular and tissue homeostasis, although the underlying mechanism remains elusive. Here, we generate knockout mice lacking Smg6/Est1, a key nuclease in NMD and a telomerase cofactor. While the complete loss of Smg6 causes mouse lethality at the blastocyst stage, inducible deletion of Smg6 is compatible with embryonic stem cell (ESC) proliferation despite the absence of telomere maintenance and functional NMD. Differentiation of Smg6-deficient ESCs is blocked due to sustained expression of pluripotency genes, normally repressed by NMD, and forced down-regulation of one such target, c-Myc, relieves the differentiation block. Smg6-null embryonic fibroblasts are viable as well, but are refractory to cellular reprograming into induced pluripotent stem cells (iPSCs). Finally, depletion of all major NMD factors compromises ESC differentiation, thus identifying NMD as a licensing factor for the switch of cell identity in the process of stem cell differentiation and somatic cell reprograming.
Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Degradação do RNAm Mediada por Códon sem Sentido/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Diferenciação Celular/genética , Clonagem Molecular , Biologia Computacional , Primers do DNA/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas Histológicas , Immunoblotting , Hibridização in Situ Fluorescente , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNARESUMO
Stem cells (SCs) have self-renew ability and give rise to committed progenitors of a single or multiple lineages. Elucidating the genetic circuits that govern SCs to self-renew and to differentiate is essential to understand the roles of SCs and promise of these cells in regenerative medicine. MicroRNAs are widespread agents playing critical roles in regulatory networks of transcriptional expression and have been strongly linked with SCs for simultaneous maintenance of pluripotency properties such as self-renewal. This review aims to provide state-of-the-art presentations on microRNA-dependent molecular mechanisms contribute to the maintenance of pluripotency. Understanding the microRNA signature interactions, in conjunction with cell signaling, is critical for development of improved strategies to reprogram differentiated cells or direct differentiation of pluripotent cells.