RESUMO
In people with sickle cell disease (SCD), oral abscesses are concerning clinical conditions and carry a high risk of postoperative sickle cell complications. We present an unusual case of a 14-year-old girl with SCD whose initial presentation of facial swelling, headaches, jaw pain, and paresthesia mimicked an odontogenic abscess. She was diagnosed with vaso-occlusive crisis in the mandibular bone and successfully managed noninvasively. This is among the youngest cases of paresthesia in the lower lip in SCD, which provided a clue that postponing invasive aspiration or biopsy was possible under empiric antibiotics and close observation.
Assuntos
Anemia Falciforme , Doenças Maxilomandibulares , Abscesso/diagnóstico , Abscesso/etiologia , Adolescente , Anemia Falciforme/complicações , Feminino , Humanos , Mandíbula , Dor/diagnóstico , Dor/etiologia , Parestesia/complicaçõesRESUMO
Glioblastomas are the most prevalent and lethal primary brain tumor and are comprised of hierarchies with self-renewing cancer stem cells (CSCs) at the apex. Like neural stem cells (NSCs), CSCs reside in functional niches that provide essential cues to maintain the cellular hierarchy. Bone morphogenetic proteins (BMPs) instruct NSCs to adopt an astrocyte fate and are proposed as anti-CSC therapies to induce differentiation, but, paradoxically, tumors express high levels of BMPs. Here we demonstrate that the BMP antagonist Gremlin1 is specifically expressed by CSCs as protection from endogenous BMPs. Gremlin1 colocalizes with CSCs in vitro and in vivo. Furthermore, Gremlin1 blocks prodifferentiation effects of BMPs, and overexpression of Gremlin1 in non-CSCs decreases their endogenous BMP signaling to promote stem-like features. Consequently, Gremlin1-overexpressing cells display increased growth and tumor formation abilities. Targeting Gremlin1 in CSCs results in impaired growth and self-renewal. Transcriptional profiling demonstrated that Gremlin1 effects were associated with inhibition of p21(WAF1/CIP1), a key CSC signaling node. This study establishes CSC-derived Gremlin1 as a driving force in maintaining glioblastoma tumor proliferation and glioblastoma hierarchies through the modulation of endogenous prodifferentiation signals.
Assuntos
Glioma/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Proteína Morfogenética Óssea 2/metabolismo , Ciclo Celular/genética , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/genética , Glioma/patologia , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Células-Tronco Neoplásicas/patologia , Transdução de SinaisRESUMO
This article reviews the current trends and management of respiratory emergencies in children. Respiratory emergencies are a common report in pediatrics and often require prompt recognition and intervention. It is important to differentiate upper from lower respiratory disease processes because the management is often different. With the advent of many vaccinations, the concern for certain diseases has changed with variations in the prevalence of other organisms. This article discusses detection and management of many respiratory emergencies. [Pediatr Ann. 2023;52(4):e146-e152.].
Assuntos
Emergências , Insuficiência Respiratória , Criança , Humanos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/terapiaRESUMO
Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.