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1.
Cancer Sci ; 114(11): 4355-4364, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37688294

RESUMO

Accumulating evidence suggests an association between iron metabolism and lung cancer progression. In biological systems, iron is present in either reduced (Fe2+ ; ferrous) or oxidized (Fe3+ ; ferric) states. However, ferrous and ferric iron exhibit distinct chemical and biological properties, the role of ferrous and ferric iron in lung cancer cell growth has not been clearly distinguished. In this study, we manipulated the balance between cellular ferrous and ferric iron status by inducing gene mutations involving the FBXL5-IRP2 axis, a ubiquitin-dependent regulatory system for cellular iron homeostasis, and determined its effects on lung cancer cell growth. FBXL5 depletion (ferrous iron accumulation) was found to suppress lung cancer cell growth, whereas IRP2 depletion (ferric iron accumulation) did not suppress such growth, suggesting that ferrous iron but not ferric iron plays a suppressive role in cell growth. Mechanistically, the depletion of FBXL5 impaired the degradation of the cyclin-dependent kinase inhibitor, p27, resulting in a delay in the cell cycle at the G1/S phase. FBXL5 depletion in lung cancer cells also improved the survival of tumor-bearing mice. Overall, this study highlights the important function of ferrous iron in cell cycle progression and lung cancer cell growth.


Assuntos
Proteínas F-Box , Neoplasias Pulmonares , Animais , Camundongos , Complexos Ubiquitina-Proteína Ligase/química , Complexos Ubiquitina-Proteína Ligase/genética , Complexos Ubiquitina-Proteína Ligase/metabolismo , Neoplasias Pulmonares/genética , Ferro/metabolismo , Ubiquitina/metabolismo , Compostos Férricos , Proteínas F-Box/genética , Proteínas F-Box/metabolismo
2.
J Stroke Cerebrovasc Dis ; 28(7): e83-e91, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31080139

RESUMO

Neurofibromatosis type 1 (NF1) is a rare disease with an incidence of approximately one in every 3000 births. NF1 is mainly recognized as a tumor suppressor. Vasculopathy in NF1 is well described in the literature, but the association between NF1 and cerebral aneurysm has not been determined. We report a case of a 67-year-old female with NF1 accompanied by 8 cerebral aneurysms. Two of the patient's unruptured aneurysms, the large distal anterior cerebral artery (ACA) aneurysm and anterior communicating artery aneurysm, were initially treated with microsurgical clipping. The peripheral ACA aneurysm gradually increased in size and ruptured after 5 years. Coil embolization was performed for the ruptured aneurysm. Four of the 5 remaining unruptured aneurysms were treated surgically. The patient is currently well, without neurological deficit, and coil embolization is scheduled for the last remaining aneurysm. NF1 is a probable risk factor for multiple cerebral aneurysms due to vessel wall vulnerability. Therapeutic indications for patients with NF1 who show multiple cerebral aneurysms include strict follow-up and aggressive treatment to avoid subarachnoid hemorrhage.


Assuntos
Aneurisma Roto/etiologia , Aneurisma Intracraniano/etiologia , Neurofibromatose 1/complicações , Idoso , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/terapia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Embolização Terapêutica , Procedimentos Endovasculares , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Neurofibromatose 1/diagnóstico , Procedimentos Neurocirúrgicos , Fatores de Risco , Resultado do Tratamento
3.
Cureus ; 16(3): e56918, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665710

RESUMO

Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.

4.
World Neurosurg ; 105: 1037.e13-1037.e16, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28634065

RESUMO

BACKGROUND: Spinal dural arteriovenous fistula (DAVF) is a rare disease, and multiple concurrent lesions are extremely rare. Such multiple spinal DAVFs have similar outflow routes at neighboring levels. However, there have been no reported cases of remote lesions of multiple spinal DAVFs. The authors herein report a case of double synchronous cervical and sacral DAVFs. CASE DESCRIPTION: A 56-year-old man with no previous history of disease presented with progressive myelopathy, and spinal magnetic resonance imaging showed extensive edema of the spinal cord from the conus to T7. The initial angiography incidentally revealed a C1 DAVF, but the sacral DAVF was not diagnosed. The C1 DAVF was treated surgically, because of the risk of subarachnoid hemorrhage. A second angiography was performed 2 months after the first surgery because of high clinical suspicion, and the sacral DAVF was diagnosed at that time. The sacral DAVF was treated surgically, and the symptoms gradually resolved within 6 months after surgery. CONCLUSIONS: Spinal DAVF is a rare disease, but clinicians should be aware of the possibility of the concurrence of multiple spinal fistulas located at different levels in the same patient.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/cirurgia , Vértebras Cervicais/cirurgia , Sacro/cirurgia , Medula Espinal/cirurgia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Sacro/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem
5.
World Neurosurg ; 105: 1036.e15-1036.e19, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28625904

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a rare disease with an incidence of 1 in every 3000 births. Numerous studies have focused on the main function of NF1 as a tumor suppressor, whereas few have examined the cerebrovascular abnormalities observed in patients with NF1. It is worth noting that intracranial aneurysms are uncommon in this condition. CASE DESCRIPTION: We report a case of NF1 with a dissection of the distal segment of the superior cerebellar artery. A 36-year-old woman presented with a distal superior cerebellar artery (SCA) dissection causing subarachnoid hemorrhage. Subsequently, because of the rich collateral blood flow distal to the dissection, N-butyl cyanoacrylate (NBCA) glue embolization was unsuccessful. Therefore, direct trapping of the artery was necessary. The patient was discharged after an uneventful postoperative period, and has remained without complications. CONCLUSIONS: In the treatment of subarachnoid hemorrhage because of a distal SCA dissection in patients with NF1, NBCA glue embolization may be a safer option than microsurgery or coil embolization, in the acute phase, considering the possible vulnerability of the vessel wall, accessibility, morphology of the lesions, and the risk of developing unpredictable infarcts in the case of parent artery occlusion. However, regular reevaluation of the blood flow is necessary to monitor recurrence, given the rich collateral circulation.


Assuntos
Dissecção Aórtica/cirurgia , Cerebelo/irrigação sanguínea , Cerebelo/cirurgia , Aneurisma Intracraniano/cirurgia , Neurofibromatose 1/cirurgia , Hemorragia Subaracnóidea/cirurgia , Adulto , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Feminino , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia
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