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1.
Pediatr Neurosurg ; 57(5): 358-364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35988537

RESUMO

INTRODUCTION: Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collections between the two bony tables of the calvaria resulting from postsurgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. In this regard, we also review the literature on the few recognized cases of OIP. CASE PRESENTATION: The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission, the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. CONCLUSION: Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion.


Assuntos
Astrocitoma , Fossa Craniana Posterior , Humanos , Feminino , Criança , Adolescente , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/cirurgia , Vazamento de Líquido Cefalorraquidiano/etiologia , Osso Occipital/diagnóstico por imagem , Osso Occipital/cirurgia , Craniotomia/efeitos adversos , Craniotomia/métodos , Astrocitoma/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
2.
Pituitary ; 23(5): 552-557, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32562134

RESUMO

PURPOSE: The aim of the present study is to assess the predictive value of the suprasellar volume (SSV) of nonfunctioning pituitary adenomas (NFPAs) for visual field (VF) impairment in order to guide clinical decision-making and improve neurosurgical management. METHODS: Two independent samples of patients with NFPAs (exploratory population N = 50, testing population N = 98) were included in the present study. In the first phase, we determined the optimal cut-off value of the SSV correlating with VF deficits in the exploratory population. In the second phase, we then studied the accuracy of identified cut-off in predicting a VF deficit in the testing population. RESULTS: In the exploratory population, the optimal cut-off value of the SSV to determine the presence of a VF deficit was 1.5 mL. Sensitivity and specificity of the cut-off were 81.3 and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 100 and 75%, respectively. When we checked the identified cut-off score on the testing population, we found a sensitivity of 71% and a specificity of 100%. The PPV and NPV were 100 and 59.2%, respectively. In six cases with VF defects and SSV inferior to 1.5 mL, the displacement of optic chiasm was in superior position. CONCLUSION: The SSV may represent an accurate method in routinely clinical practice for predicting VF deficit in patients affected by NFPA.


Assuntos
Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/fisiopatologia , Estudos Retrospectivos , Testes de Campo Visual , Campos Visuais/fisiologia
3.
Acta Neurochir (Wien) ; 162(4): 803-812, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31993749

RESUMO

BACKGROUND: Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12-16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery. METHODS: One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered. RESULTS: First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered. CONCLUSION: Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.


Assuntos
Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/cirurgia , Cognição , Glioma/psicologia , Glioma/cirurgia , Testes Neuropsicológicos , Complicações Pós-Operatórias/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Disfunção Cognitiva , Estudos de Viabilidade , Feminino , Seguimentos , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
4.
PLoS Biol ; 14(7): e1002507, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27389535

RESUMO

Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB) in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer.


Assuntos
Endopeptidase Clp/metabolismo , Metabolismo Energético , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Endopeptidase Clp/genética , Feminino , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Pessoa de Meia-Idade , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Metástase Neoplásica , Neoplasias/genética , Neoplasias/patologia , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteômica/métodos , Interferência de RNA , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Survivina , Transplante Heterólogo
5.
Neurosurg Focus ; 47(4): E12, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574466

RESUMO

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.


Assuntos
Hidrocefalia/cirurgia , Meningomielocele/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Adulto , Feminino , Fetoscopia/métodos , Idade Gestacional , Humanos , Recém-Nascido , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Gravidez , Resultado do Tratamento
6.
J Neurooncol ; 137(3): 611-619, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29330748

RESUMO

Surgical treatment of elderly patients with meningioma is has proved to be safe, especially when patients are selected using dedicated surgical scores. These scores take into account tumor size, edema, location and patient's co-morbidities. Neuropsychological functioning (NPF) of this kind of patients has been poorly studied in literature and it is not taken into account by these scores. Aim of our study was to describe the long-term outcome in terms of NPF of elderly patients undergoing surgery. Patients older than 70 years of age affected by intracranial meningioma and selected with the Clinical-Radiological Grading Score were included in our study. Neuropsychological testing was performed using a dedicated battery of tests before surgery, 3 and 12 months after surgery. Clinical, neurological and radiological outcomes were studied as well. Forty-one patients with a median age of 74 years were included in this study. Preoperatively only 1/41 patients showed a normal NPF with all tests scoring normally. Four out of 39 patients showed a complete neuropsychological recovery after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF showed a trend of progressive improvement after surgery. Our study is the first experience reported in literature describing a long term follow-up in elderly patients after surgery for intracranial meningioma. In our series, surgery determined an improvement of NPF over time; especially with a low complication rate related to the selection of patients obtained through the CRGS. Further studies need to be performed in order to understand how brain edema, tumor size, volume and tumor location affect NPF in both short and long term.


Assuntos
Neoplasias Meníngeas/psicologia , Neoplasias Meníngeas/cirurgia , Meningioma/psicologia , Meningioma/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Processos Mentais , Gradação de Tumores , Testes Neuropsicológicos , Complicações Pós-Operatórias , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
7.
J Neurooncol ; 138(2): 401-406, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29500662

RESUMO

The surgical resection of meningiomas can be complicated by venous thromboembolism (VTE) in the post-operative period, but the exact incidence of this event is not known. Aim of this study was to assess the occurrence of VTE in patients operated for meningioma who underwent a post-operative clinical and objective screening for VTE. Patients undergoing meningioma resection between 2000 and 2010 who accepted to be investigated for VTE in the post-operative period were included in the study. The screening included daily clinical assessment, pulmonary perfusion scintigraphy (Q-SCAN) on day 2 and venous compression ultrasonography (CUS) of the lower limbs within day 7. The univariate and multivariate statistical analysis of risk factors for VTE included sex, age, presence of comorbidities, pre- and post-operative Karnofsky Performance scale (KPS), post-operative neurological worsening and post-operative walking ability. Two-hundred and seventy-five patients were included in the study. VTE was diagnosed in 82 patients (29.8%). Univariate analysis revealed that age ≥ 65 years, cardiovascular comorbidities, pre- and post-operative KPS < 80/100, post-operative neurological worsening and impaired post-operative walking ability were significantly associated with VTE. Multivariate analysis confirmed only age ≥ 65 years (p = 0.011) and post-operative KPS < 80/100 (p = 0.002) as independent risk factors for VTE. Patients operated for meningioma have a 30% risk of VTE. Age ≥ 65 years and post-operative KPS < 80 were independent risk factors for VTE.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Avaliação de Estado de Karnofsky , Extremidade Inferior/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Masculino , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Pessoa de Meia-Idade , Imagem de Perfusão , Complicações Pós-Operatórias/diagnóstico por imagem , Fatores de Risco , Ultrassonografia , Tromboembolia Venosa/diagnóstico por imagem
8.
Proc Natl Acad Sci U S A ; 112(28): 8638-43, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26124089

RESUMO

Molecular therapies are hallmarks of "personalized" medicine, but how tumors adapt to these agents is not well-understood. Here we show that small-molecule inhibitors of phosphatidylinositol 3-kinase (PI3K) currently in the clinic induce global transcriptional reprogramming in tumors, with activation of growth factor receptors, (re)phosphorylation of Akt and mammalian target of rapamycin (mTOR), and increased tumor cell motility and invasion. This response involves redistribution of energetically active mitochondria to the cortical cytoskeleton, where they support membrane dynamics, turnover of focal adhesion complexes, and random cell motility. Blocking oxidative phosphorylation prevents adaptive mitochondrial trafficking, impairs membrane dynamics, and suppresses tumor cell invasion. Therefore, "spatiotemporal" mitochondrial respiration adaptively induced by PI3K therapy fuels tumor cell invasion, and may provide an important antimetastatic target.


Assuntos
Inibidores Enzimáticos/farmacologia , Mitocôndrias/efeitos dos fármacos , Invasividade Neoplásica , Inibidores de Fosfoinositídeo-3 Quinase , Transporte Biológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Citoesqueleto/metabolismo , Metabolismo Energético , Humanos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
9.
J Neurooncol ; 134(2): 377-385, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28685404

RESUMO

High grade gliomas (HGG) are tumors with a rapidly progressive course and the standard of care consists of surgery and chemo-radiotherapy. Elderly patients with HGG usually have a worse prognosis due to their comorbidities and difficulties in accessing or completing adjuvant treatments. The purpose of our study was to assess the influence of pre-operative factors (MMSE, age, sex, KPS, tumor volume) on the post-operative access to chemo-radiotherapy in the elderly population. In addition, the influence of the access to adjuvant therapies on overall survival (OS) was assessed. We retrospectively reviewed our consecutive case series of 117 elderly patients (≥65 years) with HGG treated in our Institution. All the clinical records regarding age, sex, tumor location, MMSE, KPS, access to adjuvant treatments and OS were analyzed. 72 males and 45 females with a median age of 71 years were analyzed. Adjuvant therapies were considered; concomitant chemo-radiotherapy with standard radiotherapy or hypofractionated radiation regimen. 84 patients had access to adjuvant therapies. Access to therapies was associated with a median age of 71(range 66-80) years, a median MMSE of 26(range 5-30), and a median tumor volume of 24 cm3(range 1-140). The median OS was 13 months for patients who had access to adjuvant therapies and 5 months for patients who did not. In the elderly patients with HGG, the MMSE, age and tumor volume were predictive of post-surgery access to adjuvant treatments. OS was significantly longer in elderly patients with HGG who had access to post-surgery chemo-radiotherapy.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia , Glioma/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/psicologia , Feminino , Glioma/mortalidade , Glioma/patologia , Glioma/psicologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Testes de Estado Mental e Demência , Gradação de Tumores , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , Carga Tumoral
10.
Platelets ; 28(6): 585-594, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27897101

RESUMO

Glioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in GBM. Different cells appear to act as triggers of the aberrant angiogenesis, and, among them, platelets act as key participants. In order to provide further insights into the platelet features and angiogenic role in GBM, this study investigated the effects of platelet releasate on GBM-derived endothelial cells (GECs) and the levels of VEGF and endostatin, as pro- and anti-angiogenic components of platelet releasate from GBM patients. We demonstrate for the first time that: 1) platelet releasate exerts powerful pro-angiogenic effect on GECs, suggesting it might exert a role in the aberrant angiogenesis of GBM; 2) ADP and thrombin stimulation leads to significantly higher level of VEGF, but not of endostatin, in the releasate of platelets from GBM patients than those from healthy subjects; and 3) the intraplatelet concentrations of VEGF were significantly elevated in GBM patients as compared to controls. Moreover, we found a direct correlation between platelet-released VEGF and overall survival in our patient cohort. Although preliminary, these findings prompt further investigations to clarify the biologic relevance of platelet VEGF in GBM and prospective studies for screening GBM patients for anti-VEGF therapy and/or to optimize this treatment.


Assuntos
Plaquetas/metabolismo , Neoplasias Encefálicas/metabolismo , Células Endoteliais/metabolismo , Glioblastoma/metabolismo , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Plaquetas/patologia , Neoplasias Encefálicas/patologia , Células Endoteliais/patologia , Feminino , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Células Tumorais Cultivadas
11.
J Transl Med ; 14(1): 127, 2016 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-27160012

RESUMO

BACKGROUND: The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders. METHODS: We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration. RESULTS: One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up. CONCLUSIONS: We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach. Trial registration ClinicalTrials.gov NCT01824121.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Transtornos Parkinsonianos/terapia , Paralisia Supranuclear Progressiva/terapia , Idoso , Fenômenos Biomecânicos , Medula Óssea/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único
12.
Crit Care Med ; 43(1): 168-76, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25318385

RESUMO

OBJECTIVES: To describe mean intracranial pressure after aneurysmal subarachnoid hemorrhage, to identify clinical factors associated with increased mean intracranial pressure, and to explore the relationship between mean intracranial pressure and outcome. DESIGN: Analysis of a prospectively collected observational database. SETTING: Neuroscience ICU of an academic hospital. PATIENTS: One hundred sixteen patients with subarachnoid hemorrhage and intracranial pressure monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Episodes of intracranial pressure greater than 20 mm Hg lasting at least 5 minutes and the mean intracranial pressure for every 12-hour interval were analyzed. The highest mean intracranial pressure was analyzed in relation to demographic characteristics, acute neurologic status, initial radiological findings, aneurysm treatment, clinical vasospasm, and ischemic lesion. Mortality and 6-month outcome (evaluated using a dichotomized Glasgow Outcome Scale) were also introduced in multivariable logistic models. Eighty-one percent of patients had at least one episode of high intracranial pressure and 36% had a highest mean intracranial pressure more than 20 mm Hg. The number of patients with high intracranial pressure peaked 3 days after subarachnoid hemorrhage and declined after day 7. Highest mean intracranial pressure greater than 20 mm Hg was significantly associated with initial neurologic status, aneurysmal rebleeding, amount of blood on CT scan, and ischemic lesion within 72 hours from subarachnoid hemorrhage. Patients with highest mean intracranial pressure greater than 20 mm Hg had significantly higher mortality. When death, vegetative state, and severe disability at 6 months were pooled, however, intracranial pressure was not an independent predictor of unfavorable outcome. CONCLUSIONS: High intracranial pressure is a common complication in the first week after subarachnoid hemorrhage in severe cases admitted to ICU. Mean intracranial pressure is associated with the severity of early brain injury and with mortality.


Assuntos
Pressão Intracraniana/fisiologia , Hemorragia Subaracnóidea/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Feminino , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Prospectivos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Cytotherapy ; 17(3): 310-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25457277

RESUMO

BACKGROUND AIMS: In attempting to develop new strategies to circumvent the immunosuppression associated with glioblastoma (GB), novel approaches have been designed using dendritic cell (DC)-based vaccination, which is considered a promising strategy to attack high-grade glioma. In previous studies, we demonstrated that human mesenchymal stromal cells without genetic manipulation but primed with Paclitaxel (PTX) acquire a potent anti-tumor activity, providing an interesting new biological approach for drug delivery. On the basis of these results, we here investigated whether both CD14+ and their derived DCs may behave like mesenchymal stromal cells acquiring anti-tumor activity on priming with PTX. METHODS: Human CD14+ cells were isolated from peripheral blood. Fluorescence-activated cell sorter analysis was performed to determine the purity of CD14+ and their differentiation into mature DCs. Cells were primed by incubation with 1 µg/mL of PTX for 24 h, and the PTX released by cells was assessed by mass spectrometry analysis. Anti-tumor activity was checked by testing the conditioned medium (CM) on the proliferation of U87 MG, a GB cell line. RESULTS: Both CD14+ and DCs were able to incorporate PTX and release the drug in the CM in a time-dependent manner (maximal release over 24 h). The addition of CM from CD14+ and DCs loaded with PTX strongly inhibits proliferation of U87 MG cells. CONCLUSIONS: Our results are the first demonstration that peripheral blood-derived CD14+ and DCs, in addition to their application for immunotherapy for GB, could also be used to delivery anti-cancer drugs, such as PTX, to kill GB cells.


Assuntos
Antineoplásicos/administração & dosagem , Meios de Cultivo Condicionados/farmacologia , Células Dendríticas/imunologia , Glioblastoma/terapia , Células-Tronco Mesenquimais , Paclitaxel/administração & dosagem , Vacinas Anticâncer/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos , Sistemas de Liberação de Medicamentos , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Receptores de Lipopolissacarídeos/análise , Transplante de Células-Tronco Mesenquimais
14.
BMC Geriatr ; 15: 116, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26438346

RESUMO

BACKGROUND: Patients aged 65 years and older are not traditionally considered optimal candidates for subthalamic deep brain stimulation (STN-DBS), mainly for their presumed increased incidence of surgical complications. The aim of this study was to assess STN-DBS surgery safety in relation to age. METHODS: A total of 107 consecutive patients undergoing bilateral STN-DBS at our institution between 2002 and 2014 were retrospectively stratified according to age in two groups (Young group < 65 years old; Elderly group ≥ 65 years old;). Rate of short-term surgical complications (within 90 days) was reviewed and compared between the two groups. RESULTS: Pre-operative baseline data were comparable between the two groups. The 90-days post-operative mortality rate was 0%. Overall incidence of complications related to surgery was 6,54%. In the Elderly group we observed 3 post-operative intra-cerebral haematomas (7,89%), 1 requiring urgent surgical evacuation. In the Young group we observed 2 post-operative asymptomatic intra-cerebral haematomas (2,89%) and 2 wound infections (2,89%), 1 requiring system removal. No others surgical complications were noticed in both groups. CONCLUSIONS: Chronological age ≥ 65 years old should not be considered alone as exclusion criteria to STN-DBS surgery.


Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Doença de Parkinson/diagnóstico , Doença de Parkinson/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Núcleo Subtalâmico , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Estimulação Encefálica Profunda/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Núcleo Subtalâmico/fisiologia , Fatores de Tempo
15.
Glia ; 62(12): 1968-81, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25042636

RESUMO

Accumulating reports suggest that human glioblastoma contains glioma stem-like cells (GSCs) which act as key determinants driving tumor growth, angiogenesis, and contributing to therapeutic resistance. The proliferative signals involved in GSC proliferation and progression remain unclear. Using GSC lines derived from human glioblastoma specimens with different proliferative index and stemness marker expression, we assessed the hypothesis that sphingosine-1-phosphate (S1P) affects the proliferative and stemness properties of GSCs. The results of metabolic studies demonstrated that GSCs rapidly consume newly synthesized ceramide, and export S1P in the extracellular environment, both processes being enhanced in the cells exhibiting high proliferative index and stemness markers. Extracellular S1P levels reached nM concentrations in response to increased extracellular sphingosine. In addition, the presence of EGF and bFGF potentiated the constitutive capacity of GSCs to rapidly secrete newly synthesized S1P, suggesting that cooperation between S1P and these growth factors is of central importance in the maintenance and proliferation of GSCs. We also report for the first time that S1P is able to act as a proliferative and pro-stemness autocrine factor for GSCs, promoting both their cell cycle progression and stemness phenotypic profile. These results suggest for the first time that the GSC population is critically modulated by microenvironmental S1P, this bioactive lipid acting as an autocrine signal to maintain a pro-stemness environment and favoring GSC proliferation, survival and stem properties.


Assuntos
Neoplasias Encefálicas/patologia , Proliferação de Células/fisiologia , Glioblastoma/patologia , Lisofosfolipídeos/metabolismo , Células-Tronco Neoplásicas/fisiologia , Esfingosina/análogos & derivados , Animais , Células Cultivadas , Ceramidas/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Cloridrato de Fingolimode , Humanos , Imunossupressores/farmacologia , Antígeno Ki-67/metabolismo , Lisofosfolipídeos/farmacologia , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/efeitos dos fármacos , Propilenoglicóis/farmacologia , Esfingolipídeos/metabolismo , Esfingosina/metabolismo , Esfingosina/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Childs Nerv Syst ; 29(7): 1107-12, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23595805

RESUMO

PURPOSE: We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1-2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies. METHODS: Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan. RESULTS: Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32% of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28 ± 10% and 0%, respectively, for OS, they were 44 ± 12% and 22 ± 10% but no patient was cured. The median PFS after a first relapse was 7 months (range 1-29); the median OS was 7 months (range 4-44). No patients died due to treatment toxicity. Late recurrence (more than 1-2 years after diagnosis) and involvement of single sites were favorable prognostic factors. CONCLUSIONS: Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/terapia , Irradiação Craniana/métodos , Meduloblastoma/terapia , Recidiva Local de Neoplasia/terapia , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Neoplasias Encefálicas/terapia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Irinotecano , Masculino , Melfalan/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Seleção de Pacientes , Qualidade de Vida , Radioterapia/métodos , Estudos Retrospectivos , Terapia de Salvação , Temozolomida , Adulto Jovem , Gencitabina
18.
Acta Neurochir (Wien) ; 155(1): 125-30; discussion 130, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23180167

RESUMO

BACKGROUND: Transphenoidal surgery is an effective treatment for acromegalic patients with growth hormone (GH) producing pituitary adenomas. Since acromegaly is a systemic disease which causes multiple bony alterations, we hypothesized that it could affect the sphenoid sinus anatomy. The aim of the study was to determine whether acromegalic patients have sphenoid sinus alterations with potential surgical impact. METHODS: Fourty-six consecutive patients (23 acromegalics-GH group, 23 non-acromegalics-nGH group) undergoing transphenoidal surgery were included in this study. Pre-operative volumetric CT scan of the head was used to assess the following anatomic characteristics: type of sphenoid sinus (sellar, pre-sellar, conchal); number of intrasphenoid septa; number of carotid-directed septa; intercarotid distance; depth of the sphenoid sinus; depth and size of the sella. RESULTS: The sphenoid sinus was of the pre-sellar/conchal type in 26 % of the patients with acromegaly (n = 23) versus 9 % of the patients of the nGH group (n = 23). The number of intrasphenoid septations was significantly higher in the GH group than in the nGH group (P = .03). Interestingly, the intercarotid distance was smaller in GH patients than in nGH displaying a trend toward significance (P = .05). The sphenoid bone was deeper in the GH group as compared to the nGH group (P = .01) but the distance sphenoid sinus-sella was reduced (P < .01). Finally, the sella was not deeper, nor larger in acromegalic patients. CONCLUSIONS: The sphenoid sinus of acromegalic patients resulted in being deeper, characterized by more septa and by a reduced intercarotid distance. These alterations deserve special pre- and intraoperative care, being potentially responsible for surgical difficulties.


Assuntos
Acromegalia/patologia , Acromegalia/cirurgia , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Seio Esfenoidal/patologia , Seio Esfenoidal/cirurgia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seio Carotídeo/patologia , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sela Túrcica/patologia , Resultado do Tratamento , Adulto Jovem
20.
Clin Neurophysiol ; 133: 29-38, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34794045

RESUMO

OBJECTIVES: To evaluate spectra and their correlations with clinical symptoms of local field potentials (LFP) acquired from wide- and close-spaced contacts (i.e. between contacts 0-3 or LFP03, and contacts 1-2 or LFP12 respectively) on the same DBS electrode within the subthalamus (STN) in Parkinson's disease (PD), before and after levodopa administration. METHODS: LFP12 and LFP03 were recorded from 20 PD patients. We evaluated oscillatory power, local and switched phase-amplitude coupling (l- and Sw-PAC) and correlation with motor symptoms (UPDRSIII). RESULTS: Before levodopa, both LFP03 and LFP12 power in the α band inversely correlated with UPDRSIII. Differences between contacts were found in the low-frequency bands power. After levodopa, differences in UPDRSIII were associated to changes in LFP03 low-ß and LFP12 HFO (high frequency oscillations, 250-350 Hz) power, while a modulation of the low-ß power and an increased ß-LFO (low frequency oscillations, 15-45 Hz) PAC was found only for LFP12. CONCLUSION: This study reveals differences in spectral pattern between LFP12 and LFP03 before and after levodopa administration, as well as different correlations with PD motor symptoms. SIGNIFICANCE: Differences between LFP12 and LFP03 may offer an opportunity for optimizing adaptive deep brain stimulation (aDBS) protocols for PD. LFP12 can be used to detect ß-HFO coupling and ß power (i.e. bradykinesia), while LFP03 are optimal for low frequency oscillations (dyskinesias).


Assuntos
Potenciais da Membrana/fisiologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Adulto , Idoso , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Estimulação Encefálica Profunda , Eletrodos Implantados , Feminino , Humanos , Levodopa/farmacologia , Levodopa/uso terapêutico , Masculino , Potenciais da Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Núcleo Subtalâmico/efeitos dos fármacos
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