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1.
Neurosurg Rev ; 47(1): 245, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809287

RESUMO

PURPOSE: Lateral interbody fusion (LIF) is an increasingly popular minimally-invasive spine procedure. This study identifies notable trends in LIF literature and provides a detailed review of the bibliometric aspects of the top 100 most-cited articles. METHODS: Articles were queried from the Web of Science database. Inclusion criteria consisted of peer-reviewed articles, full-text availability, and LIF focus. Network analysis including co-authorship mapping and bibliographic coupling were complemented by trend analysis to determine prominent contributors and themes. Analyses were conducted using VOSviewer and Bibliometrix (RStudio). RESULTS: There has been a rapid increase in LIF publication and citation count since 1998. Leading journals were Spine (n = 24), Journal of Neurosurgery Spine (n = 22), and European Spine Journal (n = 12). NuVasive funded the most publications (n = 17), followed by DePuy Synthes Spine (n = 4). The United States was the most represented country (n = 81); however, trend analysis suggests a steadily growing international contribution. The most prolific author was J.S. Uribe (n = 16), followed by a tie in second place by E. Dakwar and L. Pimenta (n = 8). The most frequent keywords, "complication" (n = 34), "surgery" (n = 30), and "outcomes" (n = 24), demonstrated a patient-centric theme. CONCLUSIONS: This bibliometric analysis provides in-depth insights into the evolution and trends of LIF over the last two decades. The trends and themes identified demonstrate the innovative, collaborative, and patient-focused characteristics of this subfield. Future researchers can use this as a foundation for understanding the past and present state of LIF research while designing investigations.


Assuntos
Bibliometria , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Fusão Vertebral/tendências
2.
Micromachines (Basel) ; 15(5)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38793132

RESUMO

Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

3.
Pharmaceuticals (Basel) ; 17(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38543086

RESUMO

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

4.
Clin Spine Surg ; 37(6): 245-251, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38419161

RESUMO

STUDY DESIGN: Case report and narrative review. OBJECTIVE: To explore the therapeutic role of surgical and nonsurgical treatment of diaphragmatic paralysis secondary to spinal cord and nerve root compression. SUMMARY OF BACKGROUND DATA: Phrenic nerve dysfunction due to central or neuroforaminal stenosis is a rare yet unappreciated etiology of diaphragmatic paralysis and chronic dyspnea. Surgical spine decompression, diaphragmatic pacing, and intensive physiotherapy are potential treatment options with varying degrees of evidence. METHODS: The case of a 70-year-old male with progressive dyspnea, reduced hemi-diaphragmatic excursion, and C3-C7 stenosis, who underwent a microscopic foraminotomy is discussed. Literature review (MEDLINE, PubMed, Google Scholar) identified 19 similar reports and discussed alternative treatments and outcomes. RESULTS AND CONCLUSIONS: Phrenic nerve root decompression and improvement in neuromonitoring signals were observed intraoperatively. The patient's postoperative course was uncomplicated, and after 15 months, he experienced significant symptomatic improvement and minor improvement in hemi-diaphragmatic paralysis and pulmonary function tests. All case reports of patients treated with spinal decompression showed symptomatic and/or functional improvement, while one of the 2 patients treated with physiotherapy showed improvement. More studies are needed to further describe the course and outcomes of these interventions, but early identification and spinal decompression can be an effective treatment. OCEBM LEVEL OF EVIDENCE: Level-4.


Assuntos
Vértebras Cervicais , Paralisia Respiratória , Estenose Espinal , Humanos , Masculino , Idoso , Paralisia Respiratória/etiologia , Paralisia Respiratória/cirurgia , Paralisia Respiratória/terapia , Vértebras Cervicais/cirurgia , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Resultado do Tratamento , Descompressão Cirúrgica
5.
Neurosurgery ; 95(2): 392-399, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421190

RESUMO

BACKGROUND AND OBJECTIVES: Pituitary adenomas (PAs) are the most common intrasellar tumor. Clinically relevant adenomas have a prevalence of 1 per 1000 in the general population. Transsphenoidal surgery (TSS) is the most common surgical treatment and is the first-line management for most PAs. Most patients fare well postoperatively, but a subset of patients experience a prolonged length of stay (PLOS). In this article, we aim to identify demographic and clinical factors associated with PLOS after TSS for PA. METHODS: Patients with sellar pathologies surgically treated at a single tertiary center from March 1, 2009, to May 31, 2020, were retrospectively reviewed. All patients older than 18 years receiving nonemergent endoscopic TSS for pituitary adenoma were included. Clinical and demographic characteristics were analyzed using χ 2 -tests and student t -tests. For those factors with a P -value less than .01, multivariate logistic regression and negative binomial regression models were constructed to estimate the adjusted odds of PLOS across predictive factors. RESULTS: A total of 301 patients were included in the study. This cohort had an average age of 54.65 ± 15.06 years and an average body mass index of 29.47 ± 6.69. The median length of stay was 54.9 hours [25th-75th percentiles: 43.5-72.9]. Postoperative cerebrospinal fluid leak ( P < .01), postoperative diabetes insipidus (DI) ( P < .01), increased surgery duration ( P = .01), and elevated maximal tumor dimension ( P = .01) were predictive of PLOS in logistic regression. Increased surgery duration, previous pituitary radiation, intraoperative complications, and postoperative DI (all P < .01) were associated with increased rate of PLOS in negative binomial regression. CONCLUSION: Patients undergoing endoscopic TSS for PA resection demonstrate prolonged lengths of stay if they have higher tumor burden, have lengthier surgeries with intraoperative complications, or develop postoperative complications such as cerebrospinal fluid leak or DI. Careful monitoring of these factors will allow for better resource optimization, reducing costs to both the hospital and the patient.


Assuntos
Adenoma , Tempo de Internação , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Humanos , Neoplasias Hipofisárias/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Adenoma/cirurgia , Adulto , Idoso , Fatores de Risco , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neuroendoscopia/métodos , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/etiologia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos
6.
World Neurosurg ; 178: 152-161.e1, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37422186

RESUMO

Data on the effectiveness of transcranioplasty ultrasonography through sonolucent cranioplasty (SC) are new and heterogeneous. We performed the first systematic literature review on SC. Ovid Embase, Ovid Medline, and Web of Science Core Collection were systematically searched and published full text articles detailing new use of SC for the purpose of neuroimaging were critically appraised and extracted. Of 16 eligible studies, 6 reported preclinical research and 12 reported clinical experiences encompassing 189 total patients with SC. The cohort age ranged from teens to 80s and was 60% (113/189) female. Sonolucent materials in clinical use are clear PMMA (polymethylmethacrylate), opaque PMMA, polyetheretherketone, and polyolefin. Overall indications included hydrocephalus (20%, 37/189), tumor (15%, 29/189), posterior fossa decompression (14%, 26/189), traumatic brain injury (11%, 20/189), bypass (27%, 52/189), intracerebral hemorrhage (4%, 7/189), ischemic stroke (3%, 5/189), aneurysm and subarachnoid hemorrhage (3%, 5/189), subdural hematoma (2%, 4/189), and vasculitis and other bone revisions (2%, 4/189). Complications described in the entire cohort included revision or delayed scalp healing (3%, 6/189), wound infection (3%, 5/189), epidural hematoma (2%, 3/189), cerebrospinal fluid leaks (1%, 2/189), new seizure (1%, 2/189), and oncologic relapse with subsequent prosthesis removal (<1%, 1/189). Most studies utilized linear or phased array ultrasound transducers at 3-12 MHz. Sources of artifact on sonographic imaging included prosthesis curvature, pneumocephalus, plating system, and dural sealant. Reported findings were mainly qualitative. We, therefore, suggest that future studies should collect quantitative measurement data during transcranioplasty ultrasonography to validate imaging techniques.

7.
World Neurosurg ; 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37343676

RESUMO

BACKGROUND: Thoracic spinal deformities may reduce chest wall compliance, leading to respiratory complications. The first SARS-CoV-2 (L-variant) strain caused critical respiratory illness, especially in vulnerable patients. This study investigates the association between scoliosis and SARS-CoV-2 (COVID-19) disease course severity. METHODS: Clinical data of 129 patients treated between March 2020 to June 2021 who received a positive COVID-19 polymerase chain reaction result from Mount Sinai and had a scoliosis ICD-10 code (M41.0-M41.9) was retrospectively analyzed. Degree of coronal plane scoliosis on imaging was confirmed by 2 independent measurers and grouped into no scoliosis (Cobb angle <10°), mild (10°-24°), moderate (25°-39°), and severe (>40°) cohorts. Baseline characteristics were compared, and a multivariable logistic regression controlling for clinically significant comorbidities examined the significance of scoliosis as an independent risk factor for hospitalization, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS), mechanical ventilation, and mortality. RESULTS: The no (n = 42), mild (n = 14), moderate (n = 44), and severe scoliosis (n = 29) cohorts differed significantly only in age (P = 0.026). The percentage of patients hospitalized (P = 0.59), admitted to the ICU (P = 0.33), developing ARDS (P = 0.77), requiring mechanical ventilation (P = 1.0), or who expired (P = 0.77) did not significantly differ between cohorts. The scoliosis cohorts did not have a significantly higher likelihood of hospital admission (mild P = 0.19, moderate P = 0.67, severe P = 0.98), ICU admission (P = 0.97, P = 0.94, P = 0.22), ARDS (P = 0.87, P = 0.74, P = 0.94), mechanical ventilation (P = 0.73, P = 0.69, P = 0.70), or mortality (P = 0.74, P = 0.87, P = 0.66) than the no scoliosis cohort. CONCLUSIONS: Scoliosis was not an independent risk factor for critical COVID-19 illness. No trends indicated any consistent effect of degree of scoliosis on increased adverse outcome likelihood.

8.
J Asthma ; 58(5): 633-644, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-31959019

RESUMO

Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reformulated to replace the previously marketed epinephrine chlorofluorocarbon (CFC) MDI. In addition to the HFA propellant change, several enhanced modifications (i.e. changed from solution to suspension, 43% dose reduction, etc.) were made to the formulation of epinephrine HFA MDI. This study evaluates the 6-month long-term safety and efficacy profile of the new epinephrine HFA MDI.Method: The long-term safety study consists of two 3-month, multi-center, double- or evaluator-blinded, parallel-group, placebo, and active controlled stages. In each stage, subjects aged ≥12 years with intermittent or mild-to-moderate persistent asthma were randomized to receive epinephrine HFA (2 × 125 mcg/inhalation), placebo HFA, or epinephrine CFC (2 × 220 mcg/inhalation). Bronchodilator efficacy was assessed in Stage 1 and was determined primarily by the change in the forced expiratory volume in 1 s (ΔFEV1) at Week 12, relative to the same day baseline.Results: The primary efficacy endpoint (AUC0-6hrs of %ΔFEV1 at Week 12) for epinephrine HFA (47.3 ± 54.2) closely paralleled those for the active control, epinephrine CFC (41.0 ± 43.4). Both groups were found to be overall comparable in bronchodilator efficacy. Both also showed low incidence rates of AEs with tremor being most commonly reported for epinephrine HFA. All AEs found were non-serious and non-significant. The observed changes in vital signs, ECG, serum glucose, and potassium were minimal and not clinically relevant.Conclusion: This study demonstrated that the new epinephrine HFA is overall comparable, in both safety and efficacy, to the previous epinephrine CFC.


Assuntos
Propelentes de Aerossol , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Epinefrina/administração & dosagem , Hidrocarbonetos Fluorados , Adolescente , Adulto , Idoso , Broncodilatadores/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Método Duplo-Cego , Epinefrina/efeitos adversos , Feminino , Humanos , Masculino , Inaladores Dosimetrados , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
9.
J Aerosol Med Pulm Drug Deliv ; 33(5): 282-287, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32423275

RESUMO

Background: Primatene® MIST CFC, an epinephrine metered-dose inhaler (MDI), was discontinued from the market owing to environmental concerns from its use of chlorofluorocarbon (CFC) propellant. As a result, a new epinephrine MDI was developed using hydrofluoroalkane (HFA) propellant. This article reports the pharmacokinetic (PK) profile of the newly Food and Drug Administration-approved epinephrine HFA MDI. Methods: A randomized, evaluator-blinded, active-controlled, single-dose, two-arm crossover study was conducted to evaluate the PK profile of epinephrine HFA (Primatene® MIST) and epinephrine CFC (Primatene® MIST CFC) in 23 healthy volunteers to characterize the epinephrine absorption extent and rate. The study was performed at a high dose of five times the normal dose to obtain measurable plasma epinephrine levels. Plasma epinephrine levels were measured and safety was assessed by adverse events (AEs), vital signs, clinical laboratory tests, and physical examinations. Results: Epinephrine HFA demonstrated a greater systemic drug exposure (greater area under the curve) than that of epinephrine CFC (∼37% higher). The Cmax occurred at ∼2 minutes and was significantly higher in the epinephrine HFA group (0.18 ng/mL) compared with the CFC version (0.046 ng/mL) at normal dose. Within 20 minutes, both groups demonstrated comparable plasma epinephrine levels. No clinically significant adverse effects were found to be associated with epinephrine HFA, even after an ultrahigh dose (i.e., 10 inhalations). Conclusions: The systemic exposure of epinephrine HFA was found to be higher for the first 20 minutes, and then comparable with epinephrine CFC. Minimal AEs were found in this study despite the very high 1250-2200 µg inhaled doses (i.e., 10 inhalations) used for PK characterization.


Assuntos
Propelentes de Aerossol/química , Broncodilatadores/administração & dosagem , Epinefrina/administração & dosagem , Hidrocarbonetos Fluorados/química , Administração por Inalação , Adolescente , Adulto , Área Sob a Curva , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacocinética , Clorofluorcarbonetos/química , Estudos Cross-Over , Relação Dose-Resposta a Droga , Epinefrina/efeitos adversos , Epinefrina/farmacocinética , Feminino , Humanos , Masculino , Inaladores Dosimetrados , Método Simples-Cego , Adulto Jovem
10.
J Aerosol Med Pulm Drug Deliv ; 33(4): 186-193, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32150492

RESUMO

Background: Two sequential single-dose crossover dose-ranging studies were performed to evaluate the clinical efficacy and safety profile of epinephrine hydrofluroalkane (HFA) metered-dose inhaler (MDI) formulation at various doses in subjects with asthma. Methods: In these multicenter, multiarm, double-blinded, or evaluator-blinded studies, subjects were randomized to receive the epinephrine HFA (Primatene® MIST HFA) MDI medication at doses ranging from 90 to 440 µg/dose, as well as to a placebo (PLA) control and an active control of epinephrine CFC (chlorofluorocarbon) MDI (Primatene® MIST CFC) at 220 µg/inhalation. Results: Spirometry testing for FEV1 (Forced Expiratory Volume in one second) demonstrated statistically significant improvements over PLA for epinephrine HFA MDI at all doses above 125 µg, as the amount out of the actuator (i.e., mouthpiece). The efficacy results for epinephrine HFA MDI in the dose range of 125-250 µg were also comparable to epinephrine CFC MDI (220 µg/inh). Safety assessments demonstrated minimal safety concerns for all treatment groups. No notable safety differences were observed between the studied doses of epinephrine HFA MDI and the active control formulation of epinephrine CFC MDI. Conclusion: The findings indicate that epinephrine HFA MDI provided clinically significant bronchodilator efficacy with minimal safety concerns in a dose range of 125-250 µg. These findings confirmed the optimal treatment doses of 125-250 µg that were appropriate for use in longer term 12 and 26 week chronic dosing studies of epinephrine HFA MDI for patients with intermittent or mild to moderate persistent asthma. Clinical trials registration number: NCT01025648.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Epinefrina/administração & dosagem , Hidrocarbonetos Fluorados/química , Administração por Inalação , Adulto , Propelentes de Aerossol/química , Asma/fisiopatologia , Broncodilatadores/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Epinefrina/efeitos adversos , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Inaladores Dosimetrados , Espirometria , Resultado do Tratamento
11.
Pharmacol Res Perspect ; 7(5): e00515, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31452900

RESUMO

Thymol is generally recognized as a safe substance by the FDA and has been widely used in the pharmaceutical, food, and cosmetic industries. Pharmacokinetic (PK) studies of thymol have been previously conducted for oral administration, but there has been no PK study for inhalation administration or intravenous (IV) injection. This study aims at exploring and comparing the inhalation and IV PK profile of thymol in a mouse model. The inhalation PK for mouse model was corrected with fur/skin absorption. Thirty-two male CD-1 mice were randomized into two study arms, Arm-A for intravenous (n = 16) and Arm-B for inhalation (n = 16). The amount of thymol in the mouse serum was measured for Arm-A and for Arm-B at the highest dose. Furthermore, 48 mice were utilized for fur/skin absorption of thymol. In total, 320 mouse serum samples for thymol were analyzed by LC/MS method. After inhalation, the peak concentration of thymol in mouse serum was 42.3 ng/mL (Cmax ) and occurred at 2 minutes (tmax ). The AUC of the inhaled thymol at 0-60 minutes (AUC0-60) was 464 ng/mL/min. From 10-60 minutes post-dose, the PK inhalation curve appeared to be higher than that for the IV injection. This is likely attributed to the effect of absorption of thymol through the fur/skin of mice. After an adjustment by fur/skin absorption, the PK profile for net inhalation closely matched the two-compartment model. In fact, the bioavailability for the net inhalation of thymol was 74% and 77% relative to that for IV injection per AUC0-60min and AUC0-infinite, respectively.


Assuntos
Timol/administração & dosagem , Timol/farmacocinética , Administração por Inalação , Animais , Disponibilidade Biológica , Cromatografia Líquida , Injeções Intravenosas , Masculino , Espectrometria de Massas , Camundongos , Modelos Animais , Distribuição Aleatória
12.
Pharmacol Res Perspect ; 7(5): e00516, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31467680

RESUMO

Epinephrine HFA (Primatene® Mist) is a newly formulated asthma metered dose inhaler developed to replace the previous Primatene® Mist CFC. The formulation of Epinephrine HFA contains thymol, a substance recognized to be safe by the FDA. Although the content of thymol contained in Epinephrine HFA is much lower compared to many common foods and medications available, there are no known nonclinical data about the chronic toxicity of thymol through inhalation. Two sequential 6-month studies of identical design were conducted to assess the chronic toxicity of inhaled thymol in mice. Four treatment groups, (a) Air; (b) vehicle control; (c) Article-1 (thymol 0.1%); and (d) Article-2 (thymol 0.5%) were assessed in 128 mice for 26 weeks. The mice were sacrificed at the end of the treatment period and a histopathologic evaluation was performed with respect to lungs, bronchial lymph nodes, nasal passages/nasopharynx, and trachea. Forty-five pathologic assessment parameters (PAPs) were evaluated. In total, 5591 data points from 487 mouse organs were assessed. Chronic toxicity index was calculated for 16 PAPs that had multiple histopathologic abnormal observations. The t tests were conducted for these 16 PAPs (Articles-1 and 2 versus Air and vehicle control, respectively), and all P-values were greater than .05 indicating no significant differences between all treatment groups. An evaluation was also conducted for 25 PAPs that had only a very small number of pathologic abnormalities. No significant differences for chronic toxicity were found when comparing mice under long-term repeated exposure of high doses of inhaled thymol and mice that inhaled no thymol.


Assuntos
Epinefrina/química , Pulmão/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Timol/toxicidade , Administração por Inalação , Animais , Estudos de Casos e Controles , Feminino , Pulmão/citologia , Masculino , Camundongos , Modelos Animais , Sistema Respiratório/citologia , Testes de Toxicidade Crônica
13.
Phys Rev Lett ; 117(3): 037602, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27472141

RESUMO

The metal-to-insulator transition in BaTiO_{3} is investigated using electrostatic doping, which avoids effects from disorder and strain that would accompany chemical doping. SmTiO_{3}/BaTiO_{3}/SrTiO_{3} heterostructures are doped with a constant sheet carrier density of 3×10^{14} cm^{-2} that is introduced via the polar SmTiO_{3}/BaTiO_{3} interface. Below a critical BaTiO_{3} thickness, the structures exhibit metallic behavior with high carrier mobilities at low temperatures, similar to SmTiO_{3}/SrTiO_{3} interfaces. Above this thickness, data indicate that the BaTiO_{3} layer becomes ferroelectric. The BaTiO_{3} lattice parameters increase to a value consistent with a strained, tetragonal unit cell, the structures are insulating below ∼125 K, and the mobility drops by more than an order of magnitude, indicating self-trapping of carriers. The results shed light on the interplay between charge carriers and ferroelectricity.

14.
Oncotarget ; 7(26): 39556-39571, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27127173

RESUMO

TBLR1/TBL1XR1, a core component of the nuclear receptor corepressor (NCoR) complex critical for the regulation of multiple nuclear receptors, is a transcriptional coactivator of androgen receptor (AR) and functions as a tumor suppressor when expressed in the nucleus in prostate. Subcellular localization of a protein is critical for its function, and although TBLR1, as a transcriptional cofactor, has been primarily viewed as a nuclear protein, many cells also express variable levels of cytoplasmic TBLR1 and its cytoplasmic specific functions have not been studied. Prostate cancer (PCa) cells express moderately higher level of cytoplasmic TBLR1 compared to benign prostate cells. When comparing androgen-dependent (AD) to androgen-independent (AI) PCa, AI cells contain very high levels of TBLR1 cytoplasmic expression and low levels of nuclear expression. Overexpression of cytoplasmic TBLR1 in AD cells inhibits apoptosis induced by androgen deprivation therapy, either in an androgen free condition or in the presence of bicalutamide. Additionally, we identified a cytoplasmic specific isoform of TBLR1 (cvTBLR1) approximately 5 kDa lower in molecular weight, that is expressed at higher levels in AI PCa cells. By immunoprecipitation, we purified cvTBLR1 and using mass spectrometry analysis combined with N-terminal TMPP labeling and Edman degradation, we identified the cleavage site of cvTBLR1 at amino acid 89, truncating the first 88 amino acids of the N-terminus of the full length protein. Functionally, cvTBLR1 expressed in the cytoplasm reduced apoptosis in PCa cells and promoted growth, migration, and invasion. Finally, we identified a nuclear export signal sequence for TBLR1 cellular localization by deletion and site-directed mutagenesis. The roles of TBLR1 and cvTBLR1 provide novel insights into the mechanism of castration resistance and new strategies for PCa therapy.


Assuntos
Apoptose , Citoplasma/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Transporte Ativo do Núcleo Celular , Androgênios/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos , Células HEK293 , Humanos , Masculino , Mutagênese Sítio-Dirigida , Invasividade Neoplásica , Domínios Proteicos , Receptores Androgênicos/metabolismo
15.
Sci Rep ; 6: 23652, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27033955

RESUMO

Bulk NdNiO3 exhibits a metal-to-insulator transition (MIT) as the temperature is lowered that is also seen in tensile strained films. In contrast, films that are under a large compressive strain typically remain metallic at all temperatures. To clarify the microscopic origins of this behavior, we use position averaged convergent beam electron diffraction in scanning transmission electron microscopy to characterize strained NdNiO3 films both above and below the MIT temperature. We show that a symmetry lowering structural change takes place in case of the tensile strained film, which undergoes an MIT, but is absent in the compressively strained film. Using space group symmetry arguments, we show that these results support the bond length disproportionation model of the MIT in the rare-earth nickelates. Furthermore, the results provide insights into the non-Fermi liquid phase that is observed in films for which the MIT is absent.

16.
Sci Rep ; 6: 20865, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26861764

RESUMO

We examine the carrier density dependence of the scattering rate in two- and three-dimensional electron liquids in SrTiO3 in the regime where it scales with T(n) (T is the temperature and n ≤ 2) in the cases when it is varied by electrostatic control and chemical doping, respectively. It is shown that the scattering rate is independent of the carrier density. This is contrary to the expectations from Landau Fermi liquid theory, where the scattering rate scales inversely with the Fermi energy (EF). We discuss that the behavior is very similar to systems traditionally identified as non-Fermi liquids (n < 2). This includes the cuprates and other transition metal oxide perovskites, where strikingly similar density-independent scattering rates have been observed. The results indicate that the applicability of Fermi liquid theory should be questioned for a much broader range of correlated materials and point to the need for a unified theory.

17.
Sci Rep ; 5: 12419, 2015 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-26206489

RESUMO

Variable-angle high-angle annular dark-field (HAADF) imaging in scanning transmission electron microscopy is developed for precise and accurate determination of three-dimensional (3D) dopant atom configurations. Gd-doped SrTiO3 films containing Sr columns containing zero, one, or two Gd dopant atoms are imaged in HAADF mode using two different collection angles. Variable-angle HAADF significantly increases both the precision and accuracy of 3D dopant profiling. Using image simulations, it is shown that the combined information from the two detectors reduces the uncertainty in the dopant depth position measurement and can uniquely identify certain atomic configurations that are indistinguishable with a single detector setting. Additional advances and applications are discussed.

18.
Nat Commun ; 5: 4258, 2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25005611

RESUMO

Quantum phase transitions are driven by quantum fluctuations that alter the nature of the electronic quasiparticles, resulting in phenomena such as non-Fermi liquid behaviour. Oxide heterostructures offer fundamentally new ways of manipulating quantum criticality. Here, we report on non-Fermi liquid behaviour in thin SrTiO3 quantum wells that are embedded in insulating, antiferromagnetic SmTiO3, as a function of temperature, quantum well thickness and SmTiO3 layer thickness in superlattices. Such quantum wells contain very high sheet carrier densities on the order of one electron per pseudocubic planar unit cell. We show that the quantum well thickness is a tuning parameter for non-Fermi liquid behaviour. Increasing the thickness by a single atomic layer and coupling in superlattices recover the Fermi liquid behaviour. The critical exponents, the symmetry of the order parameter, the role of carrier densities and symmetry-lowering distortions are discussed, and the results are compared with those of quantum wells embedded in ferrimagnetic GdTiO3.

19.
Sci Rep ; 3: 3284, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24257578

RESUMO

Heterointerfaces in complex oxide systems open new arenas in which to test models of strongly correlated material, explore the role of dimensionality in metal-insulator-transitions (MITs) and small polaron formation. Close to the quantum critical point Mott MITs depend on band filling controlled by random disordered substitutional doping. Delta-doped Mott insulators are potentially free of random disorder and introduce a new arena in which to explore the effect of electron correlations and dimensionality. Epitaxial films of the prototypical Mott insulator GdTiO3 are delta-doped by substituting a single (GdO)(+1) plane with a monolayer of charge neutral SrO to produce a two-dimensional system with high planar doping density. Unlike metallic SrTiO3 quantum wells in GdTiO3 the single SrO delta-doped layer exhibits thermally activated DC and optical conductivity that agree in a quantitative manner with predictions of small polaron transport but with an extremely high two-dimensional density of polarons, ~7 × 10(14) cm(-2).

20.
Phys Rev Lett ; 110(25): 256401, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23829748

RESUMO

We report on structural distortions in extreme-electron density (∼6×10(14) cm(-2)) confined quantum wells of SrTiO3 embedded in GdTiO3. Sr-column displacements are measured using high-angle annular dark-field imaging in scanning transmission electron microscopy. Using thick SrTiO3 layers as a reference, orthorhombic-like Sr-site displacements are observed when SrTiO3 quantum wells are thinner than 4 SrO layers, in precise agreement with an experimentally observed metal-to-insulator transition. It is shown that the structural displacements are absent in thicker quantum wells, even in the immediate proximity to the orthorhombic GdTiO3. The results are discussed in the context of strong electron correlations in this system.

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