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1.
Sci Rep ; 10(1): 2701, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060336

RESUMO

A multifunctional sensor capable of simultaneous sensing of temperature, pressure, and proximity has been developed. This transparent and body-attachable device is also capable of providing heat under low voltage. The multi-sensor consists of metal fibers fabricated by electrospinning and electroplating. The device comprises randomly deposited metal fibers, which not only provide heating but also perform as thermal and proximity sensors, and orderly aligned metal fibers that act as a pressure sensor. The sensor is fabricated by weaving straight rectangular electrodes on a transparent substrate (a matrix). The sensitivity is readily enhanced by installing numerous matrices that facilitate higher sensing resolution. The convective heat transfer coefficient of the heater is h = 0.014 W·cm-2·°C-1. The temperature coefficient of resistivity (TCR) and pressure sensitivity (ηP) are 0.038 °C-1 and 5.3 × 10-3 kPa-1, respectively. The superior sensitivity of the device is confirmed via quantitative comparison with similar devices. This multifunctional device also has a superior convective heat transfer coefficient than do other heaters reported in the literature.

2.
Ann Surg Oncol ; 27(3): 802-811, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894481

RESUMO

BACKGROUND: This study aimed to compare the long-term survival of patients undergoing minimally invasive gastrectomy and those undergoing open gastrectomy for gastric adenocarcinoma (GA) in the United States and China. METHODS: Data on patients with GA who underwent gastrectomy without neoadjuvant therapy were retrieved from prospectively maintained databases at Memorial Sloan Kettering Cancer Center (MSKCC) and Fujian Medical University Union Hospital (FMUUH). Using propensity score-matching (PSM), equally sized cohorts of patients with similar clinical and pathologic characteristics who underwent minimally invasive versus open gastrectomy were selected. The primary end point of the study was 5-year overall survival (OS). RESULTS: The study identified 479 patients who underwent gastrectomy at MSKCC between 2000 and 2012 and 2935 patients who underwent gastrectomy at FMUUH between 2006 and 2014. Of the total 3432 patients, 1355 underwent minimally invasive gastrectomy, and 2059 underwent open gastrectomy. All the patients had at least 5 years of potential follow-up evaluation. Before PSM, most patient characteristics differed significantly between the patients undergoing the two types of surgery. After PSM, each cohort included 889 matched patients, and the actual 5-year OS did not differ significantly between the two cohorts, with an OS rate of 54% after minimally invasive gastrectomy and 50.4% after open gastrectomy (p = 0.205). Subgroup analysis confirmed that survival was similar between surgical cohorts among the patients for each stage of GA and for those undergoing distal versus total/proximal gastrectomy. In the multivariable analysis, surgical approach was not an independent prognostic factor. CONCLUSIONS: After PSM of U.S. and Chinese patients with GA undergoing gastrectomy, long-term survival did not differ significantly between the patients undergoing minimally invasive gastrectomy and those undergoing open gastrectomy.

3.
Cell Metab ; 31(1): 174-188.e7, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31761563

RESUMO

The remarkable cellular and genetic heterogeneity of soft tissue sarcomas (STSs) limits the clinical benefit of targeted therapies. Here, we show that expression of the gluconeogenic isozyme fructose-1,6-bisphosphatase 2 (FBP2) is silenced in a broad spectrum of sarcoma subtypes, revealing an apparent common metabolic feature shared by diverse STSs. Enforced FBP2 expression inhibits sarcoma cell and tumor growth through two distinct mechanisms. First, cytosolic FBP2 antagonizes elevated glycolysis associated with the "Warburg effect," thereby inhibiting sarcoma cell proliferation. Second, nuclear-localized FBP2 restrains mitochondrial biogenesis and respiration in a catalytic-activity-independent manner by inhibiting the expression of nuclear respiratory factor and mitochondrial transcription factor A (TFAM). Specifically, nuclear FBP2 colocalizes with the c-Myc transcription factor at the TFAM locus and represses c-Myc-dependent TFAM expression. This unique dual function of FBP2 provides a rationale for its selective suppression in STSs, identifying a potential metabolic vulnerability of this malignancy and possible therapeutic target.

4.
Acta Biomater ; 101: 285-292, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610340

RESUMO

Recently, endovascular coil embolization has been introduced to treat intracranial aneurysms because it has lower morbidity and mortality than surgical clipping. The endovascular coils prevent the extravasation of blood by decreasing the permeability of an aneurysm flow governed by Darcy's law. Here, we developed and explored Pt-coated micro-ropes for potential use as endovascular coils. Electrospinning with subsequent electroplating were employed to fabricate Pt-coated nanofibers, which were tightly twisted to form micro-ropes. The compatibility of Pt micro-ropes with commercial delivery catheters was verified and their performance was experimentally explored in an in vitro experimental model. The developed Pt-coated micro-ropes demonstrated feasibility as efficient and low-cost endovascular coils. STATEMENT OF SIGNIFICANCE: The use of Platinum (Pt)-coated polymer nanofibers to prevent blood extravasation has been demonstrated. These Pt nanofibers were installed within a microfluidic channel, and the resulting reduced permeability was evaluated using a fluid similar to blood. Based on the obtained results, these newly developed nanofibers are expected to decrease the operation cost for aneurysmal subarachnoid hemorrhage (SAH), owing their reduced size and low material cost. Overall, the use of this new material should reduce the operational risk associated with the multiple steps required to place the Pt coils at the SAH site. The compatibility of Pt micro-ropes with commercial delivery catheters was verified and their performance was experimentally explored in an in vitro experimental model. The developed Pt-coated micro-ropes demonstrated feasibility as efficient and low-cost endovascular coils.

5.
Adv Mater ; 32(2): e1905028, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31747097

RESUMO

Supersonic cold spraying is an emerging technique for rapid deposition of films of materials including micrometer-size and sub-micrometer metal particles, nanoscale ceramic particles, clays, polymers, hybrid materials composed of polymers and particulates, reduced graphene oxide (rGO), and metal-organic frameworks. In this method, particles are accelerated to a high velocity and then impact a substrate at near ambient temperature, where dissipation of their kinetic energy produces strong adhesion. Here, recent progress in fundamentals and applications of cold spraying is reviewed. High-velocity impact with the substrate results in significant deformation, which not only produces adhesion, but can change the particles' internal structure. Cold-sprayed coatings can also exhibit micro- and nanotextured morphologies not achievable by other means. Suspending micro- or nanoparticles in a liquid and cold-spraying the suspension produces fine atomization and even deposition of materials that could not otherwise be processed. The scalability and low cost of this method and its compatibility with roll-to-roll processing make it promising for many applications, including ultrathin flexible materials, solar cells, touch-screen panels, nanotextured surfaces for enhanced heat transfer, thermal and electrical insulation films, transparent conductive films, materials for energy storage (e.g., Li-ion battery electrodes), heaters, sensors, photoelectrodes for water splitting, water purification membranes, and self-cleaning films.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31678201

RESUMO

Hereditary diffuse gastric cancer (HDGC) syndrome results from a germline CDH1 mutation, and microscopic foci of signet-ring carcinoma cells (SRCC) are present in nearly all gastrectomy specimens.1 The lifetime risk of invasive gastric cancer (GC) has been thought to be 70%,2 but recent data have suggested a lower risk of 37%.3 Prophylactic total gastrectomy is considered the standard of care, but many patients choose surveillance endoscopy instead. We sought to define the outcomes in CDH1-positive individuals who pursued endoscopic surveillance.

7.
ACS Appl Mater Interfaces ; 11(43): 40232-40242, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571474

RESUMO

The demand for wearable, stretchable soft electronics for human-machine interface applications continues to grow given the potential of these devices in humanoid robotics, prosthetics, and health-monitoring devices. We demonstrate fabrication of multifunctional sensors with simultaneous temperature-, pressure-, proximity-, and strain (or bending)-sensing capabilities, combined with heating and UV-protection features. These multifunctional sensors are flexible, light, and transparent and are thus body-attachable. Silver nanowires are supersonically sprayed on a large-scale transparent and flexible roll-to-roll substrate. The junctions between nanowires are physically fused by a strong impact resulting from supersonic spraying, which promotes adhesion and efficient deposition of the nanowire network. Accordingly, nanowires are strongly interconnected, facilitating efficient propagation of electric signals through the fused nanowire network, which allows simultaneous operation of such sensors while maintaining significant transparency. These multifunctional sensors are mechanically durable and retain long-term stability. A theoretical discussion is provided to explain the respective mechanisms of heating and proximity, pressure, and strain sensing.

8.
Mol Cancer Res ; 17(11): 2169-2183, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416838

RESUMO

Intestinal-type gastric cancer often results from Helicobacter pylori infection through intestinal metaplasia, a transdifferentiated premalignant phenotype. Because H. pylori virulence factor CagA has been associated with aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with H. pylori infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines. Infection of HFE 145 cells with CagA+ H. pylori increased expression of CDX1, as well as the epithelial-to-mesenchymal transition (EMT) markers Snail and Slug, increased invasion and migration, but those effects were not found in HFE 145 cells infected with CagA-deficient H. pylori. CDX1 overexpression increased expression of the intestinal markers Villin, sucrose isomaltase (SI), and MUC2, induced spheroid formation, and enhanced expression of the stem cell markers CD44, SOX2, Oct4, and Nanog, while CDX1 knockdown inhibited proliferation and intestinal stemness. Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation. In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone. Patients with more advanced intestinal metaplasia staging exhibited higher CDX1 expression than those with earlier intestinal metaplasia staging (P = 0.039), and those with H. pylori tended to have more CDX1 expression than noninfected patients (P = 0.061). Finally, human tissue samples with higher CDX1 levels showed prominent CD44/SOX2 expression. Our findings indicate CagA+ H. pylori-induced CDX1 expression may enhance gastric cancer tumorigenesis and progression, and support therapeutic targeting of CDX1 in gastric cancer. IMPLICATIONS: This study shows that CDX1 contributes to the tumorigenesis and progression of gastric cancer and suggests the potential of targeting CDX1 to treat this malignancy.

9.
Ann Surg ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31283560

RESUMO

OBJECTIVE: We sought to define the prognostic significance of histologic subtype for extremity/truncal liposarcoma (LPS). BACKGROUND: LPS, the most common sarcoma, is comprised of 5 histologic subtypes. Despite their distinct behaviors, LPS outcomes are frequently reported as a single entity. METHODS: We analyzed data on all patients from a single-institution prospective database treated from July 1982 to September 2017 for primary, nonmetastatic, extremity or truncal LPS of known subtype. Clinicopathologic variables were tested using competing risk analyses for association with disease-specific death (DSD), distant recurrence (DR), and local recurrence (LR). RESULTS: Among 1001 patients, median follow-up in survivors was 5.4 years. Tumor size and subtype were independently associated with DSD and DR. Size, subtype, and R1 resection were independently associated with LR. DR was most frequent among pleomorphic and round cell LPS; the former recurred early (43% by 3 years), and the latter over a longer period (23%, 3 years; 37%, 10 years). LR was most common in dedifferentiated LPS, in which it occurred early (24%, 3 years; 33%, 5 years), followed by pleomorphic LPS (18%, 3 years; 25%, 10 years). CONCLUSIONS: Histologic subtype is the factor most strongly associated with DSD, DR, and LR in extremity/truncal LPS. Both risk and timing of adverse outcomes vary by subtype. These data may guide selective use of systemic therapy for patients with round cell and pleomorphic LPS, which carry a high risk of DR, and radiotherapy for LPS subtypes at high risk of LR when treated with surgery alone.

10.
ACS Appl Mater Interfaces ; 11(29): 26323-26332, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31259518

RESUMO

Particulate matter (PM) from ever-increasing industrialization poses a great public health risk. Although fiber-based filters are used effectively to block PM, filters with high packing densities suffer from excessive pressure drops. Electret filters bypass intermediate- or large-sized particles and thus capture only small particles, the motion of which can be influenced by weak electrostatic fields. In this study, we demonstrate the fabrication of metallized fibers that produce intense electric fields, thereby enabling capture of PMs of a variety of sizes produced by burning incense. The filter consisting of these metallized fibers effectively removes moving particles from air. An electricity-driven filter is relatively thin and has a low packing density, making it light, portable, transparent, and inexpensive. The sizes of the pores between the metallized fibers are readily controlled by manipulating the electrospinning and electroplating times. Sufficiently large pores permit efficient airflow and thus increase permeability without risking an excessive pressure drop. The metallized fiber filter is washable and thus reusable. In this study, a PM removal rate of >97% was recorded using a filter designed under optimal conditions.

11.
Mol Cancer Res ; 17(9): 1945-1957, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31217166

RESUMO

Our previous work showed that in a mouse model of gastric adenocarcinoma with loss of p53 and Cdh1 that adding oncogenic Kras (a.k.a. Tcon mice) accelerates tumorigenesis and metastasis. Here, we sought to examine KRAS activation in epithelial-to-mesenchymal transition (EMT) and generation of cancer stem-like cells (CSC). Transduction of nontransformed HFE-145 gastric epithelial cells with oncogenic KRASG12V significantly decreased expression of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin and the EMT transcription factor Slug, and increased migration and invasion by 15- to 17-fold. KRASG12V also increased expression of self-renewal proteins such as Sox2 and increased spheroid formation by 2.6-fold. In tumor-derived organoids from Tcon mice, Kras knockdown decreased spheroid formation, expression of EMT-related proteins, migration, and invasion; similar effects, as well as reversal of chemoresistance, were observed following KRAS knockdown or MEK inhibition in patient tumor-derived gastric adenocarcinoma cell lines (AGS and KATOIII). KRAS inhibition in gastric adenocarcinoma spheroid cells led to reduced AGS flank xenograft growth, loss of the infiltrative tumor border, fewer lung metastases, and increased survival. In a tissue microarray of human gastric adenocarcinomas from 115 patients, high tumor levels of CD44 (a marker of CSCs) and KRAS activation were independent predictors of worse overall survival. In conclusion, KRAS activation in gastric adenocarcinoma cells stimulates EMT and transition to CSCs, thus promoting metastasis. IMPLICATIONS: This study provides rationale for examining inhibitors of KRAS to block metastasis and reverse chemotherapy resistance in gastric adenocarcinoma patients.

12.
Ann Surg ; 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30946076

RESUMO

MINI: In the pre-imatinib era, primary tumor site, size, and mitotic rate predicted outcome as expected. In the modern era, survival was dramatically longer. While primary tumor high-risk features were associated with imatinib treatment, only tumor size >10 cm remained associated with outcome. Imatinib should be prescribed for high-risk features. OBJECTIVE: To characterize the results of surgery for gastrointestinal stromal tumor (GIST) in the pre and post-imatinib eras at a single institution and to identify current prognostic clinicopathologic factors. BACKGROUND: Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined. METHODS: We retrospectively analyzed 1000 patients who underwent surgery for GIST at our institution from 1982 to 2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM + MET), or metachronous recurrence/metastases (MET), and also imatinib era (before and after it became available). Cox proportional-hazard models and Kaplan-Meier methods were used to model and estimate overall survival (OS) and recurrence-free survival (RFS). RESULTS: OS was longer in the imatinib era compared with the pre-imatinib era in each presentation group, including in Miettinen high-risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10 cm remained independently prognostic of RFS [hazard ratio (HR) 3.85, 95% confidence interval (CI) 2.00-7.40, P < 0.0001) and OS (HR 3.37, 95% CI 1.60-7.13, P = 0.001)]. CONCLUSIONS: Patients treated in the imatinib era had prolonged OS across all presentations. In the imatinib era, among site, size, and mitotic rate, high-risk features were associated with treatment with the drug, but only size >10 cm correlated with outcome. Imatinib should still be prescribed for patients with high-risk features.

14.
Nanoscale ; 10(42): 19825-19834, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30334563

RESUMO

Electrospun metal-plated nanofibers and supersonically sprayed nanowires were used to fabricate hybrid films exhibiting a superior low sheet resistance of 0.18 Ω sq-1, a transparency of 91.1%, and a figure-of-merit of 2.315 Ω-1. The films are suitable to serve as thermal sensors and heaters. Such hybrid transparent conducting films are highly flexible and thus wearable. They can be used as body-temperature monitors and heaters. The employed hybrid approach improved the sheet resistance diminishing it to a minimum, while maintaining transparency. In addition, the low sheet resistance of the films facilitates their powering with a low-voltage battery and thus, portability. The thermal sensing and heating capabilities were demonstrated for such films with various sheet resistances and degrees of transparency. The temperature sensing was achieved by the resistance change of the film; the resistance value was converted back to temperature. The sensing performance increased with the improvement in the sheet resistance. The temperature coefficient of resistivity was TCR = 0.0783 K-1. The uniform distribution of the metal-plated nanofibers and nanowires resulted in a uniform Joule heating contributing to an efficient convection heat transfer from the heaters to the surrounding, demonstrated by an improved convective heat transfer coefficient.


Assuntos
Metais/química , Nanofibras/química , Nanofios/química , Dispositivos Eletrônicos Vestíveis , Materiais Biocompatíveis/química , Humanos , Prata/química , Temperatura Ambiente , Condutividade Térmica
15.
Ann Surg Oncol ; 25(12): 3629-3638, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30218243

RESUMO

OBJECTIVE: The aim of this study was to compare gastric cancer (GC) patients aged 80 years or older undergoing gastrectomy at two high-volume cancer centers in the US and China. METHODS: Patients aged ≥ 80 years who underwent R0 resection at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA (n = 159), and Fujian Medical University Union Hospital (FMUUH) in Fujian, China (n = 118) from January 2000 to December 2013 were included. Demographic, surgical, and pathologic variables were compared, and factors associated with survival were determined via multivariate analysis. RESULTS: The number of patients increased annually in the FMUUH cohort but not in the MSKCC cohort. Patients at MSKCC were slightly older (mean age 83.7 vs. 82.7 years), more commonly female (38 vs. 19%), and had higher average body mass index (BMI; 26 vs. 23). Treatment at FMUUH more frequently employed total gastrectomy (59 vs. 20%) and laparoscopic surgery (65 vs. 7%), and less frequently included adjuvant therapy (11 vs. 18%). In addition, FMUUH patients had larger tumors of more advanced T, N, and TNM stage. Morbidity (35 vs. 25%, p = 0.08) and 30-day mortality (2.5 vs. 3.3%, p = 0.67) were similar between the cohorts. For each TNM stage, there was no significant difference between MSKCC and FMUUH patients in 5-year overall survival and disease-specific survival (DSS). TNM stage was the only independent predictor of DSS for both cohorts. CONCLUSIONS: Patients ≥ 80 years of age selected for gastrectomy for GC at MSKCC and FMUUH had acceptable morbidity and mortality, and DSS was primarily dependent on TNM stage.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Gastrectomia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso de 80 Anos ou mais , China , Feminino , Gastrectomia/métodos , Hospitais com Alto Volume de Atendimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Cidade de Nova Iorque , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral
16.
Clin Cancer Res ; 24(24): 6556-6569, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30108106

RESUMO

PURPOSE: Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally genomically stable. We identified lysine (K)-specific methyltransferase 2C (KMT2C) as a frequently mutated gene and examined its role in DGA progression. EXPERIMENTAL DESIGN: We performed whole exome sequencing on tumor samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient tumors. RESULTS: KMT2C was the most frequently mutated gene (11 of 27 tumors [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with DGA undergoing gastrectomy inversely correlated with more advanced tumor stage (P = 0.023) and worse overall survival (P = 0.017). KMT2C shRNA knockdown in non-transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal transition (EMT) as demonstrated by increased expression of EMT-related proteins N-cadherin and Slug. Migration and invasion in gastric epithelial cells following KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU-668, which have lost KMT2C expression, KMT2C re-expression decreased expression of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA organoids, compared with wild-type organoids, grew more slowly and lost their infiltrative leading edge. EMT can lead to the acquisition of cancer stem cell (CSC) phenotypes. KMT2C re-expression in DGA cell lines reduced spheroid formation by 77% to 78% and reversed CSC resistance to chemotherapy via promotion of DNA damage and apoptosis. CONCLUSIONS: KMT2C is frequently mutated in certain populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse overall survival.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , Mutação , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Terapia Combinada , Análise Mutacional de DNA , Proteínas de Ligação a DNA/química , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Moleculares , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Relação Estrutura-Atividade , Sequenciamento Completo do Exoma
17.
Oncogenesis ; 7(6): 47, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29915281

RESUMO

Sarcomas are malignant tumors derived from mesenchymal tissues and may harbor a subset of cells with cancer stem-like cell (CSC) properties. Platelet-derived growth factor receptors α and ß (PDGFR-α/ß) play an important role in the maintenance of mesenchymal stem cells. Here we examine the role of PDGFR-α/ß in sarcoma CSCs. PDGFR-α/ß activity and the effects of PDGFR-α/ß inhibition were examined in 3 human sarcoma cell lines using in vitro assays and mouse xenograft models. In all three cell lines, PDGFR-α/ß activity was significantly higher in cells grown as spheroids (to enrich for CSCs) and in cells sorted for CD133 expression (a marker of sarcoma CSCs). Self-renewal transcription factors Nanog, Oct4, and Slug and epithelial-to-mesenchymal transition (EMT) proteins Snail, Slug, and Zeb1 were also significantly higher in spheroids cells and CD133(+) cells. Spheroid cells and CD133(+) cells demonstrated 2.9- to 4.2-fold greater migration and invasion and resistance to doxorubicin chemotherapy. Inhibition of PDGFR-α/ß in CSCs using shRNA or pharmacologic inhibitors reduced expression of certain self-renewal and EMT proteins, reduced spheroid formation by 74-82%, reduced migration and invasion by 73-80%, and reversed chemotherapy resistance. In mouse xenograft models, combining PDGFR-α/ß inhibition (using shRNA or imatinib) with doxorubicin had a more-than-additive effect in blocking tumor growth, with enhanced apoptosis, especially in CD133(+) cells. These results indicate that PDGFR-α/ß activity is upregulated in sarcoma CSCs and promote CSC phenotypes including migration, invasion, and chemotherapy resistance. Thus, the PDGFR-α/ß pathway represents a new potential therapeutic target to reduce metastatic potential and increase chemosensitivity.

18.
Nanoscale ; 10(20): 9720-9728, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29762621

RESUMO

Charge recombination in CuO photocathodes inhibits efficient electron flow and limits the photo-electrochemical performance of these cathodes for solar water splitting. To circumvent this shortcoming, we introduce highly conductive Ni/CuO core-shell structured fibers. The photocurrent density (PCD) achieved with these core-shell fibers exceeded that of fibers without a Ni core by a factor of 2.6. The PCD enhancement arises from increased acceptor concentration and electron-hole recombination time, as measured by electrochemical impedance spectroscopy. These core-shell nanofibers were fabricated via electrospinning and electroplating. First, a polyacrylonitrile fiber was electrospun and then seeded with metal via sputtering. Second, electroplating was used to encase and metalize the fiber with Ni and Cu. Finally, the outermost Cu shell was oxidized to CuO, which is an effective photocathode for solar water splitting. The Ni-CuO, core-shell layers were characterized by scanning electron microscopy, elemental mapping, X-ray diffraction, and X-ray photoelectron spectroscopy. The core Ni content and number of core-shell fibers per area were optimized through parametric studies.

20.
Nanoscale ; 10(14): 6589-6601, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29578221

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) is the extravasation of blood into the subarachnoid space and is fatal in most cases. Platinum coils have been used to fill the hemorrhage site and prevent the extravasation of blood. Here we explored the use of Pt-coated polymer nanofibers (NF) to prevent blood extravasation and were able to achieve improved results in vitro. The polymer nanofibers were produced via electrospinning and were subsequently electroplated with Pt, resulting in metalized nanofibers. These nanofibers were installed within a microfluidic channel, and the resulting reduction in the permeability was evaluated using a fluid similar to blood. Based on the obtained results, these newly developed nanofibers are expected to decrease the operation cost for SAH, owing to their reduced size and low material cost. Furthermore, it is expected that these nanofibers will be used in a smaller amount during SAH operation while having the same preventive effect. This should reduce the operational risk associated with the multiple steps required to place the Pt coils at the SAH site. Finally, the underlying hydrodynamic mechanism responsible for the reduced permeability of the synthesized nanofibers is described.


Assuntos
Aneurisma/terapia , Embolização Terapêutica , Nanofibras/química , Hemorragia Subaracnóidea/terapia , Humanos , Polímeros/química
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