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1.
Nature ; 579(7799): 368-374, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32188941

RESUMO

Two-dimensional van der Waals heterostructures (vdWHs) have attracted considerable interest1-4. However, most vdWHs reported so far  are created by an arduous micromechanical exfoliation and manual restacking process5, which-although versatile for proof-of-concept demonstrations6-16 and fundamental studies17-30-is clearly not scalable for practical technologies. Here we report a general synthetic strategy for two-dimensional vdWH arrays between metallic transition-metal dichalcogenides (m-TMDs) and semiconducting TMDs (s-TMDs). By selectively patterning nucleation sites on monolayer or bilayer s-TMDs, we precisely control the nucleation and growth of diverse m-TMDs with designable periodic arrangements and tunable lateral dimensions at the predesignated spatial locations, producing a series of vdWH arrays, including VSe2/WSe2, NiTe2/WSe2, CoTe2/WSe2, NbTe2/WSe2, VS2/WSe2, VSe2/MoS2 and VSe2/WS2. Systematic scanning transmission electron microscopy studies reveal nearly ideal vdW interfaces with widely tunable moiré superlattices. With the atomically clean vdW interface, we further show that the m-TMDs function as highly reliable synthetic vdW contacts for the underlying WSe2 with excellent device performance and yield, delivering a high ON-current density of up to 900 microamperes per micrometre in bilayer WSe2 transistors. This general synthesis of diverse two-dimensional vdWH arrays provides a versatile material platform for exploring exotic physics and promises a scalable pathway to high-performance devices.

2.
Nano Lett ; 22(11): 4429-4436, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35616710

RESUMO

Schottky diode is the fundamental building blocks for modern electronics and optoelectronics. Reducing the semiconductor layer thickness could shrink the vertical size of a Schottky diode, improving its speed and integration density. Here, we demonstrate a new approach to fabricate a Schottky diode with ultrashort physical length approaching atomic limit. By mechanically laminating prefabricated metal electrodes on both-sides of two-dimensional MoS2, the intrinsic metal-semiconductor interfaces can be well retained. As a result, we demonstrate the thinnest Schottky diode with a length of 2.6 nm and decent rectification behavior. Furthermore, with a diode length smaller than the semiconductor depletion length, the carrier transport mechanisms are investigated and explained by thickness-dependent and temperature-dependent electrical measurements. Our study not only pushes the scaling limit of a Schottky diode but also provides a general double-sided electrodes integration approach for other ultrathin vertical devices.

3.
Nanotechnology ; 33(39)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35675787

RESUMO

The increase of gate leakage current when the gate dielectric layer is thinned is a key issue for device scalability. For scaling down the integrated circuits, a thin gate dielectric layer with a low leakage current is essential. Currently, changing the dielectric layer material or enhancing the surface contact between the gate dielectric and the channel material is the most common way to reduce gate leakage current in devices. Herein, we report a technique of enhancing the surface contact between the gate dielectric and the metal electrode, that is constructing an Au/Al2O3/Si metal-oxide-semiconductor device by replacing the typical evaporated electrode/dielectric layer contact with a transferred electrode/high-κdielectric layer contact. The contact with a mild, non-invasive interface can ensure the intrinsic insulation of the dielectric layer. By applying 2-40 nm Al2O3as the dielectric layer, the current density-electrical field (J-E) measurement reveals that the dielectric leakage generated by the transferred electrode is less than that obtained by the typical evaporated electrode with a ratio of 0.3 × 101 âˆ¼ 5 × 106atVbias = 1 V. Furthermore, atJ = 1 mA cm-2, the withstand voltage can be raised by 100-102times over that of an evaporated electrode. The capacitance-voltage (C-V) test shows that the transferred metal electrode can efficiently scale the equivalent oxide layer thickness (EOT) to 1.58 nm, which is a relatively smaller value than the overall reported Si-based device's EOT. This finding successfully illustrates that the transferred electrode/dielectric layer's mild contact can balance the scaling of the gate dielectric layer with a minimal leakage current and constantly reduce the EOT. Our enhanced electrode/dielectric contact approach provides a straightforward and effective pathway for further scaling of devices in integrated circuits and significantly decreases the overall integrated circuit's static power consumption (ICs).

4.
Small ; 17(33): e2101616, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34270865

RESUMO

Phase controllable synthesis of 2D materials is of significance for tuning related electrical, optical, and magnetic properties. Herein, the phase-controllable synthesis of tetragonal and hexagonal FeTe nanoplates has been realized by a rational control of the Fe/Te ratio in a chemical vapor deposition system. Using density functional theory calculations, it has been revealed that with the change of the Fe/Te ratio, the formation energy of active clusters changes, causing the phase-controllable synthesis of FeTe nanoplates. The thickness of the obtained FeTe nanoplates can be tuned down to the 2D limit (2.8 nm for tetragonal and 1.4 nm for hexagonal FeTe). X-ray diffraction pattern, transmission electron microscopy, and high resolution scanning transmission electron microscope analyses exhibit the high crystallinity of the as-grown FeTe nanoplates. The two kinds of FeTe nanoflakes show metallic behavior and good electrical conductivity, featuring 8.44 × 104 S m-1 for 9.8 nm-thick tetragonal FeTe and 5.45 × 104 S m-1 for 7.6 nm-thick hexagonal FeTe. The study provides an efficient and convenient route for tailoring the phases of FeTe nanoplates, which benefits to study phase-sensitive properties, and may pave the way for the synthesis of other multiphase 2D nanosheets with controllable phases.

5.
Lab Invest ; 100(4): 619-629, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31748682

RESUMO

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.


Assuntos
Quimiocina CCL8/metabolismo , Glioblastoma/metabolismo , Macrófagos/metabolismo , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Invasividade Neoplásica/fisiopatologia , Células-Tronco Neoplásicas/citologia , Células Tumorais Cultivadas
6.
J Am Chem Soc ; 140(43): 14217-14223, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30346160

RESUMO

Two-dimensional (2D) layered materials have stimulated extensive research interest for their unique thickness-dependent electronic and optical properties. However, the layer-number-dependent studies on 2D materials to date are largely limited to exfoliated flakes with relatively small lateral size and poor yield. The direct synthesis of 2D materials with a precise control of the number of atomic layers remains a substantial synthetic challenge. Here we report a systematic study of chemical vapor deposition synthesis of large-area atomically thin 2D nickel telluride (NiTe2) single crystals and investigate the thickness dependent electronic properties. By controlling the growth temperature, we show that the highly uniform NiTe2 single crystals can be synthesized with precisely tunable thickness varying from 1, 2, 3, . . . to multilayers with a standard deviation (∼0.3 nm) of less than the thickness of a monolayer layer NiTe2. Our studies further reveal a systematic evolution of single crystal domain size and nucleation density with the largest lateral domain size up to ∼440 µm. X-ray diffraction, transmission electron microscopy, and high resolution scanning transmission electron microscope studies demonstrate that the resulting 2D crystals are high quality single crystals and adopt hexagonal 1T phase. Electrical transport studies reveal that the 2D NiTe2 single crystals show a strong thickness-tunable electrical properties, with an excellent conductivity up to 7.8 × 105 S m-1 and extraordinary breakdown current density up to 4.7 × 107 A/cm2. The systematic study and robust synthesis of NiTe2 nanosheets defines a reliable chemical route to 2D single crystals with precisely tailored thickness and could enable the design of new device architectures based on thickness-tunable electrical properties.

7.
Nanotechnology ; 29(47): 474002, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30188325

RESUMO

Doping can effectively regulate the electrical and optical properties of two-dimensional semiconductors. Here, we present high-quality Pb-doped SnSe2 monolayer exfoliated using a micromechanical cleavage method. X-ray photoelectron spectroscopy measurement demonstrates that Pb content of the doped sample is ∼3.6% and doping induces the downward shift of the Fermi level with respect to the pure SnSe2. Transmission electron microscopy characterization exhibits that Pb0.036Sn0.964Se2 nanosheets have a high-quality hexagonal symmetry structure and Pb element is uniformly distributed in the nanosheets. The current of the SnSe2 field effect transistors (FETs) was found to be very difficult to turn off due to the high electron density. The FETs based on the Pb0.036Sn0.964Se2 monolayer show n-type behavior with a high on/off ratio of 106 which is higher than any values of SnSe2 FETs reported at the moment. The estimated carrier concentration of Pb0.036Sn0.964Se2 is approximately six times lower than that of SnSe2. The results suggest that the method of reducing carrier concentration by doping to achieve high on/off ratio is effective, and Pb-doped SnSe2 monolayer has significant potential in future nanoelectronic and optoelectronic applications.

8.
Nat Commun ; 15(1): 385, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195636

RESUMO

Exploring the dynamic structural evolution of electrocatalysts during reactions represents a fundamental objective in the realm of electrocatalytic mechanism research. In pursuit of this objective, we synthesized PhenPtCl2 nanosheets, revealing a N2-Pt-Cl2 coordination structure through various characterization techniques. Remarkably, the electrocatalytic performance of these PhenPtCl2 nanosheets for hydrogen evolution reaction (HER) surpasses that of the commercial Pt/C catalyst across the entire pH range. Furthermore, our discovery of the dynamic coordination changes occurring in the N2-Pt-Cl2 active sites during the electrocatalytic process, as clarified through in situ Raman and X-ray photoelectron spectroscopy, is particularly noteworthy. These changes transition from Phen-Pt-Cl2 to Phen-Pt-Cl and ultimately to Phen-Pt. The Phen-Pt intermediate plays a pivotal role in the electrocatalytic HER, dynamically coordinating with Cl- ions in the electrolyte. Additionally, the unsaturated, two-coordinated Pt within Phen-Pt provides additional space and electrons to enhance both H+ adsorption and H2 evolution. This research illuminates the intricate dynamic coordination evolution and structural adaptability of PhenPtCl2 nanosheets, firmly establishing them as a promising candidate for efficient and tunable electrocatalysts.

9.
Adv Mater ; : e2309296, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065546

RESUMO

Downsizing silicon-based transistors can result in lower power consumption, faster speeds, and greater computational capacity, although it is accompanied by the appearance of short-channel effects. The integration of high-mobility 2D semiconductor channels with ultrathin high dielectric constant (high-κ) dielectric in transistors is expected to suppress the effect. Nevertheless, the absence of a high-κ dielectric layer featuring an atomically smooth surface devoid of dangling bonds poses a significant obstacle in the advancement of 2D electronics. Here, ultrathin van der Waals (vdW) lanthanum oxychloride (LaOCl) dielectrics are successfully synthesized by precisely controlling the growth kinetics. These dielectrics demonstrate an impressive high-κ value of 10.8 and exhibit a remarkable breakdown field strength (Ebd ) exceeding 10 MV cm-1 . Remarkably, the conventional molybdenum disulfide (MoS2 ) field-effect transistor (FET) featuring a dielectric made of LaOCl showcases an almost negligible hysteresis when compared to FETs employing alternative gate dielectrics. This can be attributed to the flawlessly formed vdW interface and excellent compatibility established between LaOCl and MoS2 . These findings will motivate the further exploration of rare-earth oxychlorides and the development of more-than-Moore nanoelectronic devices.

10.
Nat Commun ; 14(1): 2340, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095079

RESUMO

The practical application of two-dimensional (2D) semiconductors for high-performance electronics requires the integration with large-scale and high-quality dielectrics-which however have been challenging to deposit to date, owing to their dangling-bonds-free surface. Here, we report a dry dielectric integration strategy that enables the transfer of wafer-scale and high-κ dielectrics on top of 2D semiconductors. By utilizing an ultra-thin buffer layer, sub-3 nm thin Al2O3 or HfO2 dielectrics could be pre-deposited and then mechanically dry-transferred on top of MoS2 monolayers. The transferred ultra-thin dielectric film could retain wafer-scale flatness and uniformity without any cracks, demonstrating a capacitance up to 2.8 µF/cm2, equivalent oxide thickness down to 1.2 nm, and leakage currents of ~10-7 A/cm2. The fabricated top-gate MoS2 transistors showed intrinsic properties without doping effects, exhibiting on-off ratios of ~107, subthreshold swing down to 68 mV/dec, and lowest interface states of 7.6×109 cm-2 eV-1. We also show that the scalable top-gate arrays can be used to construct functional logic gates. Our study provides a feasible route towards the vdW integration of high-κ dielectric films using an industry-compatible ALD process with well-controlled thickness, uniformity and scalability.

11.
Brain Tumor Pathol ; 38(3): 189-200, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34231121

RESUMO

Current conventional treatment strategies for glioblastoma (GBM) have limited efficacy due to the rapid development of resistance to temozolomide (TMZ). It is particularly urgent to develop novel therapeutic strategies that can overcome TMZ resistance and provide patients with better prognoses. Here, a TMZ-resistant GBM cell strain and a mouse model of TMZ resistance are established as valuable tools to explore novel therapeutic strategies against TMZ resistance. Experimentally, p38MAPK inhibitor reduces the accumulation of F4/80+/CD11b+ macrophages/microglia in glioma and prolongs the survivals of glioma-bearing mice. Glioma-associated macrophages/microglia have a significanct expression of PD-L1. p38MAPK inhibitor in combination with PD-L1 antibody can effectively prolongs the survivals of TMZ-resistant GBM-bearing hosts, and differentially reduces the accumulation of circulating monocytes-derived tumor-associated macrophages and PD-L1 abundances of resident glioma-associated microglia. This combination therapy could be a treatment option for patients at the recurrence or chronic TMZ maintenance stages. A clinical study to confirm the safety and effectiveness of this combination therapy is warranted.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Alquilantes/farmacologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/genética , Glioblastoma/patologia , Microglia/metabolismo , Temozolomida/farmacologia , Macrófagos Associados a Tumor/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Antineoplásicos Alquilantes/uso terapêutico , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Quimioterapia Combinada , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Humanos , Camundongos , Taxa de Sobrevida
12.
Nat Commun ; 11(1): 1866, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313257

RESUMO

Two-dimensional (2D) semiconductors have attracted considerable attention for the development of ultra-thin body transistors. However, the polarity control of 2D transistors and the achievement of complementary logic functions remain critical challenges. Here, we report a doping-free strategy to modulate the polarity of WSe2 transistors using same contact metal but different integration methods. By applying low-energy van der Waals integration of Au electrodes, we observed robust and optimized p-type transistor behavior, which is in great contrast to the transistors fabricated on the same WSe2 flake using conventional deposited Au contacts with pronounced n-type characteristics. With the ability to switch majority carrier type and to achieve optimized contact for both electrons and holes, a doping-free logic inverter is demonstrated with higher voltage gain of 340, at the bias voltage of 5.5 V. Furthermore, the simple polarity control strategy is extended for realizing more complex logic functions such as NAND and NOR.

13.
ACS Omega ; 5(14): 8293-8298, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32309740

RESUMO

The dependence of plasmon resonance on the size, shape, and interparticle spacing of single, isolated nanostructures inherently limits their light-harvesting capability to a narrow spectral band. Here, we report a facile overcurrent electrodeposition strategy to prepare fractal plasmonic black gold (B-Au) with broad-band absorption properties (over 80% throughout the range of 300-1800 nm). The broad-band absorption properties are attributed to the excitation of multiple plasmons in the B-Au, which results in strong light-matter interaction over a broad-band spectral window. Consequently, the B-Au can produce strong broad-band surface-enhanced Raman scattering (SERS) regardless of the excitation light used. These findings demonstrate that the fractal B-Au allows efficient utilization of broad spectral photons and opens up exciting opportunities for highly sensitive SERS detection, photocatalysis, and photovoltaic devices.

14.
Biotechniques ; 68(3): 130-137, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31870167

RESUMO

Considering the importance of gene expression studies for understanding the biology of glioma stem cells (GSCs), we aimed to identify the reliable reference genes in GSCs that were derived from the glioma cell lines T98G, LN229, 090116 and 091214. Quantitative real-time reverse-transcription PCR was employed using 11 reference genes identified through a PubMed literature search, and the assessment of stability through the geNorm, Normfinder and coefficient of variation methods was performed to select suitable reference genes. We found that HPRT1 and RPL13A were the most suitable reference genes, and validated the geometric mean of these genes to normalize the expression of stemness genes by GSCs. Therefore, it is necessary to select novel cell-specific reference genes with greater expression stability for gene expression studies in GSCs.


Assuntos
Genes Neoplásicos/genética , Glioma/genética , Células-Tronco Neoplásicas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/normas , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Humanos , Padrões de Referência
15.
Nat Commun ; 11(1): 1151, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123176

RESUMO

Strain engineering is a promising method to manipulate the electronic and optical properties of two-dimensional (2D) materials. However, with weak van der Waals interaction, severe slippage between 2D material and substrate could dominate the bending or stretching processes, leading to inefficiency strain transfer. To overcome this limitation, we report a simple strain engineering method by encapsulating the monolayer 2D material in the flexible PVA substrate through spin-coating approach. The strong interaction force between spin-coated PVA and 2D material ensures the mechanical strain can be effectively transferred with negligible slippage or decoupling. By applying uniaxial strain to monolayer MoS2, we observe a higher bandgap modulation up to ~300 meV and a highest modulation rate of ~136 meV/%, which is approximate two times improvement compared to previous results achieved. Moreover, this simple strategy could be well extended to other 2D materials such as WS2 or WSe2, leading to enhanced bandgap modulation.

16.
Nat Commun ; 11(1): 659, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005802

RESUMO

In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics.

17.
Stem Cell Res Ther ; 10(1): 330, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747975

RESUMO

BACKGROUND: The existing cell surface markers used for sorting glioma stem cells (GSCs) have obvious limitations, such as vulnerability to the enzymatic digestion and time-consuming labeling procedure. Reduced nicotinamide adenine dinucleotide (NADH) as a cellular metabolite with property of autofluorescence has the potential to be used as a new biomarker for sorting GSCs. METHODS: A method for sorting GSCs was established according to the properties of the autofluorescence of NADH. Then, the NADHhigh and NADHlow subpopulations were sorted. The stem-like properties of the subpopulations were evaluated by qRT-PCR, western blot analyses, limiting dilution assay, cell viability assay, bioluminescence imaging, and immunofluorescence analysis in vitro and in vivo. The relationship between CD133+/CD15+ cells and NADHhigh subpopulation was also assessed. RESULTS: NADHhigh cells expressed higher stem-related genes, formed more tumor spheres, and harbored stronger pluripotency in vitro and higher tumorigenicity in vivo, compared to NADHlow subpopulation. NADHhigh glioma cells had the similar stemness with CD133+ or CD15+ GSCs, but the three subpopulations less overlaid each other. Also, NADHhigh glioma cells were more invasive and more resistant to chemotherapeutic drug temozolomide (TMZ) than NADHlow cells. In addition, the autofluorescence of NADH might be an appropriate marker to sort cancer stem cells (CSCs) in other cancer types, such as breast and colon cancer. CONCLUSION: Our findings demonstrate that intracellular autofluorescence of NADH is a non-labeling, sensitive maker for isolating GSCs, even for other CSCs.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Citometria de Fluxo , Glioma/patologia , NAD/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Antígenos CD/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Feminino , Fluorescência , Glioma/tratamento farmacológico , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Temozolomida/farmacologia , Temozolomida/uso terapêutico
18.
Cancer Med ; 8(17): 7207-7218, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605439

RESUMO

AIMS: The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD-L1high /TILhigh ; TMIT II, PD-L1low /TILlow ; TMIT III, PD-L1high /TILlow ; and TMIT IV, PD-L1low /TILhigh ) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry (IHC) was applied to evaluate the expression of PD-L1 and the spatial distribution of programmed cell death 1 (PD-1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD-1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma. The density of TILs was a poor prognostic factor in LAC but a favorable one in SCC. PD-L1 levels and its clinical prognostic significance differed in LAC vs SCC. LAC patients with TMIT III and SCC patients with TMIT I had the longest survival, respectively (P = .0197 and .0049). Moreover, TMIT stratification based on tumor cell PD-L1 expression and stromal CD8+ TILs could be considered as an independent prognostic factor of SCC patients' survival as determined by both univariate and multivariate analysis. CONCLUSION: Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of LAC and SCC patients and highlights the importance of the integrative assessment of PD-L1 status and TILs' spatial distribution to predict patients' prognosis.


Assuntos
Adenocarcinoma de Pulmão/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Pulmonares/imunologia , Microambiente Tumoral/imunologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pulmão/imunologia , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Prognóstico , Estudos Retrospectivos , Análise Espacial
19.
Cancer Biol Med ; 16(3): 595-605, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31565488

RESUMO

OBJECTIVE: Glioblastoma (GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy. Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM. METHODS: Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes (DEGs) through DESeq2 or LIMMA methods. The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression. Based on the gene signature of multiple survival-associated DEGs, a risk score model was established, and its prognostic and predictive role was estimated through Kaplan-Meier analysis and log-rank test. Gene set enrichment analysis (GSEA) was conducted to explore high-risk score-associated pathways. Western blot was used for protein detection. RESULTS: Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10. The four-gene signature-derived risk score was higher in GBM than in normal brain tissues. GBM patients with a high-risk score had poor survival outcomes. The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group. GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion. Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells. CONCLUSIONS: The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients.

20.
Cancer Lett ; 442: 445-452, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30472185

RESUMO

Hybrid formation is a fundamental process in normal development and tissue homeostasis, while the presence and the biological role of hybrids between tumor-associated macrophages (TAMs) and glioblastoma (GBM) cells remain elusive. In this study, we observed that TAM-GBM cell hybrids existed in human GBM specimens as demonstrated by co-expression of glioma biomarkers (GFAP, IDH1R132H and PDGFRA) and macrophage biomarkers (CD68 and CD14). Furthermore, TAM-GBM cell hybrids could also be found in C57BL/6 mice orthotopically inoculated with mouse GBM cells labeled with RFP and after co-culture of bone marrow-derived macrophages from GFP-expressed mice with RFP-labeled GBM cells. The hybrids underwent nuclear reprogramming with unique gene expression profile as compared to parental cells. Moreover, glioma invasion-associated genes were enriched in the hybrids that possessed higher invasiveness, and more hybrids in the invasive margin of GBM were observed as compared to GBM core area. Our data demonstrate the presence of TAM-GBM cell hybrids that enhance GBM invasion. With a better understanding of TAM-GBM cell hybrids, new therapeutic strategies targeting GBM will be developed to treat GBM patients.


Assuntos
Neoplasias Encefálicas/patologia , Movimento Celular , Reprogramação Celular , Glioblastoma/secundário , Células Híbridas/patologia , Macrófagos/patologia , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Células Híbridas/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Invasividade Neoplásica , Fenótipo , Transcriptoma , Microambiente Tumoral
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