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1.
ACS Appl Mater Interfaces ; 16(8): 10295-10306, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38379515

RESUMEN

The aim of this study was to clarify the effectiveness and challenges of applying mesoporous tin oxide (SnO2)-based supports for Pt catalysts in the cathodes of polymer electrolyte fuel cells (PEFCs) to simultaneously achieve high performance and high durability. Recently, the focus of PEFC application in automobiles has shifted to heavy-duty vehicles (HDVs), which require high durability, high energy-conversion efficiency, and high power density. It has been reported that employing mesoporous carbon supports improves the initial performance by mitigating catalyst poisoning caused by sulfonic acid groups of the ionomer as well as by reducing the oxygen transport resistance through the Pt/ionomer interface. However, carbon materials in the cathode can degrade oxidatively during long-term operation, and more stable materials are desired. In this study, we synthesized connected mesoporous Sb-doped tin oxides (CMSbTOs) with controlled mesopore sizes in the range of 4-11 nm and tested their performance and durability as cathode catalyst supports. The CMSbTO supports exhibited higher fuel cell performance at a pore size of 7.3 nm than the solid-core SnO2-based, solid-core carbon, and mesoporous carbon supports under dry conditions, which can be attributed to the mitigation of the formation of the Pt/ionomer interface and the better proton conductivity within the mesopores even at the low-humidity conditions. In addition, the CMSbTO supports exhibited high durability under oxidative conditions. These results demonstrate the promising applicability of mesoporous tin oxide supports in PEFCs for HDVs. The remaining challenges, including the requirements for improving performance under wet conditions and stability under reductive conditions, are also discussed.

2.
J Am Chem Soc ; 144(29): 13242-13253, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35830247

RESUMEN

The two-dimensional (2-D) framework, [Cu(BTDAT)(MeOH)] {BTDAT = bis-[1,2,5]-thiadiazolo-tetracyanoquinodimethane}, possesses remarkable multi-step redox properties, with electrochemical studies revealing six quasi-stable redox states in the solid state. In situ electron paramagnetic resonance and visible-near infrared spectroelectrochemistry elucidated the mechanism for these multi-step redox processes, as well as the optical and electrochromic behavior of the BTDAT ligand and framework. In studying the structural, spectroscopic, and electronic properties of [Cu(BTDAT)(MeOH)], the as-synthesized framework was found to exist in a mixed-valence state with thermally-activated semiconducting behavior. In addition to pressed pellet conductivity measurements, single-crystal conductivity measurements using a pre-patterned polydimethylsiloxane layer on a silicon substrate provide important insights into the anisotropic conduction pathways. As an avenue to further understand the electronic state of [Cu(BTDAT)(MeOH)], computational band structure calculations predicted delocalized electronic transport in the framework. On the balance of probabilities, we propose that [Cu(BTDAT)(MeOH)] is a Mott insulator (i.e., electron correlations cause a metal-insulator transition). This implies that the conductivity is incoherent. However, we are unable to distinguish between activated transport due to Coulombically bound electron-hole pairs and a hopping mechanism. The combined electrochemical, electronic, and optical properties of [Cu(BTDAT)(MeOH)] shine a new light on the experimental and theoretical challenges for electroactive framework materials, which are implicated as the basis of advanced optoelectronic and electrochromic devices.

3.
Chem Sci ; 13(17): 4902-4908, 2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35655871

RESUMEN

Electrical conduction among metallocycles has been unexplored because of the difficulty in creating electronic transport pathways. In this work, we present an electrocrystallization strategy for synthesizing an intrinsically electron-conductive metallocycle, [Ni6(NDI-Hpz)6(dma)12(NO3)6]·5DMA·nH2O (PMC-hexagon) (NDI-Hpz = N,N'-di(1H-pyrazol-4-yl)-1,4,5,8-naphthalenetetracarboxdiimide). The hexagonal metallocycle units are assembled into a densely packed ABCABC… sequence (like the fcc geometry) to construct one-dimensional (1D) helical π-stacked columns and 1D pore channels, which were maintained under the liberation of H2O molecules. The NDI cores were partially reduced to form radicals as charge carriers, resulting in a room-temperature conductivity of (1.2-2.1) × 10-4 S cm-1 (pressed pellet), which is superior to that of most NDI-based conductors including metal-organic frameworks and organic crystals. These findings open up the use of metallocycles as building blocks for fabricating conductive porous molecular materials.

4.
Cannabis Cannabinoid Res ; 6(2): 148-155, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33912679

RESUMEN

Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate. Results: We confirmed that ID1 was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation. Conclusion: Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.


Asunto(s)
Cannabidiol , Regulación Neoplásica de la Expresión Génica , Neoplasias , Cannabidiol/farmacología , Línea Celular Tumoral , Proliferación Celular , Expresión Génica , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Oncogenes
5.
Angew Chem Int Ed Engl ; 60(9): 4789-4795, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33236501

RESUMEN

A series of stable radical 2D metal-organic frameworks has been assembled. (m-TTFTB)3 (m-Tetrathiafulvalene-tetrabenzoate) trimer building blocks are beneficial for the stability of the radicals due to delocalization of the unpaired electron. Hexanuclear rare-earth-cluster-based 1D chains further enhance the stability of the frameworks. The radical state of the middle TTF in the trimer has been observed by the change of central C-C and C-S bond distances and the configuration of the TTF by single-crystal X-ray diffraction. The radical characteristics are also confirmed by electron paramagnetic resonance, UV/Vis-NIR absorption, and X-ray photoelectron spectroscopy experiments. Stability tests showed that the radicals are stable even in solutions and under acid/base environments (pH 1-12). Owing to efficient light absorption due to intramolecular charge transfer, low thermal conductivity, and outstanding stability, the radical 2D Dy-MOF shows excellent photothermal properties, an increase of 34.7 °C within 240 s under one-sun illumination.

6.
Nat Commun ; 11(1): 2808, 2020 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-32499512

RESUMEN

Reversible structural transformations of porous coordination frameworks in response to external stimuli such as light, electrical potential, guest inclusion or pressure, amongst others, have been the subject of intense interest for applications in sensing, switching and molecular separations. Here we report a coordination framework based on an electroactive tetrathiafulvalene exhibiting a reversible single crystal-to-single crystal double [2 + 2] photocyclisation, leading to profound differences in the electrochemical, optical and mechanical properties of the material upon light irradiation. Electrochemical and in situ spectroelectrochemical measurements, in combination with in situ light-irradiated Raman spectroscopy and atomic force microscopy, revealed the variable mechanical properties of the framework that were supported using Density Functional Theory calculations. The reversible structural transformation points towards a plethora of potential applications for coordination frameworks in photo-mechanical and photoelectrochemical devices, such as light-driven actuators and photo-valves for targeted drug delivery.

7.
Inorg Chem ; 59(6): 3619-3630, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32124614

RESUMEN

A 2-D coordination framework, (NEt4)2[Fe2(fan)3] (1·5(acetone); H2fan = 3,6-difluoro-2,5-dihydroxy-1,4-benzoquinone), was synthesized and structurally characterized. The compound is structurally analogous to a formerly elucidated framework, (NEt4)2[Fe2(can)3] (H2can = 3,6-dichloro-2,5-dihydroxy-1,4-benzoquinone), and adopts a 2-D (6,3) topology with the symmetrical stacking of [Fe2(fan)3]2- sheets that are held in position by the NEt4+ cations between the sheets. The investigation of the dc and ac magnetic properties of 1·5(acetone) revealed ferromagnetic ordering behavior and slow magnetization relaxation, as evinced from ac susceptibility measurements. Furthermore, the exposure of 1·5(acetone) to air led to the formation of a heptahydrate 1·7H2O which displayed distinct magnetic properties. The study of the redox state and extent of delocalization in 1·5(acetone) was undertaken via crystallography, in combination with Mössbauer and vis-NIR spectroscopy, to reveal the mixed-valence and delocalized nature of the as-synthesized material. As a result, the conductivity studies conducted on a pressed pellet showed a relatively high conductivity of 1.8 × 10-2 S cm-1 (300 K). In order to compare structurally related anilate-based structures, a relationship among the redox state, spectroscopic properties, and electronic properties was elucidated in this work. A preliminary investigation of 1·5(acetone) as a candidate anode material in lithium ion batteries revealed a high reversible capacity of 676.6 mAh g-1 and high capacity retention.

8.
Philos Trans A Math Phys Eng Sci ; 377(2149): 20180226, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31130095

RESUMEN

Electroactive and conducting framework materials, encompassing coordination polymers and metal-organic frameworks, have captured the imagination of the scientific community owing to their highly designable nanoporous structures and their potential applications in electrochromic devices, electrocatalysts, porous conductors, batteries and solar energy harvesting systems, among many others. While they are now considered integral members of the broader field of inorganic materials, it is timely to reflect upon their strengths and challenges compared with 'traditional' solid-state materials such as minerals, pigments and zeolites. Indeed, the latter have been known since ancient times and have been prized for centuries in fields as diverse as art, archaeology and industrial catalysis. This opinion piece considers a brief historical perspective of traditional electroactive and conducting inorganic materials, with a view towards very recent experimental progress and new directions for future progress in the burgeoning area of coordination polymers and metal-organic frameworks. Overall, this article bears testament to the rich history of electroactive solids and looks at the challenges inspiring a new generation of scientists. This article is part of the theme issue 'Mineralomimesis: natural and synthetic frameworks in science and technology'.

9.
Inorg Chem ; 58(6): 3698-3706, 2019 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-30830770

RESUMEN

Metal-organic frameworks (MOFs) incorporating lanthanide nodes and tetrathiafulvalene (TTF) linkers offer a viable approach for combining redox activity and magnetism in one material. Four rare-earth lanthanide ions (RE = Tb, Dy, Ho, and Er) were found to form isostructural MOFs consisting of metal chains bridged by redox-active tetrathiafulvalene-tetrabenzoate (TTFTB4-) whereby the carboxylate moieties act in both anti- anti and syn- syn coordination modes. These materials display tunable redox-active properties and slow magnetic relaxation phenomenon (Er and Dy). While the as-synthesized crystals contain the neutral diamagnetic TTF moiety, using either a solid-solution electrochemical method or iodine oxidation transforms part of the latter to the paramagnetic TTF•+ radical in a single-crystal-to-single-crystal manner without altering the internal structure of the building chains and the frameworks. This is accompanied by inclusion of I3- replacing some of the solvents, as well as changes in the central C-C bond length of TTFTB, a strong EPR response at g ∼ 2, and an enhancement of the reflectance at low energies originating from absorption by the radical.

10.
Inorg Chem ; 56(23): 14373-14382, 2017 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-29125761

RESUMEN

The fundamentally important phenomenon of mixed valency has been discussed in detail over the past 50 years, predominantly in the context of dinuclear complexes, which are used as model systems for understanding electron delocalization in more complex biological and physical systems. Very recently, mixed valency has been shown to be an important mechanism for charge transfer, leading to delocalization and conductivity in two- and three-dimensional framework materials such as metal-organic frameworks and related systems including covalent organic frameworks and semicrystalline semiconducting metal-organic graphenes. This Viewpoint provides a current perspective on the field of mixed-valence frameworks, where the property is either intrinsic or generated postsynthetically via an external stimulus. Aspects of the spectroscopy and applications of these materials are also discussed, highlighting the future potential for exploiting mixed valency in extended solid-state systems.

11.
Inorg Chem ; 56(15): 9025-9035, 2017 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-28723082

RESUMEN

A pair of coordination polymers of composition (NBu4)2[M2(fan)3] (fan = fluoranilate; M = Fe and Zn) were synthesized and structurally characterized. In each case the compound consists of a pair of interpenetrating three-dimensional, (10,3)-a networks in which metal centers are linked by chelating/bridging fluoranilate ligands. Tetrabutylammonium cations are located in the spaces between the two networks. Despite the structural similarity, significant differences exist between (NBu4)2[Fe2(fan)3] and (NBu4)2[Zn2(fan)3] with respect to the oxidation states of the metal centers and ligands. For (NBu4)2[Fe2(fan)3] the structure determination as well as Mössbauer spectroscopy indicate the oxidation state for the Fe is close to +3, which contrasts with the +2 state for the Zn analogue. The differences between the two compounds extends to the ligands, with the Zn network involving only fluoranilate dianions, whereas the average oxidation state for the fluoranilate in the Fe network lies somewhere between -2 and -3. Magnetic studies on the Fe compound indicate short-range ordering. Electrochemical and spectro-electrochemical investigations indicate that the fluoranilate ligand is redox-active in both complexes; a reduced form of (NBu4)2[Fe2(fan)3] was generated by chemical reduction. Conductivity measurements indicate that (NBu4)2[Fe2(fan)3] is a semiconductor, which is attributed to the mixed valency of the fluoranilate ligands.

12.
Oncol Lett ; 14(6): 7965-7969, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29344239

RESUMEN

Failure to detect recurrence and lymph node metastasis early represents a fundamental barrier to the improvement of survival rate in early stage oral squamous cell carcinoma (OSCC). The present study evaluated the association between serum interleukin-6 (IL-6) level and clinical outcomes in patients with early stage OSCC patients defined by sentinel node biopsy (SNB). A total of 53 patients with clinical stage I/II OSCC who underwent SNB were enrolled. SNB was determined by a radioisotope method, and was evaluated by histopathological examination and genetic analysis. Preoperative sera were measured for IL-6 by ELISA. In the clinical stage I/II patients, disease-free survival (DFS) was demonstrated to be higher in patients with negative SNB compared with patients with positive SNB. In total, 13 patients were demonstrated to exhibit lymph node metastasis by SNB or were reclassified to pathological stage T4 subsequent to analysis of the surgically resected specimens. Thus, 40 patients were diagnosed with early stage OSCC. Of these 40 patients, DFS of the patients with low serum IL-6 was significantly higher compared with the patients with high serum IL-6 (P=0.012). In 19 patients with negative SNB and low serum IL-6, the disease-free rate was 100%. These findings suggested that SNB staging and serum IL-6 level have a high prognostic value in patients with early stage OSCC. Additional investigation and longer follow-up times are warranted to improve understanding of the group of patients that may benefit from this procedure.

13.
Anticancer Res ; 36(11): 6071-6075, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27793934

RESUMEN

BACKGROUND/AIM: Androgens are known to play a critical role in prostate cancer progression, but their effect on malignant phenotypes in salivary gland cancer is unclear. The androgen-androgen receptor (AR) axis may be involved in malignant phenotypes of salivary duct carcinoma (SDC) cells and therefore may be a new target for SDC treatment. To test this hypothesis, we investigated the effect of the androgen 5α-dihydrotestosterone (DHT) on proliferation, migration, and invasiveness of SDC cells. MATERIALS AND METHODS: We used a wound-healing assay to measure cell migration and a Boyden chamber invasion assay to investigate SDC cell invasive capacity. RESULTS: DHT treatment increased cell proliferation, migration, and invasion. However, treatment with flutamide, an AR inhibitor, blocked the effects of DHT. CONCLUSION: These results suggest that the androgen-AR axis is involved in SDC malignancy and may be an effective therapeutic target for treatment of human SDC.


Asunto(s)
Antagonistas de Andrógenos/farmacología , Flutamida/farmacología , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Humanos , Masculino , Fenotipo , Neoplasias de las Glándulas Salivales/patología
14.
Cancer Lett ; 377(1): 11-6, 2016 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-27087608

RESUMEN

Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cannabidiol/farmacología , Carcinoma Adenoide Quístico/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Progesterona/farmacología , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Animales , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/secundario , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteína 1 Inhibidora de la Diferenciación/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones Desnudos , Invasividad Neoplásica , Interferencia de ARN , Receptores de Progesterona/agonistas , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Transducción de Señal/efectos de los fármacos , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Br J Oral Maxillofac Surg ; 54(2): e21-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26705861

RESUMEN

Implant-retained overdentures are known to improve oral function, but the clinical impact on patients who have had mandibular resections is still debatable. We have treated 16 patients who had such resections for oral cancer and consequent loss of the alveolar ridge, with overdentures supported by osseointegrated implants and ball attachments. To quantify their functional improvement, we evaluated their maximum bite force and masticatory performance. Their function improved significantly, (from 77.5N - 365N, 371% increase in maximum bite force, p<0.001) and masticatory performance increased (from 2.5 - 7.7, 208%, p<0.0001) after the overdentures had been inserted. While individual changes in maximum bite force showed no significant correlation, those in masticatory performance correlated significantly, which suggests that the subjects with poor masticatory function are likely to benefit from retention of an implant. These results indicate that implant-retained overdentures are an effective way to rehabilitate patients after marginal mandibular resection.


Asunto(s)
Prótesis de Recubrimiento , Mandíbula/cirugía , Fuerza de la Mordida , Prótesis Dental de Soporte Implantado , Retención de Dentadura , Humanos , Procedimientos Quirúrgicos Orales , Satisfacción del Paciente
16.
Br J Pharmacol ; 171(19): 4464-77, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24910342

RESUMEN

BACKGROUND AND PURPOSE: The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. EXPERIMENTAL APPROACH: To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. KEY RESULTS: CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. CONCLUSIONS AND IMPLICATIONS: O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cannabidiol/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Resorcinoles/uso terapéutico , Animales , Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Cannabidiol/farmacología , Línea Celular Tumoral , Femenino , Humanos , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Neoplasias Pulmonares/secundario , Ratones Endogámicos BALB C , Ratones Desnudos , Especies Reactivas de Oxígeno/metabolismo , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/metabolismo , Resorcinoles/farmacología
17.
BMC Cancer ; 13: 141, 2013 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-23517130

RESUMEN

BACKGROUND: Salivary gland cancer (SGC) is one of the common malignancies of the head and neck area. It develops in the minor and major salivary glands and sometimes metastasizes to other organs, particularly to the lungs. Inhibitors of differentiation (Id) proteins are negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior and tumor aggressiveness in many tissues. In this study, our goal was to determine the potential role of Id proteins, particularly Id1, during human SGC cell progression. METHODS: We first determined the expression levels of Id1 and Id2 in four SGC cell lines: two adenocarcinoma of the salivary gland (HSG and HSY) and two adenoid cystic carcinoma (ACC2 and ACCM) cell lines. We then used constructs that expressed antisense cDNAs to Id1 or Id2 to knockdown the expression of these proteins in cell lines where they were highly expressed, and determined the effects of the knockdown on cell proliferation, migration and invasion. RESULTS: Id1 mRNA and protein were detectable in all cell lines, and expression of Id2 was variable, from absent to high. The ACC2 and ACCM cell lines expressed both Id1 and Id2, but Id1 was expressed at a higher level in the more aggressive ACCM cell line in comparison to ACC2 cells as confirmed by Id1 promoter-reporter assays. We therefore focused on the ACCM cells for the remainder of the study. We found that proliferation and invasiveness of ACCM cells were strongly reduced after Id1 knockdown whereas Id2 suppression had only a slight effect. Results of scratch and colony formation assays also confirmed that ACCM cell aggressiveness was significantly reduced upon Id1 knockdown. Finally, this knockdown resulted in reduced c-myc and enhanced cyclin-dependent kinase inhibitor p21 expression. CONCLUSIONS: These results demonstrate that Id1 plays an important role in the control of human SGC cell aggressiveness and suggest a potential role as a marker of diagnosis, prognosis and progression of SGCs. Id1 suppression could represent a novel and effective approach for the treatment of salivary gland cancer.


Asunto(s)
Adenocarcinoma/genética , Carcinoma Adenoide Quístico/genética , Proteína 1 Inhibidora de la Diferenciación/genética , Neoplasias de las Glándulas Salivales/genética , Adenocarcinoma/metabolismo , Carcinoma Adenoide Quístico/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Proteína 2 Inhibidora de la Diferenciación/genética , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias de las Glándulas Salivales/metabolismo , Ensayo de Tumor de Célula Madre , Regulación hacia Arriba
18.
Cancer Res ; 73(5): 1559-69, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23243024

RESUMEN

Glioblastoma is the most common form of primary adult brain tumors. A majority of glioblastomas grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control glioblastoma invasiveness and target them therapeutically. We show here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of glioblastoma cell lines and primary glioblastoma cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathologic grades in patient biopsies. Id-1 knockdown dramatically reduces glioblastoma cell invasion that is accompanied by profound morphologic changes and robust reduction in expression levels of "mesenchymal" markers, as well as inhibition of self-renewal potential and downregulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human glioblastoma. Furthermore, we show that a nontoxic compound, cannabidiol, significantly downregulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. In addition, cannabidiol significantly inhibits the invasion of glioblastoma cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in glioblastoma and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of patients with glioblastoma.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteína 1 Inhibidora de la Diferenciación/fisiología , Invasividad Neoplásica/genética , Animales , Neoplasias Encefálicas/patología , Cannabidiol/farmacología , Línea Celular Tumoral , Femenino , Glioblastoma/patología , Humanos , Proteína 1 Inhibidora de la Diferenciación/antagonistas & inhibidores , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Ratones , Ratones Desnudos , Neurospora , Interferencia de ARN , Trasplante Heterólogo , Regulación hacia Arriba
19.
Int J Clin Exp Pathol ; 5(8): 830-3, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23074540

RESUMEN

A 55-year-old woman consulted our hospital for an epulis-like small mass in the anterior region of the mandible. A biopsy of the tumor was performed. Histological analysis showed that the tumor consisted of spindle-shaped and polygonal cells with hyperchromatic nuclei, and intracytoplasmic vacuoles and mitotic figures were scattered. Immunohistochemical staining revealed that the tumor cells were positive for factor VIII-related antigen, CD31, αSMA, and vimentin, but negative for pancytokeratins, S100 protein, neuron-specific enolase, and CD56. The Ki-67 labeling index was more than 50%. Based on these findings, a final pathological diagnosis of angiosarcoma was made. The tumor did not invade into the surrounding tissue. The operation was performed with about a 20-mm surgical margin that was negative for tumor invasion. After a 4-year follow-up, no metastatic lesions were found, and the primary site was covered with a partial denture.


Asunto(s)
Enfermedades de las Encías/patología , Hemangiosarcoma/patología , Neoplasias Mandibulares/patología , Biomarcadores de Tumor/metabolismo , Femenino , Enfermedades de las Encías/metabolismo , Hemangiosarcoma/metabolismo , Hemangiosarcoma/cirugía , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Mandibulares/metabolismo , Neoplasias Mandibulares/cirugía , Persona de Mediana Edad , Resultado del Tratamiento
20.
Int J Otolaryngol ; 2011: 187623, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22164169

RESUMEN

Malignant salivary gland tumors (MSGTs) account for 2-6% of all head and neck cancers. Despite the rarity, MSGTs have been of great interest due to a wide variety of pathological features and high metastasis rates resulting in poor prognosis. Surgical resection followed by radiation therapy represents the main treatment of this malignancy. Adjuvant therapy is reserved for the management of local recurrence, no longer amenable to additional local therapy, and for metastasis. Based on the studies from other types of tumors, particularly breast cancer, the expression and function of sex steroid hormone receptors in cancer have been extensively studied and applied to diagnosis and treatment. Although a number of studies in MSGTs have been published, the rationale for hormone therapy is still controversial due to the disparate results and insufficient number of cases. However, some recent reports have demonstrated that certain salivary gland neoplasms are similar to breast cancer, not only in terms of the pathological features, but also at the molecular level. Here, we shed light on the biological similarity between MSGTs and certain types of breast cancer, and describe the potential use of hormone and additional therapies for MSGTs.

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