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Introduction: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred. Methods: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, Service Members and Veterans whose mild TBI occurred outside of deployment, and Service Members and Veterans who had no lifetime history of TBI. Results: FC patterns differed for the two contextual types of mild TBI. Service Members and Veterans with deployment-related mild TBI demonstrated increased FC between the right caudate and lateral occipital regions relative to both the non-deployment mild TBI and TBI-negative groups. When evaluating the association between FC from the caudate and gait, the non-deployment mild TBI group showed a significant positive relationship between walking time and FC with the frontal pole, implicated in navigational planning, whereas the deployment-related mild TBI group trended towards a greater negative association between walking time and FC within the occipital lobes, associated with visuo-spatial processing during navigation. Discussion: These findings have implications for elucidating subtle motor disruption in Service Members and Veterans with deployment-related mild TBI. Possible implications for future walking performance are discussed.
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PURPOSE: Various chemotherapy administration methods have been used to prevent liver metastasis (LM) in patients with colorectal cancer (CRC). This network meta-analysis evaluated the efficacy of these different methods in preventing LM in CRC patients who underwent curative surgery. METHOD: A systematic search of randomized controlled trials reporting the efficacy of various adjuvant chemotherapy methods in patients with colorectal cancer who underwent curative surgery was conducted. The primary outcome was the LM rate. RESULTS: This network meta-analysis included 19 studies reporting on 12,588 participants, comparing portal vein infusion chemotherapy (PVIC) versus hepatic arterial infusion chemotherapy (HAIC) versus systematic chemotherapy (SC) versus surgery alone. The HAIC group had the lowest LM rate when compared to the other three groups (odds ratio [OR] of PVIC vs. HAIC: 1.86; OR of SC vs. HAIC: 1.98; and HAIC vs. surgery alone: 0.43). The LM rate did not differ significantly between PVIC, SC, and surgery alone. The recurrence rates were lower for PVIC and HAIC than for surgery alone (the ORs for PVIC and HAIC were 0.73 [95% CI: 0.58-0.92] and 0.45 [95% CI: 0.26-0.77]). The mortality rates of patients undergoing PVIC and HAIC were lower than that of patients undergoing surgery alone (the ORs for PVIC and HAIC were 0.77 [95% CI: 0.64-0.93] and 0.49 [95% CI: 0.24-0.98]). Anastomotic leakage, cardiopulmonary leakage, diarrhea, nausea and vomiting, oral ulceration, wound infection, or ileus did not differ significantly between the four groups. PVIC showed the highest hepatic toxicity rate compared to those for SC, HAIC, and surgery alone. CONCLUSION: HAIC might be a satisfactory method for preventing LM in patients with CRC undergoing curative surgery.
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Carcinoma Hepatocelular , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Hepáticas/patología , Infusiones Intraarteriales , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Fluorouracilo , Carcinoma Hepatocelular/patología , Resultado del Tratamiento , Arteria Hepática/patologíaRESUMEN
The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.
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Curcumina , Dieta Cetogénica , MicroARNs , Oldenlandia , Neoplasias Gástricas , Animales , Ratas , Curcumina/farmacología , Extractos Vegetales/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Proteínas Proto-Oncogénicas c-akt , Ratas Wistar , Apoptosis , Estrés Oxidativo , MicroARNs/genética , MicroARNs/farmacología , Inflamación , Carcinogénesis , AutofagiaRESUMEN
Research investigating the intricacies of how self-regulated writing strategies are used in a finely focused area of the second language (L2) writing process is still lacking. This study takes a mixed-methods approach to explore Chinese English as a Foreign Language (EFL) learners' use of self-regulated writing strategies when revising based on automated, peer, and teacher feedback in an online EFL writing context. Thirty-six Chinese university learners filled in three questionnaires (one per feedback source). In addition, four learners followed a think-aloud protocol while revising and responding to a stimulated recall interview to provide further data. The results revealed that learners employed an array of self-regulated writing strategies to attain their feedback revision goals. Learners used more cognitive strategies when revising based on automated feedback compared with peer and teacher feedback and more motivational strategies when revising based on teacher feedback. The think-aloud data and stimulated recall interviews coincided with the quantitative findings. Textual analysis revealed that feedback type and quantity were associated with self-regulated writing strategy use.
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The coupling of aromatic electrophiles (aryl halides, aryl ethers, aryl acids, aryl nitriles etc.) with nucleophiles is a core methodology for the synthesis of aryl compounds. Transformations of aryl ketones in an analogous manner via carbon-carbon bond activation could greatly expand the toolbox for the synthesis of aryl compounds due to the abundance of aryl ketones. An exploratory study of this approach is typically based on carbon-carbon cleavage triggered by ring-strain release and chelation assistance, and the products are also limited to a specific structural motif. Here we report a ligand-promoted ß-carbon elimination strategy to activate the carbon-carbon bonds, which results in a range of transformations of aryl ketones, leading to useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The use of a pyridine-oxazoline ligand is crucial for this catalytic transformation. A gram-scale borylation reaction of an aryl ketone via a simple one-pot operation is reported. The potential utility of this strategy is also demonstrated by the late-stage diversification of drug molecules probenecid, adapalene, and desoxyestrone, the fragrance tonalid as well as the natural product apocynin.
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Cervical cancer is one of the most common malignancies that seriously threatens women's health. Krüppellike factors (KLFs) have been reported to be associated with the progression of cervical cancer. The role of KLF1 in cervical cancer, which still remains unclear, was investigated in the present study. The expression of KLF1 was detected in different cervical cell lines by reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blotting. Cell proliferation, metastasis and invasion were respectively detected by Cell Counting Kit8, wound healing and transwell assays. Associated factor expression was also detected by RTqPCR and western blotting. In addition, the phosphorylation levels of phosphatidylinositol3kinase (PI3K) and protein kinase B (Akt) were determined by western blot analysis. The results revealed that KLF1 expression was promoted in SiHa, Caski and C41 cervical cancer cells. However, KLF1 knockdown suppressed cell proliferation, metastasis and invasion in SiHa cervical cancer cells. KLF1 knockdown also inhibited the expressions of Ki67, metastasisassociated antigen 1 and matrix metalloproteinase (MMP)2. KLF1 knockdown promoted the expressions of nonmetastatic clone 23 type 1 and tissue inhibitor of metalloproteinase2, and the expression of MMP9 was promoted slightly as well. In addition, KLF1 knockdown inhibited the PI3K/Akt signaling pathway. Hence, it was concluded that KLF1 promoted metastasis and invasion via the PI3K/Akt signaling pathway in cervical cancer cells.
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Regulación hacia Abajo/genética , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Transducción de Señal , TransfecciónRESUMEN
OBJECTIVES: Investigate the relation of chronic pain interference to functional connectivity (FC) of brain regions and to cortical thickness in post-911 Veterans and Service Members (SMs) who sustained a mild traumatic brain injury (mTBI). METHODS: This is an observational study with cross-sectional analyses. A sample of 65 enrollees completing initial evaluation at a single site of the Chronic Effects of Neurotrauma Consortium (CENC) reported pain interference ratings on the TBI QOL. Functional connectivity and cortical thickness were measured. RESULTS: Severity of pain interference was negatively related to FC of the default mode network (DMN), i.e., participants who reported more severe pain interference had less FC between mesial prefrontal cortex and posterior regions of the DMN including posterior cingulate cortex and precuneus. Cortical thickness of specific regions was positively related to severity of pain interference. CONCLUSION: The more that pain was perceived to interfere with daily life, the less the FC between regions in a network associated with self-referential thought and mind wandering. Although cortical thickness in specific brain regions was positively related to severity of pain interference, follow-up longitudinal data, control group data, and study of individual differences in this cohort will expand this initial report and replicate these findings.
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Corteza Cerebral/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/etiología , Vías Nerviosas/diagnóstico por imagen , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/diagnóstico por imagen , Adulto , Campaña Afgana 2001- , Estudios Transversales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Guerra de Irak 2003-2011 , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Dimensión del Dolor , Calidad de Vida , Trastornos por Estrés Postraumático/psicología , VeteranosRESUMEN
Currently, harmful algal blooms are being one of ever-increasing global environmental problems. Much attention has been paid to the use of natural products as the selective algaecides due to their low toxicity, high selectivity and eco-friendly properties. In the present study, the thiazole alkaloid (1), originally isolated from Thermoactino-myces strain TM-64, was shown to exhibit potent algicidal activity against three typically harmful cyanobacterial algae, S. obliqnus, M. aeruginosa, and C. pyrenoidosa. Based on our previous work, a practical, scalable synthesis of alkaloid (1) was developed and reaction could be readily scaled up to more than 100 g. In addition, twenty-six analogues of alkaloid (1) by replacement of tryptamine moiety with different aromatic and aliphatic amines were also prepared. The bioassay results showed that most of these derivatives displayed potent algicidal activity against three harmful algae S. obliqnus, M. aeruginosa, and C. pyrenoidosa with IC50 values in the range of 1.5-5.0 µg/mL. Amongst them, compounds (10) and its hydrochloric salt (10S) were found to reveal powerful growth inhibitory activity against harmful cyanobacterial algae with IC50 values as low as 0.08 µg/mL, comparable to those of commercial algicide CuSO4 and herbicide Diuron.
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Amidas , Cianobacterias/crecimiento & desarrollo , Herbicidas , Tiazoles , Amidas/síntesis química , Amidas/química , Amidas/farmacología , Herbicidas/síntesis química , Herbicidas/química , Herbicidas/farmacología , Tiazoles/síntesis química , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
Although great progress has been made in hybrid iodocuprates(i) as lighting phosphors, the effects of aromatic and aliphatic structure directing agents (SDAs) on their water stability, structure and photoluminescence (PL) properties are still not clear. Herein, aromatic N-heterocyclic 1,2-di(4-pyridyl)ethylene (dpe), aliphatic N-heterocyclic 1,8-diazabicyclo[5.4.0]undec-7-ene (dbu) and N-aminoethylpiperazine (app) were selected to be SDAs to construct two types of hybrid iodocuprates(i) via a facile in situ approach. Aromatic dpe-derived cations are successfully directed to form (Me2dpe)(CuI3) (1), (Me2dpe)n(Cu4I6)n (2), (Et2dpe)2(Cu6I10) (3), and (H2dpe)n(Cu2I4)n (4). Three of them contain unprecedented inorganic iodocuprate clusters or chains. The aliphatic N-heterocyclic dbu- and app-derivative cations are responsible for the formation of (Hdbu)n(Cu2I3)n (5) and (H3app)2(Cu2I6)·2I·2H2O (6), which contain a (Cu2I3)- chain and a (Cu2I6)4- binuclear cluster, respectively. For the first time, the influence mechanisms of the water stabilities of iodocuprate-based PL materials were disclosed, by analyzing the possible interactions between SDAs and water molecules. 1-2 are PL silent due to their "self-quenching effect". 3, 4 and5 exhibit bright red, orange and yellow solid-state PL emissions at room temperature respectively, originating from the charge transfer between inorganic iodocuprate species and organic N-heterocycles. The co-template approach leads to multiple charge transfers in 6, which features a tunable PL behavior from bluish green to white by varying the excitation light, and has a quantum yield up to 43% (the highest value among hybrid iodocuprates containing (Cu2I6)4- clusters). The comparative study not only helps us to rationally synthesize iodocuprate-based PL materials with enhanced performance, but also provides a new method to obtain wavelength-dependent PL materials.
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A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C-C bond cleavage of unreactive cyclopropanes.
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Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A-C, alkaloid (1), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue (10d) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa, suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms.
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Alcaloides/farmacología , Chlorophyta/efectos de los fármacos , Floraciones de Algas Nocivas , Herbicidas/farmacología , Tiazoles/farmacología , Triptaminas/farmacología , Ecosistema , Agua Dulce , Floraciones de Algas Nocivas/efectos de los fármacos , Biología MarinaRESUMEN
In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO2 films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV-Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses, the multi-modification could not only extend the optical response of TiO2 to visible light region but also decrease the recombination rate of electron-hole pairs. XRD results revealed that the multi-modified TiO2 film had an anatase-brookite biphase heterostructure. FE-SEM results indicated that the multi-modified TiO2 film without cracks was composed of smaller round-like nanoparticles compared to pure TiO2. BET surface area results showed that the specific surface area of pure TiO2 and the multi-modified TiO2 sample was 47.8 and 115.8 m²/g, respectively. By degradation of formaldehyde and oxytetracycline, experimental results showed that the multi-modified TiO2 film had excellent photodegradation performance under visible light irradiation.
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Formaldehído/química , Nanopartículas/química , Oxitetraciclina/química , Titanio/química , Catálisis , Formaldehído/efectos de la radiación , Hierro/química , Luz , Oxitetraciclina/efectos de la radiación , Fotoquímica , Fotólisis , Espectrofotometría UltravioletaRESUMEN
An ortho-selective rhodium-catalyzed direct C-H arylation of 1,1'-bi-2-naphthol (BINOL), to deliver the widely used but not easily available 3,3'-diaryl BINOL, has been developed. This highly efficient one-step synthetic approach is the shortest route to date and is greatly facilitated by the newly developed ligand system comprising tBu2 PCl, Ph2 -cod, and Cy3 Pâ HBF4 . In addition, the same procedure can facilitate the challenging syntheses of 3-bulkyaryl BINOLs in good to excellent yields.
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The introduction of the aliphatic amines en (ethylenediamine), aep (N-(2-aminoethyl)piperazine) and tepa (tetraethylenepentamine), and the aromatic species 2,2'-bipy (2,2'-bipyridine) and dpe (1,2-di(4-pyridyl)ethylene) as structure directing agents (SDAs) into inorganic iodoplumbates affords six hybrids, namely [(Hen)4(H2.5O)2I](PbI6) (1), Cs2n[Pb3I8(en)2]n (2), (H3tepa)n(PbI5)n (3), (H2aep)n(PbI4)n (4), (Et22,2'-bipy)n(Pb2I6)n (5) and (Et2dpe)n(Pb2I6)n (6). 1 contains a discrete octahedral (PbI6)(4-) anion generated under the direction of a novel co-template, [(Hen)4(H2.5O)2I](4+). 2 contains inorganic Cs(+) ions and a novel hybrid anionic layer [Pb3I8(en)2]n(2n-) that has never been encountered in iodoplumbate hybrids. 3 features a zigzag (PbI5)(3-) chain with the charge being compensated by a triprotonated tepa cation. 4 is composed of perovskite sheets of lead(ii) octahedra and aep cations that are generated from tepa via an unprecedented in situ ligand reaction. Both 5 and 6 have (Pb2I6)n(2n-) chains and represent the first example of introducing a 2,2'-bipy or dpe derivative cation in iodoplumbate hybrids, respectively. The comparative study reveals that aliphatic amines and aromatic species contribute differently to the crystal and electronic structures, and the properties of the hybrids. Importantly, 1-4 exhibit interesting water induced structure conversions, while 5 and 6 can be used as heterogeneous photocatalysts for dye wastewater treatment under visible light irradiation.
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AIM: To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo. METHODS: We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown. RESULTS: Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction. CONCLUSION: Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.
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Cadherinas/deficiencia , Técnicas de Silenciamiento del Gen , Terapia Genética , Neoplasias Hepáticas/prevención & control , Neoplasias Pulmonares/prevención & control , Neoplasias Gástricas/terapia , Animales , Cadherinas/genética , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Proteómica/métodos , Interferencia de ARN , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Espectrometría de Masas en Tándem , Factores de Tiempo , Transfección , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: To investigate the mechanisms of the biological roles of Dickkopf-3 (Dkk-3) in cell invasion, survival and apoptosis in colon cancer cells. METHODS: Three human colon cancer cell lines, i.e., HT-29, LoVo and SW480, were used. Overexpression of Dkk-3 induced by pEGFP-N1-Dkk-3-GFP plasmid in LoVo cells was performed using Lipofectamine 2000 reagent. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of Dkk-3, respectively. Cell proliferation assay, cell cycle analysis, hoechst 33258 assay and Matrigel invasion assay were performed on Dkk-3 overexpressing transfectants. RESULTS: The mRNA and protein expressions of Dkk-3 in HT-29 (mRNA: 0.06 ± 0.02, protein: 0.06 ± 0.01) and LoVo (mRNA: 0.07 ± 0.02, protein: 0.07 ± 0.02) cells were significantly lower than that in SW480 cells (mRNA: 0.92 ± 0.04, protein: 0.69 ± 0.13; all P < 0.05), and the greatest levels of invasiveness was in LoVo cells. Dkk-3 overexpression inhibited the proliferation and invasion of LoVo cells and induced cell cycle arrest at G(0)/G(1) phase and subsequent apoptosis, as indicated by increased chromatin condensation and fragments, upregulated Bax and cytochrome c protein, downregulated survivin and Bcl-2 protein, and the activation of caspase-3 and caspase-9. Furthermore, Dkk-3 overexpression reduced the accumulation of cytosolic fraction of ß-catenin. CONCLUSION: Dkk-3 overexpression induced apoptosis in human colon cancer possibly through the mitochondrial pathway. Dkk-3 may be involved in the Wnt/ß-catenin signaling pathways in colon cancer.
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Adenocarcinoma/metabolismo , Apoptosis/fisiología , Neoplasias del Colon/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Mitocondrias/metabolismo , ARN Mensajero/análisis , Proteínas Adaptadoras Transductoras de Señales , Línea Celular Tumoral , Proliferación Celular , Quimiocinas , Puntos de Control de la Fase G1 del Ciclo Celular/fisiología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células HT29 , Humanos , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismoRESUMEN
Somatostatin analogues, which are used to treat neuroendocrine tumors, target the high levels of somatostatin receptor subtype 2 (SSTR1; alias sst2) expressed in these cancers. However, some tumors are resistant to somatostatin analogues, and it is unknown whether the defect lies in sst2 activation or downstream signaling events. Because sst2 phosphorylation occurs rapidly after receptor activation, we examined whether sst2 is phosphorylated in neuroendocrine tumors. The sst2 receptor phosphorylation was evaluated by IHC and Western blot analysis with the new Ra-1124 antibody specific for the sst2 receptor phosphorylated at Ser341/343 in receptor-positive neuroendocrine tumors obtained from 10 octreotide-treated and 7 octreotide-naïve patients. The specificity, time course, and subcellular localization of sst2 receptor phosphorylation were examined in human embryo kinase-sst2 cell cultures by immunofluorescence and confocal microscopy. All seven octreotide-naïve tumors displayed exclusively nonphosphorylated cell surface sst2 expression. In contrast, 9 of the 10 octreotide-treated tumors contained phosphorylated sst2 that was predominantly internalized. Western blot analysis confirmed the IHC data. Octreotide treatment of human embryo kinase-sst2 cells in culture demonstrated that phosphorylated sst2 was localized at the plasma membrane after 10 seconds of stimulation and was subsequently internalized into endocytic vesicles. These data show, for the first time to our knowledge, that phosphorylated sst2 is present in most gastrointestinal neuroendocrine tumors from patients treated with octreotide but that a striking variability exists in the subcellular distribution of phosphorylated receptors among such tumors.
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Antineoplásicos Hormonales/farmacología , Carcinoma Neuroendocrino/metabolismo , Octreótido/farmacología , Receptores de Somatostatina/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugía , Quimioterapia Adyuvante , Humanos , Microscopía Confocal , Microscopía Fluorescente , Proteínas de Neoplasias/efectos de los fármacos , Proteínas de Neoplasias/metabolismo , Octreótido/uso terapéutico , Fosforilación/efectos de los fármacos , Receptores de Somatostatina/efectos de los fármacosRESUMEN
Regioregular poly(3-hexylthiophene) (P3HT) was employed as a hole transport material and assistant light absorber for the fabrication of a CdS quantum dot-sensitized solid-state solar cell, by which a power-conversion efficiency of 1.42% was achieved under an AM1.5 G (100 mW cm(-2)) condition.
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In this communication, a novel bulk heterojunction solar cell based on an electron donor-acceptor conjugated triphenylamine dye was fabricated, and a high conversion efficiency of 1.23% was achieved under AM 1.5 illumination (100 mW cm(-2)).