RESUMEN
Haloacetamides (HAcAms) are an emerging class of nitrogenous disinfection by-products (N-DBPs) with high cytotoxicity and genotoxicity, which are widely detected in drinking water. The toxicity of trichloroacetamide (TCAcAm) is significantly higher than traditional DBPs. In this study, ultraviolet (UV) treatment was combined with sodium sulphite (Na2SO3) to remove TCAcAm from water. The effects of different light intensities, different agent dosages (Na2SO3), and pH conditions on the removal of TCAcAm by UV/Na2SO3 advanced reduction process were investigated. The results showed that TCAcAm could be rapidly degraded by the UV/Na2SO3 system. The degradation effect was directly proportional to light intensity, dosage of Na2SO3, and pH. Moreover, the pH had a significant effect on the reaction rate and degradation rate. As the pH increased from 6 to 9, the degradation rate of TCAcAm increased from 12.8% to 99.6%, in 120 min. The removal rate of TCAcAm reached 99.4% when the UV light intensity, pH, Na2SO3 dosage, and reaction time were 450 µW·cm-2, 9, 1.00 mmol·L-1, and 30 min, respectively. The experimental results indicated that the UV/Na2SO3 system is an efficient advanced reduction process for the removal of TCAcAm, and it has the potential to reduce other halogenated DBPs. Therefore, it could be used for the degradation of halogenated DBPs in the treatment of drinking water.
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Colon cancer is the second most common cause of cancer-associated mortality in human populations. The aim of the present study was to identify the role of cyclooxygenase-2 (COX-2) in Smad3 mutant mice, which are known to develop colon cancer. Homozygous Smad3 (-/-) mutant mice were generated from inbred and hybrid Smad3 mouse strains by intercrossing the appropriate heterozygotes. Immunohistochemistry with COX-2 antibody was performed throughout this experiment and the data was validated and cross-checked with reverse transcription-polymerase chain reaction (RT-PCR). Homozygous mutant Smad3 mice were generated and the overexpression pattern of COX-2 was identified by immunohistochemistry and validated with RT-PCR. The results of the present study demonstrated a link between the Smad3 mutant mice, colon cancer and COX-2. In addition, the overexpression pattern of COX-2 in Smad3 mutant mice that develop colon cancer was identified.
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Topoisomerase 2α (Topo2A) is a key enzyme in replication. It functions as a cell proliferation and cell cycle-specific marker and it is identified mainly in the interphase nuclei of proliferating cells. Many studies have shown that Topo2A protein expression is up-regulated in various cancers including esophageal cancer. However, to date, no studies have adequately addressed the prognostic value of Topo2A in patients with resectable esophageal squamous cell carcinoma (ESCC). Therefore, we conducted a large-scale retrospective study investigating the expression of Topo2A and the clinicopathological characteristics or prognosis of ESCC patients. Eight hundred and twenty-nine specimens of ESCC from patients who underwent complete esophageal cancer resection were evaluated using an immunohistochemical assay. Among them, 404 (48.7 %) cases with a score >2 were determined to be positive for Topo2A expression. Topo2A overexpression was significantly associated with poorer differentiation (P = 0.007) and perineural invasion (P = 0.046). The median progression-free survival (PFS) of 319 patients with Topo2A-positive expression and 336 patients with Topo2A-negative expression was 19.5 and 26.5 months, respectively (P = 0.000). The overall survival (OS) in patients with and without Topo2A expression was 34.0 and 44.5 months, respectively (P = 0.002). In the multivariate analysis, Topo2A overexpression was identified as an independent prognostic factor for PFS (P = 0.001) and OS (P = 0.009). We determined that Topo2A overexpression was not only associated with poorer differentiation and perineural invasion, but it could also act as an independent risk factor for ESCC.
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Antígenos de Neoplasias/biosíntesis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , ADN-Topoisomerasas de Tipo II/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Neoplasias Esofágicas/patología , Adulto , Anciano , Antígenos de Neoplasias/análisis , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/mortalidad , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Supervivencia sin Enfermedad , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
PURPOSE: Eyelid tension seems to be related to corneal astigmatism and to affect the ocular surface. The aim of this study is to determine the lower eyelid tension in young adults with a simple lid tensiometer. METHODS: A commercially available precision digital pressure gauge that was connected to a pressure-guided tube full of water with a sensor at its end being placed between the lower eyelid and ocular surface was used as the lid tensiometer to measure the lower eyelid pressure at the central lid in 8 male and 12 female subjects aged between 20 and 39 years with normal healthy eyes. Measurements were respectively performed by 2 operators under the same conditions to test possible interoperator variation. RESULTS: The lower eyelid pressures of the 20 subjects measured by 2 operators at the central lid were 445.28 ± 121.17 and 458.65 ± 127.15 Pa, respectively. The test of interoperator variation demonstrated that there was good agreement between 2 operators (intraclass correlation coefficient = 0.965, F = 56.09, P < 0.001). CONCLUSIONS: Our simple lid tensiometer is a viable option for measuring eyelid pressure with good repeatability.
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Técnicas de Diagnóstico Oftalmológico/instrumentación , Párpados/fisiología , Tono Muscular/fisiología , Músculos Oculomotores/fisiología , Presión , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Manometría/instrumentación , Adulto JovenRESUMEN
OBJECTIVE: To investigate the relationship between the occurrence and development of conjunctivochalasis and bulbar conjunctival lymphangiectasia. METHODS: Case control study. One hundred cases with conjunctivochalasis treated from January to March 2012 were selected to study, and 100 cases with no conjunctivochalasis as the control group at the same time. To observe bulbar conjunctiva lymphatic duct dilatation using slit lamp microscope, analysis bulbar conjunctiva and fascia images by OCT scanning, and ablate lymphatic of conjunctival tissue for pathologic examine. RESULTS: Twenty-nine eyes of the bulbar conjunctiva lymphangiectasia associated with 100 cases (183 eyes) conjunctivochalasis patients, accounting for 15.84%; 8 eyes of the ball conjunctival lymphatic dilation in control group of 100 cases ( 200 eyes), accounting for 4.00%. The difference between the two groups was statistically significant (χ(2) = 15.36, P < 0.001). OCT scanning showed that lymphangiectasia of the conjunctiva is at the subcutaneous mainly, some in the conjunctival lamina propria. They are border-clear, full-filled fluid, single-lumen or multi lumens, not involving the fascia. The histopathological examination showed that the lamina propria of the bulbar conjunctiva mildly chronic inflammatory changes accompanied by a large number of lymphangiectasia. CONCLUSION: Bulbar conjunctival lymphangiectasia may be one of the reasons for the conjunctivochalasis.
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Enfermedades de la Conjuntiva/patología , Linfangiectasia/patología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Recent studies have revealed the additional beneficial effects of acetylsalicylic acid (aspirin) in the medication of cardiovascular diseases. The small GTPase RhoA as an important signaling factor is implicated in a wide range of cell functions. This study aimed to investigate the regulatory effect of acetylsalicylic acid on RhoA in vascular smooth muscle cells (VSMCs). We found that aspirin at 300 µM suppressed VSMCs proliferation stimulated by LPS, and this inhibitory effect was partially mediated by inhibiting the iNOS/NO pathway. RhoA overexpression was downregulated by aspirin (both 30 and 300 µM) because of enhanced degradation of RhoA protein. The effect of LPS on increasing active RhoA level was significantly attenuated by aspirin (300 µM), which exerted no effect on RhoA translocation. The promoted RhoA phosphorylation under LPS stimulation, coupled with RhoA protein expression, was greatly decreased by aspirin treatment. No effect of aspirin was found on the expression, activation, and phosphorylation of RhoA in VSMCs devoid of inflammatory stimulation. Our investigation indicates that the regulation of RhoA by aspirin in VSMCs under inflammatory stimulus could be a novel mechanism via which aspirin, apart from the COX-dependent action, exerted the multiple beneficial effects.
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Aspirina/farmacología , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Inflamación , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. METHODS: A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. RESULTS: Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. CONCLUSION: Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer.
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Doxorrubicina/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Micelas , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Citometría de Flujo , Humanos , Neoplasias Pulmonares/patología , Microscopía Confocal , Nanocápsulas/química , Polietilenglicoles/química , Tolerancia a Radiación/efectos de los fármacos , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/efectos de la radiación , Células Tumorales CultivadasRESUMEN
Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-ß1 (HRG-ß1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-ß1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-ß1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-ß1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.
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Neoplasias de la Mama/patología , Movimiento Celular , Neurregulina-1/metabolismo , Receptores de Estrógenos/biosíntesis , Receptores Acoplados a Proteínas G/biosíntesis , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Invasividad Neoplásica , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Regulación hacia ArribaRESUMEN
RhoA has been shown to play a major role in vascular processes and acetylsalicylic acid (aspirin) is known to exert a cytoprotective effect via multiple mechanisms. In the present study, we aimed at investigating the effect of aspirin on RhoA expression under a stress state in rat VSMCs (vascular smooth muscle cells) and the underlying mechanisms. The expression of iNOS (inducible nitric oxide synthase) and iNOS activity as well as NO concentration was significantly promoted by LPS (lipopolysaccharide) accompanying the elevation of RhoA expression, which was blocked by the addition of the iNOS inhibitor L-NIL [L-N6-(1-iminoethyl)lysine dihydrochloride]. Aspirin (30 µM) significantly attenuated the elevation of RhoA, while indomethacin and salicylate had no similar effect. The sGC (soluble guanylate cyclase) inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) showed the same effect as aspirin in down-regulating RhoA but was reversed by the addition of the cGMP analogue 8-Br-PET-cGMP (ß-phenyl-1,N2-ethano-8-bromoguanosine 3',5'-cyclic monophosphorothioate). 8-Br-PET-cGMP solely enhanced the RhoA expression that was abrogated by preincubation with aspirin. Degradation analysis indicated that aspirin enhanced the protein degradation rate of RhoA and GDP-bound RhoA seemed to be more susceptible to aspirin-enhanced degradation compared with the GTP-bound form. Our results indicate that aspirin attenuates the LPS-induced overexpression of RhoA both by inhibiting new synthesis and accelerating protein degradation, which may help elucidate the multiple beneficial effects of aspirin.
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Aspirina/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Proteína de Unión al GTP rhoA/genética , Animales , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Guanilato Ciclasa/metabolismo , Masculino , Miocitos del Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/metabolismo , Guanilil Ciclasa Soluble , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
OBJECTIVE: We aimed to perform a preliminary study of the association between induced pluripotent stem cell (iPS)-related genes and biological behavior of human colorectal cancer (CRC) cells, and the potential for developing anti-cancer drugs targeting these genes. METHODS: We used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG, OCT4, SOX2, C-MYC and KLF4 in CRC cell lines and cancer stem cells (CSCs)-enriched tumor spheres. NANOG was knockdowned in CRC cell line SW620 by lentiviral transduction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, plate colony formation, and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 cells. Also, mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil (5-FU) and survival rate was measured by MTT assay to evaluate drug sensitivity. RESULTS: A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was observed. NANOG knockdown suppressed proliferation, colony formation, and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells. 5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG, OCT4, and SOX2. CONCLUSIONS: These results collectively suggest an overlap between iPS-related genes and CSCs in CRC. Quenching a certain gene NANOG may truncate the aggressiveness of CRC cells.
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Antimetabolitos Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/farmacología , Células Madre Pluripotentes Inducidas/fisiología , Animales , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/genética , Femenino , Células HT29 , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Ratones Desnudos , Proteína Homeótica Nanog , Trasplante de Neoplasias , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Proyectos Piloto , ARN/química , ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismoRESUMEN
Vascular-targeting agents (VTAs) can be divided into two groups: anti-angiogenesis agents and vascular disrupting agents (VDAs). The purpose of this study was to evaluate the antineoplastic activity of a combination of the anti-angiogenesis agent, Endostar, and the VDA combretastatin, A4 phosphate (CA4P). This study is the first to evaluate the activity of this combination against tumors and the first to investigate the activity of the combination against osteosarcoma. Endostar combined with CA4P had a good anti-tumor effect with no significant toxicity, and was at least not inferior to adriamycin, which is the main drug for osteosarcoma. The use of VDAs combined with anti-angiogenic drugs can result in significantly enhanced anti-tumor effects, providing a novel approach to cancer treatment, which could effectively complement standard treatments. It is believed that this exciting new treatment has the potential to transform the management of cancer.