RESUMO
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.
Assuntos
Doenças da Túnica Conjuntiva/patologia , Linfangiectasia/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Neoplasias da Mama/patologia , Movimento Celular , Neuregulina-1/metabolismo , Receptores de Estrogênio/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Invasividade Neoplásica , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Regulação para CimaRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , DNA Topoisomerases Tipo II/biossíntese , Proteínas de Ligação a DNA/biossíntese , Neoplasias Esofágicas/patologia , Adulto , Idoso , Antígenos de Neoplasias/análise , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , DNA Topoisomerases Tipo II/análise , Proteínas de Ligação a DNA/análise , Intervalo Livre de Doença , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
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.
Assuntos
Técnicas de Diagnóstico Oftalmológico/instrumentação , Pálpebras/fisiologia , Tono Muscular/fisiologia , Músculos Oculomotores/fisiologia , Pressão , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Manometria/instrumentação , Adulto JovemRESUMO
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.
Assuntos
Aspirina/farmacologia , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Inflamação , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Aspirina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/genética , Animais , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Guanilato Ciclase/metabolismo , Masculino , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/metabolismo , Guanilil Ciclase Solúvel , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
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.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Feminino , Células HT29 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Camundongos Nus , Proteína Homeobox Nanog , Transplante de Neoplasias , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Projetos Piloto , RNA/química , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismoRESUMO
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.
Assuntos
Doxorrubicina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Micelas , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/patologia , Microscopia Confocal , Nanocápsulas/química , Polietilenoglicóis/química , Tolerância a Radiação/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/efeitos da radiação , Células Tumorais CultivadasRESUMO
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.