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OBJECTIVE: To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. METHODS: Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. RESULTS: The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. CONCLUSION: DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.
Assuntos
Carcinoma de Células de Transição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Carcinoma de Células de Transição/patologia , Progressão da Doença , Humanos , Metástase Linfática , Prognóstico , Neoplasias da Bexiga Urinária/patologia , Urotélio/metabolismoRESUMO
OBJECTIVE: To investigate the role of the hedgehog (HH) signaling pathway transcription factor glioma-associated oncogene hoinolog 1 (GLI-1) in EGF-regulated enhancement of the invasiveness of the prostate cancer ARCaP(E) cell line in vitro. METHODS: The expressions of EGFR and GLI-1 in prostate cancer ARCaP(E) cells were analyzed by immunofluorescence staining. ARCaP(E) cells were treated with EGF at 100 ng/ml, followed by detection of the changes in cell morphology and invasiveness, as well as in the expressions of p-ERK, ERK and GLI-1. Migration transwell assay was used to determine the effects of 100 ng/ml EGF and GLI-1 antagonist GANT61 on the invasiveness of the ARCaP(E) cells. RESULTS: Both EGFR and GLI-1 were expressed in the ARCaP(E) cells. EGF induced morphological transition of epithelial-like ARCaP(E) cells to mesenchymal-like cells, increased their in vitro invasiveness, and significantly upregulated the expressions of p-ERK and GLI-1 in the ARCaP(E) cells (P<0.05). GANT61 significantly inhibited the in vitro invasiveness of the ARCaP(E) cells and reduced the enhancing effect of EGF on their invasiveness (P<0.05). CONCLUSION: The results from ARCaP(E) cells shed light on the cross-talk of the HH pathway with the EGF/ERK signaling pathway. GLI-1 might be responsible for EGF-regulated enhancement of the invasiveness of ARCaP(E) cells in vitro.
Assuntos
Fator de Crescimento Epidérmico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Transdução de Sinais , Fatores de Transcrição/genética , Proteína GLI1 em Dedos de ZincoRESUMO
High-valence metal doping and abundant grain boundaries (GBs) have been proved to be effective strategies to promote the oxygen evolution reaction (OER). However, the reasonable design of the two to facilitate OER collaboratively is challenging. Herein, a convenient and novel one-step molten salt decomposition strategy is proposed to fabricate segregated-Mo doped nickle nitrate hydroxide with substantial GBs on MoNi foam (Mo-NNOH@MNF). When processed in molten salt, the Mo species on the conductive substrate migrates unevenly to the surface of Mo-NNOH@MNF, which not only induces the formation of abundant GBs to modulate electronic structure, but also improves the intrinsic activity as high-valence dopants, synergistically elevating OER activity. As verification, the optimized Mo-NNOH@MNF-10h exhibits low overpotential of 150 mV at 10 mA cm-2, which can be attributed to the reduced valence charge transition energy of Ni by high-valence Mo dopant, coupled with the fine-tuning of d-band center bond and corresponding local electron density by induced GBs and Mo doping, as DFT calculations revealed. Moreover, the intrinsic robustness and strong adhesion ensure the long-term stability of 6 h at 500 mA cm-2. This work provides a promising molten salt decomposition approach to synthesize advanced materials with unique structures.
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OBJECTIVE: To investigate the role and significance of epithelial-mesenchymal transition (EMT) and its transcriptional regulator Twist1 in the development of the human fetal prostate. METHODS: Twenty-five human fetal prostate specimens at various developmental stages (16-39 weeks) were included in this study. EMT markers, such as E-Cadherin, N-Cadherin and Vimentin, and EMT transcriptional regulator Twist1 were determined by immunohistochemistry, and their relationship with the development of the human fetal prostate was analyzed. RESULTS: E-Cadherin was expressed in the fetal prostate epithelium only, while Vimentin, N-Cadherin and Twist1 in both the epithelium and the stroma. The expression of E-Cadherin gradually increased, but those of Vimentin, N-Cadherin and Twist1 gradually decreased with the gestation stages. No significant changes were observed in the staining patterns of Vimentin, N-Cadherin and Twist1 in the stroma during the whole developmental process. CONCLUSION: EMT is involved in the development of the human fetal prostate, which may promote epithelial cell motility to form prostatic bud tubules in early gestation stages and boost the differentiation of prostate epithelia in later stages.
Assuntos
Transição Epitelial-Mesenquimal , Desenvolvimento Fetal , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Caderinas/metabolismo , Desdiferenciação Celular , Células Epiteliais/metabolismo , Humanos , Masculino , Mesoderma/metabolismo , Proteínas Nucleares/metabolismo , Próstata/embriologia , Proteína 1 Relacionada a Twist/metabolismo , Vimentina/metabolismoRESUMO
In the mol-ecule of the title compound, C(28)H(32)N(2), the benzimidazole ring system is almost planar [maximum deviation = 0.0221â (15)â Å] and forms dihedral angles of 85.86â (4) and 32.09â (6)° with the benzene rings. In the crystal structure, mol-ecules are linked into chains running parallel to the a axis by inter-molecular C-Hâ¯N hydrogen bonds. The methyl groups of a tert-butyl group are rotationally disordered over two positions with refined site-occupancy factors of 0.636â (4) and 0.364â (4).
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The mol-ecule of the title compound, C(16)H(15)N(3), displays a trans configuration with respect to the C=N double bond. The mol-ecule is not planar, the dihedral angle between the benzene rings being 57.83â (9)°. The crystal packing is stabilized only by van der Waals inter-actions.
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The mol-ecule of the title compound, C(18)H(19)N(3)O, displays a trans configuration with respect to the C=N double bond. There is a strong intra-molecular O-Hâ¯N hydrogen-bonding inter-action between the hydr-oxy group and imine N atom. The dihedral angle between the aromatic rings is 30.35â (8)°. The crystal packing is stabilized by O-Hâ¯N links.
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In the mol-ecule of the title compound, C(15)H(12)N(2)O(2), the aromatic rings are oriented at a dihedral angle of 28.11â (3)°. Intra-molecular O-Hâ¯N hydrogen bonding results in the formation of a planar six-membered ring, which is nearly coplanar with the adjacent ring at a dihedral angle of 1.53â (3)°. In the crystal structure, π-π contacts between the benzene rings [centroid-centroid distance = 3.841â (1)â Å] may stabilize the structure.
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The title compound, C(18)H(12)N(2)O, crystallizes in a phenol-imine tautomeric form with a Z conformation for the imine functionality. The dihedral angle between the aromatic rings is 8.98â (9)°. A strong intra-molecular O-Hâ¯N hydrogen-bond inter-action between the hydroxyl group and imine N atom occurs.
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The asymmetric unit of the title compound, C(22)H(26)N(2)O, contains three crystallographically independent mol-ecules, in which the aromatic rings are oriented at dihedral angles of 21.74â (5), 27.59â (5) and 27.87â (5)°. Intra-molecular O-Hâ¯N hydrogen bonds result in the formation of planar six-membered rings, and these are nearly coplanar with the adjacent rings. In the crystal structure, π-π contacts between the benzene rings [centroid-centroid distances = 3.989â (2), 3.802â (1) and 3.882â (1)â Å] may stabilize the structure.
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In the mol-ecule of the title compound, C(14)H(9)BrN(2)O, the dihedral angle between the aromatic rings is 1.09â (4)°. Intra-molecular O-Hâ¯N hydrogen bonding results in the formation of a planar (r.m.s. deviation = 0.0140â Å) six-membered ring. In the crystal structure, inter-molecular C-Hâ¯N inter-actions link the mol-ecules into chains.
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The mol-ecule of the title compound, C(15)H(12)N(2)O(2), displays a trans configuration with respect to the C=N double bond. The dihedral angle between the two benzene rings is 30.46â (14)°. A strong intra-molecular O-Hâ¯O hydrogen bond stabilizes the mol-ecular structure.
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We have recently reported tumor suppressive role of DAB2IP in RCC development. In this study, We identified one CpG methylation biomarker (DAB2IP CpG1) located UTSS of DAB2IP that was associated with poor overall survival in a cohort of 318 ccRCC patients from the Cancer Genome Atlas (TCGA). We further validated the prognostic accuracy of DAB2IP CpG methylation by pyrosequencing quantitative methylation assay in 224 ccRCC patients from multiple Chinese centers (MCHC set), and 239 patients from University of Texas Southwestern Medical Center at Dallas (UTSW set) by using FFPE samples. DAB2IP CpG1 can predict the overall survival of patients in TCGA, MCHC, and UTSW sets independent of patient age, Fuhrman grade and TNM stage (all p<0.05). DAB2IP CpG1 successfully categorized patients into high-risk and low-risk groups with significant differences of clinical outcome in respective clinical subsets, regardless of age, sex, grade, stage, or race (HR: 1.63-7.83; all p<0.05). The detection of DAB2IP CpG1 methylation was minimally affected by ITH in ccRCC. DAB2IP mRNA expression was regulated by DNA methylation in vitro. DAB2IP CpG1 methylation is a practical and repeatable biomarker for ccRCC, which can provide prognostic value that complements the current staging system.
Assuntos
Carcinoma de Células Renais/genética , Metilação de DNA , Neoplasias Renais/genética , Proteínas Ativadoras de ras GTPase/genética , Biomarcadores Tumorais/genética , Ilhas de CpG/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , PrognósticoRESUMO
Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96-4.82; P=3.9 × 10(-6)-2.2 × 10(-9)), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual 'stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system.