RESUMO
Purpose This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma. Methods Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall. Results There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.0490.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.0150.998, p = 0.050). Conclusions After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Ácido Aminolevulínico , Isocitrato Desidrogenase , Fármacos Fotossensibilizantes , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Glioblastoma/metabolismo , Glioblastoma/cirurgia , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genéticaRESUMO
PURPOSE: This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma. METHODS: Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall. RESULTS: There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049-0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015-0.998, p = 0.050). CONCLUSIONS: After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells. The remnant definitive infiltrating tumor cells in the resection cavity and ventricle wall significantly influenced the prognosis of patients with glioblastoma. Aggressive surgical removal of infiltrating tumor cells may improve their prognosis.
Assuntos
Ácido Aminolevulínico/metabolismo , Neoplasias Encefálicas/patologia , Movimento Celular , Glioblastoma/patologia , Isocitrato Desidrogenase , Fármacos Fotossensibilizantes/metabolismo , Idoso , Ácido Aminolevulínico/administração & dosagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Ventrículos Cerebrais/metabolismo , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Fluorescência , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Protoporfirinas/metabolismo , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses. RESULTS: In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns. CONCLUSIONS: Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.
Assuntos
Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Transcriptoma/fisiologia , Aumento de Peso/imunologia , Aumento de Peso/fisiologia , Tecido Adiposo Branco/química , Animais , Perfilação da Expressão Gênica , Gônadas/química , Gônadas/metabolismo , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
At third-generation light sources, the photon beam position stability is a critical issue for user experiments. In general, photon beam position monitors are developed to detect the real photon beam position, and the position is controlled by a feedback system in order to maintain the reference photon beam position. At Pohang Light Source II, a photon beam position stability of less than 1â µm r.m.s. was achieved for a user service period in the beamline, where the photon beam position monitor is installed. Nevertheless, a detailed analysis of the photon beam position data was necessary in order to ensure the performance of the photon beam position monitor, since it can suffer from various unknown types of noise, such as background contamination due to upstream or downstream dipole radiation, and undulator gap dependence. This paper reports the results of a start-to-end study of the photon beam position stability and a singular value decomposition analysis to confirm the reliability of the photon beam position data.
RESUMO
AIM: Active surveillance is the recommended treatment of option for men with very low-risk prostate cancer. In this study, the clinicopathological results of patients who were initially treated with active surveillance and subsequently underwent robot-assisted radical prostatectomy during follow-up are described. METHODS: A prospective cohort of 106 men enrolled in active surveillance was reviewed. Pathologic specimens for patients who ultimately underwent robot-assisted radical prostatectomy for progression or personal preference were analyzed. RESULTS: After exclusion of 14 patients who were lost to follow-up or with incomplete data collection, 92 men were included in the present analyses. Median follow-up was 27.6 months (range 3.3 to 193.1). Twenty-nine patients underwent robot-assisted radical prostatectomy. Progression occurred in 32 patients (34.8%), of which 23 men elected to undergo surgery. Robot-assisted radical prostatectomy was performed in 6 additional patients who chose definitive intervention due to anxiety. Pathologic analyses revealed organ-confined disease in 24 patients (82.8%), and Gleason score was ≥ 7 in nine (31%). Fourteen (48.3%) specimens were identified as having an advanced disease (Gleason score ≥ 7 and/or T3). In comparison to the patients with low-risk disease post-operatively (Gleason score <7 and T2), patients with advanced disease had significantly higher PSA density level and lower prostate volume. CONCLUSION: In this prospective active surveillance cohort, the progression rate was 34.8% over the follow-up period of 27.6 months. In specimens of patients who underwent robot-assisted radical prostatectomy, 48.3% displayed advanced pathologic features. Therefore we recommend that patients considering active surveillance should be counseled on risk of advanced disease as a possible hazard.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , New Jersey , Estudos Prospectivos , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante/métodos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
PURPOSES: We evaluated patient or tumor factors associated with the preoperative restaging accuracy of magnetic resonance imaging (MRI) for determining T and N stages as well as circumferential resection margin (CRM) involvement after chemoradiation (CRT) in patients with locally advanced rectal cancer. METHODS: Seventy-seven patients with rectal cancer that were treated with preoperative CRT (50.4 Gy) followed by radical resection were included. Post-CRT MRI was performed approximately 4 weeks after preoperative CRT. RESULTS: The median tumor distance from the anal verge was 6 cm, 48 (62%) of which were anterior and 29 (38%) posterior. The median tumor diameter was 3 cm. A stage-by-stage comparison showed that correct staging occurred in 62%, 43%, and 86% of patients for T staging, N staging, and CRM prediction, respectively. Shorter distance to the anal verge (<5 cm), smaller tumor diameter (<1 cm), and anterior tumor location were associated with incorrect T staging. There were no significant variables in terms of N staging accuracy. Shorter tumor distance and anterior tumor location were associated with incorrect CRM prediction. CONCLUSIONS: Our findings suggest that specific tumor factors such as small, distal, or anterior rectal tumors are closely associated with the accuracy of MRI after preoperative CRT.
Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasia Residual , Cuidados Pré-Operatórios , Carga TumoralRESUMO
Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Curcumina/análogos & derivados , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Inibidores de Proteassoma/farmacologia , Fator de Transcrição CHOP/metabolismo , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , Fatores de Tempo , Fator de Transcrição CHOP/genética , Transfecção , Carga Tumoral/efeitos dos fármacos , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Androgen ablation is the first-line therapy for patients with metastatic prostate cancer (CaP). However, castration resistance will eventually emerge. In the present study, we have investigated the role of bone morphogenetic protein-6 (BMP-6) in the development of castration-resistant prostate cancer (CRPC) in the context of bone metastases. METHODS: We initially investigated the clinical course of 158 men with advanced CaP who were treated with primary androgen deprivation therapy. To elucidate the underlying mechanism of CRPC in the context of bone metastases, we examined the impact of bone stromal cells on CaP in the absence of androgens using a co-culture model. RESULTS: In the 158 patients, we found that the median time to prostate-specific antigen progression was significantly shorter when bone metastases were present (14 months (95% CI, 10.2-17.8 months) vs 57 months (95% CI, 19.4-94.6 months)). These results suggest that bone-tumour interactions may accelerate castration resistance. Consistent with this hypothesis, in vitro co-cultures demonstrated that CaP cells proliferated under an androgen-depleted condition when incubated with bone stromal cells. Mechanistically, gene expression analysis using quantitative polymerase chain reaction arrays showed a dramatic induction of BMP-6 by CaP cell lines in the presence of bone stromal cells. Further studies revealed that WNT5A derived from bone stromal cells induced the expression of BMP-6 by CaP cells; BMP-6 in turn stimulated cellular proliferation of CaP cells in an androgen-deprived media via a physical interaction between Smad5 and ß-catenin. Intracellularly, WNT5A increased BMP-6 expression via protein kinase C/NF-κB pathway in CaP cell lines. CONCLUSIONS: These observations suggest that bone-CaP interaction leads to castration resistance via WNT5A/BMP-6 loop.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Proteína Morfogenética Óssea 6/biossíntese , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Wnt/biossíntese , Adulto , Anilidas/uso terapêutico , Proteína Morfogenética Óssea 6/metabolismo , Neoplasias Ósseas/metabolismo , Comunicação Celular/fisiologia , Processos de Crescimento Celular , Linhagem Celular Tumoral , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas/uso terapêutico , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Androgênicos/metabolismo , Estudos Retrospectivos , Células Estromais/patologia , Compostos de Tosil/uso terapêutico , Proteínas Wnt/metabolismo , Proteína Wnt-5aRESUMO
BACKGROUND: Few studies have analyzed factors that influence longitudinal changes in patient-perceived satisfaction during the recovery period following robot-assisted radical prostatectomy (RARP) for prostate cancer. We investigated variables that were associated with patient-perceived satisfaction after RARP using the expanded prostate cancer index composite (EPIC) survey. METHODS: Of 175 men who underwent RARP between 2010 and 2011, 140 men completed the EPIC questionnaire preoperatively and 3, 6 and 12 months postoperatively. On the basis of the EPIC question no. 32 (item number 80), patients were divided into four groups according to the pattern of satisfaction change at postoperative 3 and 12 months: satisfied to satisfied (group 1); satisfied to dissatisfied (group 2); dissatisfied to satisfied (group 3); and dissatisfied to dissatisfied (group 4). Longitudinal changes in EPIC scores over time in each group and differences in EPIC scores of each domain subscale between groups at each follow-up were analyzed. A linear mixed model with generalized estimating equation approach was used to identify independent factors that influence overall satisfaction among repeated measures from same patients. RESULTS: On the basis of the pattern of satisfaction change, groups 1, 2, 3 and 4 had 103 (74.3%), 21 (15.0%), 11 (7.9%) and 5 (2.9%) patients, respectively. The factor that was associated with overall satisfaction was urinary bother (UB) (ß=0.283, 95% confidence interval (0.024, 0.543 ); P=0.033) adjusted for other factors under consideration. CONCLUSIONS: UB was the independent factor influencing patient-perceived satisfaction after RARP. During post-RARP follow-up, physician should have the optimal management for the patient's UB.
Assuntos
Satisfação Pessoal , Prostatectomia , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Rádio (Elemento)/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Orquiectomia , Neoplasias da Próstata/patologia , Radioisótopos/farmacocinética , Radioisótopos/farmacologia , Radioisótopos/uso terapêutico , Rádio (Elemento)/farmacocinética , Rádio (Elemento)/farmacologia , Taxa de SobrevidaRESUMO
In this study, we analyzed the waveform characteristics of resting tremor by accelerometer recordings in patients with drug-induced parkinsonism (DIP) and Parkinson's disease (PD). We prospectively recruited 12 patients with tremulous PD and 12 patients with DIP presenting with resting tremor. Tremor was recorded from the more affected side and was recorded twice for a 60 s period in each patient. Peak frequency, amplitude and all harmonic peaks were obtained, and the asymmetry of the decay of the autocorrelation function, third momentum and time-reversal invariance were also computed using a mathematical algorithm. Among the parameters used in the waveform analysis, the harmonic ratio, time-reversal invariance and asymmetric decay of the autocorrelation function were different between PD and DIP at a statistically significant level (all p < 0.01). The total harmonic peak power and third momentum in the time series were not significantly different. The clinical characteristics of DIP patients may be similar to those of PD patients in some cases, which makes the clinical differentiation between DIP and PD challenging. Our study shows that the identification of parameters reflecting waveform asymmetry might be helpful in differentiating between DIP and PD.
Assuntos
Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson Secundária/fisiopatologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Tremor/diagnóstico , Tremor/fisiopatologia , Análise de Ondaletas , Idoso , Diagnóstico Diferencial , Feminino , Humanos , MasculinoRESUMO
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge, given the mechanistic heterogeneity due to a complex signal transduction network. Enzalutamide (MDV-3100), recently approved by the U.S. Food and Drug Administration (FDA) at a dose of 160 mg/day for the treatment of CRPC, blocks androgen signaling by directly binding to the androgen receptor (AR) and inhibiting nuclear translocation and coactivator recruitment of the ligand-receptor complex. In preclinical studies, enzalutamide has been shown to block the binding of AR to DNA, resulting in apoptosis and retardation of tumor growth. Clinically, a phase I/II study (N = 140) revealed that enzalutamide had an optimal safety profile and significant antitumor activity in patients with CRPC regardless of prior chemotherapy. In the AFFIRM phase III trial (N = 1,199), oral enzalutamide significantly improved survival in men with metastatic CRPC after chemotherapy. Currently, a phase III trial (PREVAIL) is under way to determine the effectiveness of enzalutamide in patients who have not received prior docetaxel chemotherapy.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Castração , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/farmacocinética , Animais , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacocinética , Benzamidas , Castração/métodos , Interações Medicamentosas , Humanos , Masculino , Neoplasias Hormônio-Dependentes/metabolismo , Nitrilas , Feniltioidantoína/efeitos adversos , Feniltioidantoína/farmacocinética , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
PURPOSE: Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RESULTS: RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. CONCLUSIONS: RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR.
Assuntos
Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Progressão da Doença , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Bexiga Urinária/patologia , Adulto JovemRESUMO
BACKGROUND: Runt-related transcription factor 2 (RUNX2) is a transcription factor that is closely related to bone formation, and prostate cancer (CaP) is the most common cancer to metastasize to bone. The present study investigated the expression levels of RUNX2 in human prostate tissue, and the correlation between RUNX2 levels and the clinicopathological characteristics of CaP. METHODS: A case-control study was conducted including 114 cases of newly diagnosed CaP and 114 age-matched BPH patients as controls. RUNX2 expression was estimated using real-time PCR and immunohistochemical staining. RESULTS: The mRNA expression of RUNX2 did not differ between CaP tissues and non-cancer BPH controls (P=0.825). However, RUNX2 expression was significantly decreased in patients with elevated PSA levels (≥20 ng ml(-1)), a Gleason score ≥8 and metastatic disease compared to those with low PSA, low Gleason score and non-metastatic disease (P=0.023, 0.005 and 0.014, respectively). Immunohistochemical analysis showed that 65.2% of the patients with positive RUNX2 nuclear staining had metastatic disease, which was present in only 25.9% of those with negative staining (P=0.010). CONCLUSIONS: RUNX2 mRNA expression was negatively correlated with CaP aggressiveness. Moreover, the nuclear location of RUNX2 may be a prognostic marker of metastasis in CaP.
Assuntos
Neoplasias Ósseas , Subunidade alfa 1 de Fator de Ligação ao Core , Neoplasias da Próstata , Transcrição Gênica , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Nucléolo Celular/metabolismo , Nucléolo Celular/ultraestrutura , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair from oxidatively damaged DNA. A case-control study was conducted to evaluate the correlation between the susceptibility and clinicopathological outcomes of prostate cancer (CaP) and hOGG1 genotype. PATIENTS AND METHODS: Subjects were recruited from 266 CaP patients and 266 age-matched benign prostatic hyperplasia patients. The hOGG1 codon 326 genotype was determined by peptide nucleic acid-mediated PCR clamping and compared with Gleason score and tumor stage. RESULTS: The Cys allele at codon 326 of hOGG1 was associated with an increased risk of CaP in comparison with the Ser allele (P = 0.005). Gleason scores of 8 or higher were observed more often in patients with the mutant genotypes Ser/Cys and Cys/Cys than in those with a wild-type genotype (P = 0.045), and the Cys/Cys homozygous genotype was associated with a significantly higher risk of metastatic disease in comparison with the Ser/Ser genotype (P = 0.017). CONCLUSIONS: These results suggest that hOGG1 is associated with the susceptibility to CaP and its aggressive clinicopathological characteristics.
Assuntos
DNA Glicosilases/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , República da Coreia , Fatores de RiscoRESUMO
OBJECTIVE: The aim of this study was to retrospectively assess the diagnostic performance of multidetector CT (MDCT) for the diagnosis of acute cholangitis using a new scoring method. METHODS: Of 80 patients with suspected biliary disease who underwent biphasic CT and endoscopic retrograde cholangiography, 39 were diagnosed as having acute cholangitis (Group 1) and 41 patients were classified as suspected biliary disease (Group 2). 100 age-matched patients without evidence of biliary disease were selected randomly as a control group (Group 3). Each patient's axial scan was scored by two independent radiologists for the extent of transient hepatic attenuation difference, the presence of biliary dilatation and identification of a biliary obstructive lesion. The difference in the scores among the three groups was evaluated and the optimal cut-off score for the diagnosis of acute cholangitis was determined. Interobserver agreement was also evaluated. RESULTS: The total scores (mean ± standard deviation) for Groups 1, 2 and 3 were 7.0 ± 2.0, 4.4 ± 2.4 and 0.9 ± 1.2, respectively, for Reviewer 1 and 7.2 ± 2.7 and 0.7 ± 1.1, respectively, for Reviewer 2. Significant differences were found for the subscores and the total scores among the three groups (p < 0.001). Using a cut-off score of ≥ 5, the sensitivity and specificity for diagnosing acute cholangitis were 84.6% and 83.7%, respectively, for Reviewer 1 and 89.7% and 83.7%, respectively, for Reviewer 2. Agreement for the subscores between readers was good to excellent (κ = 0.74-0.86). CONCLUSION: Based on dynamic MDCT and the described CT scoring method, the diagnosis of acute choangitis can be made with high sensitivity and specificity.
Assuntos
Colangite/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the potential of our newly developed three-dimensional immersive virtual reality (VR) program modeled on a real street crossing as an assessment tool for extrapersonal neglect in stroke patients. METHODS: Thirty-two patients with right-hemispheric stroke (neglect group, 16; non-neglect group, 16) were enrolled. The deviation angle, reaction time, left-to-right reaction time ratio, visual and auditory cue rates, and failure rate were evaluated during missions to keep a virtual avatar safe from a traffic accident in the VR program. The line bisection test and letter cancellation test were also evaluated. RESULTS: The deviation angle, left-to-right reaction time ratio, left visual and auditory cue rates and left failure rate in the VR program showed significant differences between the two groups (P < 0.05). Depending on the direction of approach of the virtual car, the left parameters were significantly higher than the right parameters in the neglect group (P < 0.05). In the neglect group, the line bisection test correlated significantly with the deviation angle (P < 0.05). None of the other virtual reality parameters significantly correlated with the paper and pencil tests. CONCLUSION: Post-stroke neglect in the extrapersonal space can be easily and safely detected and measured using our three-dimensional immersive virtual street crossing program.
Assuntos
Gráficos por Computador , Transtornos da Percepção/diagnóstico , Espaço Pessoal , Percepção Espacial/fisiologia , Interface Usuário-Computador , Estimulação Acústica/métodos , Idoso , Sinais (Psicologia) , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos da Percepção/etiologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Mechanistically similar selenophosphate synthetases (SPS) have been isolated from different organisms. SPS from Escherichia coli is an ATP-dependent enzyme with a C-terminal glycine-rich Walker sequence that has been assumed to take part in the first step of ATP binding. Three C-terminally truncated mutants of SPS, containing the N-terminal 238 (SPS(238)), 262 (SPS(262)), and 332 (SPS(332)) amino acids of the 348-amino-acid protein, have been extracted from cell pellets, and two of these (SPS(262) and SPS(332)) have been purified to homogeneity. SPS(238) has been obtained in a highly purified form. Binding of the fluorescent ATP-derivative TNP-ATP and Mn-ATP to the proteins was examined for all truncated mutants of SPS and a catalytically inactive C17S mutant. It has been shown that TNP-ATP can be used as a structural probe for ATP-binding sites of SPS. We observed two TNP-ATP binding sites per molecule of enzyme for wild-type SPS and SPS(332) mutant and one TNP-ATP binding site for SPS(238) mutant. The stoichiometry of Mn-ATP-binding was 2 mol of ATP per mol of protein determined with [(14)C]ATP by HPLC gel-filtration column chromatography under saturating conditions. The binding stoichiometries for SPS(332), SPS(262), and SPS(238) were 2, 1.6, and 1, respectively. The C17S mutant exhibits about one third of wild type SPS TNP-ATP-binding ability and converts 12% of ATP in the ATPase reaction to ADP in the absence of selenide. The C-terminus contributes two thirds to the TNP-ATP binding; SPS(238) likely has one ATP-binding site removed by truncation.