RESUMO
Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Idoso , Quimioembolização Terapêutica/métodos , Prognóstico , Resultado do Tratamento , Adulto , Quimiorradioterapia/métodosRESUMO
Vitamin D plays a central role in cellular proliferation, apoptosis induction, and tumor growth suppression. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. A series of epidemiological studies have examined the association between the VDR FokI polymorphism and breast cancer risk, but the findings remain inconclusive. Fifteen eligible case-control studies involving 15,681 cancer cases and 20,632 control subjects were identified through searching PubMed, Embase, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Heterogeneity across studies was examined with the chi-square-based Q test and the I (2) index. Begg's and Egger's test were also performed to determine publication bias. All statistical data were analyzed by STATA software. The combined estimates did not show significant risks correlated with the FokI polymorphism. However, we found an increased risk in the subgroup analysis by source of control (OR = 1.11, 95% CI = 1.01-1.22; heterogeneity test: P = 0.116, I(2) = 0.0% for ff vs FF; OR = 1.10, 95% CI = 1.01-1.21; heterogeneity test: P = 0.832, I(2) = 0.0% for ff vs Ff + FF). This meta-analysis suggests that the presence of FokI polymorphism may contribute to the risk of breast cancer in Caucasians.
Assuntos
Neoplasias da Mama/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Predisposição Genética para Doença , Polimorfismo Genético , Receptores de Calcitriol/genética , População Branca/genética , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Viés de PublicaçãoRESUMO
For the surface sediment samples of Taihu Lake in 2010, the eight physicochemical indices of pH, temperature, Eh, water content, porosity, grain size, total phosphorus, and Loss-on-ignition were measured and analyzed, along with the contents of nine heavy metals:Cu, Zn, Ni, Cr, Pb, Ba, Mn, Co, and V. The order of magnitudes of heavy metal content of surface sediments in Taihu Lake was:Mn>Ba>Zn>Cr>V>Ni>Pb>Cu>Co. This suggested that the contents of the nine heavy metals were beyond the background value, which had a close connection to the geology of the Taihu Lake Basin and were influenced by human activity to varying degrees. The clustering analysis and the spatial distribution of the heavy metals revealed that the concentrations of heavy metals in the North and South Taihu Lake sections decreased from the lake shore to the lake center, the concentrations of heavy metals in the West Taihu Lake section increased from the lake shore to the lake center, and the distribution of heavy metals in the center of the lake remained relatively uniform. According to the correlation study, the metal elements were positively correlated with one another to varying degrees, indicating that they originate from the same source of pollution. According to the PCA and PMF analyses, there were some different sources of heavy metals in Taihu Lake, in which the transportation and industrial complex source were the most important sources, the diagenesis was the second major source, and agriculture was the third major source. Furthermore, the heavy metal pollution was evaluated using the geoaccumulation and the potential ecological risk indices. This offers a solid theoretical backing for the future management of heavy metal pollution in Taihu Lake.
RESUMO
BACKGROUND: Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied. METHODS: We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models. RESULTS: Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT. CONCLUSION: Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.
Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Neoplasias do Colo do Útero/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Antígenos CD/genética , Caderinas/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/biossíntese , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Transição Epitelial-Mesenquimal , Feminino , Células HeLa , Xenoenxertos , Humanos , Metástase Linfática , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Oxirredução , Transfecção , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
BACKGROUND AND AIMS: Reactive oxygen species (ROS) and numerous carcinogens may cause DNA damage including oxidative base lesions that contribute to the risk of lung cancer. The base excision repair (BER) pathway could effectively remove oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key roles. The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer. METHODS: In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models. RESULTS: Individuals homozygous for the variants APE1 -141GG showed a protective effect for lung cancer overall (OR=0.62; 95% CI: 0.42-0.91; p=0.02) and for lung adenocarcinoma (OR=0.65; 95% CI, 0.44-0.96; p=0.03). When analyzing the combined effects of variant alleles, 84 patients and controls were identified who were homozygous for two or three of the potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 -141G). ORs were significantly reduced when all patients were analyzed (OR=0.62; 95% CI: 0.38-0.99; p=0.05). CONCLUSIONS: The combined effects of polymorphisms within BER genes may contribute to the tumorigenesis of lung cancer.
Assuntos
Adenocarcinoma/genética , Carcinoma de Células Pequenas/genética , Carcinoma de Células Escamosas/genética , DNA Glicosilases/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Substituição de Aminoácidos , Povo Asiático , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Análise de Sequência de DNA , Fumar , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
PURPOSE: To observe, by retrospective analysis, the curative effects and complications due to californium-252 (252Cf) neutron intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT) in the treatment of cervical cancer. METHODS AND MATERIALS: From February 1999 to December 2007, 696 patients with cervical cancer (Stages IB to IIIB) were treated with 252Cf-ICBT in combination of EBRT. Of all, 31 patients were at Stage IB, 104 at IIA, 363 at IIB, 64 at IIIA, and 134 at IIIB. Californium-252 ICBT was delivered at 7-12 Gy per insertion per week, with a total dose of 29-45 Gy to reference point A in three to five insertions. The whole pelvic cavity was treated with 8-MV X-ray external irradiation at 2 Gy per fraction, four times per week. After 16-38 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield, with a total external irradiation dose of 44-56 Gy. The total treatment course was 5 to 6 weeks. RESULTS: Overall survival rate at 3 and 5 years for all patients was 76.0% and 64.9%, respectively. Disease-free 3- and 5-year survival rates of patients were 71.2% and 58.4%, respectively. Late complications included vaginal contracture and adhesion, radiation proctitis, radiation cystitis, and inflammatory bowel, which accounted for 5.8%, 7.1%, 6.2%, and 4.9%, respectively. Univariate analysis results showed significant correlation of stage, age, histopathologic grade, and lymph node status with overall survival. Cox multiple regression analysis showed that the independent variables were stage, histopathologic grade, tumor size, and lymphatic metastasis in all patients. CONCLUSION: Results of this series suggest that the combined use of 252Cf-ICBT with EBRT is an effective method for treatment of cervical cancer.