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BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.
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BACKGROUND: Intestinal senescence is associated with several aging-related diseases. l-Theanine (LTA) has demonstrated strong potential as an antioxidant and antisenescence agent. This study investigated the regulatory effect of LTA on cellular senescence using an in vitro model of d-galactose (D-Gal)-induced senescence in the rat epithelial cell line, intestinal epithelioid cell-6 (IEC-6). RESULTS: Treatment of IEC-6 cells with 40 mg/mL D-Gal for 48 h resulted in the successful development of the senescent cell model. Compared with D-Gal alone, both LTA preventive and delayed intervention increased cell viability and the ratio of JC-1 monomers to aggregates, increased the antioxidant capacity, and decreased the advanced glycation end product (AGE) levels and the overall number of senescent cells. Preventive and delayed intervention with 1000 µM LTA alleviated the D-Gal-induced cell cycle arrest by regulating p38, p53, CDK4, and CDK6 expression at the mRNA and protein levels, and further induced CycD1 proteins. Moreover, LTA preventive intervention reduced apoptosis to a greater degree than delayed intervention by upregulating the expression of the receptors of AGEs, Bax, Bcl-2, and NF-κB at the mRNA and protein levels. CONCLUSION: Our findings indicate that LTA intervention could attenuate senescence in IEC-6 cells by regulating the cell cycle and inhibiting apoptosis. © 2023 Society of Chemical Industry.
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Antioxidantes , Glutamatos , Estresse Oxidativo , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galactose , Senescência Celular , Ciclo Celular , Apoptose , RNA Mensageiro/metabolismo , Envelhecimento/metabolismoRESUMO
BACKGROUND: Heat stress (HS) damages the intestines, disrupting gut microbiota and immune balance. l-Theanine (LTA), found in tea, alleviates oxidative stress and cell apoptosis under HS; however, its effects on gut microbiota and immunity under HS remain unclear. To investigate this, we administered LTA doses of 100, 200, and 400 mg·kg-1 ·d-1 to C57BL/6J mice. On day 44, the model group and LTA intervention group were subjected to continuous 7-day HS treatment for 2 h per day. RESULTS: The results demonstrated that LTA intervention improved food intake, body weight, and intestinal epithelium, and reduced the water intake of heat-stressed mice. It increased the abundance of Turicibacter, Faecalibaculum, Bifidobacterium, and norank_f_Muribaculaceae, while reducing that of Lachnoclostridium and Desulfovibrio. LTA intervention also increased the concentrations of amino acid and lipid metabolites, regulated macrophage differentiation stimulated by gut microbiota and metabolites, reduced the antigen presentation by macrophages to the specific immune system, promoted B-cell differentiation and sIgA secretion, inhibited pro-inflammatory factors, and enhanced intestinal defense. Mechanistically, LTA downregulated heat shock protein 70 expression and the TLR4/NF-κB/p38 MAPK signaling pathway, restoring gut microbiota and immune balance. CONCLUSION: We suggest that LTA can alleviate HS by modulating gut microbiota, metabolites, and immunity, indicating its potential as a natural active ingredient for anti-HS food products. © 2023 Society of Chemical Industry.
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Microbioma Gastrointestinal , Glutamatos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Resposta ao Choque Térmico , MacrófagosRESUMO
Ovalbumin (OVA), a common food protein, can cause deadly allergies with intestine-specific immune reactions. L-Theanine (LTA) shows great potential for regulating intestinal immunity. To investigate the regulatory effect of LTA intervention on intestine-specific immunity, a 41 day experiment was performed on BALB/c OVA-sensitized mice. The results show that injecting female mice intraperitoneally with 50 µg of OVA and administering 30 mg of OVA 4 times can successfully establish an OVA-sensitized mouse model. LTA intervention significantly increased weight gain and thymus index (p < 0.05), decreased allergy and diarrhea scores (p < 0.05), and improved jejunum structure. Meanwhile, the histological score and degranulation of mast cells decreased. LTA intervention increased Clostridiales, Lachnospiraceae, Lactobacillus, Prevotella, and Ruminococcus abundance while decreasing Helicobacter abundance. Flow cytometry and Western blotting results indicated that 200 and 400 mg/kg of LTA upregulated the expression of T-bet and Foxp3 proteins (p < 0.05), thus promoting the differentiation of jejunum CD4+ T cells to Th1 and Tregs and increasing the cytokines IFN-γ, IL-10, and TGF-ß (p < 0.05). We found that 200 and 400 mg/kg of LTA downregulated the expression of RORγt and GATA3, thus inhibiting the differentiation of Th2 and Th17 cells and decreasing cytokines IL-4, IL-5, IL-13 TNF-α, IL-6, and IL-17A (p < 0.05). LTA inhibited the degranulation of mast cells and significantly decreased the serum levels of OVA-IgE, HIS, and mouse MCPT-1 (p < 0.05). Therefore, LTA intervention alleviated OVA allergy by improving intestine-specific immunity.
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Linfócitos T CD4-Positivos , Hipersensibilidade , Feminino , Camundongos , Animais , Ovalbumina , IntestinosRESUMO
The aim of this study is to evaluate the anti-inflammatory and protective effects of L-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with L-theanine at 0, 50, 200, or 800 mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that L-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200 mg/kg/day L-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200 mg/kg/day L-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of L-theanine in DSS-induced IBD, with a high representation of genes in "Cholesterol metabolism" and "Retinol metabolism" pathways. Analysis of protein-protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose L-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism.
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Anti-Inflamatórios/farmacologia , Glutamatos/farmacologia , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Colesterol/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutamatos/administração & dosagem , Inflamação/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Vitamina A/metabolismoRESUMO
Objective: To investigate the association between tumor PD-L1 expression and patient survival to determine whether PD-L1 represents an independent prognostic feature for patients with non-metastatic clear cell renal cell carcinoma (RCC). Patients and Methods: The tissue bank of the Fudan University Shanghai Cancer Center was queried to identity tissue samples of patients treated with radical nephrectomy, for non-metastatic sporadic clear cell RCC (ccRCC) between 2008 and 2015. Real-time polymerase chain reaction and immunohistochemistry staining was performed to detect the expression level of PD-L1 in paired cancer tissue and paracancerous tissue. Results: Three-hundred-and-thirty patients were enrolled in this study, with a mean age of 55.0 years at surgery and a mean tumor size of 5.2 cm. Two-hundred-and-forty-two (73.3%) and 88 (26.7%) patients showed a high and low expression of PD-L1 mRNA, respectively, while 254 patients had positive PD-L1 immunohistochemistry staining. Two-hundred-and-ninety-two patients had consistent results for mRNA and the PD-L1 protein based on these different detection methods. Patients with high PD-L1 expression were more likely to exhibit adverse pathologic features including an advanced T stage (P = 0.002) and lymph node metastasis (P = 0.044). The Kaplan-Meier curves of PFS and OS stratified by PD-L1 expression had a statistically significant difference. PD-L1 expression maintained a significant predictive role for PFS and OS in the multivariate cox model. Conclusions: Our data suggests that PD-L1 correlates with prognosis in RCC and targeting the PD-1/PD-L1 pathway should be considered in the treatment of RCC patients.
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BACKGROUND: The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease. OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines. METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses. RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003). CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.
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Fidelidade a Diretrizes/estatística & dados numéricos , Linfonodos/cirurgia , Neoplasias Penianas/cirurgia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Idoso , Estudos de Coortes , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Programa de SEER , Procedimentos Cirúrgicos Operatórios , Taxa de SobrevidaRESUMO
OBJECTIVES: This study aimed to evaluate the eighth edition of the American Joint Committee on Cancer (AJCC) for clinical staging of prostate cancer based upon Surveillance, Epidemiology and, End Results (SEER) database. MATERIALS AND METHODS: Patients diagnosed as prostate adenocarcinoma during 2004-2009 without any surgical treatment to the primary site were selected from the SEER registry. Excluded were cases with incomplete or unavailable staging, PSA and Gleason score information. RESULTS: A total of 144,443 cases were identified. The median follow-up time was 84 months. The median age at diagnosis was 69 years, and median PSA was 7 ng/ml. CSS at 10th years was 96.2% for cT2a and 86.2% for cT2b/2c, respectively. The survival differences between clinical stage cT2a and cT2b/2c still had statistical significance (P < 0.001). For patients with grade group 1, there was no statistically significant difference for CCS between the cT2a and cT1 (P = 0.310), and between the subgroup of cT1/cT2a with 10 ng/ml ≤ PSA < 20 ng/ml and the subgroup of cT2b/2c with PSA < 20 ng/ml (P = 0.126), respectively. The CSS of IIIA (T1/2 with PSA ≥ 20 ng/ml) was less than IIC (P < 0.001), which has worst prognosis within stage I/II. The prognosis of T1/2 stage with Gleason score grade group 5 and PSA < 20 ng/ml was not only worse than AJCC IIC (P < 0.001) but also worse than AJCC IIIB (P < 0.001). CONCLUSION: It is necessary to maintain a three-tier system to subdivide T2 disease clinically. For patients with grade group 1, cT2a and cT1 could merge into one group. Organ-confined disease with PSA ≥ 20 ng/ml or grade group 5 should be separated from stage II.
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Adenocarcinoma , Próstata/patologia , Neoplasias da Próstata , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Programa de SEER/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
This study aimed to evaluate the major changes of the eighth edition of the American Joint Committee on Cancer (AJCC) pathologic staging for prostate cancer treated with radical prostatectomy. A total of 138,176 patients diagnosed with prostate adenocarcinoma undergoing radical prostatectomy were selected from the Surveillance, Epidemiology and End Results (SEER) database during 2004-2014 period. Excluded were cases with incomplete or unavailable staging, PSA and Gleason score information. Two subgroups were established: group a, T2 stage with PSA≥20ng/ml; group b, T2 stage with Gleason score grade group 5 and PSA<20ng/ml. The median follow-up time was 58 months. The median age at diagnosis for the overall group was 61 years, and the median PSA was 5.7ng/ml. Cancer-specific survival (CSS) at tenth years was 99.3% for T2a/T2b, 99.2% for T2c, respectively. The survival differences between T2a/T2b and T2c did not have statistical significance (P = .323). It was necessary for the current eighth edition to define a single pathologic T2 category, eliminating the subcategories, for all organ-confined disease.CSS at the tenth years was 98.4% for group a, 92.6% for group b, respectively. The prognosis of group a was worse than AJCC II (P = .002). The prognosis of group b was not only worse than AJCC II (P < .001), but also worse than AJCC IIIB. There was necessity to separate the disease with PSA≥20ng/ml or Gleason score grade group 5 from other organ-confined disease. The present study supported the scientificity of the eighth edition of AJCC pathologic staging for prostate cancer.
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Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Prognóstico , Prostatectomia , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b. Phosphorylations of extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase were stimulated by dihydrotestosterone or fibroblast growth factor 8b. Among these major downstream pathways for mitogen-activated protein kinase, c-Jun NH2-terminal kinase signaling was most significantly enhanced. Protein kinase C phosphorylation was higher than AKT by the combined stimulation of dihydrotestosterone and fibroblast growth factor 8b. The phosphorylation of CDC2 was significantly induced by dihydrotestosterone and fibroblast growth factor 8b synergetically, and Smad underwent the same induction as CDC2. So the promoting effect of fibroblast growth factor 8b on cell cycle might contribute to the G2/M transition. This study indicated that the functional interaction between fibroblast growth factor 8b and androgen was essential for the prostate cancer cell proliferation.
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Proliferação de Células/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Fator 8 de Crescimento de Fibroblasto/farmacologia , Fase G2/efeitos dos fármacos , Neoplasias da Próstata/patologia , Proteína Quinase CDC2 , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator 8 de Crescimento de Fibroblasto/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Smad/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Surgical excision is essential for management of the rare and aggressive neoplasm adrenal cortical carcinoma (ACC). Five-year overall survival (OS) after surgery for ACC is dependent on disease stage, but for all stages the risk of death declines with time after surgery. We calculated the effect of post-surgical duration on conditional survival (CS) among ACC patients. A total of 641 patients with M0 ACC were selected from the Surveillance, Epidemiology, and End Results (SEER) registry (1988-2012). OS for the entire cohort at 1, 2, 3, 4, 5 and 6 years was 81.4%, 66.8%, 56.3%, 50.3%, 47.2% and 44.3%, respectively. CS for an additional year given prior survival for 0, 1, 2, 3, 4 or 5 years was 81.4%, 81.1%, 83.0%, 87.5%, 93.4% and 93.4%, respectively. Age, tumor stage, tumor grade and marital status affected OS and CS. Increases in 1-year CS over time were more pronounced in patients with poorer prognostic factors. With longer follow-up, tumor stage- and grade-dependent differences in CS decreased or even disappeared. CS may provide more meaningful life expectancy predictions for survivors of ACC than conventional survival analysis.
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Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia/efeitos adversos , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Expectativa de Vida , Masculino , Estado Civil , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Programa de SEER , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent. METHODS: A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. RESULTS: Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 - 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 - 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 - 2.049), Japan (OR = 0.812; 95%CI = 0.545 - 1.211), and Korea (OR = 1.056; 95%CI = 0.727 - 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 - .094) and Korea (OR = 1.914; 95%CI = 1.311 - 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 - 1.321). CONCLUSIONS: In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.
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Glutationa Transferase/genética , Neoplasias da Próstata/genética , Povo Asiático/genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo Genético , Neoplasias da Próstata/enzimologia , Fatores de RiscoRESUMO
Okra is a widely distributed crop in the tropics, subtropics, and warmer areas of the temperate zones. Its major potential uses as a vegetable, oil and protein source, and source of paper pulp and fuel, or biomass are compatible. It is expected to have high value of exploitation and application. Due to the limited number of molecular studies focused on okras, the methods of morphological and ISSR markers were used to analysis the genetic diversity of 48 okras in the present study. The 22 primers were picked for ISSR-PCR, and a total of 154 fragments were amplified with an overall average polymorphism of 54.55 %. We used the 154 markers to construct the dendrogram based on the unweighted pair group method with arithmetic means (UPGMA). A high level of genetic diversity was found among 48 individuals. The 48 Okras was divided into four clusters at Dice's coefficient of 0.19 with clustering analysis. Based on these data of the genetic diversity, it will be possible to exploit the available resources of okra in more valuable ways.
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PURPOSES: To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. MATERIALS AND METHODS: From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. RESULTS: Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. CONCLUSION: The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era.
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Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Fatores Etários , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Programa de SEER , Fatores Sexuais , Fatores Socioeconômicos , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
Purposes To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. Materials and Methods From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. Results Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. Conclusion The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era. .
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /genética , Movimento Celular , Proliferação de Células , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Interferência de RNA , /metabolismo , Linhagem Celular Tumoral , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Fatores de Risco , RNA Mensageiro/metabolismo , Fatores de Tempo , TransfecçãoAssuntos
Aneurisma da Aorta Torácica/diagnóstico , Criança , Pré-Escolar , Erros de Diagnóstico , Feminino , Humanos , Lactente , MasculinoRESUMO
This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa). We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP) and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS), pathological stage and lymph node involvement (LNI) in RP specimens. Preoperative prostate-specific antigen (PSA) levels, biopsy GS (bGS), and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC) curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510-27.010), 3.270 (95% CI: 1.470-7.278) for high levels of TG for pT3-4 disease, and 2.670 (95% CI: 1.134-6.287) for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.
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Biomarcadores Tumorais/sangue , Progressão da Doença , Lipídeos/sangue , Prostatectomia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Índice de Gravidade de Doença , Idoso , Biópsia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Análise de Regressão , Estudos RetrospectivosRESUMO
AIM: To investigate the role of sorafenib dosage escalation in Asian patients with metastatic renal cell carcinoma that had progressed after routine dosages. PATIENTS & METHODS: Sorafenib dosage escalation to 600 or 800 mg twice a day was offered to 41 patients with metastatic renal cell carcinoma who had progressed on normal dosages. Clinical outcome, toxicity and favorable clinical covariables for progression-free survival (PFS) were evaluated. RESULTS: The median PFS with dosage-escalated therapy was 7 months. Drug-related adverse events were tolerable. The pre-escalation Karnofsky performance status, serum calcium concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at the routine dosage were associated with a longer PFS in the dosage-escalation period. CONCLUSION: Sorafenib dosage escalation was efficacious and tolerable in Asian patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (no. ChiCTR-ONRC-12002088).
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Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Povo Asiático , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Sorafenibe , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese cohort. PATIENTS AND METHODS: A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS: Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.
Assuntos
Carcinoma de Células Renais/complicações , Gordura Intra-Abdominal , Neoplasias Renais/complicações , Obesidade Abdominal/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Carcinoma de Células Renais/patologia , China , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/patologia , Gordura Subcutânea Abdominal , Adulto JovemRESUMO
OBJECTIVE: To explore the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma (RCC) . METHODS: A total of 136 patients with advanced RCC were treated with sunitinib from 2008 to 2011. There were 91 males and 45 females with an average age of 56 years. Their 6-week therapy cycle was 4 weeks of sunitinib 50 mg daily followed by 2-week off-treatment (schedule 4/2). The median follow-up time was 15 months. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model.Log-rank test and Cox proportional hazard model were used to assess the value of drug toxicity as the prognostic factors. RESULTS: The increased hemoglobin on cycle 1 day 14 (HR:0.950, 95%CI:0.923-0.978) and the increased lymphocytes on cycle 1 days 28 and 42 (HR:0.405, 95%CI:0.203-0.809, HR:0.394, 95%CI:0.179-0.867) were significantly associated with OS (P adj = 0.001, 0.014 and 0.022 respectively). Hypertension class III/IV (HR:0.066, 95%CI:0.008-0.582), and the number of neutrophils screening and lymphocyte count ratio (HR:2.537, 95%CI:1.182-5.404) were the survival prognosis independent predictors. CONCLUSION: Early hematopoietic toxicities may potentially predict the outcomes of advanced RCC after a therapy of sunitinib.