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Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.
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5-Aza-2'-deoxycytidine (5-Aza-CdR) is currently acknowledged as a demethylation drug, and causes a certain degree of demethylation in a variety of cancer cells, including pancreatic cancer cells. Emodin, a traditional Chinese medicine (TCM), is an effective monomer extracted from rhubarb and has been reported to exhibit antitumor activity in different manners in pancreatic cancer. In the present study, we examined whether emodin caused demethylation and increased the demethylation of three tumor-suppressor genes P16, RASSF1A and ppENK with a high degree of methylation in pancreatic cancer when combined with 5-Aza-CdR. Our research showed that emodin inhibited the growth of pancreatic cancer Panc-1 cells in a dose- and time-dependent manner. Dot-blot results showed that emodin combined with 5-Aza-CdR significantly suppressed the expression of genome 5mC in PANC-1 cells. In order to verify the effect of methylation, methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP) combined with TA were selected for the cloning and sequencing. Results of MSP and BSP confirmed that emodin caused faint demethylation, and 5-Aza-CdR had a certain degree of demethylation. When emodin was combined with 5-Aza-CdR, the demethylation was more significant. At the same time, fluorescent quantitative PCR and western blot analysis results confirmed that when emodin was combined with 5-Aza-CdR, the expression levels of P16, RASSF1A and ppENK were increased more significantly compared to either treatment alone. In contrast, the expression levels of DNA methyltransferase 1 (DNMT1) and DNMT3a were more significantly reduced with the combination treatment than the control or either agent alone, further proving that emodin in combination with 5-Aza-CdR enhanced the demethylation effect of 5-Aza-CdR by reducing the expression of methyltransferases. In conclusion, the present study confirmed that emodin in combination with 5-Aza-CdR enhanced the demethylation by 5-Aza-CdR of tumor-suppressor genes p16, RASSF1A and ppENK by reducing the expression of methyltransferases DNMT1 and DNMT3a.
Assuntos
Azacitidina/análogos & derivados , Metilação de DNA/efeitos dos fármacos , Emodina/farmacologia , Encefalinas/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Precursores de Proteínas/genética , Proteínas Supressoras de Tumor/genética , Azacitidina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina , Decitabina , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Regiões Promotoras Genéticas/efeitos dos fármacos , Análise de Sequência de DNA/métodosRESUMO
Emodin, a natural anthraquinone derivative isolated from Rheum palmatum, has been reported to inhibit the growth of pancreatic cancer cells through different modes of action; yet, the detailed mechanism remains unclear. In the present study, we hypothesized that emodin exerts its antitumor effect by participating in the regulation of the DNA methylation level. Our research showed that emodin inhibited the growth of pancreatic cancer PANC-1 cells in a dose- and time-dependent manner. Dot-blot results showed that 40 µM emodin significantly inhibited genomic 5 mC expression in the PANC-1 cells, and mRNA-Seq showed that different concentrations of emodin could alter the gene expression profile in the PANC-1 cells. BSP confirmed that the methylation levels of P16, RASSF1A and ppENK were decreased, while concomitantly the unmethylated status was increased. RT-PCR and western blotting results confirmed that the low expression or absence of expression of mRNA and protein in the PANC-1 cells was re-expressed following treatment with emodin. In conclusion, our study for the first time suggests that emodin inhibits pancreatic cancer cell growth, which may be related to the demethylation of tumor-suppressor genes. The related mechanism may be through the inhibition of methyltransferase expression.
Assuntos
Encefalinas/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Precursores de Proteínas/genética , Proteínas Supressoras de Tumor/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina , Metilação de DNA/efeitos dos fármacos , Emodina/administração & dosagem , Encefalinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Precursores de Proteínas/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
<p><b>OBJECTIVE</b>To compare clinical results of treatment of Pipkin type I and II femoral head fractures through modified Smith-Peterson(S-P) approach and modified Hardinge approach.</p><p><b>METHODS</b>From July 2005 to July 2014, 42 patients with Pipkin type I and II femoral head fractures were treated with operation. A total of 23 patients in anterior group was treated with modified S-P approach including 17 males and 6 females with an average age of (29.3±9.4) years old, 5 cases of type I by excision of the fragement, 3 cases of type I and 15 cases of type II cases by fixation of the fragement. While a total of 19 patients in the lateral group was treated with modified Hardinge approach including 15 males and 4 females with an average age of (31.4±10.0) years old, 3 cases of type I by excision of the fragement, 4 cases of type I and 12 cases of type II by fixation of the fragement. Operative time, blood loss during operation and fracture healing time were observed and compared. The clinical and radiographic outcomes of the patients were measured using Thompson-Epstein scoring scale. The effect of hip reduction time of less than 6 h, 6 to12 h, and more than 12 h, the effect of surgery time within 24 h and more than 24 h after injury were compared.</p><p><b>RESULTS</b>All patients were followed up from 24 to 60 months with an average of(30.29±6.95) months. The operation time (61.96±12.22) min, blood loss (46.09±18.03) ml, and (74.74±10.06) min, blood loss (72.11±19.88) ml in lateral group in the anterior group were better than those of lateral group(<0.05). In anterior group, fracture healing time was(12.22±1.70) weeks, the results were excellent in 8 cases, good in 10 cases, fair in 4 cases and poor in 1 case, the excellent and good rate was 78.3%, the incidence of avascular necrosis of femoral head was 8.69%(2/23), and the incidence of heterotopic ossification was 13.04%(3/23). While in lateral group, the fracture healing time was(12.42±1.95) weeks, the results were excellent in 6 cases, good in 7 cases, fair in 3 cases and poor in 3 cases, the excellent and good rate was 68.4%, the incidence of avascular necrosis of femoral head was 10.53%(2/19), and the incidence of heterotopic ossification was 5.26%(1/19). There was no significant difference in fracture healing time, postoperative effect and postoperative complications between the anterior group and lateral group(<0.05). The effect of patients with reduction time of hip dislocation less than 12 h was significantly better than that of more than 12 h, there was no significant difference in the effect between reduction time within 6 h and 6 to 12 h. There was no significant difference in the outcome between surgical patients within 24 h and more than 24 h after injury.</p><p><b>CONCLUSIONS</b>Dislocated hip of Pipkin type I and II femoral head fractures should be closed reduction within 6 h. If conditions are limited, the reduction time can be accepted within 12 h. Both of modified S-P approach and modified Hardinge approach are effective in treating Pipkin type I and II femoral head fractures, and can obtain excellent outcomes. Moreover, modified S-P approach has advantage of less trauma, less blood loss, shorter operative time.</p>
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<p><b>OBJECTIVE</b>To investigate the relationship of upper cervical pedicle and vertebral artery (VA) location in order to improve the safety of transpedicular screw insertion.</p><p><b>METHODS</b>The vertebral arteries on 12 sides of 6 adult pate cadaverous specimens were dissected. The distance between VA and VA groove at the atlas needling point of transpedicle screw, and the distance between VA and the inner edge of axis cervical foramen, and the VA external diameter in axis cervical foramen were measured respectively.</p><p><b>RESULTS</b>The distance between VA and VA groove was (1.96 ± 0.72) mm on the left and (1.99 ± 0.61)mm on the right at the atlas needling point of transpedicle screw, the distance between VA and the inner edge of axis cervical foramen was (2.23 ± 0.43) mm on the left and (2.30 ± 0.39) mm on the right, the VA external diameter in axis cervical foramen was (3.03 ± 0.48) mm on the left and (2.98 ± 0.75) mm on the right.</p><p><b>CONCLUSION</b>It is unlikely to injury VA when the transpedicle screws of upper cervical vertebrae were implanted correctly besides high straddled VA, and the individualization must be performed in the process.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vértebras Cervicais , Cirurgia Geral , Fixação Interna de Fraturas , Métodos , Parafusos Pediculares , Artéria VertebralRESUMO
<p><b>OBJECTIVE</b>To analyze the clinical performance of TP antibody detection by CLIA kits and evaluate whether the CLIA kits made in China is suitable for clinical use.</p><p><b>METHODS</b>1200 samples were collected from Beijing Hospital including 300 samples with confirmed TP infection and 900 healthy control samples. To detect the TP antibody of the 1200 sanples separately by the CLIA kits and the ELISA kits at the same time. The test results were analyzed with statistical methods.</p><p><b>RESULTS</b>The sensitivity and specificity of the CLIA kits were 99.3% and 99.9% respectively, and positive predictive value of 99.7%, negative predictive value of 100%. With the ELISA method, the positive coincidence rate was 98.7%, the negative coincidence rate was 99.8%, and the total coincidence rate was 99.5%.</p><p><b>CONCLUSION</b>The CLIA kits showed good clinical performance and the agreement rate with the ELISA kits was. The CLIA kits are suitable for clinical use.</p>
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Humanos , Anticorpos Antibacterianos , Sangue , China , Ensaio de Imunoadsorção Enzimática , Economia , Métodos , Medições Luminescentes , Economia , Métodos , Kit de Reagentes para Diagnóstico , Economia , Sensibilidade e Especificidade , Sífilis , Sangue , Diagnóstico , Sorodiagnóstico da SífilisRESUMO
<p><b>OBJECTIVE</b>To analyze the clinical performance of free prostate-specific antigen (fPSA) detection by ECLIA method, and evaluate whether ECLIA is suitable for clinical use.</p><p><b>METHODS</b>341 samples were collected and tested prostate-specific antibodies with CMIA and ECLIA methods. These samples contain: 97 samples with abnormal high PSA value tested by CMIA method, and 244 normal PSA samples. Use CMIA as the reference method, and detect fPSA, tPSA levels, and the ratio of fPSA/tPSA. Analyze the testing results with statistical methods.</p><p><b>RESULTS</b>Compared with CMIA, correlation coefficent of ECLIA fPSA detection is 0.99; correlation coefficent of f/tPSA ratio detection is 0.96; the sensitivity, specificity of ECLIA f/tPSA ratio detection are 85.71%, 92.6% respectively, the agreement rate with ECLIA is 87.4%. No cross reaction with bilirubin, lipohemia, hemolysis, RF, CEA, AFP, CA125, CA153, CA199 were found in the tests.</p><p><b>CONCLUSION</b>The ECLIA method for free prostate-specific antigen detection showed good clinical performance; and is suitable for clinical use.</p>
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Humanos , Masculino , Técnicas Eletroquímicas , Métodos , Antígeno Prostático Específico , Sangue , Neoplasias da Próstata , Sangue , Diagnóstico , Sensibilidade e EspecificidadeRESUMO
Prostate cancer growth is almost wholly dependent on the route of the androgen receptor and most therapies aimed at blocking this signaling axis are useful tools in the management of this disease. Unfortunately such therapies invariably fail, and the cancer progresses to an androgen-independent stage. In such cases, androgen receptor mutation almost always occurs and much evidence suggests the continuous growth of the tumor. One mechanism by which the receptor is thought to remain active is mutation. This paper reviews the molecular mechanism of tumor growing after androgen receptor mutation and some of the promising management principles and systemic chemotherapy options against prostate cancer.
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Humanos , Masculino , Progressão da Doença , Mutação , Neoplasias da Próstata , Genética , Patologia , Receptores Androgênicos , GenéticaRESUMO
<p><b>OBJECTIVE</b>To investigate the seroprevalence of hepatitis C viruse infection in the human population in six regions of Beijing, Heilongjiang, Shandong, Ningxia, Gansu and Sichuan in China.</p><p><b>METHODS</b>ELISA was used for detecting anti-HCV IgG of the serum samples. All sample were collected in 2006-2008 in six areas.</p><p><b>RESULTS</b>9538 samples were detected. The total positive rate of anti-HCV was 0.39% (37), 0.23% (3/1328) in Beijing, 0.74% (12/1629) in Heilongjiang, 0.26% (5/1962) in Shandong, 0.1% (1/1000) in Ningxia, 0.44% in Gansu (9/2 037) and Sichuan (7/1582), respectively. The 37 positive samples at the sex were 19 (51.35%) of man and 18 (48.65%) of female. At the age group were 1 (2.70%) of < 10 years old, 5 (13.51%) of 10-19 years old, 4 (10.81%) of 20-29 years old, 6 (16.22% ) of 30-39 years old, 9 (24.32%) of 4049 years old, 12 (32.43%) of > or = 50 years old. The positive samples were detected anti-HAV-IgG, anti-HEV-IgG and HBsAg/ HBcAb /HBeAb. The positive Number was 35 (94.59%), 10 (27.03%) and 2 (5.41%) respectively.</p><p><b>CONCLUSIONS</b>HCV infection rate in the population was 0.1% -0.74%, 1/3 of > or = 50 years old in HCV positive. Hepatitis C virus co-infection with HAV, HEV and HBV.</p>
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Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , China , Epidemiologia , Hepatite C , Epidemiologia , Anticorpos Anti-Hepatite C , SangueRESUMO
<p><b>OBJECTIVE</b>To evaluate the antibacterial efficacy of KaVo KEY laser on Enterococcus faecalis (E. faecalis) within infected root canals and roots surface in vitro.</p><p><b>METHODS</b>Fifty single-rooted teeth were selected, and infected root canals and roots surface vitro models were prepared. Then, these specimens were divided into three groups. First group were untreated as blank control. The other two groups were the laser groups: Irradiated 15 s and 30 s respectively with 80 mJ and 140 mJ in root canals and on roots surface. Microbiological samples were collected from root canals and roots surface at two time points (before irrigation and immediately after irrigation). The dentin chips from three different zone of part of root canals in each group were immediately collected and were cultured for 24 h in brain heart infusion (BHI).</p><p><b>RESULTS</b>The number of E. faecalis in root canal and root surface in each of the groups were effectively reduced (P < 0.05), and there was no significant difference between each two groups (P > 0.05). Compared with the blank control, the bacterial number in 100 microm of dental tubules decreased after specimens treated with 80 mJ, and the experimental group irradiated 15 s was a significant decease (P < 0.05). The other groups were no changed in different zone of dental tubules.</p><p><b>CONCLUSION</b>KaVo KEY laser is effective on sterilizing infected root canals and roots surface. It has also significant effect on bacterial in superficial dental tubules with low energy and short time.</p>