RESUMO
The antitumor effects elicited by immune checkpoint inhibitors (ICIs) have transformed cancer treatments. However, severe immune-related adverse events (irAEs) resulting from these treatments have restricted the application of ICIs. To overcome the adverse events, we developed a tumor lesion-selective pro-PD-1Ig that is activated by proteases overexpressed in tumors. We genetically linked albumin to the N-terminus of a modified PD-1Ig (termed mutPD-1Ig hereafter) via an MMP substrate sequence to form Alb-hinge-mutPD-1Ig. We demonstrate that the binding activity of nondigested Alb-hinge-mutPD-1Ig is approximately 11-folds lower than mutPD-1Ig. However, digestion by type IV collagenase restored the binding activity of Alb-hinge-mutPD-1Ig to a level comparable to that of native mutPD-1Ig. In order to enhance the masking efficiency of Alb-mutPD-1Ig, we simulated the effects of diverse MMP substrate linkers for connecting albumin and PD-1 at various starting positions by bioinformatics tools. Our validation experiments indicate Alb-hinge-mutPD-1Ig displayed the best masking efficiency among all simulated constructs. Our study suggests that albumin may be best applicable to mask a target protein whose binding motif is centralized and in the proximity of the N-terminus of the protein.
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Ectopic prostatic tissue is rare, and it is usually only discovered by chance during imaging examinations or surgery. However, between 1967 and 2021, reports of ectopic prostatic tissue in the medical literature increased. It is rarely reported that ectopic prostatic tissue can be misdiagnosed as a nephrogenic adenoma (NA). This case study aimed to increase the awareness of ectopic prostatic tissue to improve its rates of diagnosis. This paper is focused on a 45-year-old male patient with a history of bladder lesions that were accidentally discovered through a health examination. A computed tomography scan revealed a homogeneous isoechoic mass in the posterior inferior wall of the bladder. At first, a transurethral cystoscopy revealed a smooth sessile mass covering the normal bladder mucosa, which was located in the middle of the interureteric ridge. The biopsy results suggested a possible intravesical NA. The mass was then completely resected under pneumovesicoscopy, and the pathological diagnosis was ectopic prostatic tissue. The clinical symptoms of ectopic prostatic tissue are similar to other bladder neoplasms, but there are too few characteristics available in imaging examinations to allow for an accurate diagnosis. Since ectopic prostatic tissue can present as a tumor in the bladder, urologists may easily misdiagnose the condition. Surgery is the basis of treatment for ectopic prostatic tissue, and it has a good prognosis.
Assuntos
Coristoma , Neoplasias da Bexiga Urinária , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Cistoscopia , Coristoma/diagnóstico por imagem , Coristoma/patologia , Erros de DiagnósticoRESUMO
Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids; however, steroids may lead to considerable side effects. Using a mouse model of AH (experimental autoimmune hypophysitis, EAH), we show that interleukin-1 receptor-associated kinase 1 (IRAK1) is upregulated in the pituitaries of mice that developed EAH. We identified rosoxacin as a specific inhibitor for IRAK1 and found it could treat EAH. Rosoxacin treatment at an early stage (day 0-13) slightly reduced disease severity, whereas treatment at a later stage (day 14-27) significantly suppressed EAH. Further investigation indicated rosoxacin reduced production of autoantigen-specific antibodies. Rosoxacin downregulated production of cytokines and chemokines that may dampen T cell differentiation or recruitment to the pituitary. Finally, rosoxacin downregulated class II major histocompatibility complex expression on antigen-presenting cells that may lead to impaired activation of autoantigen-specific T cells. These data suggest that IRAK1 may play a pathogenic role in AH and that rosoxacin may be an effective drug for AH and other inflammatory diseases involving IRAK1 dysregulation.
Assuntos
Hipofisite Autoimune , Quinases Associadas a Receptores de Interleucina-1 , Autoantígenos , Hipofisite Autoimune/terapia , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Animais , CamundongosRESUMO
BACKGROUND: CCL22 played critical roles in Tregs recruitment. The upstream regulators modulating CCL22 in hepatocellular carcinoma (HCC) were not clearly understood. METHODS: MiR-23a, p-p65, p65, CCL22, and Foxp3 levels were monitored by RT-qPCR and western blotting. Immunofluorescence assay was used to perform the costaining of Foxp3 and CD4 on liver tissues. Transwell assay was applied to evaluate the migration ability of Tregs. Dual-luciferase assay was performed to determine relationship of miR-23a/CCL22 and p65/miR-23a. Chromatin immunoprecipitation (ChIP) was applied to detect the direct binding of p65 to miR-23a promoter. Xenograft tumor models were developed to investigate the functions of p65 and miR-23a in vivo. RESULTS: HBV infection was associated with reduced survival and increased Tregs recruitment in HCC patients. MiR-23a was decreased, whereas p65, CCL22, and Foxp3 were increased in HBV+ tumors. MiR-23a was inversely correlated with CCL22 and Foxp3 expression in HCC. MiR-23a directly targeted CCL22 3'UTR, leading to CCL22 reduction and attenuated Tregs recruitment. Meanwhile, p65 functioned as a transcription repressor of miR-23a by directly binding to its promoter. Inhibition of p65 induced miR-23 expression, leading to less CCL22 expression and Tregs recruitment in vitro. CCL22 was the indispensable effector underlying p65/miR-23a axis and Tregs recruitment. MiR-23a inhibitor promoted xenografted tumor growth accompanying with upregulation of CCL22, whereas p65 inhibition exerted opposite effects. CONCLUSION: Blockage of p65 disinhibited miR-23a expression, leading to CCL22 reduction and repress Tregs recruitment. Targeting p65/miR-23a/CCL22 axis was a novel approach for HBV+ HCC treatment.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Quimiocina CCL22/metabolismo , Hepatite B/complicações , MicroRNAs/genética , Linfócitos T Reguladores/imunologia , Fator de Transcrição RelA/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Proliferação de Células , Quimiocina CCL22/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B/virologia , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Fator de Transcrição RelA/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs. AIM: To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir. METHODS: This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls. RESULTS: Level of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively. CONCLUSION: HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.
Assuntos
Antivirais/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/diagnóstico , Adulto , Biomarcadores/sangue , DNA Viral/sangue , DNA Viral/isolamento & purificação , Progressão da Doença , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
No consensus exists with respect to positive hepatitis B virus (HBV) DNA results and persistent normal or mildly elevated alanine aminotransferase (ALT). The aim of this study is to investigate the appropriate management and prognosis of these populations with chronic hepatitis B (CHB). A total of 235 subjects with positive HBV DNA results and persistent normal or mildly elevated ALT were enrolled in this study. Liver biopsy and liver stiffness measurements (LSM) were performed in all participants at baseline. Antiviral therapy was initiated in patients with significant hepatic inflammation (G ≥ 2) and/or fibrosis (S ≥ 2). The patients were divided into entecavir and adefovir groups based on HBV DNA load (>2000 IU/mL vs <2000 IU/mL). The liver biopsies were repeated at 72 weeks for the patients received antiviral therapy. We found that 112 subjects were hepatitis B e antigen (HBeAg) positive, and 123 subjects were negative. The corresponding median ALTs were 46 (39.5-52.5) and 48 (41.5-57.0) U/mL, respectively. G ≥ 2 and/or S ≥ 2 diseases were present in 48.8% (82/168) of the HBeAg-positive and 51.2% (86/168) of HBeAg-negative patients, respectively. In addition, 96 HBeAg-positive and 72 HBeAg-negative patients were divided into entecavir and adefovir groups. Meanwhile, liver biopsies had greater diagnostic accuracy for determining cirrhosis than LSM (0.711 vs 1.0, P < 0.0001). At the end of the study period, undetectable HBV DNA levels and normal ALT levels were observed in CHB-infected patients. Furthermore, the patients showed histologic improvement at 72 weeks compared with baseline measurements (G, 1.72 ± 1.00 vs 0.73 ± 0.88, P = 0.0002; S, 1.484 ± 0.90 vs 0.99 ± 1.13, P < 0.0001). Collectively, liver biopsy enhanced diagnostic accuracy for CHB-infected individuals with persistent normal or mildly elevated aminotransferase levels. Moreover, antiviral therapy can improve or regress the hepatic fibrosis and cirrhosis.
Assuntos
Alanina Transaminase/metabolismo , Antivirais/efeitos adversos , DNA Viral/análise , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/diagnóstico , Adenina/efeitos adversos , Adenina/análogos & derivados , Adulto , Biópsia , Gerenciamento Clínico , Feminino , Guanina/efeitos adversos , Guanina/análogos & derivados , Vírus da Hepatite B/enzimologia , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/enzimologia , Masculino , Organofosfonatos/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC. METHODS: We investigated 1200 patients with CHB who were treated with NAs for at least four years and evaluated the association of the variables ALT, HBsAg, HBV DNA, age and platelet count with the occurrence of HCC. We used multivariable analysis to identify independent risk factors for the development of HCC. RESULTS: HCC developed in 153 NA-treated patients. Serum HBV DNA levels of 18.17% (218/1200) patients were>2000IU/mL. The median level of liver stiffness measurement (LSM) of all patients was 8.3±6.7kPa vs. 19.8±10.1kPa in patients with HCC. Advanced age, lower platelet counts, positive HBV DNA load, lower ALB concentration and relatively advanced liver disease were associated with an increased risk of developing HCC. Further, TGF-ß and IFN-γ levels were higher and lower in patients with HCC or CHB, respectively. CONCLUSIONS: Hepato-carcinogenesis occurred more frequently in patients with a positive HBV DNA load and relatively advanced liver disease. Therefore, it is important to administer antiviral therapy to patients with CHB before they develop HBV-related cirrhosis.
Assuntos
Povo Asiático/estatística & dados numéricos , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/etnologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/etiologia , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/diagnóstico , China/epidemiologia , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Incidência , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de TempoAssuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Antivirais , Hepacivirus , Hepatite C , Hepatite C Crônica , Humanos , IncidênciaRESUMO
It has been suggested that Hepatitis C virus (HCV) core protein is associated with metabolic disorders of liver cell. However, the precise mechanism is still unclear. The aim of the present study was to explore the impact of HCV core protein on hepatocyte metabolism by HepG2 and the possible involvement of long non-coding (lnc) RNAs in this process. The effect of HCV core protein on lncRNAs expression was examined with quantitative RT-PCR (qRT-PCR). Manipulation of HVC core protein and lncRNA HOTAIR was to evaluate the role of interaction between them on cell metabolism-related gene expression and cellular metabolism. The potential downstream Sirt1 signal was examined by western blotting and qRT-PCR. Our data suggested that suppression of HOTAIR abrogates HCV core protein-induced reduction in Sirt1 and differential expression of glucose- and lipid-metabolism-related genes. Also it benefits for metabolic homoeostasis of hepatocyte indicated by restoration of cellular reactive oxygen species (ROS) level and NAD/NADH ratio. By manipulation of HOTAIR, we concluded that HOTAIR negatively regulates Sirt1 expression through affecting its promotor methylation. Moreover, overexpression of Sirt1 reverses pcDNA-HOTAIR-induced glucose- and lipid-metabolism-related gene expression. Our study suggests that HCV core protein causes dysfunction of glucose and lipid metabolism in liver cells through HOTAIR-Sirt1 signalling pathway.
Assuntos
Hepacivirus/fisiologia , Hepatite C/metabolismo , Hepatócitos/virologia , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Proteínas do Core Viral/metabolismo , Metilação de DNA , Regulação da Expressão Gênica , Glucose/metabolismo , Células Hep G2 , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Metabolismo dos Lipídeos , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genéticaRESUMO
This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.
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Medula Óssea/metabolismo , Leucemia/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteína Rica em Cisteína 61/metabolismo , Feminino , Humanos , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34) peptide main chain was 2.509 3, indicating that the differences between the two main chain structural conformation was relatively small; the interaction energy between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by 7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)-(RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co-culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a higher biological activity than PTH (1-34) standard reagents.
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Proteínas Mutantes/genética , Mutação , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Teriparatida/farmacologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Técnicas de Cocultura , Camundongos , Proteínas Mutantes/farmacologia , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoprotegerina/genética , Ligante RANK/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismoRESUMO
The study was aimed to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow (BM) of leukemia patients and investigate the interaction of CYR61, CTGF, VEGF-C, VEGFR-2 proteins in occurrence, development, infiltration and metastasis of leukemia and its clinical significance, to find a new tumor marker for diagnosis and treatment of leukemia with some new directions. 74 patients with leukemia were enrolled in this study, 38 out of them were males and 36 were females, aged from 6 to 77 years old with the median age of 45 years old. In the control group, 7 males and 5 females, aged from 16 to 78 years old with the median age of 46. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA. The results showed that the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in BM of newly diagnosed patients with acute and chronic leukemia of each group were significantly higher as compared with the control group (p < 0.05). The levels of CYR61, CTGF mRNA in acute leukemia remission group were significantly higher than those in control group (p = 0.039, 0.025). The level of CTGF mRNA was highest in B-ALL group, and was higher than that in AML, CML, CLL, T-ALL groups (p = 0.002, 0.034, 0.002, 0.010). In AML group, mRNA expressions of CYR61 and CTGF, CYR61 and VEGF-C, CTGF and VEGFR-2 were positively correlated (r = 0.452, 0.466, 0.464; p = 0.045, 0.038, 0.039), and in CML group mRNA expression of CYR61 and VEGF-C was positively correlated (r = 0.882, p = 0.000). The expression levels of VEGF-C, VEGFR-2 mRNA in acute leukemia patients with extramedullary infiltration were higher than those in acute leukemia patients without extramedullary infiltration (p = 0.028, 0.047). VEGF-C mRNA expression and the original cell counts in AML group were positively correlated (r = 0.418, p = 0.034). It is concluded that CYR61, CTGF, VEGF-C and VEGFR-2 interact each other in the pathogenesis of leukemia, promote the development, metastasis and infiltration of leukemia; and these factors in different types of leukemia and extramedullary infiltration are different, which may become tumor markers of leukemia; and blocking VEGF-C and VEGFR-2 may block tumor growth and metastasis.
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Medula Óssea/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteína Rica em Cisteína 61/metabolismo , Leucemia/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Humanos , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Adulto JovemRESUMO
OBJECTIVE: This article aims to review recent studies on the biological characteristics of long non-coding RNAs (lncRNAs), transcription regulation by lncRNAs, and the results of recent studies on the mechanism of action of lncRNAs in tumor development. DATA SOURCES: The data cited in this review were mainly obtained from the articles listed in PubMed and HighWire that were published from January 2002 to June 2010. The search terms were "long non-coding RNA", "gene regulation", and "tumor". STUDY SELECTION: The mechanism of lncRNAs in gene expression regulation, and tumors concerned with lncRNAs and the role of lncRNAs in oncogenesis. RESULTS: lncRNAs play an important role in transcription regulation by controlling chromatin remodeling, transcriptional control, and post-transcriptional controlling. lncRNAs are involved in many kinds of tumors and play key roles as both suppressing and promoting factors. CONCLUSION: lncRNAs could perfectly regulate the balance of gene expression system and play important roles in oncogenic cellular transformation.
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Transformação Celular Neoplásica/genética , Neoplasias/genética , RNA não Traduzido/genética , Animais , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , HumanosRESUMO
OBJECTIVE: To study the incidence of osteopenia in patients with initial systemic lupus erythematosus (SLE). Investigate the levels of the vitamin D (VitD) endocrine system in peripheral blood of SLE patients and its relation to bone mineral density (BMD). Analyse the relationship between the estrogen receptor (ER) and BMD and evaluate the role of ER in the pathogenesis osteopenia. METHODS: Serum levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) were detected by enzyme linked immunosorbent assay. The gene expression levels of VitD receptor (VDR) and ER were determined by real-time PCR. BMD measurements in the lumbar spine (L1-L4) and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry before treatment. RESULTS: The initial SLE patients had significantly lower BMD values, and higher frequency of bone loss at both sites of measurement compared with normal controls (P < 0.05). The levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) were lower in the initial SLE patients than normal controls (P < 0.01 both). There is no difference in the levels of 25-OH VitD(3) and 1,25-(OH)(2) VitD(3) between the osteopenia SLE group and the normal BMD SLE group (P > 0.05, P > 0.05). There are no correlations between the VitD and BMD in initial SLE patients (P > 0.05 both). The expressions of VDR gene were significantly increased in the initial SLE patients compared with the normal controls (P < 0.01). There was no difference in VDR gene expression between osteopenia SLE group and normal BMD SLE group (P > 0.05). The VDR gene expression does not correlate with the bone mass (P > 0.05). The levels of ER-beta gene expression are higher in the initial SLE group than the normal controls (P < 0.01). CONCLUSIONS: The incipient SLE patients may have lower BMD than expected. SLE patients present abnormal VitD endocrine system and higher ER-beta mRNA expression than those in normal controls, but these weren't concerned with osteopenia.
Assuntos
Densidade Óssea , Colecalciferol/sangue , Receptor beta de Estrogênio/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Adolescente , Adulto , Doenças Ósseas Metabólicas/complicações , Estudos de Casos e Controles , Criança , Receptor beta de Estrogênio/genética , Feminino , Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Receptores de Calcitriol/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To evaluate the impact of HIV co-infection with HCV or HBV on the efficacy of highly active anti-retroviral therapy (HARRT). METHODS: The patients were divided into three groups: HIV + HBV + HCV co-infection group (23 patients), HIV + HCV co-infection group (166 patients), and HIV-only group (178 patients). HIV RNA, HCV RNA or HBV DNA were detected by real time PCR before treatment and 1, 3, 6, 9 and 12 months after treatment, meanwhile the counts of CD(4)(+) T lymphocyte and liver function including ALT, AST and TBil were tested. RESULTS: During one-year HAART, HIV RNA of HIV-only group, HIV + HBV + HCV co-infection group and HIV + HCV co-infection group decreased significantly from (6.78 ± 1.08), (6.23 ± 1.34), (6.54 ± 1.23) lg copies/ml to (0.53 ± 0.15), (0.67 ± 0.16), (0.43 ± 0.11) lg copies/ml respectively (P < 0.001). And CD(4)(+) T lymphocyte counts of the three groups elevated significantly from (197 ± 127), (184 ± 113), (213 ± 143) cells/µl to (382 ± 74), (383 ± 70), (378 ± 76) cells/µl respectively (P < 0.001). However there were no differences among the three groups in HIV RNA and CD(4)(+) T lymphocyte counts. There were no differences in liver functions including ALT, AST and TBil among the three groups. CONCLUSIONS: HIV co-infected with HBV and/or HCV does not impact on the efficacy of HAART. What more, HAART does not impact HCV replication.
Assuntos
Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite B/tratamento farmacológico , Hepatite C/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Coinfecção/virologia , HIV , Hepacivirus , Vírus da Hepatite B , Humanos , Resultado do TratamentoRESUMO
The objective of this study was to investigate the effect of cyclooxygenase-2 (COX-2) in the angiogenesis of bone marrow in leukemia patients. 51 patients with newly diagnosed acute leukemia were taken as study objects, 18 healthy volunteers were enrolled in the control group. Bone marrow microvessel density (MVD) in bone marrow biopsy tissue section was determined with immunohistochemistry method, the vascular endothelial growth factor level in serum was detected with ELISA method and the expression of cyclooxygenase-2 in bone marrow cells was assayed by flow cytometry. The results showed that the MVD, VEGF level, positive rate of COX-2 expression in leukemia group all obviously increased as compared with the control group (p < 0.05). The correlative coefficients of MVD, VEGF level and COX-2 expression rate were 0.614, 0.423 and 0.577 respectively (p < 0.05). In conclusion, as well as solid tumors, leukemia may be also a angiogenesis-dependent malignant tumor. Coordination of COX-2 with VEGF may promote angiogenesis in bone marrow.
Assuntos
Células da Medula Óssea/metabolismo , Ciclo-Oxigenase 2/metabolismo , Leucemia/metabolismo , Adolescente , Adulto , Idoso , Células da Medula Óssea/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression-profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3-Di-O-galloyl-4,6-(s)-HHDP-b-D-glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG(2) cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG(2) cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG(2) cells. Our results suggested that BJA3121-modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG(2) cancer cells.
Assuntos
Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica , Taninos Hidrolisáveis/farmacologia , MicroRNAs/metabolismo , Fenóis/farmacologia , Balanophoraceae/química , Linhagem Celular Tumoral , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Estrutura Molecular , Análise de Sequência com Séries de Oligonucleotídeos , PolifenóisRESUMO
OBJECTIVE: To isolate and purify a new phospholipase A2 (PLA2) homologue from Agkistrodon blomhoffii siniticus and investigate its effects on the gene expression profile of Hep3B cells. METHODS: The PLA2 homologue was isolated and purified by reverse-phase high-performance liquid chromatography (HPLC) and its purity was determined also by HPLC. The relative molecular mass of the homologue was measured by electrospray ionization mass spectrum. The gene expression profile of Hep3B cells was detected with gene chip after exposure of the cells to 139 microg/ml PLA2 homologue for 12 h. RESULTS: The purity of the PLA2 homologue was 97.2%, whose relative molecular mass was 13,900. After exposure of Hep3B cells to 139 microg/ml PLA2 homologue for 12 h, 19 genes were down-regulated and 20 up-regulated in the cells. The genes showing altered expressions in response to the exposure were mainly involved in cell cycle control and DNA damage repair, cell apoptosis and senescence, production of signal transduction molecules and transcription factors, cell adhesion, angiogenesis, and tumor invasion and metastasis. CONCLUSIONS: The PLA2 homologue induces alterations in the expression of a wide variety of genes involved in the growth and metastasis of tumor cells. The results of this study provide clues for further study of the possible mechanism for the action of PLA2 homologue on Hep3B cells.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/genética , Fosfolipases A/farmacologia , Venenos de Serpentes/enzimologia , Agkistrodon , Animais , Carcinoma Hepatocelular/genética , Cromatografia Líquida de Alta Pressão , Dano ao DNA/efeitos dos fármacos , Perfilação da Expressão Gênica , Receptores de Hialuronatos/biossíntese , Receptores de Hialuronatos/genética , Isoenzimas , Fosfolipases A/isolamento & purificação , Fosfolipases A2 , Proteínas Proto-Oncogênicas c-bcr/biossíntese , Proteínas Proto-Oncogênicas c-bcr/genética , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the inhibitory effect of the small peptide SV-PP-3 from the venom of Agkistrodon blomhoffii siniticus on platelet aggregation. METHODS: The small peptide SV-PP-3 was isolated and purified by centrifugation at low temperature, sephadex G-75 column chromatography and reverse-phase (HPLC) on C-18 column. The platelet aggregation induced by adenosine diphosphate (ADP) was measured by LBY-NJ aggregometer. RESULTS: SV-PP-3 was purified from the venom of Agkistrodon blomhoffii siniticus, which inhibited the platelet ADP-induced platelet aggregation in a dose-dependent manner. CONCLUSION: SV-PP-3 can inhibit ADP-Induced platelet aggregation.