RESUMO
BACKGROUND: Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis owing to its resistance to radiation and chemotherapy. Thus, novel therapeutic strategies for SS are urgently required. Anlotinib, a new oral tyrosine kinase inhibitor, is designed to primarily inhibit multi-targets in vasculogenesis and angiogenesis. This study was designed to characterize its antitumor efficacy and possible mechanism in patients with advanced refractory synovial sarcoma. METHODS: Anlotinib's antitumor effect was evaluated in vivo and vitro. Downstream targets of anlotinib in treating synovial sarcoma were analyzed through microarray assay. Cell proliferation and apoptosis analyses were performed to evaluate the impact of candidate downstream gene depletion in synovial sarcoma cells. Microarray assay were carried out to investigate potential signal network related with candidate downstream gene. RESULTS: Anlotinib significantly suppresses synovial sarcoma proliferation in PDTX model and cell lines. Additionally, GINS1 (also named as PSF1, Partner of SLD Five 1), rather than other conventional gene target, was demonstrated to be a vital target of anlotinib's antitumor effect in synovial sarcoma through microarray assay. Expression of GINS1 was remarkably higher in synovial sarcoma tumor samples and related with poor outcome. Knockdown of GINS1 expression could remarkably inhibit proliferation and promote apoptosis in vitro. Meanwhile, through microarray assay, CITED2, EGR1, SGK1 and SPP1 were identified and further validated by qPCR/WB as downstream targets of GINS1. CONCLUSION: Anlotinib might suppress proliferation of SS through a novel downstream GINS1-regulated network which plays a vital function in SS proliferation and also demonstrated that targeting the GINS1-regulated signal pathway could be a potential strategy for management of SS.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Proteínas de Ligação a DNA/efeitos dos fármacos , Indóis/uso terapêutico , Proteínas de Neoplasias/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Sarcoma Sinovial/tratamento farmacológico , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/genética , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Proteína 1 de Resposta de Crescimento Precoce/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Proteínas Imediatamente Precoces/efeitos dos fármacos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Osteopontina/efeitos dos fármacos , Osteopontina/genética , Osteopontina/metabolismo , Análise Serial de Proteínas , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/análise , Proteínas Repressoras/efeitos dos fármacos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sarcoma Sinovial/genética , Transativadores/efeitos dos fármacos , Transativadores/genética , Transativadores/metabolismoRESUMO
The aim of this study was to evaluate the radiosensitizing effects of gemcitabine towards human pancreatic cancer xenografts. A human pancreatic cancer xenograft model was established in nude mice, 36 of which were randomly divided into 6 treatment groups. Tumors were measured every 2 days, and the tumor volumes, growth delays, and inhibition rates were compared to evaluate the gemcitabine enhancement factor. The apoptotic index was determined by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay, and apoptosis inhibitory protein Bcl-2 and apoptosis-related protein Bax expression were detected by immunohistochemistry. Compared with the control group, xenograft growth was significantly inhibited in the 25 (G25) and 50 mg/kg gemcitabine (G50) groups (P < 0.05). In the 25 (G25R) and 50 (G50R) mg/kg gemcitabine + radiotherapy groups, local tumor growth was significantly inhibited, with inhibition rates of 88.22 and 91.23%, respectively, significantly higher than those of the simple radiotherapy (SR), G25, and G50 groups (44.11, 72.88, and 77.53%, respectively; P < 0.05). The tumor growth delay in the G25R and G50R groups were 9 and 15 days, respectively, higher than the SR, G25, and G50 groups (each 4 days, P < 0.05). The apoptosis of tumor cells in the intervention groups significantly increased, and the apoptotic index among the intervention groups exhibited significant differences (P < 0.05). The immunohistochemical results indicated that Bcl-2 was downregulated to different degrees in the intervention groups, whereas Bax was upregulated (P < 0.05). Therefore, gemcitabine appears to enhance the radiotherapeutic sensitivity of human pancreatic cancer xenografts significantly.
Assuntos
Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Animais , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/radioterapia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , GencitabinaRESUMO
To determine the risk factors associated with adverse aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with Stanford type B aortic dissection, we performed a retrospective analysis of 54 patients between January 2009 and June 2012 at the First Affiliated Hospital of Soochow University. All patients underwent TEVAR of the descending thoracic aorta. Multiple-logistic regression analyses were performed to identify risk factors associated with aortic remodeling. True-lumen and false-lumen volumes were increased (P < 0.001) and decreased (P < 0.001) after surgery, respectively. Therefore, the remodeling index increased after surgery (1.04 ± 0.6 to 2.06 ± 1.12, P < 0.001). Remodeling index and true-lumen volume were higher in the favorable aortic remodeling group compared to the adverse aortic remodeling group (P < 0.001), while the false-lumen volume was lower in the favorable aortic remodeling group (P < 0.001). Multivariate analyses revealed a branch originating from the false lumen (OR = 39.9, P < 0.01) and multiple tears (OR = 27.4, P < 0.01) to be independent risk factors for adverse aortic remodeling. Therefore, a branch originating from the false lumen and multiple tears were determined to be independent risk factors for adverse aortic remodeling after TEVAR in patients with Stanford type B aortic dissection.
Assuntos
Aneurisma da Aorta Torácica/patologia , Dissecção Aórtica/patologia , Procedimentos Endovasculares/métodos , Remodelação Vascular , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is one of the most life-threatening malignancies worldwide. Defects in DNA repair genes may increase the risk of HCC. X-ray cross-complementing group 1 gene (XRCC1) is a major DNA repair gene involved in base excision re-pair. Recently, several studies have indicated that an association exists between XRCC1 polymorphism and HCC, particularly the Arg280His polymorphism. However, the data is inconsistent and incomplete. In this study, we conducted a meta-analysis to investigate the association between the XRCC1 Arg280His polymorphism and HCC risk. A total of 10 case-control studies included 1848 HCC cases and 1969 controls were examined in this analysis. Our results suggest that variant geno-types of the XRCC1 Arg280His gene are associated with a significantly increased risk of HCC in homozygote comparison (HisHis vs ArgArg, odds ratio, 1.55, 95% confidence interval, 1.10-2.18, P = 0.013); no het-erogeneity was observed (I2 = 0%). Our analysis suggests that the XRCC1 Arg280His polymorphism is associated with a higher risk of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Expressão Gênica , Homozigoto , Humanos , Neoplasias Hepáticas/patologia , Modelos Genéticos , Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
The fruit peach originated in China and has a history of domestication of more than 4000 years. Numerous local cultivars were selected during the long course of cultivation, and a great morphological diversity exists. To study the diversity and genetic background of local peach cultivars in China, a set of 158 accessions from different ecological regions, together with 27 modern varieties and 10 wild accessions, were evaluated using 49 simple sequence repeats (SSRs) covering the peach genome. Broad diversity was also observed in local cultivars at the SSR level. A total of 648 alleles were amplified with an average of 13.22 observed alleles per locus. The number of genotypes detected ranged from 9 (UDP96015) to 58 (BPPCT008) with an average of 27.00 genotypes per marker. Eight subpopulations divided by STRUCTURE basically coincided with the dendrogram of genetic relationships and could be explained by the traditional groups. The 8 subpopulations were juicy honey peach, southwestern peach I, wild peach, Buddha peach + southwestern peach II, northern peach, southern crisp peach, ornamental peach, and Prunus davidiana + P. kansuensis. Most modern varieties carried the genetic backgrounds of juicy honey peach and southwestern peach I, while others carried diverse genetic backgrounds, indicating that local cultivars were partly used in modern breeding programs. Based on the traditional evolution pathway, a modified pathway for the development of local peach cultivars in China was proposed using the genetic background of subpopulations that were identified by SSRs. Current status and prospects of utilization of Chinese local peach cultivars were also discussed according to the SSR information.
Assuntos
Evolução Biológica , Variação Genética , Repetições de Microssatélites/genética , Prunus persica/genética , Alelos , China , Ecótipo , Genética Populacional , Geografia , Heterozigoto , Linhagem , FilogeniaRESUMO
In this study, 33 homeodomain-leucine zipper (HD-ZIP) genes were identified in peach using the HD-ZIP amino acid sequences of Arabidopsis thaliana as a probe. Based on the phylogenetic analysis and the individual gene or protein characteristics, the HD-ZIP gene family in peach can be classified into 4 subfamilies, HD-ZIP I, II, III, and IV, containing 14, 7, 4, and 8 members, respectively. The most closely related peach HD-ZIP members within the same subfamilies shared very similar gene structure in terms of either intron/exon numbers or lengths. Almost all members of the same subfamily shared common motif compositions, thereby implying that the HD-ZIP proteins within the same subfamily may have functional similarity. The 33 peach HD-ZIP genes were distributed across scaffolds 1 to 7. Although the primary structure varied among HD-ZIP family proteins, their tertiary structures were similar. The results from this study will be useful in selecting candidate genes from specific subfamilies for functional analysis.
Assuntos
Genoma de Planta , Proteínas de Homeodomínio/genética , Zíper de Leucina/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica/genética , Filogenia , Prunus , Fatores de TranscriçãoRESUMO
OBJECTIVE: The aim of this study was to determine the correlation between human adrenocortical carcinoma and the proteins involved in tumor angiogenesis, and to evaluate the angiogenic status of adrenocortical carcinoma. METHODS: The expression of signal transducer and activator of transcription 3 and insulin-like growth factor 2 as well as microvessel density was measured in a series of tissue samples from 44 human sporadic adrenocortical tumors by immunohistochemistry. These specimens were classified as adenomas (n = 20) and carcinomas (n = 24) according to the histological criteria defined by Weiss. RESULTS: A total of 19 of 24 (79.17 %) malignant cases showed positive staining for signal transducer and activator of transcription 3 and 4 of 20 (20.00 %) benign cases showed positive, the difference of signal transducer and activator of transcription 3 expression between adrenocortical adenomas and adrenocortical carcinomas was statistically significant (P < 0.001). Similarly, insulin-like growth factor 2 staining was seen in 70.83 % (17/24) of the malignant cases versus 25.00 % (5/20) of the benign, the difference of insulin-like growth factor 2 expression among two groups was statistically significant (P = 0.002). Malignant cases showed higher microvessel density compared to benign tumors (84.70 ± 12.44 vs 21.05 ± 8.07, P < 0.001). Signal transducer and activator of transcription 3 and insulin-like growth factor 2 expression were positively correlated with microvessel density in all specimens (r_s = 0.832, P < 0.001; r_s = 0.703, P = 0.001). CONCLUSIONS: This study has confirmed that adrenocortical carcinoma overexpress signal transducer and activator of transcription 3 and insulin-like growth factor 2; these results suggest that angiogenesis of human adrenocortical carcinoma may be mediated by these proteins and they could represent selective targets for the molecularly targeted treatments of adrenocortical carcinoma.
Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Fator de Crescimento Insulin-Like II/biossíntese , Neovascularização Patológica/patologia , Fator de Transcrição STAT3/biossíntese , Neoplasias do Córtex Suprarrenal/irrigação sanguínea , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/irrigação sanguínea , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/irrigação sanguínea , Carcinoma Adrenocortical/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Estudos RetrospectivosAssuntos
Linfoma Anaplásico de Células Grandes/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Neoplasias Retroperitoneais/patologia , Biópsia , Diagnóstico Diferencial , Humanos , Masculino , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/secundário , Pancreatite/fisiopatologia , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/secundário , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
DNA markers have useful applications in cultivar identification. A novel analysis approach called cultivar identification diagram (CID) was developed using DNA markers in the separation of plant individuals. This new strategy is less time- and cost-consuming, has reliable results, and was constructed for fingerprinting. Ten 11-mer primers were used to amplify the genotypes; all 95 peach genotypes (from the National Peach Germplasm Repository, in Nanjing, China) were distinguished by a combination of 54 primers. The utilization of the CID among these 95 peach cultivars was also verified by the identification of three randomly chosen groups of cultivars. This identification showed some advantages including the use of fewer primers and easy separation of all cultivars by the corresponding primers marked in the right position on the CID. This peach CID could provide the information to separate any peach cultivars of these 95, which may be of help to the peach industry in China and for the utilization of DNA markers to identify other plant species.
Assuntos
DNA de Plantas/genética , Marcadores Genéticos , Prunus/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Sequência de Bases , Primers do DNARESUMO
BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause of cancer mortality in Chilean women. Incidence rates for this tumor vary widely on a worldwide basis, being approximately 30 times higher in high-risk than in low-risk populations, suggesting that environmental factors such as infectious microorganisms, carcinogens, and nutrition play a role in its pathogenesis. Because several Helicobacter sp. colonize the livers of animals and induce hepatitis, the aim of this study was to determine whether Helicobacter infection was associated with cholecystitis in humans. METHODS: Bile or resected gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA primers. RESULTS: Recovery of Helicobacter sp. from frozen specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter-specific PCR amplicons were sequenced and subjected to phylogenetic analysis. Five sequences represented strains of H. bilis, two strains of "Flexispira rappini" (ATCC 49317), and one strain of H. pullorum. CONCLUSIONS: These data support an association of bile-resistant Helicobacter sp. with gallbladder disease. Further studies are needed to ascertain whether similar Helicobacter sp. play a causative role in the development of gallbladder cancer.