RESUMO
Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.
Assuntos
Metilação de DNA , Perfilação da Expressão Gênica , Inativação Gênica/fisiologia , Centro Germinativo/patologia , Linfoma de Células B/patologia , Receptor EphA7/antagonistas & inibidores , Receptor EphA7/genética , Animais , Linhagem Celular , Proliferação de Células , Centro Germinativo/metabolismo , Humanos , Linfoma de Células B/metabolismo , Camundongos , Camundongos Transgênicos , Metástase Neoplásica , Transplante de Neoplasias , Proto-Oncogene Mas , Receptor EphA7/biossíntese , Receptor EphA7/metabolismoRESUMO
Aberrant nuclear factor (NF)-κB activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-κB pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-κB regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in 15% of human epithelial cancers. Suppression of TRAF2 in cancer cells harboring TRAF2 copy number gain inhibits proliferation, NF-κB activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-κB for survival. The phosphorylation of TRAF2 at serine 11 is essential for the survival of cancer cells harboring TRAF2 amplification. Together, these observations identify TRAF2 as a frequently amplified oncogene.
Assuntos
NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fator 2 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/metabolismo , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Xenoenxertos , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Fosforilação , Transdução de SinaisRESUMO
76 cases of counterattack induced by acute organic phosphorus pesticides intoxication were analysed. The activity of cholinesterase did not show a significant difference before the counterattack as compared to that after the counterattack (P > 0.05). The average dosage of atropine for pre-atropinization was 58.6 +/- 2.7 mg/h and it was 203.9 +/- 17.7 mg/h between the post-counterattack and the second atropinization (P < 0.01). Compared the mortality in reaching and non-reaching the second atropinization was 22.8% VS 100% (P < 0.01). The survival rate was 37.5% in collaborating blood transfusion cases and 20.6% in noncollaborating ones (P > 0.05). We also studied on the treatment, mechanism, precursory symptoms, causes of death, degrees of intoxication and pesticide types etc.
Assuntos
Atropina/uso terapêutico , Inseticidas/intoxicação , Compostos Organofosforados , Adolescente , Adulto , Colinesterases/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação/diagnóstico , Intoxicação/tratamento farmacológico , Intoxicação/mortalidade , Recidiva , Taxa de SobrevidaRESUMO
The IκB Kinase (IKK)-related kinases TBK1 and IKKÉ have essential roles as regulators of innate immunity by modulating interferon and NF-κB signaling. Recent work has also implicated these non-canonical IKKs in malignant transformation. IKKÉ is amplified in â¼30% of breast cancers and transforms cells through the activation of NF-κB. TBK1 participates in RalB-mediated inflammatory responses and cell survival, and is essential for the survival of non-small cell lung cancers driven by oncogenic KRAS. The delineation of target substrates and downstream activities for TBK1 and IKKÉ has begun to define their role(s) in promoting tumorigenesis. In this review, we will highlight the mechanisms by which IKKÉ and TBK1 orchestrate pathways involved in inflammation and cancer.
Assuntos
Adenocarcinoma/enzimologia , Neoplasias da Mama/enzimologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Quinase I-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Adenocarcinoma/imunologia , Apoptose/imunologia , Neoplasias da Mama/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Transformação Celular Neoplásica/metabolismo , Feminino , Humanos , Quinase I-kappa B/imunologia , Imunidade Inata , Inflamação/enzimologia , Inflamação/imunologia , Interferons/imunologia , NF-kappa B/imunologia , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais/imunologia , Proteínas ras/imunologia , Proteínas ras/metabolismoRESUMO
The purpose of studying the relationship between degree of gastric filling and vomiting during chemotherapy is to reduce the occurrence of vomiting. 42 patients were selected to give intravenous chemotherapy at 3-4 h after a small simple breakfast. The result showed that there was a relationship between the degree of gastric filling and vomiting during chemotherapy.