RESUMO
Mouse models of cancer play an important role in elucidating the molecular mechanisms that contribute to tumorigenesis. The extent to which these models resemble one another and their human counterparts at the molecular level is critical in understanding tumorigenesis. In this study, we carried out a comparative gene expression analysis to generate a detailed molecular portrait of a transgenic mouse model of IGFIR-driven lung cancer. IGFIR-driven tumors displayed a strong resemblance with established mouse models of lung adenocarcinoma, particularly EGFR-driven models highlighted by elevated levels of the EGFR ligands Ereg and Areg. Cross-species analysis revealed a shared increase in human lung adenocarcinoma markers including Nkx2.1 and Napsa as well as alterations in a subset of genes with oncogenic and tumor suppressive properties such as Aurka, Ret, Klf4 and Lats2. Integrated miRNA and mRNA analysis in IGFIR-driven tumors identified interaction pairs with roles in ErbB signaling while cross-species analysis revealed coordinated expression of a subset of conserved miRNAs and their targets including miR-21-5p (Reck, Timp3 and Tgfbr3). Overall, these findings support the use of SPC-IGFIR mice as a model of human lung adenocarcinoma and provide a comprehensive knowledge base to dissect the molecular pathogenesis of tumor initiation and progression.
Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Mensageiro/genética , Receptores de Somatomedina/genética , Animais , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Transgênicos , Anotação de Sequência Molecular , Receptores de Somatomedina/metabolismo , Especificidade da Espécie , TranscriptomaRESUMO
Bacillus anthracis, the causative agent of anthrax, relies on multiple virulence factors to subvert the host immune defense. Using Caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants of B. anthracis Sterne for decreased virulence. One of the attenuated mutants resulted in loss of expression of yceG and yceH, the last two genes in a six-gene cluster of tellurite resistance genes. We generated an analogous insertional mutant to confirm the phenotype and characterize the role of yceGH in resistance to host defenses. Loss of yceGH rendered the mutants more sensitive to tellurite toxicity as well as to host defenses such as reactive oxygen species and the cathelicidin family of antimicrobial peptides. Additionally, we see decreased survival in mammalian models of infection, including human whole blood and in mice. We identify a novel role for the yceGH genes in B. anthracis Sterne virulence and suggest that C. elegans is a useful infection model to study anthrax pathogenesis.
Assuntos
Antraz/imunologia , Bacillus anthracis/genética , Bacillus anthracis/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Telúrio/imunologia , Animais , Antraz/microbiologia , Caenorhabditis elegans/imunologia , Caenorhabditis elegans/microbiologia , Imunidade Inata/genética , Imunidade Inata/imunologia , Mutação/genética , Mutação/imunologia , Virulência/genética , Virulência/imunologia , Fatores de Virulência/genética , Fatores de Virulência/imunologiaRESUMO
The ultrasonographic image of an organ is a product of scattering and reflection of high-frequency ultrasound beams by discrete units of tissue. The number of acoustic tissue interfaces and vascularity affects the quantitative characteristics of grey-scale ultrasonographic images. This study was undertaken to examine the influences of scrotal/testicular integument and blood flow on testicular echotexture parameters in the ram. Serial ultrasonographic images were obtained during surgical castration of 7 Rideau Arcott rams aged 20-22 weeks. The first 2 sets of images were taken through the scrotum, prior to and after induction of anaesthesia. The third set was taken through the tunica vaginalis, the fourth set was obtained through the tunica albuginea, the fifth set was taken when the testicular cord and internal blood vessels were clamped, and the final set of images was recorded after allowing the blood to drain from dissected testicles (5 min). All images were then subjected to computerized image analyses and the testicles were processed for histology. The removal of the scrotal skin and tunica vaginalis both resulted in significant (P < 0.05) increments in numerical pixel values (NPVs) and pixel heterogeneity (standard deviation of pixel values) of the testicular parenchyma. There were no differences (P > 0.05) in testicular echotexture between images taken just before or after clamping the testicular cord vessels, or after draining. At all stages, NPVs were correlated (P