RESUMO
Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.
Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas/terapia , Vacinas Bacterianas , Antígeno Carcinoembrionário , Ensaios Clínicos como Assunto , Vírus da Varíola das Aves Domésticas , Gastrinas , Genes ras/genética , Proteínas de Choque Térmico , Proteínas Inibidoras de Apoptose , Cinesinas , Listeria monocytogenes , Mucina-1 , Mutação , Peptídeos , Survivina , Telomerase , Vacinas Atenuadas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Vacinas Virais , Proteínas WT1RESUMO
E4orf6 plays an important role in the transportation of cellular and viral mRNAs and is known as an oncogene product of adenovirus. Here, we show that E4orf6 interacts with pp32/leucine-rich acidic nuclear protein (LANP). E4orf6 exports pp32/LANP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos, c-myc, and cyclooxygenase-2, were also exported to and stabilized in the cytoplasm of E4orf6-expressing cells. The oncodomain of E4orf6 was necessary for both binding to pp32/LANP and effect for ARE-mRNA. C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and HuR proteins. Moreover, inhibition of the CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LANP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway.
Assuntos
Adenoviridae/metabolismo , Proteínas E4 de Adenovirus/metabolismo , Carioferinas/metabolismo , Neuropeptídeos/metabolismo , Proteínas Nucleares/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Adenoviridae/genética , Proteínas E1B de Adenovirus/genética , Proteínas E1B de Adenovirus/metabolismo , Proteínas E4 de Adenovirus/genética , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Proteínas ELAV , Proteína Semelhante a ELAV 1 , Humanos , Carioferinas/genética , Neuropeptídeos/genética , Proteínas Nucleares/genética , Fases de Leitura Aberta/genética , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína/fisiologia , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Proteína Exportina 1RESUMO
Group B rotaviruses detected in Bangladesh in 2000 and 2001 were analyzed genetically to clarify relatedness to human group B rotaviruses reported previously in China and India, and to animal group B rotaviruses. VP7 gene sequences of the Bangladeshi group B rotaviruses (Bang373, Bang544, Bang334, and Bang402) were almost identical to each other and also showed high sequence identity to the Indian strain CAL-1 (98%) and Chinese strain adult diarrhea rotavirus (ADRV) (92%), while identities to bovine and murine viruses were considerably low (60-63%). Other genes of Bang373 and Bang544 encoding VP2, VP4, VP6, and NSP1 through NSP5 also showed much higher sequence identities to those of CAL-1 (97.7-99.4%) than to those of ADRV (89.9-93.9%). Characterization of nucleotide substitutions among Bang373, CAL-1, and ADRV suggested that all the gene segments might have evolved neutrally at similar mutation rates, while some of the gene segments (e.g., VP2 gene) were suggested to be more conserved than others. In conclusion, group B rotaviruses detected in Bangladesh represented by Bang373 and the Indian virus CAL-1 were considered as virtually identical viruses which are distinct genetically from ADRV, and it was suggested that Bang373 (CAL-1)-like group B rotavirus (Bengali strains) might be distributed primarily in an area around the Bay of Bengal.