Search

Background information. Interferons are a family of cytokines with growth inhibitory and antiviral functions, which exert their biological actions through the expression of interferon-stimulated genes (ISGs). The human ISG12 family of proteins comprises ISG12A, ISG12B, ISG12C and ISG6-16. Due to differential splicing and a gene variation, the human ISG12A protein exists as a full-length ISG12A form and three ISG12A variants. ISG12 genes have been found transcriptionally dysregulated in many disorders. High levels of ISG12A mRNA have been found in breast and ovarian cancers. Loss of heterozygosity at the position of the ISG12 genes often occurs in ovarian carcinomas and lymphoblastic leukemias. Both ISG12A and ISG6-16 are up-regulated in psoriasis. Results. We demonstrate here that expression of the human full-length ISG12A protein sensitises cells for TNFa and the BH3 mimetic gossypol induced apoptosis, and the other ISG12A variants as well as ISG12B and ISG12C can induce apoptosis directly in HEK293 cells. Also ISG6-16 sensitises HEK293 cells for gossypol-induced apoptosis. In the ISG12 motif, two putative Bcl-2 homology (BH)3 like motifs were found, which may be decisive for the apoptotic properties of the ISG12 proteins. A series of BH3mutantswas made in ISG12AΔ-S, the smallest apoptosis-inducing ISG12A variant and our results indicate that ISG12AΔ-S indeed possesses features resembling those of BH3-only proteins. Supporting this notion are our findings that the full-length ISG12A co-immunoprecipitates with the Bcl-2 protein, and the apoptotic properties of the ISG12A variants are reduced in Bcl-2 expressing HEK293 cells. In addition, full-length ISG12A is able to form homodimers, which suggests a possible involvement in pore formation during apoptosis. The full-length ISG12A, the three ISG12A variants and the ISG12B proteins were found to be localised in the mitochondria. Conclusions. Our results suggest that the ISG12 family of proteins has an important role for the apoptotic properties induced by type 1 interferon. Significance. The ISG12 family constitute small hydrophic proteins involved in apoptosis. This is the first comparison of the apoptotic potentials of the full-length ISG12A protein and the three ISG12A variants. The differential apoptotic potentials of these proteins might have an impact on the strategies to monitor and interpret their dysregulation associated with many disorders. [ABSTRACT FROM AUTHOR]

To explore the extent of evidence-based data and cost-utility of follow-up after primary treatment of endometrial and ovarian cancer, addressing perspectives of technology, organization, economics, and patients.Systematic literature searches according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions were conducted separately for each of the 4 perspectives. In addition, the organizational analysis included a nationwide questionnaire survey among all relevant hospital departments, and the operating costs were calculated.None of the identified studies supported a survival benefit from hospital-based follow-up after completion of primary treatment of endometrial or ovarian cancer. The methods for follow-up were of low technology (gynecologic examination with or without ultrasound examination). Other technologies had poor sensitivity and specificity in detecting recurrence. Small changes in applied technologies and organization lead to substantial changes in costs. Substantial differences especially in frequency and applied methods were found between departments. The literature review did not find evidence that follow-up affects the women's quality of life.The main purpose of follow-up after treatment of cancer is improved survival. Our review of the literature showed no evidence of a positive effect on survival in women followed up after primary treatment of endometrial or ovarian cancer. The conception of follow-up among physicians, patients, and their relatives therefore needs revision. Follow-up after treatment should have a clearly defined and evidence-based purpose. Based on the existing literature, this purpose should presently focus on other end points rather than early detection of relapse and improved survival. These end points could be quality of life, treatment toxicity, and economy. [ABSTRACT FROM AUTHOR]