| 1. |
- Dujon, B, et al.
(författare)
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The nucleotide sequence of Saccharomyces cerevisiae chromosome XV
- 1997
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 387:6632, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.
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| 2. |
- Löwenberg, Bob, et al.
(författare)
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Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML : the HOVON-SAKK-132 trial
- 2021
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:4, s. 1110-1121
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Tidskriftsartikel (refereegranskat)abstract
- Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% +/- 2% standard error and overall survival, 54% = 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
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| 3. |
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| 4. |
- Zimmermannova, Olga, et al.
(författare)
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Restoring tumor immunogenicity with dendritic cell reprogramming
- 2023
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Ingår i: Science Immunology. - 2470-9468. ; 8:85
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Tidskriftsartikel (refereegranskat)abstract
- Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8 + T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8 + T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.
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