| 1. |
- Andersson, Anna, et al.
(författare)
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The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 192-330
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Tidskriftsartikel (refereegranskat)abstract
- Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
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| 2. |
- Bai, Ru, et al.
(författare)
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The NF-κB modulated miR-194-5p/IGF1R/PPFIBP axis is crucial for the tumorigenesis of ovarian cancer
- 2020
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Ingår i: Journal of Cancer. - : Ivyspring International Publisher. - 1837-9664. ; 11:12, s. 3433-3445
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Tidskriftsartikel (refereegranskat)abstract
- miRNAs are involved in the tumorigenesis of various malignancies. In the current study, we found that miR-194-5p expression is downregulated in ovarian cancer tissues, and downregulation of miR-194-5p expression promotes proliferation, invasion and migration of human ovarian cancer cells in vitro and ovarian tumor growth in nude mice. We further found that IGF1R and PPFIBP are targets of miR-194-5p, and downregulation of miR-194-5p expression increases IGF1R and PPFIBP expression, resulting in increased proliferation, invasion and migration of ovarian cancer cells. Moreover, we showed that NF-κB can bind to the promoter region of miR-194-5p, and negatively regulate the expression of miR-194-5p in ovarian cancer cells. Taken together, our results suggested a NF-κB modulated miR-194-5p/IGF1R/ PPFIBP axis that is crucial for the tumorigenesis of ovarian cancer, which provides a new insight into the development of ovarian cancer.
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| 3. |
- Bai, Ru, et al.
(författare)
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The NF-κB-modulated miR-19a-3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP-3 expression
- 2019
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Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987 .- 1098-2744. ; 58:12, s. 2254-2265
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR-19a-3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor-kappaB (NF-κB) binds to the promoter of miR-19a-3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR-19a-3p inhibits the expression of insulin-like growth factor binding protein-3 (IGFBP-3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR-19a-3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP-3 expression, and which can be inhibited by NF-κB, suggesting an NF-κB/miR-19a-3p/IGFBP-3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.
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| 4. |
- Bidleman, Terry, et al.
(författare)
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Chapter 2: Properties, sources, global fate and transport
- 2013
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Ingår i: Canadian Arctic Contaminants Assessment Report III 2013. - Ottawa : Northern Contaminants Program, Aboriginal Affairs and Northern Development Canada. - 9781100546520 ; , s. 19-146
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Bokkapitel (refereegranskat)abstract
- Part II of the second Canadian Arctic Contaminants Assessment Report (CACAR-II) began with a section on “Physicochemical Properties of Persistent Organic Pollutants”, which identified key physicochemical (pchem) properties, provided the rationale for their measurement or prediction and tabulated literature citations for chemicals that are of concern to the NCP (Bidleman et al. 2003). The section also discussed temperature dependence of pchem properties and their applications to describing partitioning in the physical environment.There is, and will continue to be, emphasis on predictive approaches to screening chemicals for persistence, bioaccumulation and toxic (PB&T)properties, as well as long-range atmospheric transport (LRAT) potential (Brown and Wania 2008, Czub et al. 2008, Fenner et al. 2005, Gouin andWania 2007, Howard and Muir 2010, Klasmeier et al. 2006, Matthies et al. 2009, Muir and Howard 2006). This has created the need for determining pchem properties of new and emerging chemicals of concern.Predicting gas exchange cycles of legacy persistent organic pollutants (POPs) and new and emerging chemicals of concern places a high demand on the accuracy of pchem properties, particularly the air/water partition coefficient, KAW. Hexachlorocyclohexanes (HCHs) in Arctic Ocean surface waters are close to air-water equilibrium, with excursions toward net volatilization or deposition that vary with location and season (Hargrave et al. 1993, Jantunen et al. 2008a, Lohmann et al. 2009, Su et al. 2006, Wong et al. 2011) while hexachlorobenzene (HCB) (Lohmann et al. 2009, Su et al. 2006, Wong et al. 2011) and some current use pesticides (CUPs) (Wong et al. 2011) are undergoing net deposition. The predicted Arctic Contamination Potential (ACP) for persistent organic chemicals is strongly influenced by ice cover due to its effect on air-water gas exchange (Meyer and Wania 2007).Many advances have taken place and numerous papers have been published since CACAR-II, which present new measurements and predictions of pchem properties. This section does not attempt to provide a comprehensive review of the field, or to compile pchem properties from the many studies. The approach taken is to highlight the reports which are most relevant to polar science, particularly in areas of improving reliability of pchem properties for POPs, improving experimental techniques and comparing predictive methods. The section ends with a discussion of polyparameter linear free energy relationships (pp-LFERs), which goes beyond partitioning descriptions based on single pchem properties by taking into account specific chemical interactions that can take place in airsurface and water-surface exchange processes. A detailed list of chemical names and nomenclature are provided in the Glossary.
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| 5. |
- Bidleman, Terry Frank, et al.
(författare)
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Chiral Chemicals as Tracers of Atmospheric Sources and Fate Processes in a World of Changing Climate
- 2013
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Ingår i: Mass Spectrometry. - 2186-5116. ; 2:19, Special Issue: Proceedings of 19th International Mass Spectrometry Conference, s. S0019-
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Tidskriftsartikel (refereegranskat)abstract
- Elimination of persistent organic pollutants (POPs) under national and international regulations reduces “primary” emissions, but “secondary” emissions continue from residues deposited in soil, water, ice and vegetation during former years of usage. In a future, secondary source controlled world, POPs will follow the carbon cycle and biogeochemical processes will determine their transport, accumulation and fate. Climate change is likely to affect mobilisation of POPs through e.g., increased temperature, altered precipitation and wind patterns, flooding, loss of ice cover in polar regions, melting glaciers, and changes in soil and water microbiology which affect degradation and transformation. Chiral compounds offer advantages for following transport and fate pathways because of their ability to distinguish racemic (newly released or protected from microbial attack) and nonracemic (microbially degraded) sources. This paper discusses the rationale for this approach and suggests applications where chiral POPs could aid investigation of climate-mediated exchange and degradation processes. Multiyear measurements of two chiral POPs, trans-chlordane and α-HCH, at a Canadian Arctic air monitoring station show enantiomer compositions which cycle seasonally, suggesting varying source contributions which may be under climatic control. Large-scale shifts in the enantioselective metabolism of chiral POPs in soil and water might influence the enantiomer composition of atmospheric residues, and it would be advantageous to include enantiospecific analysis in POPs monitoring programs.
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| 6. |
- Chen, Wei, et al.
(författare)
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Molecularly Imprinted Polymers with Stimuli-Responsive Affinity : Progress and Perspectives
- 2015
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Ingår i: Polymers. - : MDPI. - 2073-4360. ; 7:9, s. 1689-1715
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Tidskriftsartikel (refereegranskat)abstract
- Intelligent stimuli-responsive molecularly imprinted polymers (SR-MIPs) have attracted considerable research interest in recent years due to the potential applications in drug delivery, biotechnology and separation sciences. This review comprehensively summarizes various SR-MIPs, including the design and applications of thermo-responsive MIPs, pH-responsive MIPs, photo-responsive MIPs, biomolecule-responsive MIPs and ion-responsive MIPs. Besides the development of current SR-MIPs, the advantages as well as the disadvantages of current SR-MIPs were also displayed from different angles, especially preparation methods and application fields. We believe this review will be helpful to guide the design, development and application of SR-MIPs.
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| 7. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 8. |
- Liu, Anbu, et al.
(författare)
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DDR1/2 enhance KIT activation and imatinib resistance of primary and secondary KIT mutants in gastrointestinal stromal tumors
- 2024
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Ingår i: Molecular Carcinogenesis. - 0899-1987. ; 63:1, s. 75-93
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. In this study, we observed that discoidin domain receptors 1 and 2 (DDR1 and DDR2) exhibited high expression in GISTs, were associated with KIT, and enhanced the activation of both wild-type KIT and primary KIT mutants. Inhibition of DDR1/2 led to a reduction in the activation of KIT and its downstream signaling molecules, ultimately impairing GIST cell survival and proliferation in vitro. Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first-line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. In addition, DDR1/2 inhibition resulted in decreased KIT expression, while KIT inhibition led to upregulation of DDR1/2 expression in GISTs. The presence of DDR1/2 also decreased the sensitivity of wild-type KIT or primary KIT mutants to imatinib, indicating a possible role for DDR1/2 in promoting GIST survival during KIT-targeted therapy. The development of drug-resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. Similar to primary KIT mutants, DDR1/2 can associate with and enhance the activation of secondary KIT mutants, further diminishing their sensitivity to imatinib. In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
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| 9. |
- Ma, Lijun, et al.
(författare)
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Grainyhead-like 2 in development and cancer
- 2017
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Ingår i: Tumor Biology. - : IOS Press. - 1010-4283 .- 1423-0380. ; 39:5
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Forskningsöversikt (refereegranskat)abstract
- Grainyhead-like 2 is a human homolog of Drosophila grainyhead. It inhibits epithelial-to-mesenchymal transition that is necessary for cell migration, and it is involved in neural tube closure, epithelial morphogenesis, and barrier formation during embryogenesis by regulation of the expression of cell junction proteins such as E-cadherin and vimentin. Cancer shares many common characters with development such as epithelial-to-mesenchymal transition. In addition to its important role in development, grainyhead-like 2 is implicated in carcinogenesis as well. However, the reports on grainyhead-like 2 in various cancers are controversial. Grainyhead-like 2 can act as either a tumor suppressor or an oncogene with the mechanisms not well elucidated. In this review, we summarized recent progress on grainyhead-like 2 in development and cancer in order to get an insight into the regulation network of grainyhead-like 2 and understand the roles of grainyhead-like 2 in various cancers.
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| 10. |
- Ma, Li-Jun, et al.
(författare)
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Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a whole-genome duplication.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:7, s. e1000549-
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Tidskriftsartikel (refereegranskat)abstract
- Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called "zygomycetes," R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99-880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin-proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14alpha-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments.
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