| 31. |
- Gnosa, Sebastian, et al.
(författare)
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AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model
- 2016
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Ingår i: Oncotarget. - : Impact Journals. - 1949-2553. ; 7:49, s. 81634-81644
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. Several studies have shown that radiation enhances migration and invasion both in vitro and in vivo. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.Materials and Methods We evaluated the involvement of AEG-1 in migration and invasion and radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective AEG-1 knockdown cell lines. Furthermore, we injected the cells in zebrafish embryos and evaluated the amount of disseminated cells into the tail.Results Migration and invasion was decreased in all the AEG-1 knockdown cell lines. Furthermore, radiation enhanced migration and invasion, while AEG-1 knockdown could abolish this effect. The results from the zebrafish model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.Conclusion Our results demonstrate that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced migration and invasion. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression. The zebrafish model can be used to study early events in radiation-enhanced invasion.
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| 32. |
- Gómez-Maldonado, L, et al.
(författare)
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EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination.
- 2015
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 34:20, s. 2609-2620
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Tidskriftsartikel (refereegranskat)abstract
- The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation.Oncogene advance online publication, 14 July 2014; doi:10.1038/onc.2014.200.
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| 33. |
- Grinderslev, Jakob B., et al.
(författare)
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Polymorphism and solid solutions of trimethylammonium monocarboranes
- 2022
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 51:41, s. 15806-15815
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Tidskriftsartikel (refereegranskat)abstract
- Metal closo-boranes have recently received significant attention as solid-state electrolytes due to their high thermal and electrochemical stability, and the weak interaction between the cat- and anion, facilitating fast ionic conductivity. Here we report a synthesis method for obtaining a novel mixed closo-carborane compound, [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08]. The crystal structures are investigated for [NH(CH3)3][CB9H10] and [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], revealing that the latter forms a solid solution isostructural to [NH(CH3)3][CB9H10]. The compounds exhibit polymorphism as a function of temperature, and we report the discovery of four polymorphs of [NH(CH3)3][CB9H10] and four isostructural solid solution [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], along with a high-temperature decomposition intermediate of the latter. The α-polymorph is an ordered structure, with increasing amounts of disorder for the β- and γ-polymorphs, while the high temperature δ- and ϵ-polymorphs at T > 476 K are fully disordered on both the cation and anion site. These new compounds may be used as precursors for new types of solid-state ionic conductors.
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| 34. |
- Hadad, Ronza, 1984-, et al.
(författare)
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A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019
- 2020
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 128:6, s. 440-444
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates, and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.
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| 35. |
- He, Xingkang, et al.
(författare)
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Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:37, s. 22910-22919
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocyte-based immunotherapy has emerged as a break-through in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.
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| 36. |
- Hedlund, Eva-Maria, et al.
(författare)
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Harnessing Induced Essentiality : Targeting Carbonic Anhydrase IX and Angiogenesis Reduces Lung Metastasis of Triple Negative Breast Cancer Xenografts
- 2019
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Triple Negative Breast Cancer (TNBC) is aggressive, metastatic and drug-resistant, limiting the spectrum of effective therapeutic options for breast cancer patients. To date, anti-angiogenic agents have had limited success in the treatment of systemic breast cancer, possibly due to the exacerbation of tumor hypoxia and increased metastasis. Hypoxia drives increased expression of downstream effectors, including Carbonic Anhydrase IX (CAIX), a critical functional component of the pro-survival machinery required by hypoxic tumor cells. Here, we used the highly metastatic, CAIX-positive MDA-MB-231 LM2-4 orthotopic model of TNBC to investigate whether combinatorial targeting of CAIX and angiogenesis impacts tumor growth and metastasis in vivo to improve efficacy. The administration of a small molecule inhibitor of CAIX, SLC-0111, significantly reduced overall metastatic burden, whereas exposure to sunitinib increased hypoxia and CAIX expression in primary tumors, and failed to inhibit metastasis. The administration of SLC-0111 significantly decreased primary tumor vascular density and permeability, and reduced metastasis to the lung and liver. Furthermore, combining sunitinib and SLC-0111 significantly reduced both primary tumor growth and sunitinib-induced metastasis to the lung. Our findings suggest that targeting angiogenesis and hypoxia effectors in combination holds promise as a novel rational strategy for the effective treatment of patients with TNBC.
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| 37. |
- Hjorth Larsen, Ask, et al.
(författare)
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The atomic simulation environment-a Python library for working with atoms
- 2017
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Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 29:27
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Forskningsöversikt (refereegranskat)abstract
- The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.
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| 38. |
- Hosaka, Kayoko, et al.
(författare)
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Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis
- 2013
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:2129
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Tidskriftsartikel (refereegranskat)abstract
- Anti-platelet-derived growth factor (PDGF) drugs are routinely used in front-line therapy for the treatment of various cancers, but the molecular mechanism underlying their dose-dependent impact on vascular remodelling remains poorly understood. Here we show that anti-PDGF drugs significantly inhibit tumour growth and metastasis in high PDGF-BB-producing tumours by preventing pericyte loss and vascular permeability, whereas they promote tumour cell dissemination and metastasis in PDGF-BB-low-producing or PDGF-BB-negative tumours by ablating pericytes from tumour vessels. We show that this opposing effect is due to PDGF-beta signalling in pericytes. Persistent exposure of pericytes to PDGF-BB markedly downregulates PDGF-beta and inactivation of the PDGF-beta signalling decreases integrin alpha 1 beta 1 levels, which impairs pericyte adhesion to extracellular matrix components in blood vessels. Our data suggest that tumour PDGF-BB levels may serve as a biomarker for selection of tumour-bearing hosts for anti-PDGF therapy and unsupervised use of anti-PDGF drugs could potentially promote tumour invasion and metastasis.
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| 39. |
- Hu, Wei, 1985-
(författare)
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Theoretical Study on Chemical Structures and Stability of Molecules in Metallic Junctions
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, we focus on the structural identification of the interface using surface enhanced Raman spectroscopy (SERS) and inelastic electron tunnelling scattering (IETS). Two different molecular junctions, namely gold/ trans-1,2-bis (4-pyridyl) ethylene/gold junction and gold/4,4'-bipyridine/gold junctions in various conditions were studied and the corresponding configurations were determined. The enhancement in SERS was also studied by employing the time-dependent density functional theory. Furthermore, we studied some properties of the interface, such as the stability of the adsorbates and charge transfer properties of molecular junctions. The decrease in the stability of molecules was found when adsorbed on metallic surface and trapped in metallic junctions. Our studies explained several puzzles and by rational design, more stable molecular devices were obtained.
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| 40. |
- Hu, Zhiwei, et al.
(författare)
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Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis
- 2015
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP): Policy B - Oxford Open Option B. - 0143-3334 .- 1460-2180. ; 36, s. S184-S202
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Forskningsöversikt (refereegranskat)abstract
- Angiogenesis is an important hallmark of cancer. We reviewed the various pathways controlling angiogenesis, summarized the possible role of specific environmental chemicals disrupting these pathways and listed assays for assessing the effects of low-dose exposures to chemicals in promoting tumor angiogenesis.One of the important hallmarks of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.
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