| 1. |
- Josefsson, Andreas, 1979, et al.
(författare)
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Circulating tumor cells mirror bone metastatic phenotype in prostate cancer
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9, s. 29403-29413
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Tidskriftsartikel (refereegranskat)abstract
- © Josefsson A et al. Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients. Expression of nine genes (AGR2, AKR1C3, AR, CDH1, FOLH1, HER2, KRT19, MDK, and SPINK1) showed a significant correlation between the CTC and metastasis samples. Hierarchical clustering analysis showed a similar grouping of PC patients based on the expression of these nine genes in both CTC and metastasis samples. Our findings demonstrate that CTCs mirror gene expression patterns in tissue metastasis samples from PC patients. Although low detection frequency of certain genes is a limitation in CTCs, our results indicate the potential for CTC phenotyping as a tool to improve individualized therapy in metastatic prostate cancer.
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| 2. |
- Josefsson, Andreas, 1979, et al.
(författare)
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Gene expression alterations during development of castration-resistant prostate cancer are detected in circulating tumor cells
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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| 3. |
- Linder, Anna, et al.
(författare)
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RGS2 is prognostic for development of castration resistance and cancer-specific survival in castration-resistant prostate cancer
- 2020
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Ingår i: Prostate. - : Wiley. - 0270-4137. ; 80:11, s. 799-810
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Tidskriftsartikel (refereegranskat)abstract
- Background Regulator of G-protein signaling 2 (RGS2) is a multifaceted protein with a prognostic value in hormone-naive prostate cancer (PC). It has previously been associated with the development of castration resistance. However, RGS2 expression in clinical specimens of castration-resistant prostate cancer (CRPC) and its clinical relevance has not been explored. In the present study, RGS2 was assessed in CRPC and in relation to the development of castration resistance. Methods In the present study, RGS2 expression was evaluated with immunohistochemistry in patient materials of hormone-naive and castration-resistant primary tumors, also in matched specimens before and after 3 months of androgen deprivation therapy (ADT). Cox regression and Kaplan-Meier curves were used to evaluate the clinical significance of RGS2 expression. RGS2 expression in association to castration-resistant growth was assessed experimentally in an orthotopic xenograft mouse model of CRPC. In vitro, hormone depletion of LNCaP and enzalutamide treatment of LNCaP, 22Rv1, and VCaP was performed to evaluate the association between RGS2 and the androgen receptor (AR). Stable RGS2 knockdown was used to evaluate the impact of RGS2 in association to PC cell growth under hormone-reduced conditions. Gene and protein expression were evaluated with quantitative polymerase chain reaction and Western blot analysis, respectively. Results RGS2 expression is increased in CRPC and enriched under ADT. Furthermore, a high RGS2 level is prognostic for poor cancer-specific survival for CRPC patients and significantly reduced failure-free survival (FFS) after an initiated ADT. Additionally, the prognostic value of RGS2 outperforms prostate-specific antigen (PSA) in terms of FFS. The present study furthermore suggests that RGS2 expression is reflective of AR activity. Moreover, low RGS2-expressing cells display hampered growth under hormone-reduced conditions, in line with the poor prognosis associated with high RGS2 expression. Conclusions High levels of RGS2 are associated with aggressive forms of castration-resistant PC. The results demonstrate that a high level of RGS2 is associated with poor prognosis in association with castration-resistant PC growth. RGS2 alone, or in association with PSA, has the potential to identify patients that require additional treatment at an early stage during ADT.
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| 4. |
- Yakimova, Rositsa, et al.
(författare)
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Analysis of the Formation Conditions for Large Area Epitaxial Graphene on SiC Substrates
- 2010
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2009, PTS 1 AND 2. - : Trans Tech Publications Inc.. ; 565, s. 645-648
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Konferensbidrag (refereegranskat)abstract
- We are aiming at understanding the graphene formation mechanism on different SiC polytypes (6H, 4H and 3C) and orientations with the ultimate goal to fabricate large area graphene (up to 2 inch) with controlled number of monolayers and spatial uniformity. To reach the objectives we are using high-temperature atmospheric pressure sublimation process in an inductively heated furnace. The epitaxial graphene is characterized by ARPES, LEEM and Raman spectroscopy. Theoretical studies are employed to get better insight of graphene patterns and stability. Reproducible results of single layer graphene on the Si-face of 6H and 4H-SiC polytypes have been attained. It is demonstrated that thickness uniformity of graphene is very sensitive to the substrate miscut.
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| 5. |
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| 6. |
- Bayani, Amirhossein, et al.
(författare)
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Intercalation of Au Atoms into SiC(0001)/Buffer Interfaces : A First-Principles Density Functional Theory Study
- 2020
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:24, s. 14842-14846
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Tidskriftsartikel (refereegranskat)abstract
- The process of Au intercalation into a SiC/buffer interface has been theoretically investigated here by using density functional theory (DFT) and the nudged elastic band (NEB) method. Energy barriers were at first calculated (using NEB) for the transfer of an Au atom through a free-standing graphene sheet. The graphene sheet was either of a nondefect character or with a defect in the form of an enlarged hexagonal carbon ring. Defects in the form of single and double vacancies were also considered. Besides giving a qualitative prediction of the relative energy barriers for the corresponding SiC/buffer interfaces, some of the graphene calculations also proved evidence of energy minima close to the graphene sheet. The most stable Au positions within the SiC/buffer interface were, therefore, calculated by performing geometry optimization with Au in the vicinity of the buffer layer. Based on these NEB and DFT calculations, two factors were observed to have a great influence on the Au intercalation process: (i) energy barrier and (ii) preferential bonding of Au to the radical C atoms at the edges of the vacancies. The energy barriers were considerably smaller in the presence of vacancies. However, the Au atoms preferred to bind to the edge atoms of these vacancies when approaching the buffer layer. It can thereby be concluded that the Au intercalation will only occur for a nondefect buffer layer when using high temperature and/or by using high-energy impacts by Au atoms. For this type of Au intercalation, the buffer layer will become completely detached from the SiC surface, forming a single layer of graphene with an intact Dirac point.
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| 7. |
- Bayani, Amirhossein, et al.
(författare)
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The influence by substrate morphology on the Rashba band splitting in graphene
- 2020
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Ingår i: Results in Physics. - : Elsevier. - 2211-3797. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- The influence of substrate morphology on the Rashba band splitting at the Dirac point of graphene, has been theoretically investigated. More specifically, the possibility for this splitting to be caused by spin–orbit coupling (with the heavy metal substrate) was of a special interest to study. The model system consisted of a 4H-SiC (0 0 0 1)/graphene interface, with an intercalated metal layer (Ag and Au, respectively). These intercalating metal layers were built with two different types of morphologies; either flat or buckled (with different buckling positions). The results show that depending on the position of the buckled metal atom, the size of the bandgap and band splitting (at the Dirac point of graphene) will either increase (or decrease). Moreover, the enlargement of the buckling size was also shown to affect the electronic properties of graphene (i.e., by increasing the bandgap). The sizes of the bandgaps and band splitting for the different intercalating metals (Ag and Au), were also found to be different. Spin-projected band structures was also implemented in the present study, with the purpose to show the spin-texture of graphene. It was thereby shown that the spins pined to the x and y spin components for most of the cases.
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| 8. |
- Bayani, Amirhossein, et al.
(författare)
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The morphology of an intercalated Au layer with its effect on the Dirac point of graphene
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- This is a theoretical investigation where Density Functional Theory (DFT) has been used in studying the phenomenon of Au intercalation within the 4H-SiC/graphene interface. The electronic structure of some carefully chosen morphologies of the Au layer has then been of special interest to study. One of these specific Au morphologies is of a more hypothetical nature, whilst the others are, from an experimental point of view, realistic ones. The latter ones were also found to be energetically stable. Band structure calculations showed that intercalated Au layers with morphologies different from a planar Au layer will induce a band gap at the Dirac point of graphene (with up to 174 meV for the morphologies studied in the present work). It should here be mentioned that this bandgap size is four times larger than the energy of thermal motion at room temperature (26 meV). These findings reveal that a wide bandgap at the Dirac point of graphene comes from an inhomogeneous staggered potential on the Au layer, which non-uniformly breaks the sublattice symmetry. The presence of spin-orbit (SO) interactions have also been included in the present study, with the purpose to find out if SO will create a bandgap and/or band splitting of graphene.
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| 9. |
- Brisby, Helena, 1965, et al.
(författare)
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Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica.
- 2002
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Ingår i: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. - 0940-6719. ; 11:1, s. 62-6
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Tidskriftsartikel (refereegranskat)abstract
- Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1beta IL-6, IL-8, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar disc herniation and sciatica. Pain duration and pain intensity (visual analogue scale, VAS) were recorded at inclusion, and a clinical examination was performed evaluating neurological findings. The extent of disc herniation (protrusion or extrusion/sequestration) was evaluated perioperatively. Normal concentrations of IL-1beta, IL-6, IFN-gamma and TNF-alpha were present in CSF and serum in almost all patients with lumbar disc herniation. The concentrations of IL-8 in CSF were increased in 12 out of 39 patients, and these increased levels of IL-8 correlated to a short duration of pain and to more pronounced herniation (extrusion or sequestration). No relationship between IL-8 concentrations in CSF and pain intensity, positive neurological findings or a positive straight leg-raising (SLR) test was found. The observation of increased concentrations of IL-8 in CSF in patients with a short duration of symptoms supports the concept of the initial involvement of inflammatory mechanisms after a disc herniation. The finding that most of the patients with increased concentrations of IL-8 in CSF had an extrusion or a sequestration may suggest that the increase in IL-8 is related to mechanical nerve root compression, but may also indicate a biochemical effect exerted by the herniated disc on the surrounding tissue. Further studies on the potential role of IL-8 as a biomarker for disc herniation are warranted.
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| 10. |
- Buchner, Franziska, et al.
(författare)
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Early dynamics of the emission of solvated electrons from nanodiamonds in water
- 2022
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Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 14:46, s. 17188-17195
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Tidskriftsartikel (refereegranskat)abstract
- Solvated electrons are among the most reductive species in an aqueous environment. Diamond materials have been proposed as a promising source of solvated electrons, but the underlying emission process in water remains elusive so far. Here, we show spectroscopic evidence for the emission of solvated electrons from detonation nanodiamonds upon excitation with both deep ultraviolet (225 nm) and visible (400 nm) light using ultrafast transient absorption. The crucial role of surface termination in the emission process is evidenced by comparing hydrogenated, hydroxylated and carboxylated nanodiamonds. In particular, a transient response that we attribute to solvated electrons is observed on hydrogenated nanodiamonds upon visible light excitation, while it shows a sub-ps recombination due to trap states when excited with deep ultraviolet light. The essential role of surface reconstructions on the nanodiamonds in these processes is proposed based on density functional theory calculations. These results open new perspectives for solar-driven emission of solvated electrons in an aqueous phase using nanodiamonds.
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