| 1. |
- Devarajan, R., et al.
(författare)
-
Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models
- 2023
-
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 133:18
-
Tidskriftsartikel (refereegranskat)abstract
- The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs. We discovered a role for ColXVIII as a modulator of epidermal growth factor receptor tyrosine kinase (ErbB) signaling and show that it forms a complex with ErbB1 and-2 (also known as EGFR and human epidermal growth factor receptor 2 [HER2]) and alpha 6-integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/AKT cascades. Studies using Col18a1 mouse models crossed with the mouse mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT) mammary carcinogenesis model showed that ColXVIII promoted BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in the MMTV-PyMT and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII substantially improved the efficacy of ErbB-targeting therapies in both preclinical models. In summary, ColXVIII was found to sustain the stemness properties of BC cells and tumor progression and metastasis through ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have important therapeutic potential.
|
|
| 2. |
- Karppinen, J, et al.
(författare)
-
Serum biomarkers for Modic changes in patients with chronic low back pain
- 2021
-
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. - : Springer Science and Business Media LLC. - 1432-0932. ; 30:64, s. 1018-1027
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Karppinen, S. -M., et al.
(författare)
-
Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies
- 2006
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 43:11, s. 856-862
-
Tidskriftsartikel (refereegranskat)abstract
- Background: BARD1 was originally identified as a BRCA1- interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C- terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. Aim and methods: Conformation- sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high- performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case - control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. Results: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls ( 6.8% v 2.7%; p < 0.001; odds ratio ( OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/ BRCA2 mutation- positive families ( 6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. Conclusion: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.
|
|
| 4. |
- Gronbaek, J. Kjaer, et al.
(författare)
-
Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood : a prospective European multicentre study
- 2022
-
Ingår i: Child's Nervous System. - : Springer Nature. - 0256-7040 .- 1433-0350. ; 38:4, s. 747-758
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. Methods In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. Results We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). Conclusion Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.
|
|
| 5. |
- Koivisto, K, et al.
(författare)
-
The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging
- 2019
-
Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 9:4
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.
|
|
| 6. |
- Shafeie, Samrand, 1984-, et al.
(författare)
-
Phase formation, crystal structures and magnetic properties of perovskite-type phases in the system La2Co1+z(MgxTi1-x)1-zO6
- 2011
-
Ingår i: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596 .- 1095-726X. ; 184:1, s. 177-190
-
Tidskriftsartikel (refereegranskat)abstract
- Perovskite-type cobaltates in the system La(2)Co(1+z) (Mg(x)Ti(1-x))(1-z)O(6) were studied for z=0 <= x <= 0.6 and 0 <= x <= 0.9, using X-ray and neutron powder diffraction, electron diffraction (ED), magnetic susceptibility measurements and X-ray absorption near-edge structure (XANES) spectroscopy. The samples were synthesised using the citrate route in air at 1350 degrees C. The space group symmetry of the structure changes from P2(1)/n via Pbnm to R (3) over barc with both increasing Mg content and increasing Co content. The La(2)Co(Mg(x)Ti(1-x))O(6) (z=0) compounds show anti-ferromagnetic couplings of the magnetic moments for the Co below 15 K for x=0, 0.1 and 0.2. XANES spectra show for the compositions 0 <= x <= 0.5 a linear decrease in the L(3)/(L(3)+ L(2))Co-L(2.3) edge branching ratio with x, in agreement with a decrease of the average Co ion spin-state, from a high-spin to a lower-spin-state, with decreasing nominal Co(2+) ion content.
|
|
| 7. |
- Nasibulina, Larisa I., et al.
(författare)
-
Direct synthesis of carbon nanofibers on cement particles
- 2010
-
Ingår i: Transportation Research Record. - : SAGE Publications. - 0361-1981 .- 2169-4052. ; :2142, s. 96-101
-
Tidskriftsartikel (refereegranskat)abstract
- Carbon nanotubes (CNTs) and nanofibers (CNFs) are promising candidates for the next generation of high-performance structural and multifunctional composite materials. One of the largest obstacles to creating strong, electrically or thermally conductive CNT-CNF composites is the difficulty of getting a good dispersion of the carbon nanomaterials in a matrix. Typically, time-consuming steps are required in purifying and functionalizing the carbon nanomaterial. A new approach under which CNTs-CNFs are grown directly on the surface of matrix and matrix precursor particles is proposed. Cement was selected as the precursor matrix, since it is the most important construction material. A novel cement hybrid material (CHM) was synthesized in which CNTs and CNFs are attached to the cement particles by two different methods: screw feeder and fluidized bed reactors. CHM has been proved to increase the compressive strength by two times and the electrical conductivity of the hardened paste by 40 times.
|
|
| 8. |
- Mudimela, Prasantha R., et al.
(författare)
-
Synthesis of carbon nanotubes and nanofibers on silica and cement matrix materials
- 2009
-
Ingår i: Journal of Nanomaterials. - : Hindawi Limited. - 1687-4110 .- 1687-4129. ; 2009
-
Tidskriftsartikel (refereegranskat)abstract
- In order to create strong composite materials, a good dispersion of carbon nanotubes (CNTs) and nanofibers (CNFs) in a matrix material must be obtained. We proposed a simple method of growing the desirable carbon nanomaterial directly on the surface of matrix particles. CNTs and CNFs were synthesised on the surface of model object, silica fume particles impregnated by iron salt, and directly on pristine cement particles, naturally containing iron oxide. Acetylene was successfully utilised as a carbon source in the temperature range from 550 to 750 °C. 5-10 walled CNTs with diameters of 10-15nm at 600 °C and 12-20nm at 750 °C were synthesised on silica particles. In case of cement particles, mainly CNFs with a diameter of around 30nm were grown. It was shown that high temperatures caused chemical and physical transformation of cement particles. © 2009 Prasantha R. Mudimela et al.
|
|
