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- Devarajan, Raman, et al.
(författare)
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Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models
- 2023
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:18
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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 α6-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.
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- Illini, Oliver, et al.
(författare)
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Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
- 2024
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade >= 3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naive patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
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- Koivunen, Jukka, et al.
(författare)
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Dynamic multi-link indoor MIMO measurements at 5.3 GHz.
- 2007
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Ingår i: Proc 2nd European Conference on Antennas and Propagation (EuCAP 2007).
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Konferensbidrag (refereegranskat)abstract
- A dynamic multi-link MIMO channel indoor measurement campaign at 5.3 GHz is presented in this paper. The system setup is described and capacity with interference (with and without power control) results based on the dynamic multilink MIMO measurements are shown, and we experience a strong correlation between the relative capacity and SIR. Furthermore, an interference suppression metric is introduced and pathloss exponents and delay spreads are also presented, when moving from a typical office corridor to a large entrance hall at the premises of Lund University, Sweden.
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- Kolmonen, Veli-Matti, et al.
(författare)
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A dynamic dual-link wideband MIMO channel sounder for 5.3 GHz
- 2010
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Ingår i: IEEE Transactions on Instrumentation and Measurement. - 0018-9456. ; 59:4, s. 873-883
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedIn this paper, we present and evaluate the performance of a dynamic dual-link wideband multiple-input-multiple-output ( MIMO) channel sounder. The channel sounder can simultaneously measure two wideband dual-polarized links, each with a MIMO matrix size of 30 x 30 and 30 x 32. Multi-link MIMO systems, including multiuser and cooperative MIMO, are essential parts of future high-throughput wireless local area networks and fourth-generation cellular systems. To fully understand such systems, the dynamic characteristics of multilink MIMO channels have to be measured. In this paper, we present a channel sounder that enables such measurements, including double-directional parameter estimation possibility for both links. The presented dual-link MIMO channel sounder does not suffer from the deficiencies of previous "virtual multiuser" measurement systems. Furthermore, system analysis and sample results from a measurement campaign with this channel sounder at 5.3 GHz in an indoor office environment are presented.
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| 7. |
- Leskela, Hannu-Ville, et al.
(författare)
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Osteoblast recruitment from stem cells does not decrease by age at late adulthood
- 2003
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 311:4, s. 1008-1013
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Tidskriftsartikel (refereegranskat)abstract
- This study was aimed to characterize the ability of human bone marrow mesenchymal stem cells (MSC) to differentiate into osteoblasts in vitro. Twenty-three women and 20 men at late adulthood (52-92 years of age) were selected for the study. MSCs were isolated and cultured in vitro and alkaline phosphatase (ALP) activity, secretion of amino-terminal propeptide of type I procollagen (PINP), type III procollagen (PIIINP) and osteocalcin were analyzed. Matrix mineralization was analyzed by the von Kossa staining and by calcium quantification. We found that the ALP and PINP levels compared with control increased to 2.8- and 2.9-fold, respectively, when cells were cultured for three weeks. ALP activity, PINP and calcium deposition in response to dexamethasone treatment increased by age in women and was unchanged in men. Overall our data suggests that the osteogenic potential of MSCs does not decrease by age in either women or men at late adulthood.
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- Mercier, Bertrand, et al.
(författare)
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Sensor Networks for Cognitive Radio: Theory and System Design
- 2008
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Ingår i: Proceedings of the ICT Mobile and Wireless Communications Summit (ICT'08).
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Konferensbidrag (refereegranskat)abstract
- Following current trends towards dynamic spectrum allocation and cognitive radio, this paper proposes a new approach and innovative techniques to support the coexistence of licensed and unlicensed wireless users in a same area. Theproposed concept, called Sensor Network aided Cognitive Radio, consists of a wireless sensor network able to assist the cognitive network by providing information on the current spectrum occupancy. This concept, that will address various operational scenarios in the future networks, involves a set of advanced wireless communications techniques like spectrum sensing, interference management, cognitive radio reconfiguration management, cooperative communications, end-to-end protocol design and cross-layer optimisation. All these enabling techniques together will form a compound system able to improve the spectrum use in a significant way. The main target scenario we consider is the use of nomadic cognitive radios in urban and suburban areas. Our objective is to develop a proof-of-concept – scheduled in 2010 – of the Sensor Network aided Cognitive Radio technology by implementing such techniques and integrating them on a hardware radio platform, which will allow us to assess the efficiency of the technology in a realistic environment.
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| 9. |
- Norling, Rikke, et al.
(författare)
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Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas-A questionnaire survey in the Nordic countries
- 2012
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 51:3, s. 355-361
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Tidskriftsartikel (refereegranskat)abstract
- Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.
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